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PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO GRANDE DO SUL
FACULDADE DE BIOCIÊNCIAS
PROGRAMA DE PÓS-GRADUAÇÃO EM BIOLOGIA CELULAR E MOLECULAR
ESTUDO DE ASSOCIAÇÃO
ENTRE O ÁCIDO ÚRICO E
O TEMPERAMENTO
TAISE MICHELE LORENZI FERREIRA
Porto Alegre
2008
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ESTUDO DE ASSOCIAÇÃO ENTRE O ÁCIDO
ÚRICO E O TEMPERAMENTO
Projeto de pesquisa das atividades desenvolvidas com a finalidade de obtenção de
Título de Mestre em Biologia Celular e Molecular pelo PPGBCM - PUCRS
Orientador: Dr. Diogo Rizzato Lara
Porto Alegre
2008
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3
Agradecimentos
Aos meus pais, que tornaram isto tudo possível;
Ao meu orientador Diogo Rizzato Lara, por ter prontamente aceitado orientar-
me, e por todo o auxílio e amizade durante a confecção deste trabalho;
Ao meu irmão Cláudio Lorenzi Ferreira, minha cunhada Elisabete Lorensi
Ferreira e minha querida amiga Paula Simas Rocha, pela amizade e motivação
durante o desenvolvimento do estudo.
À Daniela Borba por ter ajudado significativamente na validação da escala de
temperamento.
Ao grupo de pesquisa que participo e em especial à Miriam Brusntein e Luísa
Bisol pelo enorme incentivo e ajuda na preparação da defesa do trabalho.
Ao meu colega Gustavo Dutra, por ter aberto seu laboratório para coleta e
análise dos dados desta pesquisa.
Às minhas colegas de curso, Josiane Bandinelli, Caroline Ruck e Liana
Fernandez, pela amizade e aprendizado adquirido no decorrer do curso.
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SUMÁRIO
LISTA DE ABREVIATURAS E SIGLAS..............................................................................5
RESUMO
...........................................................................................................................6
ABSTRACT
........................................................................................................................8
1. INTRODUÇÃO
...............................................................................................................9
1.1. TEMPERAMENTO
..................................................................................................9
1.2. PURINAS E ÁCIDO ÚRICO
..................................................................................11
1.2.1. Síntese DE NOVO e Via de salvamento de purinas
......................................13
1.3. HIPERURICEMIA E GOTA
.................................................................................... 15
1.4. RELAÇÃO ENTRE HIPERURICEMIA, GOTA E VARIÁVEIS PSICOLÓGICAS
.....16
1.5. ALOPURINOL: UM FÁRMACO HIPOURICEMIANTE
...........................................20
2. OBJETIVO
...................................................................................................................21
3. ARTIGO
....................................................................................................................... 22
4. DISCUSSÃO E CONCLUSÃO
..................................................................................... 36
5. REFERÊNCIAS BIBLIOGRÁFICAS
............................................................................38
ANEXO A – Escala de Temperamento Afetivo e Emocional (ETAFE)
............................ 43
ANEXO B – Termo de Consetimento
.............................................................................51
ANEXO C – Artigo da validação da escala de temperamemto
.......................................54
5
LISTA DE ABREVIATURAS E SIGLAS
ADP - Adenosina difosfato.
AMP- adenosina monofosfato.
AMPc- Adenosina monofosfato cíclico.
APRT-adenina fosforribosil transferase.
ATP- Adenosina trifosfato.
AU
– Ácido úrico.
AUS – Ácido úrico sérico.
DNA- ácido desoxirribonucleico.
ETAFE- Escala de temperamento afetivo e emocional.
GDP- guanosina difosfato.
GMP - guanosina monofosfato.
GTP- guanosina trifosfato.
HRPT - hipoxantina fosforribosil transferase.
IMP - inosina monofosfato.
NAD+ - dinucleotídeo nicotinamida-adenina .
PRPP - amidotransferase 5’-fosforribosil-1-pirofosfato.
PRS - PRPP sintetase.
RNA- ácido ribonucleico.
TDAH - transtorno de déficit de atenção.
XDH- xantina desidrogenase.
XO - xantina oxidase.
XOR-xantina oxireductase.
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RESUMO
Lorenzi, Taise Michele. Lara, Diogo. Estudo de Associação entre
ácido úrico e temperamento. Porto Alegre - RS, 2008. 78p.
Dissertação de Mestrado – Faculdade de Biociência - Programa de
Pós-Graduação em Biologia Celular e Molecular, Pontifícia
Universidade Católica do Rio Grande do Sul.
O temperamento diz respeito à natureza emocional e ao humor basal.
Propusemos uma integração dos construtos de temperamentos emocional e
afetivo baseado no princípio de ativação (vontade e raiva) e inibição (medo)
como as duas forças emocionais principais, que são reguladas por um sistema
de controle (atenção e dever). A interação dessas forças resultaria no padrão de
humor basal ou temperamento afetivo. O ácido úrico (AU) é o produto final do
metabolismo de purinas e já foi associado com variáveis psicológicas como alta
energia/vontade, afeto positivo, sucesso, alto desempenho, status social mais
elevado e liderança. No presente estudo avaliamos 129 voluntários (44 homens
e 85 mulheres) com a Escala de Temperamento Afetivo e Emocional, níveis
séricos de AU e um questionário geral de saúde. Na amostra total, os níveis
séricos de AU foram significativamente correlacionados com desinibição (r=0.36,
p<0.001) e vontade (r=0.25, p<0.01), mas não com controle, raiva ou qualquer
dos temperamentos afetivos. Entre homens, encontramos tendências de
correlação (p >0.05 and <0.07) para controle (r=0.27) e os temperamentos
afetivos irritável (r=0.29) e hipertímico (r=0.27). Entre mulheres, uma correlação
significativa foi observada somente com desinibição (r=0.34, p=0.001). O tertil
mais alto dos homens (AU sérico>6.0 mg/ml, n=16) apresentou
significativamente mais vontade (29.9±5.9 X 26.0±3.6, p=0.01) e controle no
nível de tendência (21.2±3.1 X 19.3±2.9, p=0.054) do que o resto da amostra.
Entre mulheres, o tertil superior (AU sérico>4.0 mg/ml, n=29) apresentou
maiores escores de desinibição (20.7±4.9 X 17.9±3.6, p<0.01) e mais
frequentemente escolheram os temperamentos afetivos hipertímico (8/26 X 6/59,
p=0.023) e irritável (7/26 X 5/59, p=0.031) do que o resto da amostra. Em suma,
esses resultados confirmam que traços externalizados de temperamento estão
associados com níveis mais altos de AU tanto em homens como em mulheres.
7
Palavras-chave
Temperamento, Ácido Úrico.
8
ABSTRACT
Temperament relates to the emotional nature and the quality of the
prevailing mood. We have proposed an integration of emotional and affective
temperament constructs based on the principle that activation (anger and
drive/pleasure) and inhibition (fear) are the two main emotional forces, which are
integrated by the control system (attention and duty). Their interaction would
result in the prevailing mood or affective temperaments. Uric acid (UA) is the
end-product of purine metabolism and has been associated with psychological
features such as high energy/drive, positive affect, achievement, good
performance, higher social status and leadership. In this study we evaluated 129
subjects (44 males, 85 females) with the Combined Emotional and Affective
Temperaments Scale, serum UA levels and a general health questionnaire. In
the whole sample, serum UA levels were significantly correlated with disinhibition
(r=0.36, p<0.001) and drive (r=0.25, p<0.01), but not with control, anger or any of
the affective temperament scores. Among males, we found correlations at trend
level (p >0.05 and <0.07) for control (r=0.27), irritable (r=0.29) and hyperthymic
(r=0.27) affective temperaments. Among females, a significant correlation was
found only with disinhibition (r=0.34, p=0.001). The top tertile of males (serum
UA>6.0 mg/ml, n=16) had significantly higher drive (29.9±5.9 X 26.0±3.6, p=0.01)
and higher control at trend level (21.2±3.1 X 19.3±2.9, p=0.054) than the rest of
the sample. Among women, the top tertile (serum UA>4.0 mg/ml, n=29) showed
higher disinhibition scores (20.7±4.9 X 17.9±3.6, p<0.01) and more choices of
hyperthymic (8/26 X 6/59, p=0.023) and irritable temperaments (7/26 X 5/59,
p=0.031) than the rest of the sample. In conclusion, these results confirm that
externalized traits of temperament are associated with higher serum UA levels
both in men and women.
Keywords
Temperament, Uric Acid.
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1. INTRODUÇÃO
1.1. TEMPERAMENTO
O temperamento diz respeito ao padrão emocional básico, que confere
características de variações afetivas que tendem a perdurar durante toda a vida
(Akiskal, 2005). O temperamento também pode ser considerado como a base do
humor, do comportamento e da personalidade (Lara et al., 2006b). Alguns
modelos foram propostos para caracterizá-lo e conceituá-lo.
O modelo psicobiológico dimensional de temperamento descrito por
Cloninger e colaboradores (1993) (Cloninger et al., 1993) caracteriza o
temperamento como os traços emocionais básicos que têm herança
predominantemente genética. Cada dimensão do temperamento está
relacionada às emoções básicas de medo (evitação de dano), raiva (busca de
novidades), apego (dependência de reforço social) e ambição ou determinação
(persistência). Nesse modelo, as dimensões apresentam distribuição normal,
contemplando tanto a normalidade quanto as suas variações.
Já Akiskal concebe o temperamento a partir do padrão afetivo básico, que
pode ser hipertímico, ciclotímico, irritável, depressivo ou ansioso (Akiskal, 2005).
Esse modelo foi inspirado nas observações de (Kraeplin, 1921) e está mais
voltado para a caracterização de pacientes com transtornos de humor, portanto
carece de uma proposta para pessoas sem transtornos psiquiátricos.
Medo, vontade e raiva são as emoções mais básicas que constituem o
temperamento, que são moduladas por uma função de controle (Lara and
Akiskal, 2006). O modelo dimensional baseado em traços de medo,
vontade/raiva proposto recentemente (Lara and Akiskal, 2006) adapta os
conceitos de evitação de dano e busca de novidades de Cloninger e busca
combinar as vantagens dessa abordagem ao modelo de Akiskal para
temperamentos afetivos. Essa remodelação tem como objetivo diminuir as
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limitações de ambos os modelos. Este novo modelo integrativo incorpora as
dimensões normais e patológicas, concebe transtornos de humor,
comportamento e personalidade concomitantemente, e fundamenta-se em
funções cerebrais nos níveis comportamental, cognitivo, neuroquímico e
anatômico.
A combinação dos traços de ativação (vontade/raiva), inibição (medo) e
controle (dever-atenção) geraria os principais tipos de temperamentos afetivos
propostos (Tabela 1) (Lara et al., 2006b).
Tabela 1: Temperamentos afetivos modulados por ativação e inibição emocionais
Temperamento afetivo Ativação
(vontade)
Ativação
(raiva)
Inibição
(medo)
Controle
(dever-
atenção)
Depressivo ↓↓ ↔ ↑ ↔
Ansioso ↔ ↔ ↑ ↔
Apático ↓ ↓ ↔ ↓↓
Ciclotímico/disfórico ↔ ↑↑ ↔ ↓
Eutímico ↑ ↓ ↔ ↑
Irritável ↑ ↑↑ ↔ ↑
Lábil ↓ ↑ ↔ ↓↓
Desinibido ↔ ↔ ↓ ↓
Hipertímico ↑↑ ↔ ↓↓ ↑
↓ - baixo, ↓↓ - muito baixo, ↑ - alto, ↑↑ - muito alto,↔ médio
Esses temperamentos afetivos formariam a predisposição a transtornos
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psiquiátricos, como transtorno bipolar do tipo I em hipertímicos e irritáveis, do
tipo II em irritáveis e ciclotímicos, transtornos de ansiedade em ansiosos,
depressão maior em depressivos, e TDAH (transtorno de déficit de atenção e
hiperatividade) e seus subtipos em lábeis, apáticos e desinibidos (Lara and
Akiskal, 2006).
Para testar o novo modelo, foi criada e validada a Escala de
Temperamento Afetivo e Emocional (ETAFE - Anexo A) com questões auto-
aplicáveis relacionadas aos traços de medo, raiva, vontade e controle, assim
como aos temperamentos afetivos (manuscrito submetido – Anexo B). Esta
escala possui questões auto-aplicáveis e possibilita a correlação entre os
temperamentos afetivos e os traços emocionais de medo, vontade, raiva e
controle. De maneira geral, as combinações dos traços de medo, vontade/raiva
e controle proposta pelo modelo e os 10 tipos de temperamentos afetivos foi
essencialmente confirmada.
1.2. PURINAS E ÁCIDO ÚRICO
As purinas são fundamentais nos processos relacionados à energia
celular (principalmente ATP e ADP), na sinalização transmembrana (GTP e
GDP), na sinalização intracelular (AMPc), e como parte do DNA e do RNA
(adenina e guanina) (Hediger et al., 2005).
O produto final do metabolismo de purinas no ser humano é o ácido úrico
(AU). O AU é um ácido fraco (pKa 5,8) que existe em grande quantidade como
urato (sua forma ionizada) em pH fisiológico (Choi et al., 2005) e livre de
qualquer proteína carreadora no plasma sanguíneo (Ngo and Assimos, 2007). A
biosíntese de ácido úrico é catalisada pela enzima xantina oxidase ou pela sua
isoforma, a xantina desidrogenase (Choi et al., 2005).
A excreção do ácido úrico permite eliminar o nitrogênio excedente do
organismo (Pillinger et al. 2007). A produção endógena diária de urato gira em
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torno de 300 a 400 mg, porém a excreção total pode variar dependendo da
ingestão de purinas na alimentação (Ngo and Assimos, 2007). Os rins são
responsáveis por 70% da excreção diária do AU e o restante é eliminado pelos
intestinos, pele, cabelo e unhas (Anzai et al., 2005). No intestino, o AU é
degradado em dióxido de carbono e amônia que são reabsorvidos ou liberados
como gás intestinal.
Em muitos peixes, anfíbios e mamíferos não primatas, o ácido úrico é
degradado pela uricase ou urato oxidase, enzima que catalisa a conversão de
urato em alantoína (Choi et al., 2005). Na maioria dos mamíferos, a conversão
de ácido úrico em alantoína resulta em níveis muito baixos de ácido úrico sérico
(AUS) (menos do que 1mg/dL) (Eggebeen, 2007). A alantoína, por ser uma
substância mais solúvel que o urato, é mais facilmente eliminada na urina
(Terkeltaub et al., 2006).
