Didier Schrijvers

Mechanisms of gene–environment interactions in depression: evidence that genes potentiate multiple sources of adversity

BACKGROUND Previous work suggests that daily life stress-sensitivity may be an intermediary phenotype associated with both genetic risk for depression and developmental stress exposures. In the current analysis we hypothesized that genetic risk for depression and three environmental exposures over the course of development [prenatal stress, childhood adversity and adult negative life events (NLEs)] combine synergistically to produce the phenotype of stress-sensitivity. METHOD Twin pairs (n=279) participated in a momentary assessment study using the Experience Sampling Method (ESM), collecting appraisals of stress and negative affect (NA) in the flow of daily life. Prospective data on birthweight and gestational age, questionnaire data on childhood adversity and recent NLEs, and interview data on depression were used in the analyses. Daily life stress-sensitivity was modelled as the effect of ESM daily life stress appraisals on ESM NA. RESULTS All three developmental stress exposures were moderated by genetic vulnerability, modelled as dizygotic (DZ) or monozygotic (MZ) co-twin depression status, in their effect on daily life stress-sensitivity. Effects were much stronger in participants with MZ co-twin depression and a little stronger in participants with DZ co-twin depression status, compared to those without co-twin depression. NLE main effects and NLE genetic moderation were reducible to birthweight and childhood adversity. CONCLUSIONS The findings are consistent with the hypothesis that adult daily life stress-sensitivity is the result of sensitization processes initiated by developmental stress exposures. Genes associated with depression may act by accelerating the process of stress-induced sensitization.

Action monitoring and depressive symptom reduction in major depressive disorder.

INTRODUCTION Action monitoring has been reported to be disturbed in Major Depressive Disorder (MDD). Well-known markers for this action monitoring process are the error negativity/error-related negativity (Ne/ERN) and error positivity (Pe), both event-related potentials (ERP) generated in the anterior cingulate cortex. This study aims to explore the impact of symptom severity reduction on the Ne/ERN and Pe in MDD. METHODS Behavioural and ERP measurements were obtained in 15 MDD patients during performance on a speeded flankers task during the early stages of a depressive episode and compared with those recorded after 7 weeks of treatment. The same schedule was used in 15 healthy controls. RESULTS Whereas overall Ne/ERN and Pe peak amplitudes did not improve from sessions 1 to 2 in the patients, positive correlations emerged between between-session changes in symptom severity and Ne/ERN amplitudes. No such correlations were observed for the Pe. ERP amplitudes in the controls also remained unchanged between both sessions. Significant group differences were observed between MDD patients and controls for the Pe, but not for the Ne/ERN. CONCLUSIONS Whereas a clear association was observed between the level of symptom reduction and the level of improvement in Ne/ERN amplitudes in a MDD sample, no overall Ne/ERN enhancements were observed during symptom remission. Subsequent research is needed to further investigate the possible impact of depressive symptom reduction on the action monitoring in MDD. Several factors that might explain the absence of Ne/ERN group differences between patients and healthy controls in the current sample will also be discussed.

Better to give than to take? Interactive social decision-making in severe major depressive disorder

BACKGROUND Although recent studies focusing on major depressive disorder (MDD) suggest altered social decision-making, studies using the Ultimatum Game (UG) in patients with severe, clinical MDD do not exist. Moreover, all aforementioned studies so far focused on responder behavior and thus fairness considerations; to this date, no one investigated social interactive behavior which involves proposer behavior possibly requiring second-order mentalizing as well. METHODS Thirty-nine MDD patients and 22 healthy controls played a modified UG, both in the roles of responder and proposer against the same partner. RESULTS MDD patients accepted both fair and unfair offers as many times as the healthy controls in their role as responder. Importantly, however, in the role of proposer MDD patients offered significantly more than the control group did. LIMITATIONS Most patients were treated with psychotropic medication. CONCLUSIONS Responder behavior demonstrates that MDD patients are capable of making social decisions on fairness considerations in the same way as healthy controls do. The observed proposer behavior, however, could indicate that MDD patients are more focused on avoiding rejection. These findings provide unique evidence that social decision-making--as studied in a realistic context--is disturbed in MDD.

