Paulo Pimentel

Entrapment and Defeat Perceptions in Depressive Symptomatology: Through an Evolutionary Approach.

The social rank and arrested defenses model for mood disorders bridges between animal and human models of psychopathology. There is increasing evidence that depression is associated with subordinated and loss of social rank, feeling inferior, shame, submissive behavior, and feeling defeated. These stressful states activate threat coping responses of fight and flight. If these are aroused but blocked, feelings of entrapment emerge with a negative impact on mood. The current study builds on previous studies and explores the association between depressive symptoms, social rank variables (of social comparison and submissive behavior), entrapment, and defeat in a sample of patients (n = 106) with major depression and in a sample of healthy controls (n = 116). Results showed that social rank variables, entrapment, and defeat were strongly associated with depressive symptoms in both samples. Entrapment and defeat showed significant association with other social rank variables. Logistic regression analysis revealed that defeat and internal entrapment were significant predictors of the belonging to the clinical or control groups. The present study extends previous research and supports the importance of defeat and external entrapment in clinical depression.

Common genetic polymorphisms in the ABCB1 gene are associated with risk of major depressive disorder in male Portuguese individuals.

Major depressive disorder (MDD) is a highly prevalent disorder, which has been associated with an abnormal response of the hypothalamus-pituitary-adrenal (HPA) axis. Reports have argued that an abnormal HPA axis response can be due to an altered P-Glycoprotein (P-GP) function. This argument suggests that genetic polymorphisms in ABCB1 may have an effect on the HPA axis activity; however, it is still not clear if this influences the risk of MDD. Our study aims to evaluate the effect of ABCB1 C1236T, G2677TA and C3435T genetic polymorphisms on MDD risk in a subset of Portuguese patients. DNA samples from 80 MDD patients and 160 control subjects were genotyped using TaqMan SNP Genotyping assays. A significant protection for MDD males carrying the T allele was observed (C1236T: odds ratio (OR)=0.360, 95% confidence interval [CI]: [0.140-0.950], p=0.022; C3435T: OR=0.306, 95% CI: [0.096-0.980], p=0.042; and G2677TA: OR=0.300, 95% CI: [0.100-0.870], p=0.013). Male Portuguese individuals carrying the 1236T/2677T/3435T haplotype had nearly 70% less risk of developing MDD (OR=0.313, 95% CI: [0.118-0.832], p=0.016, FDR p=0.032). No significant differences were observed regarding the overall subjects. Our results suggest that genetic variability of the ABCB1 is associated with MDD development in male Portuguese patients. To the best of our knowledge, this is the first report in Caucasian samples to analyze the effect of these ABCB1 genetic polymorphisms on MDD risk.

FAS -670A>G genetic polymorphism Is associated with Treatment Resistant Depression.

BACKGROUND Hippocampal neurogenesis has been suggested as a downstream event of antidepressants (AD) mechanism of action and might explain the lag time between AD administration and the therapeutic effect. Despite the widespread use of AD in the context of Major Depressive Disorder (MDD) there are no reliable biomarkers of treatment response phenotypes, and a significant proportion of patients display Treatment Resistant Depression (TRD). Fas/FasL system is one of the best-known death-receptor mediated cell signaling systems and is recognized to regulate cell proliferation and tumor cell growth. Recently this pathway has been described to be involved in neurogenesis and neuroplasticity. METHODS Since FAS -670A>G and FASL -844T>C functional polymorphisms never been evaluated in the context of depression and antidepressant therapy, we genotyped FAS -670A>G and FASL -844T>C in a subset of 80 MDD patients to evaluate their role in antidepressant treatment response phenotypes. RESULTS We found that the presence of FAS -670G allele was associated with antidepressant bad prognosis (relapse or TRD: OR=6.200; 95% CI: [1.875-20.499]; p=0.001), and we observed that patients carrying this allele have a higher risk to develop TRD (OR=10.895; 95% CI: [1.362-87.135]; p=0.008). Moreover, multivariate analysis adjusted to potentials confounders showed that patients carrying G allele have higher risk of early relapse (HR=3.827; 95% CI: [1.072-13.659]; p=0.039). FAS mRNA levels were down-regulated among G carriers, whose genotypes were more common in TRD patients. No association was found between FASL-844T>C genetic polymorphism and any treatment phenotypes. LIMITATIONS Small sample size. Patients used antidepressants with different mechanisms of action. CONCLUSION To the best of our knowledge this is the first study to evaluate the role of FAS functional polymorphism in the outcome of antidepressant therapy. This preliminary report associates FAS -670A>G genetic polymorphism with Treatment Resistant Depression and with time to relapse. The current results may possibly be given to the recent recognized role of Fas in neurogenesis and/or neuroplasticity.