Em humanos e na grande maioria dos macacos, o gene que produz a
uricase sofreu mutações que o deixaram inativo (Wu et al., 1989). A vantagem
evolutiva da inatividade da uricase em humanos e na maioria dos macacos não
está clara, porém uma das hipóteses é que o urato pode remover a molécula de
oxigênio e radicais livres tão efetivamente quanto a vitamina C (Choi et al.,
2005). Um estudo proposto por Watanabe e colaboradores (Watanabe et al.,
2002) sugere uma especial vantagem evolutiva na perda da uricase em
humanos e em macacos. Eles notaram que no período Miocênico, nossos
ancestrais tinham uma alimentação vegetariana, particularmente pobre em
sódio. O nefrologista Richard Johnson, baseado nesses achados, propõem que
a hipotensão é ocasionada pela dieta pobre em sódio. Mais adiante, Johnson
hipotetizou que a perda da uricase e o acúmulo de AU pode, de certo modo, ter
compensado o problema da hipotensão. E essa particularidade ocorre apenas
em humanos e macacos porque esses são os únicos mamíferos que gastam a
maior parte do tempo como bípedes e com isso são mais dependentes de maior
pressão sanguínea que mantém a perfusão cerebral (Pillinger et al., 2007).
Watanabe e colaboradores (2002) propuseram que a perda da uricase
13
nos humanos e macacos favoreceu a manutenção da pressão sanguínea para
manter a perfusão cerebral na postura bípede, especialmente em épocas de
dieta pobre em sódio.
1.2.1. Síntese de novo e via de salvamento de purinas
A síntese de novo de purinas ocorre através de vários passos e requer a
contribuição de 4 aminoácidos, sendo 1 molécula de amidotransferase 5’-
fosforribosil-1-pirofosfato (PRPP), 2 folatos e 3 moléculas de adenosina trifosfato
(ATP) para sintetizar uma molécula de inosina monofosfato (IMP) (Torres and
Puig, 2007). A PRPP é produzida pela adição de um grupo fosfato do ATP ao
açúcar modificado ribose-5-fosfato (Choi et al., 2005). O ponto inicial da síntese
de novo é a conversão da ribose-5-fosfato (uma pentose derivada do
metabolismo glicídico) em PRPP e fosforribosilamina, que será transformada em
IMP. A partir desse IMP são derivados o AMP (adenosina monofosfato), o GMP
(guanosina monofosfato), as bases púricas (adenina e guanina – úteis na
síntese de DNA e RNA) e a inosina (que será degradada em hipoxantina e
xantina até ácido úrico) (Cammalleri and Malaguarnera, 2007).
Já a via de salvamento é mediada pela hipoxantina fosforribosil
transferase (HRPT) e também pela adenina fosforribosil transferase (APRT). A
HRPT catalisa a síntese de salvamento de IMP e GMP a partir das bases
hipoxantina e guanina respectivamente (Torres and Puig, 2007). Somente uma
pequena parte dos pacientes que sofrem de superprodução de ácido úrico
possuem problemas genéticos, tais como a super atividade da enzima PRS
(PRPP sintetase) e a deficiência da enzima HRPT (que resulta no acúmulo de
hipoxantina e guanina e que são facilmente convertidas em ácido úrico através
da enzima xantina oxidase) (Choi et al., 2005).
A deficiência na enzima HRPT leva à síndrome de Lesch-Nyhan, que
caracteriza-se por hiperuricemia e hiperuricosúria e algumas manifestações
neurológicas e psiquiátricas, como retardo mental, auto-mutilação e
14
coreoatetose (Jinnah et al., 2006).
Uma elevada atividade na enzima APRT pode contribuir para a
superprodução de purinas (Torres and Puig, 2007). Condições associadas com
a degradação do ATP conduzem ao acúmulo de adenosina difosfato (ADP) e
adenosina monofosfafto (AMP), que podem ser rapidamente degradas até ácido
úrico, podendo também causar hiperuricemia (Choi et al., 2005).
Figura 1 – Síntese de novo e de salvamento de purinas (retirado de (Torres and Puig, 2007).
Entre as purinas, a adenosina é um importante neuromodulador a ser
mais estudado na psiquiatria, uma vez que modula vários sistemas
neurotransmissores e tem importantes funções por si só (Fredholm et al., 2005).
A cafeína, que é um bloqueador não seletivo de receptores adenosinérgicos (A1
e A2), pode desencadear ou agravar vários sintomas associados à raiva e ao
medo (ansiedade, ataques de pânico, hipomania e estados mistos) (Lara and
Akiskal, 2006). Em contraste, agonistas adenosinérgicos apresentaram efeitos
ansiolíticos, anti-agressivos e antipsicóticos (Fredholm et al., 2005). A ausência
15
de receptores A1 e A2 em camundongos foi associado ao comportamento
agressivo e ansioso e à instabilidade emocional (Ledent et al., 1997; Gimenez-
Llort et al., 2002; Lang et al., 2003).
1.3. HIPERURICEMIA E GOTA
Em 1776, o químico sueco Scheele (Scheele, 1776) identificou ácido úrico
na urina de pacientes com gota. Em 1797, o químico inglês, Wollaston
(Woolaston, 1797) percebeu que os tumores nas articulações causados pela
doença continham ácido úrico (Nuki and Simkin, 2006). Fischer, no mesmo
século, determinou a estrutura bioquímica do ácido úrico e sua relação com as
purinas (Katz and Weiner, 1972).
Os humanos são os únicos mamíferos que desenvolvem gota,
provavelmente em função dos altos níveis de uricemia em comparação a outras
espécies (Johnson and Rideout, 2004), uma vez que em outros animais o ácido
úrico é degradado pela uricase até alantoína. A ausência de uricase, combinada
com a grande reabsorção do urato filtrado, resulta em altos níveis de ácido úrico
no sangue (de 2 a 7 mg/dl normalmente, aproximadamente 10 vezes mais que
em outros mamíferos) (Wu et al., 1992).
A hiperuricemia caracteriza-se por concentrações de ácido úrico sérico
maiores que 7 mg/dl (miligramas por decilitro) em homens (Iwanaga et al., 2005)
e maiores que 6 mg/dl em mulheres. É o principal fator de risco para
desencadear a gota. Em um estudo de larga escala, com duração de 5 anos, o
risco de desencadear a doença foi de 0.6% para os indivíduos que
apresentaram níveis de AUS menores que 7 mg/dL e de 30.5% para aqueles
que tinham níveis de AUS iguais ou maiores que 10 mg/dL (Falasca, 2006). É
importante ressaltar que nem todos que desenvolvem hiperuricemia,
desenvolvem gota (Hediger et al., 2005). Os níveis de AUS se elevam após a
puberdade em homens e após a menopausa em mulheres, fatos que sugerem
alguma relação com os hormônio sexuais. Na população geral, os níveis de
16
ácido úrico apresentam uma distribuição normal unimodal, sugerindo herança
poligênica. A alimentação com altos níveis de purinas e o álcool, principalmente
cerveja, que contém muita guanosina (Choi et al., 2005) pode causar
hiperuricemia (Katz and Weiner, 1972).
A hiperuricemia resulta da superprodução de ácido úrico (que ocorre em
10% dos casos e está associada a defeitos congênitos e também relacionada
com problemas no metabolismo de purinas), da baixa excreção do ácido úrico
realizada pelos rins (que ocorre em 90% dos casos) ou de ambas as
possibilidades (Choi et al., 2005). Uma pequena parte dos pacientes que
apresentam superprodução de ácido úrico possuem problemas congênitos, tais
como superatividade do PRS (enzima que sintetiza PRPP) ou deficiência na
enzima HPRT.
Na gota, quando os limites locais de AUS ultrapassam o ponto crítico de
solubilidade, os cristais monossódicos de urato depositam-se nas articulações,
rins e tecidos moles. O acúmulo desta substância pode levar a artrites, formação
de massa de tecido mole (também chamado de tofo), nefrolitíases e nefropatia
de urato (Eggebeen, 2007). No entanto, nem todas as pessoas que possuem
hiperuricemia desenvolvem a doença. Não há diferença entre homens e
mulheres na chance de desenvolver gota nos vários níveis de ácido úrico (Katz
and Weiner, 1972).
1.4. RELAÇÃO ENTRE HIPERURICEMIA, GOTA E VARIÁVEIS
PSICOLÓGICAS
Hipócrates e outros médicos da antiguidade estavam familiarizados com
os sinais e sintomas da gota, mas foi Paulo de Aegina, mil anos depois de
Hipócrates, que observou que fatores emocionais poderiam precipitar ataques
da doença. A partir daí também observou-se que excessos alimentares também
poderiam induzir um episódio agudo de gota (Katz and Weiner, 1972).
17
Um fato curioso e importante é que muitas pessoas notáveis sofriam de
gota, como: Édipo, Ulisses, Alexandre o Grande, Michelangelo, a família Medicy,
Henrique VII e VIII, João Calvino, Martin Luther, Luis XIV, Isaac Newton,
Thomas Sydenham, Benjamim Franklin e Theodore Roosevelt. Cullen (1778)
observou que a gota ocorria mais freqüentemente “entre os sábios do que entre
os tolos”, estando de alguma forma correlacionada com fama e notoriedade
(Katz and Weiner, 1972).
Alguns estudos já a partir da década de 50 mostraram a correlação entre
os níveis de AUS e aspectos sociais, psicológicos e de personalidade
associados a sucesso, energia e alto desempenho (Rahe et al., 1974) e (Katz
and Weiner, 1972). No entanto, nos últimos vinte anos essa área foi pouco
estudada.
Um estudo realizado em 1959 (Stetten and Hearon, 1959) relacionou a
inteligência com os níveis de AUS. Já Dunn e colaboradores (Dunn et al., 1963)
relataram a correlação entre classe social e níveis de AUS. Consistente com
outros estudos da literatura, eles mostraram que a variação diurna ou em
períodos maiores de tempo nos níveis de AUS era insignificante em voluntários
homens adultos saudáveis sob circunstâncias normais. Nesse estudo, dividiram
os indivíduos nos seguintes grupos: gerentes, operários (artesões), cientistas
(físicos e químicos) e estudantes (de medicina e ensino médio). Foram
observados níveis mais altos de AUS entre os gerentes (5.73 mg%) comparados
aos dos operários (4.77 mg%) e também entre os indivíduos com hiperuricemia
contidos nesses dois grupos (42.5% e 12%, respectivamente). A média dos
níveis de AUS dos cientistas (5.34 mg%) em relação aos artesões mostrou-se
significativamente alta, porém mais baixa em relação aos executivos. A média
de cientistas que apresentavam hiperuricemia era de 26.3%. Quanto ao grupo
dos estudantes, não encontraram correlação entre os níveis de AUS e o exame
de adminissão na escola de medicina porém constataram uma correlação entre
os níveis de AUS e os altos escores em testes de inteligência. Encontraram
também correlação positiva entre os níveis de AUS e a quantidade de atividades
18
extracurriculares. Os estudantes que apresentavam níveis altos de AUS tinham
um perfil de maior liderança e responsabilidade.
Em 1966, Brooks e Muller (Brooks and Mueller, 1966) estudaram
covariância entre níveis de AUS e características de vontade ou drive, ativação
comportamental, realização e liderança positiva. Para isso realizaram um estudo
com 57 professores da Universidade de Michigan. Observaram que a média de
níveis de AUS encontrada no grupo de professores era de 5.66 mg% comparada
ao grupo de gerentes e cientistas do estudo de Dunn e colaboradores.
Perceberam também que a média de AUS no grupo de professores titulares era
de 5,95 mg% enquanto que nos professores assistentes ou associados era de
5,50 mg%. Observaram relação entre os níveis de AUS e os itens de
comportamento (drive, ativação comportamental, realização e liderança positiva)
com um coeficiente de correlação de 0.66 (p< 0.001). Encontraram também
correlação negativa entre níveis de AUS e níveis séricos de colesterol, e positiva
entre os níveis de AUS com obesidade, apetite e consumo de álcool.
Outro estudo realizado na mesma época encontrou correlação positiva
entre altos níveis de AUS, liderança e doenças coronárias (Montoye, 1967).
Esses resultados foram confirmados também por Mueller e colaboradores
(Mueller et al., 1970), mostrou a associação positiva entre altos níveis de AUS e
variáveis psicossociais de vontade ou drive, realização e liderança.
Em uma pesquisa desenvolvida por Lanese e associados (Lanese et al.,
1969), com um grupo de 210 empregados do sexo masculino, com idades
variando de 40 a 59 anos, foi feito uma classificação por fatores de risco de
doenças coronárias. Dos indivíduos que foram selecionados, 19,5%
apresentavam hiperuricemia. Esses indivíduos foram classificados como sendo
do grupo experimental enquanto que os demais indivíduos foram classificados
como pertencentes do grupo controle. Identificou-se os indivíduos com altos
níveis de AUS mudavam de emprego com mais freqüência, fumavam mais,
eram obesos, tinham menos estabilidade na vida e tinham pressão arterial mais
19
elevada. Os autores desse estudo observaram que havia uma associação entre
hiperuricemia e certos traços de comportamento, mas as causas e efeitos não
puderam ser determinadas somente pelas covariações desses fatores.
Kasl e colaboradores (Kasl et al., 1966) encontraram uma correlação entre
os níveis altos de ácido úrico com desejo de realização e de sucesso. Além
disso, foi observada uma correlação positiva entre níveis de AUS e obesidade. O
valor de AUS também se relacionou inversamente com os níveis séricos de
colesterol. Esse estudo foi realizado em uma escola e também identificou que
alunos que tinham notas altas apresentam níveis mais altos de ácido úrico e
mais baixos de colesterol. Outro estudo realizado com 66 marinheiros
demonstrou um aumento nos níveis de ácido úrico nos marinheiros que tinham
grandes níveis de humor positivo (Rahe et al., 1976).
Em conjunto, estes estudos sugerem várias correlações entre os valores
de AUS e variáveis sociais, psicológicas e de personalidade. No entanto, esses
estudos utilizaram instrumentos de avaliação psicológica pontuais, baseados em
construtos psicológicos antigos, e poucos estudos incluíram mulheres.
Já entre os transtornos psiquiátricos, o metabolismo purinérgico foi
associado a humor patológico por estar envolvido no aumento da excreção de
ácido úrico durante a fase de remissão do episódio maníaco (Anumonye et al.,
1968). Cobb (1971) observou que indivíduos que apresentavam perfis
emocionais mais lábeis tinham uma tendência à variação diária nos níveis de
AUS (Rubin et al., 1969).