The impact of perfectionism and anxiety traits on action monitoring in major depressive disorder

Perfectionism and anxiety features are involved in the clinical presentation and neurobiology of major depressive disorder (MDD). In MDD, cognitive control mechanisms such as action monitoring can adequately be investigated applying electrophysiological registrations of the error-related negativity (ERN) and error positivity (Pe). It is also known that traits of perfectionism and anxiety influence ERN amplitudes in healthy subjects. The current study explores the impact of perfectionism and anxiety traits on action monitoring in MDD. A total of 39 MDD patients performed a flankers task during an event-related potential (ERP) session and completed the multidimensional perfectionism scale (MPS) with its concern over mistakes (CM) and doubt about actions (DA) subscales and the trait form of the State Trait Anxiety Inventory. Multiple regression analyses with stepwise backward elimination revealed MPS-DA to be a significant predictor (R2:0.22) for the ERN outcomes, and overall MPS (R2:0.13) and MPS-CM scores (R2:0.18) to have significant predictive value for the Pe amplitudes. Anxiety traits did not have a predictive capacity for the ERPs. MPS-DA clearly affected the ERN, and overall MPS and MPS-CM influenced the Pe, whereas no predictive capacity was found for anxiety traits. The manifest impact of perfectionism on patients’ error-related ERPs may contribute to our understanding of the action-monitoring process and the functional significance of the Pe in MDD. The divergent findings for perfectionism and anxiety features also indicate that the wide range of various affective personality styles might exert a different effect on action monitoring in MDD, awaiting further investigation.

Psychomotor functioning in chronic fatigue syndrome and major depressive disorder: A comparative study

BACKGROUND Studies comparing chronic fatigue syndrome (CFS) and major depressive disorder (MDD) reported similarities as well as differences between the two disorders. However, whereas psychomotor symptoms have been studied extensively in MDD, such research in CFS is more limited. Moreover, the few studies that compared cognitive and motor performance in MDD and CFS yielded inconsistent results. This study hence directly compares fine psychomotor functioning in both syndromes. METHODS Thirty-eight patients diagnosed with CFS without a current major depressive episode (MDE), 32 MDD patients with a current MDE and 38 healthy controls performed two computerized copying tasks differing in complexity: a line-copying task that mainly requires motor effort and a figure-copying task requiring additional cognitive efforts. All participants were female. A multivariate general linear model was used to compute group differences. RESULT Overall, both patient groups performed more slowly than the controls. Compared to CFS patients, patients with MDD needed significantly more time to copy the single lines but no such between-group performance difference was observed for the figure reproductions. In this latter copying task, the increasing complexity of the figures resulted in prolonged reaction times for all three participant groups with the effect being larger and the magnitude similar for the two patient groups. LIMITATIONS All patients were female and most were on psychotropic medication. CONCLUSIONS Both the MDD and CFS patients tested demonstrated an overall fine motor slowing, with the motor component being more affected in the MDD patients than in the CFS patients while both patient groups showed similar cognitive impairments.

Psychomotor Retardation in Elderly Untreated Depressed Patients

Background: Psychomotor retardation (PR) is one of the core features in depression according to DSM V (1), but also aging in itself causes cognitive and psychomotor slowing. This is the first study investigating PR in relation to cognitive functioning and to the concomitant effect of depression and aging in a geriatric population ruling out contending effects of psychotropic medication. Methods: A group of 28 non-demented depressed elderly is compared to a matched control group of 20 healthy elderly. All participants underwent a test battery containing clinical depression measures, cognitive measures of processing speed, executive function and memory, clinical ratings of PR, and objective computerized fine motor skill-tests. Statistical analysis consisted of a General Linear Method multivariate analysis of variance to compare the clinical, cognitive, and psychomotor outcomes of the two groups. Results: Patients performed worse on all clinical, cognitive, and PR measures. Both groups showed an effect of cognitive load on fine motor function but the influence was significantly larger for patients than for healthy elderly except for the initiation time. Limitations: Due to the restrictive inclusion criteria, only a relatively limited sample size could be obtained. Conclusion: With a medication free sample, an additive effect of depression and aging on cognition and PR in geriatric patients was found. As this effect was independent of demand of effort (by varying the cognitive load), it was apparently not a motivational slowing effect of depression.

Preliminary study of associative stigma among trainee psychiatrists in Flanders, Belgium.

AIM To study the degree of stigmatization among trainee psychiatrists, individual characteristics potentially leading to higher associative stigma, and coping mechanisms. METHODS Two hundred and seven trainee psychiatrists in Flanders (Belgium), all member of the Flemish Association of Trainee Psychiatrists, were approached to participate in the survey. A non-demanding questionnaire that was specifically designed for the purpose of the study was sent by mail. The questionnaire consisted of three parts, each emphasizing a different aspect of associative stigma: devaluing and humiliating interactions, the focus on stigma during medical training, and identification with negative stereotypes in the media. Answers were scored on a Likert scale ranging from 0 to 3. The results were analyzed using SPSS Version 18.0. RESULTS The response rate of the study was 75.1%. The internal consistency of the questionnaire was good, with a Cronbachs α of 0.71. Seventy-five percent of all trainee psychiatrists confirmed hearing denigrating or humiliating remarks about the psychiatric profession more than once. Additionally, more than half of them had had remarks about the incompetence of psychiatrists directed at them. Only 1.3% remembered having stigma as a topic during their psychiatric training. Trainees who had been in training for a longer period of time had experienced a significantly higher level of stigmatization than trainees with fewer years of experience (mean total stigma scores of 16.93 ± SD 7.8 vs 14.45 ± SD 6.1, t = -2.179 and P < 0.05). In addition, senior trainees effectively kept quiet about their profession significantly more often than their junior colleagues (mean item score 0.44 ± SD 0.82 vs 0.13 ± SD 0.48, t = 2.874, P < 0.01). Comparable results were found in trainees working in adult psychiatry as were found in those working in child or youth psychiatry (mean item score 0.38 ± SD 0.77 vs 0.15 ± SD 0.53, t = -2.153, P < 0.05). Biologically oriented trainees were more inclined to give preventive explanations about their profession, which can be seen as a coping mechanism used to deal with this stigma (mean item score 2.05 ± SD 1.05 vs 1.34 ± SD 1.1, t = -3.403, P < 0.01). CONCLUSION Associative stigma in trainee psychiatrists is underestimated. More attention should be paid to this potentially harmful phenomenon in training.

