R. Belzeaux

Clinical and neuropsychological characteristics of euthymic bipolar patients having a history of severe suicide attempt.

Identifying bipolar patients at high‐suicide risk is a major health issue. To improve their identification, we compared dimensional and neuropsychological profile of bipolar patients with or without history of suicide attempt, taking into account suicidal severity (i.e. admission to intensive ward).

Predominant polarity in bipolar disorders: Further evidence for the role of affective temperaments.

BACKGROUND Literature suggests bipolars may differ in several features according to predominant polarity, but the role of temperaments remains controversial. METHODS The EPIDEP study was designed to identify bipolar patients among a large sample of major depressives. Only bipolars were included in the current study. Patients were subtyped as predominantly depressive (PD) and predominantly manic and hypomanic (PM) according to a broad (more episodes of a given polarity) and a narrow (2/3 of episodes of one polarity over the other) definition, and compared on their characteristics. RESULTS Among 278 bipolars, 182 (79.8%) could be subtyped as PD and 46 (20.2%) as PM (broad definition); the respective proportions were of 111 (81.6%) and 25 (18.4%) using narrow definition. Expanding the definition added little in detecting differences between groups. Compared to PDs, PMs showed more psychosis, rapid cycling, stressors at onset, family history of affective illness, and manic first episode polarity; they also received more antipsychotics and lithium. The PDs showed more chronic depression, comorbid anxiety, and received more antidepressants, anticonvulsants and benzodiazepines. The following independent variables were associated with manic/hypomanic predominant polarity: cyclothymic temperament, first hospitalization≤25 years, hyperthymic temperament, and alcohol use (only for broad definition). LIMITATION Cross-sectional design, recall bias. CONCLUSIONS Study findings are in accord with literature except for suicidality and mixicity which were related to predominant mania, and explained by higher levels of cyclothymic and hyperthymic temperaments. Temperaments may play a key role in the subtyping of bipolar patients according to predominant polarity, which warrants confirmation in prospective studies.

Religious involvement in major depression: Protective or risky behavior? The relevance of bipolar spectrum

BACKGROUND Religiosity has been reported to be inversely related to depression and to suicide as well, but there is a lack of studies on its impact on bipolar disorder and especially, on depressed patients belonging to the bipolar spectrum. METHODS As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 234 (55.2%) could be classified as with high religious involvement (HRI), and 190 (44.8%) as with low religious involvement (LRI), on the basis of their ratings on the Duke Religious Index (DRI). RESULTS Compared to LRI, HRI patients did not differ with respect to their religious affiliation but had a later age at onset of their affective illness with more hospitalizations, suicide attempts, associated hypomanic features, switches under antidepressant treatment, prescription of tricyclics, comorbid obsessive compulsive disorder, and family history of affective disorder in first-degree relatives. The following independent variables were associated with religious involvement: age, depressive temperament, mixed polarity of first episode, and chronic depression. The clinical picture of depressive patients with HRI was evocative of chronic mixed depressive episodes described in bipolar III patients within the spectrum of bipolar disorders. LIMITATIONS Retrospective design, recall bias, lack of sample homogeneity, no assessment of potential protective and risk factors, and not representative for all religious affiliations. CONCLUSIONS In depressive patients belonging to the bipolar spectrum, high religious involvement associated with mixed features may increase the risk of suicidal behavior, despite the existence of religious affiliation.

Potential Use of MicroRNA for Monitoring Therapeutic Response to Antidepressants

Major depressive disorder (MDD) is a serious and common psychiatric disorder that affects millions of people worldwide. The most common treatment methods for MDD are antidepressant drugs, many of which act by regulating monoamines by inhibiting pre-synaptic reuptake and/or by modulating monoamine receptors. Despite advances in antidepressants and other treatment options, therapy is often based on subjective decisions made by the physician. Moreover, it requires time to determine treatment outcome and to define whether the prescribed treatment is effective. Biomarkers may help identify individuals with MDD who are more likely to respond to specific antidepressant treatment and may thus provide more objectivity in treatment decision making. MicroRNA as biomarkers of antidepressant response has engendered substantial enthusiasm. In this review, we give a detailed overview of biomarkers, particularly the major studies that have investigated microRNA in relationship to antidepressant treatment response.

Troubles affectifs et comorbidités éthyliques

Resume La comorbidite ethylique des troubles affectifs reste insuffisamment prise en compte. Son importance est encore meconnue et mal comprise malgre la frequence relevee des comorbidites addictives dans la plupart des troubles psychiatriques. Le concept de « diagnostic double » portant sur une simple addition de deux pathologies independantes doit etre depasse pour envisager un « psychopathologie duelle » combinant les effets de l’un sur l’autre des troubles, interactions susceptibles d’engager un etat complexe appelant une lecture syndromique differente et des strategies therapeutiques adaptees appelant la necessaire integration des prises en charge. L’association d’un trouble de l’usage de l’alcool aux troubles de l’humeur, notamment dans la maladie bipolaire, est un indice de gravite correle a une symptomatologie plus severe, une evolution instable, une resistance a la therapeutique et des risques de suicide accrus. L’alcool aggrave la depression et gene la therapeutique. Alcool et manie restent un danger redoute. Le mecanisme de l’association comorbide repose moins sur une strategie comportementale de compensation que sur une vulnerabilite partagee et croisee que l’on relie a la genetique du transporteur de la serotonine et au gene d’horloge Clock. Les difficultes therapeutiques motivent la mise en place d’un dispositif « integre » qui suppose une necessaire organisation des soins facilitant les collaborations entre addictologie et psychiatrie.