Pfeiffer e colaboradores (1969) observaram elevados níveis de AUS em
pacientes esquizofrênicos não tratados, que foi interpretado como relacionado
ao cérebro em estado de alta excitação. Os níveis diminuíram com o tratamento
exceto em 3 pacientes que tinham síndrome de Tourette. Os autores sugeriram
que o estresse causado pelo estado psicótico havia aumentado o turnover de
ácidos nucléicos no SNC e que contribuíram para a elevação dos níveis de AUS
(Pfeiffer et al., 1969).
20
1.5. ALOPURINOL: UM FÁRMACO HIPOURICEMIANTE
A xantina oxidase (XO) e xantina desidrogenase (XDH) são formas
interconvertidas de uma mesma enzima conhecida como xantina oxireductase
(XOR) (Pacher et al., 2006.). A diferença entre essas enzimas é que XO pode
reduzir apenas oxigênio, enquanto que XDH pode reduzir tanto oxigênio como
NAD+ (Stirpe and Della, 1969). No entanto ambas as formas catalisam a
conversão de hipoxantina em xantina e xantina em AU nas duas reações finais
da via de degradação de purinas (Berry and Hare, 2004).
A superprodução de ácido úrico pode ser controlada com o fármaco
alopurinol, um inibidor de xantina oxidase que bloqueia as conversões de
xantina em hipoxantina e desta em ácido úrico (Hediger et al., 2005). Ao reduzir
os níveis de AUS, o tratamento com alopurinol previne as doenças associadas à
hiperuricemia, como gota e nefrolitíase (Torres and Puig, 2007).
Na neuropsiquiatria foi observado que o alopurinol tem atividade
anticonvulsivante, antiagressiva, antipsicótica e antimaníaca possivelmente
decorrente do efeito inibitório na degradação de purinas, aumentando a
atividade adenosinérgica (Lara et al., 2006a).
Na esquizofrenia o alopurinol foi eficaz como tratamento adjuvante em
casos isolados de pacientes esquizofrênicos (Machado-Vieira and Lara et al.,
2001) e em 2 ensaios clínicos recentemente publicados (Akhondzadeh et al.,
2005; Brunstein et al., 2005).
Foi observada melhora após o tratamento com alopurinol em dois
pacientes com mania refratária associada a hiperuricemia (Machado-Vieira et al.,
2001). Recentemente esses achados foram confirmados em dois ensaios
clínicos randomizados em que o alopurinol foi comparado a placebo como
medicação adjuvante ao lítio na mania aguda (Akhondzadeh et al., 2006;
Machado-Veira et al., 2008).
21
2. OBJETIVO
O objetivo principal desta pesquisa é avaliar a correlação entre os níveis
de AUS e as medidas de temperamento avaliadas com a Escala de
Temperamento Emocional e Afetivo recentemente criada e validada pelo nosso
grupo de pesquisa. Desse modo, pretendemos especificar quais traços de
temperamento estão associados aos níveis ácido úrico utilizando um
instrumento psicológico que avalia globalmente variáveis emocionais e afetivas,
tanto dimensional como categorialmente.
22
3. ARTIGO
Manuscrito a ser submetido para o Journal of Affective Disorders.
CORRELATION OF SERUM URIC ACID LEVELS WITH EMOTIONAL AND
AFFECTIVE TEMPERAMENTS
Lorenzi TM, Borba D, Dutra G, Lara DR.
Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul
Corresponding author:
Diogo R. Lara
Faculdade de Biociências – PUCRS
Av. Ipiranga, 6681 – Pd12A
Porto Alegre, RS
Brazil
90619-900
FAX: +55 51 33203612
[email protected]
23
ABSTRACT
Temperament relates to the emotional nature and the quality of the
prevailing mood. We have proposed an integration of emotional and affective
temperament constructs based on the principle that activation (anger and
drive/pleasure) and inhibition (fear) are the two main emotional forces, which are
integrated by the control system (attention and duty). Their interaction would
result in the prevailing mood or affective temperaments. Uric acid (UA) is the
end-product of purine metabolism and has been associated with psychological
features such as high energy/drive, positive affect, achievement, good
performance, higher social status and leadership. In this study we evaluated 129
subjects (44 males, 85 females) with the Combined Emotional and Affective
Temperaments Scale, serum UA levels and a general health questionnaire. In
the whole sample, serum UA levels were significantly correlated with disinhibition
(r=0.36, p<0.001) and drive (r=0.25, p<0.01), but not with control, anger or any of
the affective temperament scores. Among males, we found correlations at trend
level (p >0.05 and <0.07) for control (r=0.27), irritable (r=0.29) and hyperthymic
(r=0.27) affective temperaments. Among females, a significant correlation was
found only with disinhibition (r=0.34, p=0.001). The top tertile of males (serum
UA>6.0 mg/ml, n=16) had significantly higher drive (29.9±5.9 X 26.0±3.6, p=0.01)
and higher control at trend level (21.2±3.1 X 19.3±2.9, p=0.054) than the rest of
the sample. Among women, the top tertile (serum UA>4.0 mg/ml, n=29) showed
higher disinhibition scores (20.7±4.9 X 17.9±3.6, p<0.01) and more choices of
hyperthymic (8/26 X 6/59, p=0.023) and irritable temperaments (7/26 X 5/59,
p=0.031) than the rest of the sample. Controlling for daily intake of meat and
grains, which could lead to higher UA levels, did not change these results using a
general linear regression model. In conclusion, these results confirm that
externalized traits of temperament are associated with higher serum UA levels
both in men and women.
24
INTRODUCTION
Temperament relates to the emotional nature and the quality of the
prevailing mood, being mostly inherited and relatively stable over time (Allport
,1961; Cloninger et al., 1993). Two of the most intensively studied temperament
constructs in psychiatry are the psychobiological model by Cloninger, with a
focus on behaviors and basic emotions (Cloninger et al., 1993), and the model of
affective temperaments by Akiskal, based on Kraepelin fundamental states.
Recently we have proposed an integration of emotional and affective
temperament constructs with clinical (Lara et al., 2006), neurobiological and
treatment implications (Lara and Akiskal, 2006). This model is based on the
principle that activation (anger and drive/pleasure) and inhibition (fear) are the
two main emotional forces, which are integrated by the control system (attention
and duty). Their interaction would result in the prevailing mood or affective
temperament, namely depressive, anxious, apathetic, cyclothymic, dysphoric,
euthymic, irritable, labile, desinhibited and hiperthymic (Lara et al., 2006).
Uric acid is the end-product of purine metabolism. Purines are essential
for all human cells, but the CNS seems to be particularly affected in situations of
purine metabolism dysfunction, such as Lesch-Nyhan disease. This disorder is
due to impaired purine salvage, leading to hyperuricemia and reduced purine
pool, with severe consequences such as self-mutilation, mental retardation and
choreatethosis (Oslon and Houlihan, 2000). Purinergic neurotransmission
mediated mainly by ATP on P2 receptors and adenosine on P1 receptors have
an important role on its own and by modulating other neurotransmitters
(Burnstock, 2007). Behaviorally, the purinergic system affects sleep, motor
activity, cognition, attention, aggressive behavioral and mood (Lara et al., 2002).
Interestingly, the xanthine oxidase inhibitor allopurinol, which inhibits uric acid
production, has been shown to produce antimanic (Lara et al., 2002; Machado-
Veira et al., 2008) and antipsychotic effects (Akhondzadeh et al., 2005; Brunstein
et al., 2005).
Several studies, mostly from the 60’s, have shown an association of
25
serum uric acid with behavioral and psychological traits such as high
energy/drive, positive affect, achievement, good performance, higher social
status and leadership (Katz and Weiner, 1972). To our knowledge, there are no
studies evaluating the relationship between uric acid levels and modern
constructs of temperament.
We have recently developed and validated the Combined Emotional and
Affective Temperament Scale (CEATS), which integrates both Cloninger’s and
Akiskal’s temperament constructs in a single and shorter scale. In this study, we
assessed the relationship between uric acid levels and temperament variables in
a sample from the general population.
Materials and Methods
This study was approved by the IRB of Hospital São Lucas of Pontifícia
Universidade Católica do Rio Grande do Sul. The research goals and procedures
were explained to all volunteers, who signed an informed consent form.
Temperament was assessed with the CEATS and demographic data and
an evaluation of habits and general health was evaluated with a structured self-
applied questionnaire. Blood samples were collected with a vacutainer system in
a laboratory of clinical analysis, centrifuged at 2.000 rpm for 15 min, and serum
uric acid was determined within 2 hours in the routine of the laboratory
To be included, volunteers had to be between 18 and 60 years old and
sign the informed consent form. Exclusion criteria were TSH (thyroid stimulating
hormone) > 5 µUI/mL, acute and chronic diseases and current treatment with
drugs that may affect uric acid levels (Choi et al., 2005), such as beta-blockers,
pirazinamide, salicilates, diuretics, cyclosporine, ethambutol and tracolimus.
Statistical analysis
The correlation between uric acid levels and dimensional temperament
26
variables was performed with Pearson correlation test. Comparisons between
two variables, such as age between genders and top tertile versus the rest of the
sample, were conducted with t-test. Comparison of the top tertile with the rest of
the sample was also conducted with general linear regression, with meat and
grain intake as covariates. Distribution of the categorical affective temperaments
was compared with Fisher Exact test. Alpha level for significance was p<0.05. All
tests were conducted with the software SPSS 15.0.
RESULTS
The sample consisted of 129 subjects, with 85 females (mean age 35.1 ±
10.6) and 44 males (26.5 ± 10.3 years). Age was different between genders
(p<0.001).
In the whole sample, serum uric acid levels (in mg/ml) were significantly
correlated with disinhibition (r=0.36, p<0.001, Figure 1) and drive (r=0.25,
p<0.01), but not with control, anger or any of the affective temperament scores.
Among males, no statistically significant correlation was found, but we
found correlations at trend level (p >0.05 and <0.07) for control (r=0.27), irritable
(r=0.29) and hyperthymic (r=0.27) affective temperaments. Among females, a
significant correlation was found only with disinhibition (r=0.34, p=0.001).
As a secondary analysis, we compared temperament scores between the
top tertile of uric acid levels with the rest of the sample separately for males and
females. The top tertile of man (serum uric acid>6.0, n=16) had significantly
higher drive (29.9 ± 5.9 X 26.0 ± 3.6, p=0.01) and higher control at trend level
(21.2 ± 3.1 X 19.3 ± 2.9, p=0.054) than the rest of the sample. Among women,
the top tertile (serum uric acid>4.0, n=29) showed only higher disinhibition than
the rest of the sample (20.7 ± 4.9 X 17.9 ± 3.6, p<0.01). Controlling for daily
intake of meat and grains, which could lead to higher uric acid levels, did not
change these results using a general linear regression model.
27
Regarding the choice for categorical affective temperaments, as shown in
Figure 2, men within the top tertile less often chose the euthymic temperament
(1/16 X 9/28, p=0.045), whereas women in the higher tertile more often chose the
hyperthymic (8/26 X 6/59, p=0.023 Fisher exact test) and irritable temperaments
(7/26 X 5/59, p=0.031).
DISCUSSION
In general agreement with the literature, we found that uric acid levels
were associated with disinhibition (particularly in women) and drive (more in
men), as well as irritable and hyperthymic temperaments.
Dunn et al. (1963) has found a significant difference in mean values of serum uric
acid levels between the executives (5.73 mg%) and craftsmen (4.77 mg%) and
between the number of subjects with hyperuricemia in these two groups (42.5
and 12.0%, respectively). Brooks e Muller (Brooks and Mueller, 1966) observed
a correlation coefficient of 0.66 between uric acid levels and overall scores of
motivation and drive and SUA levels (P < .001) in a study with university
professors. Similarly, Fowler reported higher motivation, drive and leadership in
men with hyperuricemia (>7.0 mg/ml) compared to normouricemics. Another
study found a positive correlation between a motivation score and serum uric
acid levels (Rahe et al., 1976). As can be seen, these early studies point out in
the same direction, but are mostly restricted to males. Our results extend these
findings to women, whose uric acid levels were correlated with disinhibition,
which also leads to more externalized behavior.
Uric acid is under high genetic heritance (Emmerson et al., 1992; Yang et
al., 2005; Nath et al., 2007), with heritability ranging from 0.42 to 0.87, which is
also a characteristic of temperament (Cloninger et al., 1993). Hyperuricemia
results from increased absorption of precursor purines, increased de novo purine
production, diminished excretion of uric acid or some combination of these
mechanisms. Our study does not allow the evaluation of which mechanism
accounts for the higher uric acid levels in those with more disinhibited or driven
28
temperaments.
Orowan (Orowan, 1955) has suggested that uric acid has psychostimulant
properties similar to those of other xanthines, such as caffeine and theophylline.
Inhibition of uricase in rats leads to increased uric acid levels and locomotion in
rats (Barrera et al., 1989). Uric acid has also been shown to increase memory in
rats (Essman, 1967). Alternatively, uric acid may just reflect the activity of the
purinergic system or may be an index of metabolic activation as the end-product
of ATP catabolism. Uric acid excretion also increased along the remission of
manic episodes (Anumonye et al., 1968) and (Cobb, 1971) observed that those
with more marked mood lability also showed more daily variations of serum uric
acid levels (Rubin et al., 1969). Conversely, the xanthine inhibitor allopurinol can
exert antimanic (Machado-Vieira et al., 2002; Akhondzadeh et al., 2005),
antiaggressive (Lara et al., 2000; Lara et al., 2003) and antipsychotic effects
(Lara et al. 2001; Akhondzadeh et al., 2005; Brunstein et al., 2005).
This study has limitations that may have affected the results. Our
questionnaire had no data on alcohol consumption and weight, which are
variables that could be associated with higher serum uric acid (Choi et al., 2005).
Also the sample size, especially for males, was relatively small. Compared to
previous studies, however, our sample included females. Despite their lower
baseline levels compared to males, uric acid was also correlated with
temperament in a similar direction.
In conclusion, serum uric acid seems to be a biochemical marker of
temperament both in males and females. Its role as a cause or consequence of
externalized emotions remains to be established. Since this is a routine
laboratory exam, it would be interesting to investigate if baseline uric acid levels
can predict response to treatment, particularly in those with externalized
behaviors and disorders. Also, these results add a rational basis for the use of
uric acid lowering drug allopurinol as a psychiatric treatment for externalized
disorders.
29
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López-Suárez, A., J. Elvira-González, et al. (2006). "Serum urate levels and urinary uric
acid excretion in subjects with metabolic syndrome." Med Clin (Barc) 2006.
126: 321–
324.
32
Machado-Veira, R., J. Soares, et al. (2008). "A double-blind, randomized, placebo-
controlled 4-week study on the efficacy and safety of the purinergic agents allopurinol
and dipyridamole in acute bipolar mania." Journal of Clinical Psychiatry, in press.
