Jean-Philippe Boulenger

Association between violent suicidal behavior and the low activity allele of the serotonin transporter gene

There is compelling evidence that serotonin system dysfunction is associated with certain behavioral disorders, such as suicidal behavior and impulsive aggression. A functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) was recently identified and the presence of the short allele found to be associated with a lower level of expression of the gene, lower levels of 5-HT uptake, suicidal behavior and anxiety-related traits. We genotyped 51 West European Caucasians who had made violent suicide attempts and 139 controls of the same ethnic origin, with no history of suicidal behavior. The frequencies of the S allele and the SS genotype were significantly higher in the violent suicide attempters than in the controls. The odds ratio for the SS genotype vs the LL genotype was 3.63 (95% CI (1.27–10.40)). This suggests that a change in expression of the gene encoding the 5-HT transporter may be involved in violent suicidal behavior.

Suicide attempts and the tryptophan hydroxylase gene

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synthesis. In this case-control study, we investigated whether the TPH gene was a susceptibility factor for suicidal behavior. Seven polymorphisms spanning the entire gene were studied in a case-control study including 231 individuals who had attempted suicide and 281 controls. Significant associations were found between variants in introns 7, 8 and 9 (χ2 = 11.2, df = 1, P< 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3′ noncoding region (χ2 = 30.94, P = 0.0014) and suicide attempt. The association was strongest for subjects who had attempted suicide by violent means and who had a history of major depression. No significant association was observed between suicide attempts and polymorphisms in the promoter, intron 1 and intron 3. The results presented here, and those of previous studies, suggest that a genetic variant of the 3′ part of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression.

Persistence of abnormal cortisol levels in elderly persons after recovery from major depression

BACKGROUND Cortisol hypersecretion is characteristic of acute clinical depression, but little is known in fully recovered, non-treated elderly persons with a lifetime history of depression. This study was designed to examine patterns of diurnal cycle of cortisol in an elderly cohort without current depression or treatment for depression according to whether the person has or has not experienced a previous episode of depression or co-morbid depression with anxiety. METHODS Cortisol secretion was evaluated in 162 community-dwelling elderly on a stressful and a non-stressful day (basal level). Past depression and anxiety disorders were assessed using a standardized psychiatric examination based on DSM-IV criteria (the Mini International Neuropsychiatric Interview). RESULTS Antidepressant-free persons with a history of non-co-morbid major depression (6.8% of the sample) showed basal cortisol hypersecretion compared to those with depression and anxiety (8.6%) or controls. Several hours after exposure to a stressful situation, controls showed a sustained increase in cortisol secretion, which was not observed in persons with a history of depression. Persons with a history of depression with anxiety showed a similar cortisol secretion at baseline to controls but a heightened response to stressful situation; a pattern comparable to that observed in subjects with pure anxiety disorders (16.7%). CONCLUSION An abnormal HPA response persists even after effective treatment for depression. A history of co-morbid depression and anxiety gives rise to changes characteristic of anxiety alone. Our findings suggest that cortisol abnormalities may be trait markers for vulnerability to depression and for the differentiation of depression and depression with co-morbid anxiety.

No association between non-violent suicidal behavior and the serotonin transporter promoter polymorphism

There is compelling evidence that suicidal behavior is associated with the dysfunction of the serotonin system. A functional polymorphism in the promoter region of the serotonin transporter gene (5‐HTTLPR) was recently identified and the presence of the short allele was associated with lower gene expression, lower 5‐HT uptake and violent suicidal behavior. Thus, we attempted to determine whether 5‐HTTLPR is also involved in the susceptibility to non‐violent suicidal behavior. We compared the genotype from 166 West European Caucasians who attempted suicide by a non‐violent mean with 139 controls with no history of suicidal behavior from the same ethnic origin. The frequencies of the S allele and the SS genotype in the sample who attempted non‐violent suicide were not statistically different to those in the controls. Thus, the genetically altered expression of the 5‐HT transporter might be associated with more severe or violent suicidal behavior, but not with non‐violent suicidal behavior.

Early maladaptive schemas predict positive symptomatology in schizophrenia: A cross-sectional study

Recent literature has shown the role of social factors, such as childhood negative experiences and attachment styles, in the genesis of psychotic symptoms. So far, despite this association with childhood negative experiences and a wide range of psychiatric disorders, no study has yet attempted to assess early maladaptive schemas (EMSs) in patients with schizophrenia as primary diagnosis. A sample of 48 patients diagnosed with schizophrenia and 44 control participants answered the schema questionnaire short forms French validation, and were assessed with the positive and negative syndrome scale as well as a scale of depression symptomatology. Results showed that, after controlling for depression, patients with schizophrenia achieved higher scores than control subjects on six EMSs. The EMSs were associated with positive, but not negative, symptomatology. After controlling for depression, only the Mistrust/Abuse schema was a significant predictor of positive symptoms accounting for a small portion (12.4%) of the variance. The results highlight the importance of focusing not only on the schizophrenic symptoms but also on the person and his or her subjective development of self. Therefore, these results suggest that Youngs schema theory may be applied to schizophrenic patients.