Entrapment - conceito, definição e características psicométricas da versão portuguesa da Escala de Entrapment

The role of evolutionary strategies in psychopathology has been widely studied in recent years, particularly the mechanisms of fight and flight. Entrapment means the inhibition of escape strategy when it’s psychobiologically activated. Life contexts with characteristics of entrapment are linked to stress, anxiety, depression and suicide. This work presents the psychometric characteristics of the Entrapment Scale (ES) originally developed by Gilbert & Allan (1998). It consists of two scales: the Internal Entrapment Scale (IES) related to activation to escape, motivated by aversive emotional states and External Entrapment Scale (EES), when the desire to escape is stimulated by external events. The scale was evaluated in three samples: students (N = 608), general population (N = 406) and depressed patients (N = 106). The scale reproduces the results of their authors. It has demonstrated high internal consistency, with Cronbach α ranging between .85 and .93, one-dimensional structure for each scale and the extracted factors explain between 50.9% and 67.6% of total variance. Temporal stability was moderate to high (r = .66 to r = .92). Patients have significantly higher values on the IES and the EES than controls, supporting the construct validity. The moderate correlations (r = .50 to r = .64) between EE and the Beck Depression Inventory suggest a convergence between these instruments. Entrapment Scale has good psychometric characteristics, and must now broaden its application on studies of prospective nature in clinical settings.

The role of IL18-607C > A and IL18-137G > C promoter polymorphisms in antidepressant treatment phenotypes: A preliminary report

Recent studies suggest that immune activation and cytokines, such as IL-18, are involved in depression. IL-18 is expressed in brain and is increased in patients with moderate to severe depression. In this study we aim to evaluate the role of IL18-607C>A and IL18-137G>C promoter polymorphisms in antidepressant treatment phenotypes, specifically relapse and treatment resistant depression (TRD). We genotyped the referred polymorphisms in a subset of 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months. Patients carrying IL18-607 CA or AA genotypes were significantly more prone to relapse after AD treatment and present a significantly lower time to relapse than patients carrying CC genotype. Similarly, patients carrying IL18-137 GC or CC genotypes have a significantly higher risk of relapse and display relapse significantly earlier than the ones carrying GG genotype. Due to the low number of IL18-607 CC and IL18-137 GG in the relapse subgroup (n=3 and n=5, respectively), results were validated by bootstrapping analysis, and remained significant. No association was found between the evaluated genetic polymorphisms and TRD. IL18 peripheral mRNA levels were upregulated in IL18-607 CA or AA carriers. This preliminary report indicates that IL18-607C>A and IL18-137G>C genetic polymorphisms seem to influence depression relapse after antidepressant treatment in our subset of depressed patients, and may possibly contribute to the disregulated IL-18 levels found in patients with depression.

Propriedades Psicométricas da Escala de Cuidado do Questionário de Experiências de Cuidado e Abuso na Infância (Childhood Experiences of Care and Abuse – CECA.Q)

Certas formas de cuidado, como negligencia ou antipatia, o abuso infantil e a adversidade em geral sao preditores de patologia na vida adulta. As entrevistas existentes para a sua avaliacao sao muito longas tornando-se uteis so em pequenas amostras. O estudo das experiencias infantis atraves de um questionario de auto-resposta torna viavel a realizacao de investigacao em amostras mais amplas. Neste trabalho apresentam-se as propriedades psicometricas da Escala de Cuidado (EC) da versao em portugues do Questionario de Experiencias de Cuidado e Abuso na Infância (CECA.Q) (Smith, Lam, Bifulco, & Checkley, 2002). A EC avalia as experiencias de cuidado ate aos 17 anos. Na versao original apresenta uma escala com 16 itens, respondida duas vezes, uma em relacao a mae e outra em relacao ao pai, possuindo duas subescalas, negligencia e antipatia. Globalmente, o CECA.Q avalia para alem de experiencias de negligencia e antipatia, perda parental, abuso fisico e sexual. A EC foi avaliada num grupo de estudantes (N = 545), num grupo da populacao geral (N = 262) e num grupo de doentes com depressao major (N = 100). Apos um primeira analise dos dados, concluiu-se que os itens 7, 8, 11, e 15 nao possuiam qualidades psicometricas para se manterem na versao portuguesa da EC do CECA.Q, resultando entao uma versao de 12 itens. A analise factorial demonstrou a existencia de dois factores (negligencia e antipatia) nas tres amostras, verificou-se uma boa consistencia interna, entre .70 e .95 considerando os dois factores, ambos os pais, os tres grupos e ambos os generos, bem como uma adequada validade de construto e estabilidade teste-reteste entre .62 e .88 no grupo de estudantes e populacao geral. A presente versao da Escala de Cuidado do CECA.Q mostrou ter qualidades psicometricas adequadas para ser utilizada em estudantes, em sujeitos da populacao geral, bem como em populacoes com psicopatologia depressiva, sendo necessaria agora investigacao em outras amostras e utilizando estudos de seguimento.