Machado-Vieira, R., D. Lara, et al. (2001). "Therapeutic efficacy of allopurinol for mania
associated to hyperuricemia (letter)." J Clin Psypharmacol, 2001
21: 621-622.
Machado-Vieira, R., D. Lara, et al. (2002). "Therapeutic efficacy of allopurinol for mania
associated to hyperuricemia (letter). ." J Clin Psypharmacol, 2002
21: 621-622.
Montoye, H. F., JA; Dodge, HJ; et al. (1967). "Serum uric acid concentration among
business executives. With observations on other coronary heart disease risk factors."
Ann Intern Med. 66: 838-850.
Mueller, E., S. Kasl, et al. (1970). "Psychosocial correlates of serum urate levels."
Psychol. Bull.
73: 238-257, 1970.
Nath, S., V. Voruganti, et al. (2007). "Genome scan for determinants of serum uric acid
variability." J Am Soc Nephrol. 2007;
18(2): 3156-3163.
Ngo, T. and D. Assimos (2007). "Uric Acid Nephrolithiasis: Recent Progress and Future
Directions." Rev Urol.
9(1): 17-27.
Nuki, G. and P. Simkin (2006). "A concise hstory of gout and hyperuricemia and their
treatment." Arthritis Research & Therapy.
8(Suppl 1): S1.
Orowan, E. (1955). "Origin of man." Nature
175: 683-684, 1955.
Oslon, L. and D. Houlihan (2000). "A review of behavioral treatments used for Lesch-
Nyhan syndrome." Behav Modif. 2000;
24(2): 202-222.
Pacher, P., A. Nivorozhkin, et al. (2006.). "Therapeutic Effects of Xanthine Oxidase
Inhibitors:Half a Century after the Discovery of Allopurinol." Pharmacol Rev. 2006;
58(1):
87–114.
Pfeiffer, C., V. Lliev, et al. (1969). "The serum urato level reflects degree os stress." J
Clin Pharm. 9: 384-392, 1969.
Pillinger, M., P. Rosenthal, et al. (2007). "Hyperuricemia and gout: new insights into
pathogenesis and treatment." Bull NYU Hosp Jt Dis.
65(3): 215-221.
Puig, J. and M. Martınez (2008). "Hyperuricemia, gout and the metabolic syndrome."
Curr Opin Rheumatol. 20: 187-191.
Puig, J. and L. Ruilope (1999). "Uric acid as a cardiovascular risk factor in arterial
33
hypertension. ." J Hypertens 1999 17: 869–872.
Rahe, R., R. Rubin, et al. (1974). "The three investigators study. Serum uric acid,
cholesterol, and cortisol variability during stresses of everyday life." Psychosom Med.
36(3): 258-268.
Rahe, R., D. Ryman, et al. (1976). "Serum uric acid, cholesterol, and psychological
moods throughout stressful naval training. ." Aviat Space Environ Med. 1976;
47(8): 883-
888.
Rubin, R., J. Plag, et al. (1969). "Serum uric acid levels: Diurnal and hebdomadal
variability in normoactive subjects." JAMA
208: 1184-1186.
Scheele, K. (1776). "Examen chemicum calculi urinarii." Opuscula.
2: 73.
Stetten, D. and J. Hearon (1959). "Intellectual level measured by army classification
battery and serum uric acid concentration." Science
: 129-1737.
Stirpe, F. and C. Della (1969). "The regulation of rat liver xanthine oxidase – conversion
in vitro of the enzyme activity from dehydrogenase (type D) to oxidase (type O)." J Biol
Chem. 1969; 244: 3855–3863.
Strazzullo, P., A. Barbato, et al. (2006). "Abnormalities of renal sodium handling in the
metabolic syndrome: results of the Olivetti Heart Study." J Hypertens. 2006;
24: 1633–
1639.
Strazzullo, P. and J. Puig (2007). "Uric acid and oxidative stress: relative impact on
cardiovascular risk." Nutr. Metab. Cardiovasc. Dis. 2007;
17: 409–414.
Terkeltaub, R., D. Bushinsky, et al. (2006). "Recent developments in our understanding
of the renal basis of hyperuricemia and the development of novel antihyperuricemic
therapeutics." Arthritis Research & Therapy.
8(Suppl1): S4.
Torres, R. and J. Puig (2007). "Hypoxanthine-guanine phosophoribosyltransferase
(HPRT) deficiency: Lesch-Nyhan syndrome." Orphanet Journal of Rare Diseases.
2(48):
1-10.
Watanabe, S., D. Kang, et al. (2002). "Uric acid, hominoid evolution, and the
pathogenesis of salt-sensitivity." Hypertension.
40(3): 355-360.
Woolaston, W. (1797). "On gouty and urinary concretions." Philosoph Trans R Soc Lond.
87: 386-415.
Wu, X., C. Lee, et al. (1989). "Urate oxidase: primary structure and evolutionary
implications." Proc Natl Acad Sci USA
86: 9412 - 9416.
34
Wu, X., D. Muzny, et al. (1992). "Two independent mutational events in the loss of urate
oxidase during hominoid evolution." J Mol Evol.
34(78-84): 78.
Yang, Q., C. Guo, et al. (2005). "Genome-wide search for genes affecting serum uric
acid levels: the Framingham Heart Study." Metabolism. 2005;
54(11): 1435-1441.
Figure1: Correlation between disinhibition score and uric acid levels. Top, middle
and low lines show the correlation for males, the whole sample and females,
respectively.
35
0
10
20
30
40
50
60
dep anx cyc dysp euth irr lab hyp
% of subjects
low uric acid
high uric acid
MALES
0
5
10
15
20
25
30
35
40
dep anx cyc dysp euth irr disin hyp
% of subjects
low uric acid
high uric acid
FEMALES
Figure 2. Comparison of affective temperament choice between top tertile of uric
acid levels and rest of the sample in males (top) and females (bottom). Dep=depressive,
anx=anxious, cyc=cyclothymic, dysp=dysphoric, euth=euthymic, irr=irritable,
disin=disinhibited, hyp=hyperthymic. *=P<0.05, Fisher exact test.
36
4. DISCUSSÃO E CONCLUSÃO
Nosso estudo apresenta algumas limitações. Não inserimos no questionário
perguntas referentes ao consumo de álcool e à obesidade. Esses fatores podem
influenciar os níveis séricos de AU (Choi et al., 2005). Não temos como avaliar se esses
itens afetaram os resultados.
Um estudo de larga escala demonstrou os efeitos da ingestão de álcool em
relação aos níveis de urato e o risco de desenvolver gota (Choi et al., 2004). O quadro
abaixo mostra o risco de desenvolver gota em relação ao consumo diário de álcool
comparado com a abstinência:
Consumo diário (g)
Risco de desenvolver gota (%)
>10 e <14,9 32
> 15 e < 29,9 43
> 30 e < 49,9 96
>= 50g 153
Dados retirados de (Choi et al., 2004).
Estudos recentes evidenciam a hiperuricemia, aparentemente causada
pela redução de excreção do AU (López-Suárez et al., 2006) como uma
característica importante em pacientes com síndrome metabólica (Puig and
Martınez, 2008). A síndrome metabólica caracteriza-se por resistência a insulina,
obesidade, hipertensão e hipertrigliceridemia (Choi et al., 2005). A redução na
excreção de AU parece ser decorrente da hiperinsulinemia com aumento da
reabsorção de sódio. Essa condição relaciona-se com a obesidade e
hipertensão, que são as principais doenças associadas com a síndrome
metabólica (Puig and Ruilope, 1999; Strazzullo et al., 2006; Strazzullo and Puig,
2007).
Por fim, os resultados do nosso estudo mostraram associação positiva
entre AU e desinibição nas mulheres e vontade nos homens, confirmando
achados de estudos anteriores. Identificou-se também uma tendência de
37
associação entre níveis de AUS e controle nos homens. Em relação à literatura
existente, nosso estudo acrescentou dados principalmente em mulheres, que
mesmo tendo níveis médios de AU mais baixos, apresentaram correlação entre
AU e variáveis psicológicas.
38
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and Gout." Psychosomatic Medicine 34: 165-182.
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translator, GM Robertson, editor. Livingstone, Edinburgh, 1921.
Lanese, R., G. Gresham, et al. (1969). "Behavioral and physiological
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Lang, U., F. Lang, et al. (2003). "Emotional instability but intact spatial cognition
in adenosine receptor 1 knock out mice. ." Behav. Brain Res. 145: 179–
188.
Lara, D., O. Dall'Igna, et al. (2006a). "Involvement of adenosine in the
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Lara, D. R., O. Pinto, et al. (2006b). "Toward an integrative model of the
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anger traits: I. Clinical implications." Journal of Affective Disorders 94(1-3):
67-87.
Lara, D. R. and H. S. Akiskal (2006). "Toward an integrative model of the
spectrum of mood, behavioral and personality disorders based on fear and
anger traits: II. Implications for neurobiology, genetics and
psychopharmacological treatment." Journal of Affective Disorders 94(1-3):
89-103.
Ledent, C., J. Vaugeois, et al. (1997). "Aggressiveness, hypoalgesia and high
blood pressure in mice lacking the adenosine A2a receptor." Nature 388:
674–678.
López-Suárez, A., J. Elvira-González, et al. (2006). "Serum urate levels and
urinary uric acid excretion in subjects with metabolic syndrome." Med Clin
(Barc) 2006. 126: 321–324.
Machado-Veira, R., J. Soares, et al. (2008). "A double-blind, randomized,
placebo-controlled 4-week study on the efficacy and safety of the
purinergic agents allopurinol and dipyridamole in acute bipolar mania."
Journal of Clinical Psychiatry, in press.
Machado-Vieira, R., D. Lara, et al. (2001). "Therapeutic efficacy of allopurinol for
mania associated to hyperuricemia (letter)." J Clin Psypharmacol, 2001
21: 621-622.
Montoye, H. F., JA; Dodge, HJ; et al. (1967). "Serum uric acid concentration
among business executives. With observations on other coronary heart
disease risk factors." Ann Intern Med. 66: 838-850.
Mueller, E., S. Kasl, et al. (1970). "Psychosocial correlates of serum urate
levels." Psychol. Bull. 73: 238-257, 1970.
Ngo, T. and D. Assimos (2007). "Uric Acid Nephrolithiasis: Recent Progress and
Future Directions." Rev Urol. 9(1): 17-27.
Nuki, G. and P. Simkin (2006). "A concise hstory of gout and hyperuricemia and
their treatment." Arthritis Research & Therapy. 8(Suppl 1): S1.
41
Pacher, P., A. Nivorozhkin, et al. (2006.). "Therapeutic Effects of Xanthine
Oxidase Inhibitors:Half a Century after the Discovery of Allopurinol."
Pharmacol Rev. 2006; 58(1): 87–114.
Pfeiffer, C., V. Lliev, et al. (1969). "The serum urato level reflects degree os
stress." J Clin Pharm. 9: 384-392, 1969.
Pillinger, M., P. Rosenthal, et al. (2007). "Hyperuricemia and gout: new insights
into pathogenesis and treatment." Bull NYU Hosp Jt Dis. 65(3): 215-221.
Puig, J. and M. Martınez (2008). "Hyperuricemia, gout and the metabolic
syndrome." Curr Opin Rheumatol. 20: 187-191.
Puig, J. and L. Ruilope (1999). "Uric acid as a cardiovascular risk factor in arterial
hypertension. ." J Hypertens 1999 17: 869–872.
Rahe, R., R. Rubin, et al. (1974). "The three investigators study. Serum uric acid,
cholesterol, and cortisol variability during stresses of everyday life."
Psychosom Med. 36(3): 258-268.
Rahe, R., D. Ryman, et al. (1976). "Serum uric acid, cholesterol, and
psychological moods throughout stressful naval training. ." Aviat Space
Environ Med. 1976; 47(8): 883-888.
Rubin, R., J. Plag, et al. (1969). "Serum uric acid levels: Diurnal and hebdomadal
variability in normoactive subjects." JAMA 208: 1184-1186.
Scheele, K. (1776). "Examen chemicum calculi urinarii." Opuscula. 2: 73.
Stetten, D. and J. Hearon (1959). "Intellectual level measured by army
classification battery and serum uric acid concentration." Science: 129-
1737.
Stirpe, F. and C. Della (1969). "The regulation of rat liver xanthine oxidase –
conversion in vitro of the enzyme activity from dehydrogenase (type D) to
oxidase (type O)." J Biol Chem. 1969; 244: 3855–3863.
Strazzullo, P., A. Barbato, et al. (2006). "Abnormalities of renal sodium handling
in the metabolic syndrome: results of the Olivetti Heart Study." J Hypertens.
2006; 24: 1633–1639.
Strazzullo, P. and J. Puig (2007). "Uric acid and oxidative stress: relative impact
on cardiovascular risk." Nutr. Metab. Cardiovasc. Dis. 2007; 17: 409–414.
Terkeltaub, R., D. Bushinsky, et al. (2006). "Recent developments in our
understanding of the renal basis of hyperuricemia and the development of
novel antihyperuricemic therapeutics." Arthritis Research & Therapy.
42
8(Suppl1): S4.
Torres, R. and J. Puig (2007). "Hypoxanthine-guanine
phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome."
Orphanet Journal of Rare Diseases. 2(48): 1-10.
Watanabe, S., D. Kang, et al. (2002). "Uric acid, hominoid evolution, and the
pathogenesis of salt-sensitivity." Hypertension. 40(3): 355-360.
Woolaston, W. (1797). "On gouty and urinary concretions." Philosoph Trans R
Soc Lond. 87: 386-415.
Wu, X., C. Lee, et al. (1989). "Urate oxidase: primary structure and evolutionary
implications." Proc Natl Acad Sci USA 86: 9412 - 9416.
Wu, X., D. Muzny, et al. (1992). "Two independent mutational events in the loss
of urate oxidase during hominoid evolution." J Mol Evol. 34(78-84): 78.
43
ANEXO A – Escala de Temperamento Afetivo e Emocional (ETAFE)
Curso/profissão:_______________________________________________
SEXO: ( ) M ( ) F IDADE:_____________
INSTRUÇÕES:
1) Em cada uma das questões abaixo, marque a alternativa que mais
corresponde ao seu jeito de ser e de agir em geral.
2) Leia todas alternativas de cada questão antes de marcar a que mais
se aproxima ao seu perfil. Responda a todas as questões e assinale
somente uma alternativa.
3) Procure responder com atenção, mas não demore muito em cada
afirmação.
4) Lembre-se que não existem respostas certas ou erradas. Você deve
responder de acordo com o que você é, não com o que você desejaria
ser.