Difficulty leading interpersonal coordination: towards an embodied signature of social anxiety disorder

Defined by a persistent fear of embarrassment or negative evaluation while engaged in social interaction or public performance, social anxiety disorder (SAD) is one of the most common psychiatric syndromes. Previous research has made a considerable effort to better understand and assess this mental disorder. However, little attention has been paid to social motor behavior of patients with SAD despite its crucial importance in daily social interactions. Previous research has shown that the coordination of arm, head or postural movements of interacting people can reflect their mental states or feelings such as social connectedness and social motives, suggesting that interpersonal movement coordination may be impaired in patients suffering from SAD. The current study was specifically aimed at determining whether SAD affects the dynamics of social motor coordination. We compared the unintentional and intentional rhythmic coordination of a SAD group (19 patients paired with control participants) with the rhythmic coordination of a control group (19 control pairs) in an interpersonal pendulum coordination task. The results demonstrated that unintentional social motor coordination was preserved with SAD while intentional coordination was impaired. More specifically, intentional coordination became impaired when patients with SAD had to lead the coordination as indicated by poorer (i.e., more variable) coordination. These differences between intentional and unintentional coordination as well as between follower and leader roles reveal an impaired coordination dynamics that is specific to SAD, and thus, opens promising research directions to better understand, assess and treat this mental disorder.

Caffeine Model of Panic

Much attention has been focused on the neurobiology of panic disorder. According to the DSM-III-R classification of panic disorders, panic attacks are given central importance in the genesis and maintenance of secondary complications such as agoraphobia, anticipatory anxiety, and, in a subgroup of patients, major depressive symptomatology. Given this perspective, it is important to understand the pathophysiology and biological correlates of “spontaneous” or “unprovoked” panic attacks.

Plasma adenosine levels: Measurement in humans and relationship to the anxiogenic effects of caffeine

The effects of caffeine on plasma adenosine were examined in eight healthy normal volunteers. Subjects were randomly administered on 4 separate days, in a double-blind fashion, either placebo or three different doses of caffeine (240, 480, and 720 mg). Adenosine concentrations, measured by high performance liquid chromatography, were in the micromolar range when samples were drawn into tubes containing dipyridamole to prevent adenosine reuptake by red blood cells. Plasma adenosine levels did not change after caffeine administration. The effects of caffeine on anxiety were related to changes in plasma caffeine but not plasma adenosine levels. The potential interest of caffeine as a chemical model of anxiety is discussed.

Frequent attendance in family practice and common mental disorders in an open access health care system

UNLABELLED Frequent attenders in family practice are known to have higher rates of mental disorder. However little is known about specific psychiatric disorders and whether this behavior extends to specialist services, in an open access fee-for-service health care system. METHODS 1060 patients from 46 family practices completed the Patient Health Questionnaire and the Client Service Receipt Inventory. During the consultation, family practitioners blind to the questionnaire responses rated the severity of mental health and physical disorders. The 10% of patients with the highest number of 6-month consultations in six age and sex stratified groups were defined as frequent attenders. RESULTS After adjustments for sociodemographic variables, physical health and other psychiatric diagnoses, patients with a somatoform disorder were more likely to be frequent attenders, with an odds ratio of 2.3 (95% CI: 1.3-3.8, p=.002). CONCLUSION When adjusting for confounders, among the four psychiatric diagnoses investigated only somatoform disorders remain significantly associated with frequent attendance. Physical health and chronic disease were no longer associated with frequent attendance which does not support the hypothesis that in an open access fee-for-service system, patients will consult for a wider range of health problems. Greater investigation into unexplained somatic symptoms could help reduce the frequency of attendance in both primary and secondary care, as this behaviour appears to be a general health-seeking drive than extends beyond family practice.

Social motor coordination in unaffected relatives of schizophrenia patients: a potential intermediate phenotype.

Intermediate endophenotypes emerge as an important concept in the study of schizophrenia. Although research on phenotypes mainly investigated cognitive, metabolic or neurophysiological markers so far, some authors also examined the motor behavior anomalies as a potential trait-marker of the disease. However, no research has investigated social motor coordination despite the possible importance of its anomalies in schizophrenia. The aim of this study was thus to determine whether coordination modifications previously demonstrated in schizophrenia are trait-markers that might be associated with the risk for this pathology. Interpersonal motor coordination in 27 unaffected first-degree relatives of schizophrenia patients and 27 healthy controls was assessed using a hand-held pendulum task to examine the presence of interpersonal coordination impairments in individuals at risk for the disorder. Measures of neurologic soft signs, clinical variables and neurocognitive functions were collected to assess the cognitive and clinical correlates of social coordination impairments in at-risk relatives. After controlling for potential confounding variables, unaffected relatives of schizophrenia patients had impaired intentional interpersonal coordination compared to healthy controls while unintentional interpersonal coordination was preserved. More specifically, in intentional coordination, the unaffected relatives of schizophrenia patients exhibited coordination patterns that had greater variability and in which relatives did not lead the coordination. These results show that unaffected relatives of schizophrenia patients, like the patients themselves, also present deficits in intentional interpersonal coordination. For the first time, these results suggest that intentional interpersonal coordination impairments might be a potential motor intermediate endophenotype of schizophrenia opening new perspectives for early diagnosis.