Defeat - concept and assessment: psychometric properties of the Portuguese version of the Defeat Scale

A teoria do posto social (social rank theory), no contexto da psicopatologia evolucionaria, sugere que a derrota e uma resposta psicobiologica adaptativa presente sobretudo em situacoes de conflitos agonisticos. Estudos em animais e no homem demonstraram o impacto neurobiologico negativo das situacoes de derrota. No ser humano, o estado de derrota exprime o sentimento resultante de perdas na luta por objectivos importantes e de posto social. A Escala de Derrota (ED) foi desenvolvida por Gilbert e Allan (1998) com o objectivo de avaliar a intensidade da derrota. As propriedades psicometricas da ED foram avaliadas num grupo de estudantes (n = 609), num grupo da populacao geral (n = 406) e num grupo de doentes com depressao major (n = 106). A escala revelou uma estrutura unidimensional na analise factorial e uma boa consistencia interna, entre .89 e .93, nos tres grupos e em ambos os generos. A estabilidade teste-reteste, a validade convergente com sintomatologia depressiva e a validade divergente com o suporte social e o optimismo, assim como a validade de construto mostraram-se adequadas. A presente versao da Escala de Derrota mostrou ter qualidades psicometricas adequadas para ser utilizada em populacoes clinicas e nao clinicas.

IL6-174G > C genetic polymorphism influences antidepressant treatment outcome

Abstract Background: Major depressive disorder is a condition associated with dysregulated cytokine levels; among these, IL6. Furthermore, genetic variations within cytokine genes have been proposed to predict antidepressant treatment outcome. Objectives: This study aims to evaluate the role of IL6-174G > C and IL6R D358A A > C functional polymorphisms in antidepressant treatment phenotypes, specifically remission, relapse, and treatment resistant depression (TRD). Methods: The referred polymorphisms were genotyped in 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months. Results: It was found that patients carrying IL6-174 GC genotype present a protection towards the development of TRD (OR = 0.242; 95% CI = 0.068–0.869; p = .038), when compared with GG genotype. Additionally, carriers of IL6-174 CC genotype remit earlier than patients with IL6-174 GG/GC genotypes, with a median time to remission of 6 weeks for CC carriers and 15 weeks for GG or GC carriers (p = .030, Log-rank test). No association was found between IL6R D358A genetic polymorphism and any of the treatment phenotypes evaluated. Conclusions: The IL6-174G > C polymorphism influences antidepressant treatment outcome in this sub-set of MDD patients, providing a putative mechanistic link for the dysregulated IL-6 levels described in the literature in patients with TRD.

Psychometric properties of Portuguese version for the Multidimensional Scale of Perceived Social Support (MSPSS)

The Multidimensional Scale of Perceived Social Support (MSPSS) originally developed by Zimet, Dahlem, Zimet, and Farley (1998) was designed to subjectively assess social support from family, friends and significant others. This work‘s aim is to study the factorial structure, reliability and construct validity of the Portuguese version of MSPSS. The scale was assessed in a group of students (N = 454), a group of the general population (N = 261) and a group of patients with major depression (N = 100). The factor analysis revealed the existence of three factors (family, friends and significant others); and the scale showed good internal consistency with Cronbach’s alphas between .85 and .95, regarding all three factors, the three groups and both genders. The construct validity was adequate and test-retest stability in the group of students and the general population had values between .40 and .91. The Cronbach’s alphas for the retest ranged between .95 and .87. The MSPSS shown to have good psychometric properties for use in students, subjects from the general population and in populations with major depression, and need now to further research in other samples and using follow-up studies.