Adolescents with personality disorders suffer from severe psychiatric stigma: evidence from a sample of 131 patients.

Background The aim of the study is to assess the severity of psychiatric stigma in a sample of personality disordered adolescents in order to evaluate whether differences in stigma can be found in adolescents with different types and severity of personality disorders (PDs). Not only adults but children and adolescents with mental health problems suffer from psychiatric stigma. In contrast to the abundance of research in adult psychiatric samples, stigma in children and adolescents has hardly been investigated. Personality disordered adolescents with fragile identities and self-esteem might be especially prone to feeling stigmatized, an experience which might further shape their identity throughout this critical developmental phase. Materials and methods One hundred thirty-one adolescent patients underwent a standard assessment with Axis I and Axis II diagnostic interviews and two stigma instruments, Stigma Consciousness Questionnaire (SCQ) and Perceived Devaluation–Discrimination Questionnaire (PDDQ). Independent sample t-tests were used to investigate differences in the mean SCQ and PDDQ total scores for patients with and without a PD. Multiple regression main effect analyses were conducted to explore the impact of the different PDs on level of stigma, as well as comorbid Axis I disorders. Age and sex were also entered in the regression models. Results and conclusions Adolescents with severe mental health problems experience a burden of stigma. Personality disordered patients experience more stigma than adolescents with other severe psychiatric Axis I disorders. Borderline PD is the strongest predictor of experiences of stigma. More severely personality disordered adolescents tend to experience the highest level of stigma.

Prediction of electroconvulsive therapy response and remission in major depression: meta-analysis

BACKGROUND Electroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates. Aims To investigate the predictive value of age, depression severity, psychotic and melancholic features for ECT response and remission in major depression. METHOD A meta-analysis was conducted according to the PRISMA statement. A literature search identified recent studies that reported on at least one of the potential predictors. RESULTS Of the 2193 articles screened, 34 have been included for meta-analysis. Presence of psychotic features is a predictor of ECT remission (odds ratio (OR) = 1.47, P = 0.001) and response (OR = 1.69, P < 0.001), as is older age (standardised mean difference (SMD) = 0.26 for remission and 0.35 for response (P < 0.001)). The severity of depression predicts response (SMD = 0.19, P = 0.001), but not remission. Data on melancholic symptoms were inconclusive. CONCLUSIONS ECT is particularly effective in patients with depression with psychotic features and in elderly people with depression. More research on both biological and clinical predictors is needed to further evaluate the position of ECT in treatment protocols for major depression. Declaration of interest None.

Cognitive and psychomotor effects of three months of escitalopram treatment in elderly patients with major depressive disorder

BACKGROUND Although psychomotor retardation (PR) and cognitive disfunctioning are essential symptoms of elderly depressed patients, the differential effect of treatment with an SSRI in the elderly on these symptoms has hardly got any attention in studies with objective experimental measures. Since effects appear relatively slower in elderly, this study evaluates the effect on cognitive and psychomotor functioning as compared to mood, on four points during a twelve week follow up of monotreatment with escitalopram. METHOD 28 non-demented elderly unipolar depressive patients on 5-20mg escitalopram were compared to 20 matched healthy elderly. All participants underwent a test battery containing clinical depression measures, cognitive measures of processing speed, executive function and memory, clinical ratings of PR, and objective computerized fine motor skill-tests at the start and after 2, 6 and 12 weeks. Statistical analysis consisted of a General Linear Model (GLM) repeated measures multivariate analysis of variance of completers to compare the psychomotor and cognitive outcomes of the two groups. RESULTS Although, apart from the significant mood effect, no interaction effects were found for the psychomotor and cognitive tasks, the means in general show a trend of differential effects in cognitive and psychomotor functions, with smaller effects and delayed timeframes and with presence of subgroups compared to mood effects. LIMITATION Longer follow up studies are necessary to evaluate differential long term effects. CONCLUSION In elderly, moderate effects of SSRI treatment on mood precede slow or limited effects on cognition and psychomotor retardation.