1.
a) Sou uma pessoa medrosa
b) Sou um pouco mais medroso do que a maioria das pessoas
c) Sou um pouco mais ousado do que medroso
d) Sou ousado
e) Sou muito ousado
2.
a) Sou muito tímido
b) Sou mais tímido do que a maioria das pessoas
c) Sou um pouco mais extrovertido do que tímido
d) Sou extrovertido
e) Sou muito extrovertido
3.
a) Sou bastante prudente e cauteloso; é raro eu me arriscar
b) Sou prudente e cauteloso; me arrisco pouco
c) Em algumas situações sou prudente e cauteloso, mas em outras me
arrisco
d) Em geral, me arrisco um pouco mais do que os outros
e) Sou pouco prudente e cauteloso; é comum eu me arriscar
44
4.
a) Sou muito inibido
b) Sou inibido; tenho alguma dificuldade em me sentir à vontade
c) Às vezes, sou um pouco inibido, mas, em geral, consigo me sentir à
vontade
d) Sou desinibido e espontâneo
e) Sou muito desinibido e espontâneo, algumas vezes até demais
5.
a) Penso demais antes de agir; demoro demais para tomar decisões
b) Costumo pensar muito antes de agir; raramente me precipito para tomar
decisões
c) Penso antes de agir, mas não demoro muito para tomar decisões
d) Algumas vezes ajo sem ter pensado o suficiente; decido rapidamente
e) Muitas vezes ajo sem pensar, tomo decisões impulsivamente
6.
a) Me preocupo demais com as coisas
b) Me preocupo com as coisas mais do que a maioria das pessoas
c) Me preocupo com as coisas como a maioria das pessoas
d) Me preocupo menos com as coisas do que as outras pessoas
e) Me preocupo pouco com as coisas
7. Em situações de perigo, minha reação natural é:
a) ficar paralisado e tenso mesmo depois do perigo passar
b) ficar paralisado até o perigo passar
c) ficar paralisado no começo, mas logo consigo me soltar e agir
d) ter alguma reação rápida, quase não fico paralisado
e) ter reações rápidas, nunca fico paralisado
8.
a) Sou pessimista
b) Sou mais pessimista do que otimista
c) Sou um pouco mais otimista do que pessimista
d) Sou otimista
e) Sou muito otimista
9.
a) Não costumo ficar entusiasmado e excitado com novas atividades
b) Poucas atividades me deixam entusiasmado e excitado
c) É razoavelmente comum eu ficar entusiasmado e excitado com
novas atividades
d) É comum eu ficar entusiasmado e excitado com novas atividades
e) É muito comum eu ficar muito entusiasmado e excitado com novas
atividades
45
10.
a) Sinto pouco a sensação de prazer
b) Sinto menos prazer do que a maioria das pessoas
c) Sinto prazer como a maioria da pessoas
d) Sinto mais prazer do que a maioria das pessoas
e) Sinto prazer de forma muito intensa
11.
a) Sou triste e desanimado
b) Sou um pouco triste e desanimado
c) Sou razoavelmente alegre e animado
d) Sou alegre e animado
e) Sou muito alegre e muito animado
12.
a) Meus planos são modestos, tendo a pensar pequeno
b) Meus planos são mais modestos do que os dos outros
c) Tenho alguns planos ambiciosos
d) Meus planos em geral são ambiciosos
e) Meus planos são muito ambiciosos, penso grande
13.
a) Qualquer dificuldade já me desanima
b) É comum eu desanimar frente a dificuldades
c) Desanimo um pouco em algumas situações mais difíceis ou
complicadas
d) É difícil alguma coisa me desanimar
e) É muito difícil alguma coisa me desanimar
14.
a) Sou muito inseguro
b) Sou mais inseguro do que a maioria das pessoas
c) Me sinto razoavelmente seguro
d) Sou mais confiante do que os outros
e) Sou muito autoconfiante
15.
a) Tenho poucos objetivos definidos e vou atrás de poucos deles
b) Tenho alguns objetivos definidos e consigo ir atrás de alguns deles
c) Tenho alguns objetivos definidos e vou atrás da maioria deles
d) Tenho vários objetivos claros e vou atrás deles
e) Tenho muitos objetivos, inclusive alguns muito difíceis, e vou atrás deles
até o fim
46
16.
a) Sou pouco disciplinado
b) Sou menos disciplinado do que a maioria das pessoas
c) Sou razoavelmente disciplinado
d) Sou mais disciplinado do que a maioria das pessoas
e) Sou muito disciplinado
17.
a) sou pouco organizado e isso às vezes me atrapalha
b) sou menos organizado do que a maioria das pessoas
c) sou organizado em algumas coisas
d) sou mais organizado do que a maioria das pessoas
e) sou muito organizado, às vezes até demais
18.
a) sou muito dispersivo e distraído, e isso freqüentemente me
atrapalha
b) sou dispersivo e distraído; às vezes isso me atrapalha
c) fico dispersivo e distraído por alguns momentos, mas isso não chega a
me atrapalhar
d) sou menos dispersivo e distraído do que a maioria das pessoas
e) sou muito pouco dispersivo e distraído
19.
a) Muitas vezes não concluo as tarefas que começo
b) Tenho alguma dificuldade em completar as tarefas que começo
c) Concluo boa parte das tarefas que começo, mas desisto de algumas
mais difíceis
d) Costumo concluir as tarefas que inicio, inclusive algumas mais difíceis
e) Sempre concluo as tarefas que inicio, até mesmo as mais longas ou
difíceis
20.
a) Tenho dificuldade de manter a concentração e o interesse
b) Consigo manter a concentração somente se estou interessado
c) Mantenho a concentração se estou razoavelmente interessado
d) Mantenho a concentração mesmo estando pouco interessado
e) Mantenho
bem a concentração mesmo estando pouco interessado
21.
a) Sou pouco responsável
b) Sou menos responsável do que a maioria das pessoas
c) Sou razoavelmente responsável
d) Sou mais responsável do que a maioria das pessoas
e) Sou muito responsável
47
22.
a) É raro eu me irritar com alguma coisa
b) Não costumo me irritar
c) Às vezes, me irrito, mas isso não me gera grandes problemas
d) Sou mais irritado (bravo) do que a maioria das pessoas
e) Sou muito irritado (bravo) e isso freqüentemente me causa problemas
23.
a) Não sou nada agressivo e isso às vezes me atrapalha
b) Sou pouco agressivo
c) Sou um pouco menos agressivo do que as outras pessoas
d) Sou um pouco mais agressivo do que os outros
e) Sou agressivo em várias situações
24. Quando me irrito, minha raiva dura:
a) pouquíssimo tempo; é raro eu ficar muito irritado
b) pouco tempo, logo fico bem de novo
c) um pouco menos tempo do que para as outras pessoas
d) mais tempo do que para as outras pessoas
e) muito tempo (“estraga o meu dia”)
25.
a) Nunca sou explosivo
b) Sou menos explosivo do que os outros
c) Às vezes, sou explosivo
d) Sou mais explosivo do que os outros
e) Sou muito explosivo
26. Penso que estou sendo traído ou que estão armando algo contra mim:
a) Nunca
b) Quase nunca
c) Poucas vezes
d) Algumas vezes
e) Freqüentemente
27.
a) sou muito paciente, tolero bem esperar
b) sou paciente
c) sou um pouco impaciente
d) sou impaciente
e) sou muito impaciente, não tolero esperar
48
28. Marque para cada descrição abaixo a alternativa que mais corresponde a você
(marque somente uma alternativa).
A) Tenho uma tendência à tristeza e à melancolia; vejo pouca graça nas coisas; tendo a
me desvalorizar; não gosto muito de mudanças; prefiro ouvir a falar.
a) tudo a ver comigo
b) muito a ver comigo
c) algumas coisas a ver comigo
d) pouco a ver comigo
e) nada a ver comigo
B) Sou muito cauteloso e precavido; freqüentemente me sinto inseguro e apreensivo;
imagino que coisas ruins estão prestes a acontecer; tento evitar situações de risco;
estou sempre alerta e vigilante.
a) tudo a ver comigo
b) muito a ver comigo
c) algumas coisas a ver comigo
d) pouco a ver comigo
e) nada a ver comigo
C) Meu humor é imprevisível e instável (altos e baixos), muda rapidamente ou de
maneira desproporcional aos fatos; tenho fases de grande energia, entusiasmo e
agilidade que se alternam com outras fases de lentidão, perda de interesse e desânimo.
a) tudo a ver comigo
b) muito a ver comigo
c) algumas coisas a ver comigo
d) pouco a ver comigo
e) nada a ver comigo
D) Tenho uma forte tendência a me sentir agitado, ansioso e irritado ao mesmo tempo.
a) tudo a ver comigo
b) muito a ver comigo
c) algumas coisas a ver comigo
d) pouco a ver comigo
e) nada a ver comigo
E) Tenho pouca iniciativa; com freqüência me desligo do que os outros estão dizendo
ou fazendo; muitas vezes não concluo o que comecei; tendo à passividade e sou um
pouco lento.
a) tudo a ver comigo
b) muito a ver comigo
c) algumas coisas a ver comigo
d) pouco a ver comigo
e) nada a ver comigo
49
F) Meu humor é equilibrado e previsível, costuma mudar só quando há um motivo claro;
tenho boa disposição e, em geral, me sinto bem comigo mesmo.
a) tudo a ver comigo
b) muito a ver comigo
c) algumas coisas a ver comigo
d) pouco a ver comigo
e) nada a ver comigo
G) Sou muito sincero, direto e determinado, mas também irritado, explosivo e
desconfiado.
a) tudo a ver comigo
b) muito a ver comigo
c) algumas coisas a ver comigo
d) pouco a ver comigo
e) nada a ver comigo
H) Sou inquieto e dispersivo; com freqüência me desligo do que os outros estão dizendo
ou fazendo; muitas vezes ajo sem pensar nas conseqüências; às vezes sou
inconveniente e só me dou conta tarde demais; mudo de humor ou de interesse
rapidamente, e não concluo muitas coisas que começo; quando me irrito, logo fico bem
de novo.
a) tudo a ver comigo
b) muito a ver comigo
c) algumas coisas a ver comigo
d) pouco a ver comigo
e) nada a ver comigo
I) Sou inquieto, ativo, espontâneo e distraído; muitas vezes ajo de maneira precipitada e
inconseqüente; é muito comum eu deixar para fazer as coisas na última hora; quando
me irrito, logo fico bem de novo.
a) tudo a ver comigo
b) muito a ver comigo
c) algumas coisas a ver comigo
d) pouco a ver comigo
e) nada a ver comigo
J) Estou sempre de bom humor, me sinto muito confiante e me divirto
facilmente; adoro novidades e estou sempre pronto para novas atividades; faço
várias coisas sem me cansar; quando quero alguma coisa, vou atrás e consigo
conquistá-la; tenho forte tendência à liderança.
a) tudo a ver comigo
b) muito a ver comigo
c) algumas coisas a ver comigo
d) pouco a ver comigo
e) nada a ver comigo
f)
50
29. Escolha a descrição da questão 28 acima que mais se aproxima do seu perfil
(somente uma alternativa
). Leia bem todas as 10 descrições antes de optar pela
resposta (páginas 5 e 6).
A)
B)
C)
D)
E)
F)
G)
H)
I)
J)
30. Em que medida você tem ou já teve problemas ou prejuízos pessoais em
função do seu jeito de ser, do seu comportamento e/ou do seu padrão de
humor?
a) nenhum problema e nada de prejuízo
b) poucos problemas e prejuízos pequenos
c) problemas e prejuízos moderados
d) problemas e prejuízos sérios ou graves
31. Em que medida você tem ou já teve vantagens ou benefícios pessoais em
função do seu jeito de ser, do seu comportamento e/ou do seu padrão de
humor?
a) quase nenhuma vantagem e benefícios mínimos
b) poucas vantagens e benefícios pequenos
c) algumas vantagens e benefícios moderados
d) muitas vantagens e grandes benefícios
51
ANEXO B – Termo de Consetimento
Termo de Consentimento Livre e Esclarecido
“Estudo das bases genéticas do temperamento”
A Justificativa da Pesquisa
Este estudo visa caracterizar a base genética do temperamento, que é nosso padrão
emocional básico. Para isso, será necessária a aplicação de uma escala de auto-
avaliação do temperamento, assim como coleta de sangue para análise genética. O
objetivo deste estudo é avaliar o quanto traços do temperamento se relacionam com os
parâmetros biológicos que serão investigados. Os resultados poderão colaborar para a
compreensão das causas de diversos transtornos mentais, que frequentemente
apresentam variações de temperamento.
Os procedimentos a serem utilizados
Os meios utilizados para realizar este trabalho consistem no preenchimento de duas
escalas auto-aplicáveis e coleta de sangue por punção venosa (1 tubo de 5 ml).
III. Os procedimentos ou riscos esperados
A coleta de sangue por punção venosa é um procedimento invasivo corriqueiro e de
risco mínimo, podendo ocorrer pequeno hematoma autolimitado em local da punção.
IV. Os benefícios que se pode obter
Essa pesquisa busca o melhor entendimento do temperamento, auxiliando
52
assim no acúmulo de informações necessárias para que se possa reconhecer e tratar
melhor os transtornos mentais. Individualmente, o benefício nesse tipo de estudo é
ainda limitado.
V. Garantia de resposta a qualquer pergunta
Os pesquisadores garantem que responderão a qualquer pergunta referente a
esta pesquisa.
VI. Liberdade de abandonar a pesquisa sem prejuízo para si
O voluntário tem a liberdade de abandonar a pesquisa a qualquer momento,
sem prejuízo para si.
VII. Garantia de privacidade
Será mantida a privacidade do voluntário em todas as fases da pesquisa. Todos
os dados coletados serão mantidos sob sigilo.
VIII. Consentimento para pesquisas futuras
O voluntário consente que o material coletado (escalas e amostras de sangue)
poderá ser utilizado para futuras pesquisas com o fim de caracterizar e compreender a
base genética dos traços de personalidade e dos transtornos mentais.
___________________________________________________
Local e data
53
____________________________
Assinatura do voluntário
____________________________
Assinatura do pesquisador
54
ANEXO C - Artigo de desenvolvimento e validação da ETAFE
Development and validation of the Combined Emotional and Affective
Temperament Scale (CEATS): a brief self-report instrument
Diogo R. Lara
1
, Taise Lorenzi
1
, Daniela Borba
1
, Luiz Carlos Silveira
2
, Caroline Reppold
3
1. Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do
Sul, Porto Alegre, Brazil
2. Universidade Federal do Pará, Belém, Brazil
3. Fundação Faculdade de Ciências Médicas de Porto Alegre, Porto Alegre, Brazil
Corresponding author:
Diogo R. Lara
Faculdade de Biociências – PUCRS
Av. Ipiranga, 6681 – Pd12A
Porto Alegre, RS
Brazil
90619-900
FAX +55 51 33203612
diogorlara@gmail.com
ABSTRACT
Background: Temperament relates to both emotional dimensions and prevailing mood,
but these different views are rarely integrated. Based on a model where temperament
works as a system with activation, inhibition and control (inspired in Cloninger’s and
Rothbart’s models), which produce the affective tone (inspired by Akiskal’s and
Kraepelin’s model), we developed and validated the Combined Emotional and Affective
Temperament Scale (CEATS).
Methods: 1007 subjects (28% males) from the general
population and university students filled in the instrument either in the internet or in a pen
and paper version. The CEATS has an Emotional section (dimensional only), an
Affective section (both dimensional and categorical) and an evaluation of problems and
benefits related to temperament. The data was analyzed with standard psychometric
batteries and different sections were compared.
Results: In the Emotional section, 4
factors with Eingenvalue>1 explained 46% of the variation. These factors were
interpreted as drive, control, disinhibition-fear and anger, had a normal distribution and
had satisfactory Chronbach’s alphas (0.70-0.82). Anger was particularly associated with
55
problems and drive with benefits. In the Affective section, all 10 categorical affective
temperaments were selected, being euthymic and hyperthymic the most prevalent (18-
23%), followed by cyclothymic and irritable (11-13%), anxious and depressive (8-9%)
and dysphoric, disinhibited, labile and apathetic temperaments (3-7%). The dimensional
evaluation of affective temperaments showed 95% of the sample was able to ascribe to
at least one affective temperament. Only the euthymic and hyperthymic temperaments
were clearly associated with a favorable problem/benefit profile. The comparison
between the emotional and affective sections revealed that each affective temperament
had a particular emotional configuration.
Limitations: both computerized and pen and
paper versions were used. The sample was not evaluated for psychiatric symptoms.
Quantification of the dimensional assessment of affective temperament is limited.
Conclusions: the CEATS is a brief and adequate instrument to evaluate emotional and
affective aspects of temperament simultaneously.
INTRODUCTION
Temperament relates to the emotional nature and the quality of the prevailing
mood, being mostly inherited and relatively stable over time (Allport, 1961; Cloninger et
al., 1993). Since the four humours of Hippocrates and Galen, the concept of
temperament has had new interpretations by Eysenck (1987), Gray (Pickering and Gray,
1999), Cloninger (Cloninger et al. 1993), Akiskal (Akiskal et al. 1989) and others. Two of
the most intensively studied temperament constructs in psychiatry are the
psychobiological model by Cloninger, with a focus on behaviors and basic emotions, and
the model of affective temperaments by Akiskal, based on Kraepelin fundamental states.
In Cloninger’s model, the combination of four dimensions comprises the
temperament (Cloninger et al. 1993). They are named as behaviors that are routed in
basic emotions (in brackets): novelty seeking (anger), harm avoidance (fear), reward
dependence (attachment) and persistence (ambition). They are normally distributed
dimensions that can occur in any combination, as they are independently inherited. This
construct can be objectively assessed with the Temperament and Character Inventory
(TCI) and was conceived more specifically for personality disorders. However, several
studies have shown that in virtually all psychiatric disorders, including mood, behavioral
and personality disorders, at least one these temperament dimensions is altered
compared to a mentally healthy control group (see Lara et al. 2006 for review). Most
56
commonly novelty seeking (NS) and/or harm avoidance (HA) is either high or low, and
self-directedness from the character section is often reduced in psychiatric disorders.
Akiskal has conceived temperament as the affective predisposition or reactivity,
based on the original descriptions by Kraepelin (1921) of fundamental states, which
could be either manic (currently called hyperthymic), irritable, cyclothymic or depressive
(Akiskal et al., 1989). More recently, Akiskal added the concept of anxious temperament
(Akiskal, 1998). These five affective temperaments would be the predisposing ground for
the development of mood disorders. The TEMPS has been developed and validated as
the self-report scale to assess this construct (Akiskal et al., 2005). Indeed, these
affective predispositions are present in individuals that develop mood disorders, as well
as in their relatives, with different distributions according to the type of mood disorder
(e.g. more hyperthymic traits in bipolar I disorder, cyclothymic traits in bipolar II disorder
and depressive traits in unipolar depression) (Evans et al., 2005; Kesebir et al, 2005;
Akiskal et al, 2005).
As Rothbart et al. (2000), our view coincides with Allport’s (1961) definition of
temperament as ‘an individual`s emotional nature, including his susceptibility to
emotional stimulation, his costumary strength and speed of response, and the quality of
prevailing mood, these phenomena being regarded as dependent upon constitutional
make-up’. However, current temperament models assess
either the emotional nature or
the prevailing mood. Rothbart et al. (2000) thoughtfully incorporated and studied the role
of attention and self-regulation to the concept of temperament, but have not directly
addressed the prevailing mood or affective predisposition.
Recently we have proposed an integration of emotional and affective
temperament constructs, named as the fear and anger model, with clinical (Lara et al,
2006), neurobiological and treatment implications (Lara and Akiskal, 2006). This model
is based on the principle that activation (anger and drive/pleasure, related to NS) and
inhibition (fear and caution, related to HA) are the two main
emotional forces or ‘vectors
of the mind’, as coined by Thurstone (1934). Their interaction would produce a resulting
affective trend or prevailing mood. In our construct, we consider desire and pleasure as
part of the emotional terrain, at odds with other concepts that ascribe them to motivation,
as if motivation did not have a strong emotional/affective component.
Three studies (Maremmani et al. 2005; Akiskal et al. 2005; Rósza et al., 2007)
have been conducted with simultaneous assessment with the TCI and the TEMPS,
showing essentially that: hyperthymic temperament is associated with high NS and low
57
HA; irritable with high NS and moderate HA; cyclothymic with both high; anxious with
moderate NS and high HA and finally that depressive temperament is associated with
low NS and high HA. Reward dependence and persistence are weakly correlated with
these five affective temperaments. For practical reasons, the dimensions of activation
and inhibition can be conceived as high, moderate and low, as they are normally
distributed in the population. Therefore, nine combinations can arise from their 2X2
interactions. In order to complete the other putative combinations of activation and
inhibition, we have proposed and predicted four new affective temperaments:
disinhibited (originally called hyperactive) with moderate NS and low HA; labile with both
low; apathetic or passive with low NS and moderate HA, and euthymic with both
moderate (Lara et al. 2006). After pilot versions of the scale and clinical observations,
we also conceived a dysphoric predisposition, which would also be associated with the
mixture of high activation and inhibition, similar to cyclothymic temperament. Based on
other models and our preliminary versions of the scale, we also included a factor that is
related to regulation of activation and inhibition, which we called control. This concept is
highly attributed to frontal lobe function and is similar to consciousness in the big five
model (McCrae and Costa, 1985), some aspects of persistence and self-directedness in
Cloninger’s model (Cloninger et al. 1993) and also executive functions and effortful
control in Rothbart’s concept (Rothbart et al. 2000). Although control is not emotional per
se, this factor is included in the emotional construct due to its proposed role in emotional
regulation and behavioral adaptation (Rothbart et al. 2000).
Here we present the validation data of a scale developed to evaluate emotional
and affective temperaments simultaneously, trying to keep the original concepts by
Cloninger and Akiskal/Kraepelin, but making the necessary adaptations and changes to
allow for their integration. Named as the Combined Emotional and Affective
Temperament Scale (CEATS), the emotional section consists of twenty seven 5-item
multiple choice questions on disinhibition-fear, drive, control and anger, whereas the
affective section includes 10 descriptions of affective temperaments with a dimensional
5-point scale and a categorical choice of the best description. We also included two
questions that subjects could rate in a 4-point scale according to the degree of problems
and benefits related to their temperament.
MATERIALS AND METHODS
58
Preliminary versions of the scale were reviewed by psychologists familiar to
current concepts of temperament. Four preliminary pen and paper versions were
developed with around two thousand subjects of Porto Alegre, mostly university
students. The final version for construct validation was developed in a pen and paper
version with 124 university students from the city of Belém (Pará, Brazil) and 245
subjects from the city of Porto Alegre, as well as with an internet version that was
completed by the general population of the city of Porto Alegre (638 subjects). Subjects
became acquainted with the study by word of mouth and announcement of our website
through a local TV talk-show. As the overall results were similar in all samples, the
results were combined to increase statistical power (1007 subjects). The internet version
has the advantage that all items are necessarily answered and no mistakes of data
transfer are expected to occur. All participants gave their informed consent (signature or
electronic) before completing the scale. This form was elaborated to fulfill the
requirements of the National Health Council of Brazil (Resolution 196/1996). Their
participation was voluntary and they could cancel their participation at any moment
without justification. The study was approved by the Institutional Review Board of
Hospital São Lucas from Pontifícia Universidade Católica do Rio Grande do Sul.
DESCRIPTION OF THE CEATS
The CEATS (see Appendix) consists of an emotional and an affective section, as
well as two questions to evaluate problems and benefits associated with temperament. It
has 40 items total, and typically takes 20-30 min to be completed.
Emotional section
The 27 five-item multiple choice questions were developed in the preliminary
versions and arranged in the final version in following order: disinhibition-fear (7 items),
drive (8), control (6) and anger (6). The first alternative was a description of low and the
last with high expression of the trait. In order to facilitate application and rating, we chose
to reverse the fear factor as disinhibition-fear, so that low scores represent high
fear/inhibition. In this way, the order of the alternatives of disinhibition-fear, drive and
anger go from more internalizing to more externalizing traits. This principle is not easily
applied to control, but we chose to align the alternatives from low to high control since
59
we consider it a proactive trait (e.g., concludes tasks, pays attention even if uninterested,
self-regulation), although they may reduce the expression of externalizing traits. The
total score of each dimension is the sum of scores from 1 to 5 for each question.
Affective section
Ten short descriptions of the affective temperaments based on previous studies
of the TEMPS, theoretical concepts, clinical observation and preliminary versions of the
CEATS were presented with a 5-item likert scale, from ‘everything to do with me’ (rated
as 5) to ‘nothing to do with me` (rated as 1). This was called the dimensional
assessment of affective temperaments. After these 10 descriptions, one question asked
the subject to select which of these profiles was the most suitable to represent his/her
temperament. This allows for a categorical evaluation of affective temperaments. Instead
of using a statistical approach to define someone’s affective temperament, this
categorical choice results from the selection of one profile in detriment of the other nine
profiles, but the dimensional part allows for a more refined understanding of the chosen
category (e.g. subjects from the cyclothymic category may have different levels of the
other affective temperaments).
Problems and benefits
Two final questions assessed the degree of problems and benefits that one
conceives to have with his/her temperament with a 4-point scale (no, minimal, moderate
and marked problems or benefits). This strategy was used because problems and
benefits are not mutually exclusive and adaptation can be conceived as the result of
both. This is in contrast to other scales and current practice of psychiatry, which focus
mostly on problems.
Statistical analysis
The emotional section was analyzed for the evaluation of factorial structure and
internal consistency. Exploratory factorial structure was analyzed with Varimax rotation,
which allowed the selection of items in agreement with the theoretical construct that
showed a higher load for a specific factor. Only factors with an Eigenvalue>1 and items
with factorial load over 0.40 were kept in the final version of the scale. These factors
were interpreted in accordance with the theoretical construct and their means, standard
deviations and Chronbach’s alphas were calculated. Gender differences in age were
60
compared with Student’s t-test. Gender differences in emotional factors were compared
using Multivariate General Linear Model, with age as covariate.
The affective section was analyzed with Pearson’s correlation test. Also, the
number of ‘everything to do with me’ answers were counted. In those subjects who had
no such answer, we counted how many chose the ‘much to do with me’ in order to
evaluate if the 10 descriptions covered most of the population’s affective temperaments.
Comparisons between emotional and affective temperaments were performed
with ANOVA with Tukey`s test as
post hoc for the categorical and Pearson’s correlation
test for the dimensional affective temperament. Age, problems and benefits scores were
also compared with emotional and affective temperaments using Pearson’s correlation
test. Statistical significance was considered if p<0.05. The SPSS 15.0 software was
used for all analyses.
RESULTS
Our final sample consisted of 1007 subjects, with mean age of 34.9 ± 11.9 years
(16-80), being 284 (28.2%) males (32.3 ± 11.7 years) and 723 (71.8%) females (35.9 ±
11.8 years) (p<.01, Student’s t test).
EMOTIONAL SECTION
Exploratory factorial analysis revealed that the best solution involved four factors
with Eigenvalues>1, as shown in Table 1. These factors were interpreted as drive,
anger, disinhibition-fear and control. In some preliminary analysis a fifth factor arose
involving only 2 items (related to shyness-extroversion and inhibition-spontaneity, or
social fear – see Table 2), which in the final sample loaded well to the factor associated
with questions of disinhibition-fear. Twenty-seven items remained in the final version of
the scale, accounting for 46.0% of the total variation. The factors had Chronbach’s
alphas between 0.70 and 0.82 and showed normal distributions, with Liliefords with
p<0.01 (see Table 1). The factorial matrix, item descriptions and loadings are shown in
Table 2.
Table 3 shows that there was a moderately high correlation between the factors
disinhibition-fear and drive (r=0.51), and drive and control (r=0.34). Other correlations
61
between emotional factors, even if statistically significant, were weaker. Regarding age,
there was a weak but statistically significant negative correlation with drive and anger
and a weak positive correlation with control (Table 3). The perception of problems with
own mood and temperament was associated with higher anger, lower drive and lower
control, but not with disinhibition-fear. In contrast, the perception of benefits was
associated with higher drive, disinhibition-fear and control and lower anger (Table 3).
Problem and benefit scores were significantly but weakly correlated (r=-0.17, p<0.01).
Regarding gender differences, using age as covariate, males had higher scores
of disinhibition-fear and females were higher in control scores (Table 4). Males had
numerically but non-significantly higher drive and lower anger than females.
AFFECTIVE SECTION
The frequencies of the categorical choices of affective temperaments are shown
in Figure 1. Euthymic (
23%) and hyperthymic (18%) temperaments were the most
prevalent, followed by cyclothymic, irritable and anxious temperaments. The remaining
affective temperaments were all present, with apathetic and labile temperaments as the
less prevalent (3-4%). To our surprise, the frequency of the euthymic temperament,
even in previous versions of the scale solely in university students, never exceeded
30%. The major numerical differences in gender distribution were the predominance of
males among hyperthymics, labiles and disinhibited temperaments, and of females
among cyclothymic, dysphoric and irritable temperaments. The dimensional score of
affective temperaments showed that males show significantly higher scores on
disinhibited (p<0.01) and apathetic (p<0.05) temperaments, and labile temperament at
trend level (p=0.07).
As we postulate that the 10 proposed affective temperaments arise from
combinations of activation, inhibition and control, we expected that most people would
recognize at least one description as a perfect or good match (‘everything to do with me’
or ‘a lot to do with me’, respectively). Indeed, 595 subjects (59%) found at least one or
more perfect matches, and 6% found from 5 to 7 perfect matches (Figure 2). Among
those 412 (41%) individuals who failed to point out one perfect match, 364 (36% of the
total sample) found at least 1 good match. Thus, less than 5% (48 subjects) failed to
identify at least one satisfactory description for their affective temperament.
The correlations of the dimensional part of the Affective Section are shown in
62
Table 5. Except for a positive correlation with hyperthymic temperament, euthymic
temperament was negatively correlated with all temperaments, particularly with
cyclothymic, depressive, dysphoric and labile temperaments. Depressive, anxious,
cyclothymic, dysphoric, apathetic and labile temperaments were positively correlated.
Labile and disinhibited temperaments as well as dysphoric and cyclothymic
temperaments were particularly correlated (r>0.50). Inter-correlations between
externalized temperaments (hyperthymic, irritable and disinhibited) were low to
moderately positive. As expected, all categorical choices of affective temperaments were
associated with higher score of the respective temperament in the dimensional part of
Affective Section, with statistical separation from all the other groups (p<0.05), except for
labile score from categorical disinhibited temperament, labile score from dysphoric and
hyperthymic score from euthymic temperament.
Problems and benefits associated with categorical affective temperaments are
shown in Figure 4 and with dimensional affective temperament scores at the bottom of
Table 6. Only euthymic and hyperthymic temperaments are associated with a perception
of little problems and high benefits. Hyperthymic and euthymic temperaments had lower
problem scores than all the other temperaments (p<0.05), except for apathetic
temperament, which was not different from any other temperament. The remaining
affective temperaments were not significantly different among them (p>0.1). In terms of
benefits, depressive temperaments had significantly lower scores than all other
temperaments (p<0.05), except for anxious and cyclothymic, whereas hyperthymic
temperament had significantly higher scores than all others (p<0.05), except for
euthymic and disinhibited temperaments.
COMPARISON BETWEEN EMOTIONAL PROFILE AND AFFECTIVE
TEMPERAMENTS
The emotional profiles of categorical affective temperaments are shown in Figure
3 and the correlations between emotional factors and dimensional scores of affective
temperaments are shown in Table 6. In general, each affective temperament was
associated with a fairly specific emotional signatures, with the exception of dysphoric
and cyclothymic temperaments, which had similar profiles. The irritable temperament
was also similar to these two temperaments, but with numerically higher scores in the 4
factors. ANOVA with Tukey’s as the post hoc test showed 6 different statistical groups
for disinhibition: dep=anx
≤apa=cyc≤eut≤dysp≤irr=lab=htm=disin. For drive, 7 statistical
63
groups were found: dep<anx=apa≤lab=cyc≤dysp≤irr=eut=disin<htm. For control, 5
statistical groups were found: lab≤apa=disin≤dep=cyc≤dysp≤anx=irr=eut=htm. For
anger, 5 groups emerged: eut≤htm=apa≤anx≤disin=dep≤lab≤cyc=dysp=irr. As can be
seen, each emotional factor is associated with a different ranking of affective
temperaments.
DISCUSSION
The emotional section of the CEATS showed 4 four factors with satisfactory
reliability coefficients as shown by Chronbach’s alpha values between 0.70 and 0.82.
The item insecure/self-confident was kept in the drive factor despite a slightly higher
loading in the disinhibition factor based on theoretical ground, but especially because
this item ‘behaved’ as a drive item when it was analyzed in relation to affective
temperaments. Also, when only disinhibition and drive questions were analyzed, this
question loaded much more heavily on the drive factor (data not shown).
Compared to Cloninger’s model, there were some differences regarding features
of harm avoidance compared to disinhibition-fear, and novelty seeking compared to
drive and anger. The harm avoidance dimension includes energy and
pessimism/optimism (Cloninger et al. 1993), which loaded in the drive factor in CEATS.
Cloninger also attributes impulsivity to novelty seeking, whereas we consider impulsivity
as a possible outcome of disinhibition/low fear, or lack of control, or even as excessive
drive (pleasure seeking), which we have called appetitive impulsivity (Lara et al, 2006).
However, in the strict sense of impulsivity as acting without enough forethought or
reflection, impulsivity was ascribed to the disinhibition-fear factor. Also, many features of
Cloninger’s self-directedness, which is considered part of the character domain, are
similar to our drive factor. Indeed, both high harm avoidance and low self-directedness
have been the factors associated with unipolar major depression (Richter et al., 2000;
Cloninger et al., 2006), whereas in our scale, the depressive temperament was
associated with high inhibition (low disinhibition/high fear) and low drive. However,
concurrent validation between both scales is necessary to adequately address this topic.
The CEATS’ emotional factors were similar to Rothbart’s 4 main temperament
factors developed after decades of studies across the whole life span, with emphasis on
early development (Rothbart et al., 2000). These factors are fear, approach-positive
affect, anger-frustration and effortful control. As in our model, Rothbart’s construct
64
avoids factors associated with socialization, which is in contrast to Cloninger’s inclusion
of reward dependence/attachment. Although socialization factors are surely important for
personality, reward dependence is weakly associated with affective disorders and
affective temperaments (Maremanni et al, 2005; Akiskal et al, 2005; Rósza et al. 2007).
There were significant correlations between some but not all emotional factors
(Table 3). Our interpretation for the moderately high correlation (r=0.51) between drive
(activation) and disinhibition is that a combination of ‘emotional synchrony’ is favored,
i.e. a bias to avoid ambivalence between approach (drive) and avoidance (inhibition).
The positive correlation between drive and control and their negative correlation with
anger suggests that higher control favors the expression of activation as drive rather
than anger, although these two are not mutually exclusive.
The Affective Section of the CEATS included five new prototypes of affective
temperaments to be validated. Categorical euthymic temperament (
23%) arouse as the
most common, but less often than we expected. The results of the preliminary versions
in university students showed the same pattern (data not shown). The other newly
proposed affective temperaments, namely labile, disinhibited, apathetic and dysphoric,
had lower frequencies in the range of 3 to 7% of subjects. Depressive and anxious
temperaments were chosen by 7-9% of subjects, whereas higher prevalence was found
for hyperthymic (
18%), cyclothymic (13%) and irritable (11%) temperaments. This
suggests that affective temperaments related to bipolar spectrum disorders are more
common than those related to unipolar depression or attention-deficit and hyperactivity
disorders.
The categorical choice of an affective temperament relies on the idea that the
subject has to choose
one description among 10 prototypes instead of the other 9
descriptions, i.e., the best fit. This is a different approach than stratification through
standard deviations. The dimensional assessment of the affective temperaments
identified 95% of the subjects with either a perfect match (59% as everything to do with
me) or a good match (36% as mostly to do with me), and a minority (6%) chose more
than 5 perfect matches. Given that conceptually there are no ‘zones of rarity’ between
‘neighbor’ temperaments, it is quite possible that someone considered dysphoric,
cyclothymic, irritable and anxious temperaments as perfect matches, for example. We
conceive affective temperaments as essentially related to or even a product to these 4
the emotional factors (drive, disinhibition-fear, anger and control), which are usually
thought to be relatively independent. If they are categorized as low, moderate or high to
65
grossly reflect their normal distribution, theoretically there would be 81 combinations or
affective temperaments, or at least 27 if control and disinhibition influence the
expression of activation as drive or anger (therefore counting drive and anger as only
one activation factor). The 95% rate of perfect/good matches with only 10 affective
temperaments and the correlations between the emotional factors discussed above
suggest that these emotional combinations do not occur randomly.
The correlations between dimensional scores of affective temperaments were
essentially in agreement with the proposed bidimensional model (Lara et al, 2006).
‘Neighbor’ temperaments had higher positive correlations, especially the cyclothymic
and dysphoric temperaments, which were conceived as closely related, but distinct
expressions of conflicting emotional forces (ups and downs X dysphoria-agitation). Also,
moderately positive correlations were found between the most unstable temperaments,
namely cyclothymic and labile, and moderately high negative correlations were found
between hyperthymic and depressive temperaments, as expected.
Both emotional and affective temperaments were associated with gender
differences. Males showed higher disinhibition and lower control. Considering the
hypothesis that temperament differences underlie most psychiatry disorders, this profile
is compatible with the higher prevalence of externalizing and lower prevalence of
internalizing disorders in males than in females (see Lara et al, 2006 for review). This
emotional profile was also in general agreement with the numerically higher prevalence
of hyperthymic and disinhibited temperaments in males and higher cyclothymic
temperament in women. Ageing was associated with a slight decline in drive and anger
and an increase in control, and reduction of cyclothymic, dysphoric and irritable affective
temperaments, which is mostly coherent taking into account the emotional-affective
interactions. This is in general agreement with the findings in novelty seeking using the
TCI (Cloninger et al., 1993) and the TEMPS (Rósza et al. 2007), although we did not find
a decline in hyperthymic traits with age. Activation both as drive and anger have a high
influence of dopaminergic tone, which declines steadily with age (Lara and Akiskal,
2006).
In general, our results comparing the original five affective temperaments
(depressive, anxious, cyclothymic, irritable and hyperthymic) with the emotional factors
are in line with previous results comparing the TEMPS and the TCI (Maremanni et al,
2005; Akiskal et al, 2005; Rósza et al, 2007). Of note, these studies have shown that
cyclothymic temperament is associated with high harm avoidance and high novelty
66
seeking. Using the categorical cyclothymic temperament, we indeed found high anger,
which is probably related to high novelty seeking, but disinhibition (conceived as the
reverse of harm avoidance) was not low as we predicted. Disinhibition scores of
cyclothymics were similar to those of euthymic temperament, and both were
intermediate between depressive/anxious and hyperthymic temperaments. One
possibility is that ‘sunny’ (disinhibited) and ‘dark’ (inhibited) cyclothymics (Akiskal 2005)
cancel each other and produce an average score of disinhibition-fear. However, the
dimensional score of cyclothymic temperament showed a significant negative correlation
with disinhibition (i.e., the more cyclothymic, the more inhibited). Interestingly, although
the most characteristic feature of the cyclothymic temperament was high anger, the
description of this affective temperament is strictly on cycling, without any reference to
anger or irritability.
Cyclothymic, dysphoric and irritable temperaments were highly intercorrelated.
However, careful inspection reveals a gradient from cyclothymic to dysphoric to irritable
temperament from more internalizing to more externalizing features (higher disinhibition,
drive and anger) and higher control (see Figure 4 and Table 6). The irritable
temperament of the TEMPS seems to correspond to the CEATS description of dysphoric
rather than irritable temperament. Besides irritability and explosive outbursts, the CEATS
description of irritable temperament also focuses on assertiveness and goal-direction,
similar to the original observations on the irritable fundamental state by Kraepelin (1921).
Clearly the only affective temperaments associated with a perception of favorable
problem/benefit ratio were the euthymic (particularly associated with little problem) and
hyperthymic temperaments (particularly associated with high benefit). This profile is
probably due to expression of activation in these subjects as drive, rather than anger.
Depressive, cyclothymic, dysphoric and labile temperaments were particularly
problematic, and depressive temperament was more specifically associated with lack of
perceived benefit.
This study and the scale have some limitations. Data collection was done using
both internet and pen and paper versions, being part of them in university students.
Although the distribution of emotional and affective temperaments was not clearly
different between these versions and subjects, this sample cannot be considered
representative of the general population. Thus, prevalence estimates and emotional
dimensions can be different in other samples. Also, no psychiatric evaluation was
conducted in the sample. As a self-report instrument, this instrument may include some
67
degree of desirability, although more than half of the subjects chose affective
temperaments that were not associated with a particularly favorable profile in terms of
problems and benefits. The emotional section contains multiple choice questions rather
than phrases in a 5-point likert scale. This approach allows for better specification of
items, but at the cost of time to fill in the scale. The two types of ratings and the selection
of a category in the affective temperament section also requires the subject to adapt to
new presentations and rules for answering. In terms of results, the drive factor was not
as pure as the other factors, with some loadings from all the other factors. Even so, drive
was differently expressed in affective temperaments than the other emotional factors.
Finally, the dimensional assessment of affective temperaments is based on only one
question, which has limitations for quantification compared to other scales such as the
TEMPS, which has many items and wider scores.
In conclusion, the CEATS showed a satisfactory profile to assess the emotional
factors that are thought to reflect affective expression. Thus, it may be helpful to
evaluate emotional and affective temperaments in a wide range of psychiatric patients.
Application of the Harm avoidance, Novelty Seeking, Persistence and Self-Directedness
items of the TCI together with the TEMPS would typically require more than one hour,
whereas the CEATS usually takes less than 30 min to be completed. Thus, CEATS may
be a convenient instrument for both clinical and research ends to evaluate emotional and
affective temperaments simultaneously, but this requires further testing.
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Table 1. Psychometric properties of the Emotional Section of the CEATS.
Scale Factor
Number of
items
Total variation
explained (%)
Mean score ±
S.D
Alpha Skewness
Kurtosis
1.Drive 8 20.2
24.8 ± 5.8
(8-40)
.82 -.13 -.29
2. Anger 6 12.5
17.7 ± 4.6
(6-30)
.74 .16 -.34
3. Disinhibition-fear 7 8.3
19.7 ± 4.2
(7-35)
.70 -0.05 .00
4. Control 6 5.0
19.8 ± 4.1
(6-30)
.71 -.31 -.03
Total scale 27 46.0 81.9 ± 10.8 (27-
135)
.76 -.06 -.13
71
Table 2. Factorial matrix of CEATS – Emotional Section.
Factor/items
Factorial
load: F1
Factorial
load: F2
Factorial
load: F3
Factorial
load: F4
Factor 1: DRIVE
Pessimistic/optimistic
.56
-.32.
.31
Low/high excitement with novelty
.64
Low/high sense of pleasure
.68
Sad/cheerful
.63 .32
Modest/ambitious plans
.63
Easily/hardly gives up
.46 .36
.30
Insecure/self-confident
.42 .49
.31
low /high drive and goal direction
.67
.37
Factor 2: ANGER
Hardly/easily irritable
.80
Non-aggressive/very aggressive
.68
Short/long duration of anger
.56
Non explosive/very explosive
.73
Rarely/often gets suspicious
.44
Patient/very impatient
.65
Factor 3: DISINHIBITION-FEAR
Fearful/daring .32
.58
Shy/extroverted .31
.59
Cautious/risk-taking
.48
Inhibited/spontaneous
.63
Thoughtful/impulsive
.53
Worried/unworried
.51
Freezing in danger – reactive in
danger
.48
Factor 4: CONTROL
Non/very disciplined
.63
Non/very organized
.67
Distractful/ non distractful
.60
Fails to finish tasks/finishes long
tasks
.67
Low concentration and interest/high
concentration even without interest
.45
Irresponsible/very responsible
.63
Only loadings ≥0.30 and ≤-0.30 are shown.
Table 3. Correlation between emotional factors, problems, benefits and age.
72
Disinhibition
-
fear
Drive
Control
Anger
Drive
.51** -
Control
.02 .34** -
Anger
.07* -.17* -.22** -
Problem
s
-0.03 -0.28** -0.31** 0.42**
Benefits
0.31* 0.52* 0.19* -0.14**
Age
0.00 -0.13** 0.07* -0.09*
* Correlation is significant at the 0.05 level.
** Correlation is significant at the 0.01 level.
Table 4. Gender differences for mean scores of emotional factors of CEATS.
FAC
TOR
Males (n=284)
Females (n=723)
F
p
Disinhibition-fear
20.5±4.2 19.3±4.3 13,186 <0.001
Drive
25.1±5.8 24.1±5.8 2,712 0.10
Control
19.2±4.2 20.0±4.1 5,945 0.015
Anger
17.5±4.6 17.9±4.7 2,048 0.15
73
Table 5. Correlations between dimensional scores of affective temperaments.
Depr
e
Anx
i
Cyclo
Dysph
Apath
Euthy
Irrit
Labil
Disin
Anxious
.46
-
Cyclothymic
.42
.30 -
Dysphoric
.24 .27
.51
-
Apathetic
.45
.28 .32 .20 -
Euthymic
-
.43
-.22 -.53 -.37 -.28 -
Irritable
.01 .12 .26
.46
-.05 -.12 -
Labile
.18 .10
.41
.35
.41
-.34 .27 -
Disinhibited
-.01 .02 .25 .30 .23 -.12 .27
.58
-
Hyperthymic
-
.54
-.28 -.30 -.14
-
.41
.48
.11 -.13 .05
Values >0.40 and <-0.40 are in bold. Values in italics were statistically non-significant
(p>0.05).
74
Table 6. Correlation of dimensional affective temperaments with emotional factors,
problems, benefits and age.
Depr
e
Anx
i
Cycl
o
Dysp
h
Apat
h
Euth
Irrit
Lab
Disi
n
Htm
Disinhib
-
fear
-
.46
-
.41
-.12 .00 -.32 .13 .13 .05 .21 .39
Dr
ive
-
.65
-.38 -.31 -.16
-
.46
.33 .07 -.17 .01
.65
Control
-.20 -.05 -.30 -.21
-
.52
.41
-.07
-
.48
-
.40
.33
Anger
.21 .22
.43
.53
.09 -.32
.52
.30 .20 -.17
Problems
.27 .16 .32 .29 .24 -.38 .19 .28 .20 -.25
Benefits
-
.44
-.23 -.28 -.11 -.35 .32 .02 -.18 -.02
.44
Age
.02 .02 -.15 -.12 -.01 .08 -.13 -.07 -.09 -.01
Values ≥0.40 and ≤-0.40 are in bold. Values in italics were statistically non-significant
(p>0.05).
75
FIGURE LEGENDS
Figure 1. Prevalence of categorical affective temperaments in males and females.
Subjects had to choose the affective temperament description that best fitted their
profile. N = 1007, males = 284 (28.2%) females = 723 (71.8%). Dep = depressive, anx =
anxious, cyc = cyclothymic, dysp = dysphoric, apa = apathetic, eut = euthymic, irr =
irritable, lab = labile, disin = disinhibited, htm = hyperthymic.
76
Figure 2a – Total Sample (n=1007)
Figure 2b – Sample without a perfect match (n=412)
Figure 2a and Figure 2b. Frequency of perfect and good matches in the
dimensional choice of affective temperaments.
Perfect and good match are the
descriptions marked as ‘everything to do with me’ and ‘a lot to do with me’, respectively.
A = number of perfect matches in the whole sample; B = number of good matches
among those without a perfect match.
77
Figure 3. Problems and benefits scores associated with categorical affective
temperaments.
Score ranges from 1 (no problems or minimal benefits) to 4 (marked
problems or benefits). Results are shown as mean ± s.d. For statistical differences, see
Results. Dep = depressive, anx = anxious, cyc = cyclothymic, dysp = dysphoric, apa =
apathetic, eut = euthymic, irr = irritable, lab = labile, disin = disinhibited, htm =
hyperthymic.
78
Figure 4. Emotional profile of categorical affective temperaments. Scores of
disinhibition-fear (7-35), drive (8-40), control (6-30) and anger (6-30) are shown. For
statistical differences, see Results. Dep = depressive, anx = anxious, cyc = cyclothymic,
dysp = dysphoric, apa = apathetic, eut = euthymic, irr = irritable, lab = labile, disin =
disinhibited, htm = hyperthymic.
79
APPENDIX
COMBINED EMOTIONAL AND AFFECTIVE TEMPERAMENT SCALE (CEATS) (this
version has been translated, back translated and checked to correct for
discrepancies from the original version in Brazilian Portuguese, but it has not
been validated in English).
INSTRUCTIONS:
1) For each of the questions below, please mark the alternative that best matches
the way you usually are and behave.
2) Read all the alternatives for each question before marking the one that most
closely represents your profile. Answer all the questions and tick only one
alternative.
3) Please answer carefully, but do not take too long to answer the questions.
4) Remember that there are no right or wrong answers. You must answer
according to how you are, not how you wish you were.
1.
A) I am fearful
B) I am slightly more fearful than most people
C) I am slightly more daring than fearful
D) I am daring
E) I am very daring
2.
A) I am very shy
B) I am shier than most people
C) I am slightly more outgoing than shy
D) I am outgoing
E) I am very outgoing
3.
A) I am very careful and cautious; I rarely take risks
B) I am careful and cautious, I take few risks
C) In some situations I am careful and cautious, but in others I take risks
D) In general, I take more risks than most people
E) I am not careful and cautious; I often take risks
4.
A) I have great difficulty to feel at ease; I am very inhibited
B) I am inhibited, I have difficulty to feel at ease
C) Sometimes I feel a little awkward, but in general I feel at ease
D) I am spontaneous easygoing
E) I am very spontaneous, sometimes even too much
5.
A) I think too much before I do things; I take longer than others to make decisions
80
B) I think a lot before I do things; I rarely make decisions impulsively
C) I think before I do things, but I don’t take long to make decisions
D) Sometimes I do things without having thought enough; I make decisions quickly
E) I often do things without thinking, I make decisions impulsively
6.
A) I worry too much
B) I worry more than most people
C) I worry as much as most people
D) I worry less than other people
E) I practically don’t worry
7. In dangerous situations, my natural reaction is:
A) to freeze and remain tense even after the danger passes
B) to freeze until the danger is gone
C) to freeze at the beginning, but I soon manage to loosen up and act
D) to have some kind of quick reaction, I usually do not freeze
E) to react quickly, I never freeze
8.
A) I am pessimistic
B) I am more pessimistic than optimistic
C) I am a little more optimistic than pessimistic
D) I am optimistic
E) I am very optimistic
9.
A) I rarely get excited and lively about new activities
B) Sometimes I get excited and lively about new activities
C) It is fairly common for me to get excited and lively with new activities
D) It is common for me to get excited and lively with new activities
E) It is very common for me to get very excited and very lively with new activities
10.
A) I feel little pleasure and joy
B) I feel less pleasure and joy than most people
C) I feel as much pleasure and joy as most people do
D) I feel more pleasure and joy than most people
E) I feel pleasure and joy intensely
11.
A) I often get sad and miserable
B) I often get a little sad and miserable
C) I am fairly happy and content
D) I am happy and cheerful
E) I am very happy and very cheerful
81
12.
A) My plans are modest, and I think small
B) My plans are more modest than those of others
C) I have some ambitious plans
D) My plans are usually ambitious
E) My plans are very ambitious, I think big
13.
A) Any problem I have is enough to discourage me and to make me give up
B) I often get discouraged and give up when I face difficulties
C) I feel a bit discouraged when the situation is difficult or complicated
D) It is quite rare for me to feel discouraged and give up on things
E) I rarely feel discouraged and I almost never give up
14.
A) I am very insecure
B) I am less confident than most people
C) I feel reasonably confident
D) I am more confident than others
E) I am very self-confident
15.
A) I have few goals and it is hard for me to go after them
B) I have some goals and go after some of them
C) I have some goals and go after most of them
D) I have many goals and go after them
E) I have many goals, including difficult ones, and I go after all of them with vigor
16.
A) I have little discipline
B) I have less discipline than most people
C) I am reasonably disciplined
D) I have more discipline than most people
E) I have a lot of discipline
17.
A) I am disorganized and it sometimes brings me problems
B) I am less organized than most people
C) I organized in some things
D) I am more organized than most people
E) I am very organized, sometimes too much
18.
A) I easily get distracted and it often brings me problems
B) I often get distracted and sometimes it brings me problems
C) Sometimes I get distracted but it is not enough to disturb me
82
D) I get distracted less often than most people
E) I hardly get distracted
19.
A) I often fail to conclude that the tasks I start
B) I have some difficulty in completing the tasks I start
C) I conclude many of the tasks I start, but I usually give up the hard ones
D) I often complete the tasks I start, including some hard ones
E) I always conclude the tasks I start, even long or difficult ones
20.
A) It is difficult for me to keep my concentration and interest
B) I can only keep my concentration if I am interested
C) I can keep my concentration if I am fairly interested
D) I can keep my concentration even if I am not interested
E) I can keep my concentration
well even I am not interested
21.
A) I am fairly irresponsible
B) I am less responsible than most people
C) I am reasonably responsible
D) I am more responsible than most people
E) I am very responsible
22.
A) It is rare for me to get irritated with something
B) I usually don`t get irritated
C) Sometimes I get irritated, but it rarely brings me problems
D) I get irritated more often than most people
E) I often get very irritated, and it often brings me problems
23.
A) I am not at all aggressive and sometimes it is a problem for me
B) I am not aggressive
C) I am a little less aggressive than most people
D) I am a little more aggressive than most people
E) I am quite aggressive in various situations
24. When I get angry, my anger lasts:
A) for a short time and I rarely get angry
B) shortly, I quickly calm down
C) slightly less than other people
D) longer than other people
E) a long time (‘it ruins my day’)
25.
A) I am not explosive at all
B) I am less explosive than others
C) Sometimes I am explosive
D) I am more explosive than others
83
E) I am very explosive
26. I ………… feel I am being betrayed or someone is planning to do something against
me:
A) Never
B) Almost never
C) Hardly ever
D) Sometimes
E) Often
27.
A) I am very patient
B) I am patient
C) I am a little impatient
D) I am impatient
E) I am very impatient
28. For each description below check the alternative that best corresponds to you
(check only one alternative).
A) I have a tendency towards melancholy and sadness, I see little fun and joy in things; I
tend to put myself down; I don’t like changes; I prefer to listen than to talk.
a) everything to do with me
b) a lot to do with me
c) some things to do with me
d) little to do with me
e) nothing to do with me
B) I am very cautious and careful; I often feel insecure and apprehensive; I keep
imagining that bad things are about to happen, I try to avoid high-risk situations; I am
always alert and vigilant.
a) everything to do with me
b) a lot to do with me
c) some things to do with me
d) little to do with me
e) nothing to do with me
C) My mood is unpredictable and unstable (ups and downs or mood swings); my mood
changes very quickly or out of proportion to the facts; I have periods of great energy,
enthusiasm and energy that alternate with other phases of sluggishness, loss of interest
and discouragement.
a) everything to do with me
b) a lot to do with me
c) some things to do with me
d) little to do with me
e) nothing to do with me
D) I have a strong tendency to feel agitated, anxious and angry at the same time.
a) everything to do with me
b) a lot to do with me
c) some things to do with me
84
d) little to do with me
e) nothing to do with me
E) I have little initiative; I often drift away from what others are saying or doing; I often fail
to finish what I have started; I tend to be passive and a bit slow.
a) everything to do with me
b) a lot to do with me
c) some things to do with me
d) little to do with me
e) nothing to do with me
F) My mood is balanced and predictable, I usually have mood changes only when there
is a clear reason, I have good spirits and, in general, I feel good about myself.
a) everything to do with me
b) a lot to do with me
c) some things to do with me
d) little to do with me
e) nothing to do with me
G) I am very frank, direct and determined, but also angry, suspicious and explosive.
a) everything to do with me
b) a lot to do with me
c) some things to do with me
d) little to do with me
e) nothing to do with me
H) I am restless and easily distracted; often I switch off or drift away from what others
are saying or doing, I often do things without thinking about the consequences, and
sometimes I am inconvenient and only realize it when it is too late; I quickly loose
interest, and I often fail to finish what I have started; when I loose my temper, I soon
calm down.
A) everything to do me
B) a lot to do with me
C) some things to do me
D) little to do me
E) nothing to do me
I) I am restless, active, spontaneous and distracted; I often rush and do careless things; I
often leave things for the last minute; when I loose my temper, I soon get well again.
a) everything to do with me
b) a lot to do with me
c) some things to do with me
d) little to do with me
e) nothing to do with me
J) I am always in good spirits, I feel very confident and I have fun easily; I love novelty
and I am always ready for new activities; I do many things without getting tired; when I
want something, I go after and get it; I have a strong tendency for leadership.
a) everything to do with me
b) a lot to do with me
c) some things to do with me
85
d) little to do with me
e) nothing to do with me
29. Choose the description (A to J) from the question 28 above that is closest to your
profile (only ONE alternative). Please read all the 10 descriptions before choosing the
alternative.
[ ] A)
[ ] B)
[ ] C)
[ ] D)
[ ] E)
[ ] F)
[ ] G)
[ ] H)
[ ] I)
[ ] J)
30. To what extent have you had problems or personal losses due to your usual mood
and the way you are and behave?
A) no problem / no losses
B) few problems / small losses
C) some problems / moderate losses
D) marked problems/ serious losses
31. To what extent have you gained benefits and had personal advantages due to your
usual mood and the way you are and behave?
A) almost no advantage / minimal benefits
B) few advantages / small benefits
C) some advantages / moderate benefits
D) many advantages / marked benefits
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