Épisodes dépressifs mixtes : clinique et biomarqueurs neurophysiologiques

Resume Les etudes epidemiologiques des episodes depressifs majeurs (EDM) ont mis en evidence l’association frequente de symptomes ou de signes de manie ou d’hypomanie au syndrome depressif. La reconnaissance epidemiologique, plus large que la definition stricte du DSM-IV, d’un sous-groupe d’EDM caracterise par la presence de symptomes ou de signes de la polarite opposee est importante cliniquement puisqu’elle est associee a un pronostic et une reponse therapeutique pejoratifs comparativement au sous-groupe d’EDM « typique ». L’evolution du DSM-5 a tenu compte des donnees epidemiologiques et a opte pour une perspective plus dimensionnelle en transposant le concept de mixite de « l’episode » a celui de « specification » du trouble de l’humeur. Comme le souligne le DSM-5 : « Les caracteristiques mixtes specifiant un episode depressif majeur sont un facteur de risque significatif pour le developpement d’un trouble bipolaire de type 1 ou 2. Ainsi, il est cliniquement utile de noter la presence de cette specification qui orientera le choix du traitement et le suivi de la reponse therapeutique ». Cependant, la specification mixte reste parfois difficile a diagnostiquer, et des biomarqueurs neurophysiologiques seraient utiles pour aider a mieux la reconnaitre. Deux modeles neurophysiologiques permettent de mieux apprehender les EDM mixtes. D’une part, le modele de la regulation emotionnelle mettant en evidence une tendance a l’hyper-reactivite et a la labilite emotionnelle. D’autre part, le modele de la regulation de la vigilance, mettant en evidence, grâce a l’enregistrement electroencephalographique, une labilite de la vigilance. Des etudes supplementaires sont a conduire pour mieux comprendre la relation entre ces deux modeles. Ces modeles offrent l’opportunite d’un cadre d’interpretation neurophysiologique de la clinique des episodes depressifs mixtes et des biomarqueurs neurophysiologiques potentiels afin de guider les strategies therapeutiques.

Symptômes négatifs, émotions et cognition dans la schizophrénie.

For a long time, treatment of schizophrenia has been essentially focussed on positive symptoms managing. Yet, even if these symptoms are the most noticeable, negative symptoms are more enduring, resistant to pharmacological treatment and associated with a worse prognosis. In the two last decades, attention has shift towards cognitive deficit, as this deficit is most robustly associated to functional outcome. But it appears that the modest improvement in cognition, obtained in schizophrenia through pharmacological treatment or, more purposely, by cognitive enhancement therapy, has only lead to limited amelioration of functional outcome. Authors have claimed that pure cognitive processes, such as those evaluated and trained in lots of these programs, may be too distant from real-life conditions, as the latter are largely based on social interactions. Consequently, the field of social cognition, at the interface of cognition and emotion, has emerged. In a first part of this article we examined the links, in schizophrenia, between negative symptoms, cognition and emotions from a therapeutic standpoint. Nonetheless, investigation of emotion in schizophrenia may also hold relevant premises for understanding the physiopathology of this disorder. In a second part, we propose to illustrate this research by relying on the heuristic value of an elementary marker of social cognition, facial affect recognition. Facial affect recognition has been repeatedly reported to be impaired in schizophrenia and some authors have argued that this deficit could constitute an endophenotype of the illness. We here examined how facial affect processing has been used to explore broader emotion dysfunction in schizophrenia, through behavioural and imaging studies. In particular, fMRI paradigms using facial affect have shown particular patterns of amygdala engagement in schizophrenia, suggesting an intact potential to elicit the limbic system which may however not be advantageous. Finally, we analysed facial affect processing on a cognitive-perceptual level, and the aptitude in schizophrenia to manipulate featural and configural information in faces.For a long time, treatment of schizophrenia has been essentially focussed on positive symptoms managing. Yet, even if these symptoms are the most noticeable, negative symptoms are more enduring, resistant to pharmacological treatment and associated with a worse prognosis. In the two last decades, attention has shift towards cognitive deficit, as this deficit is most robustly associated to functional outcome. But it appears that the modest improvement in cognition, obtained in schizophrenia through pharmacological treatment or, more purposely, by cognitive enhancement therapy, has only lead to limited amelioration of functional outcome. Authors have claimed that pure cognitive processes, such as those evaluated and trained in lots of these programs, may be too distant from real-life conditions, as the latter are largely based on social interactions. Consequently, the field of social cognition, at the interface of cognition and emotion, has emerged. In a first part of this article we examined the links, in schizophrenia, between negative symptoms, cognition and emotions from a therapeutic standpoint. Nonetheless, investigation of emotion in schizophrenia may also hold relevant premises for understanding the physiopathology of this disorder. In a second part, we propose to illustrate this research by relying on the heuristic value of an elementary marker of social cognition, facial affect recognition. Facial affect recognition has been repeatedly reported to be impaired in schizophrenia and some authors have argued that this deficit could constitute an endophenotype of the illness. We here examined how facial affect processing has been used to explore broader emotion dysfunction in schizophrenia, through behavioural and imaging studies. In particular, fMRI paradigms using facial affect have shown particular patterns of amygdala engagement in schizophrenia, suggesting an intact potential to elicit the limbic system which may however not be advantageous. Finally, we analysed facial affect processing on a cognitive-perceptual level, and the aptitude in schizophrenia to manipulate featural and configural information in faces.

Symptômes négatifs dans la schizophrénie et addiction

Dual diagnosis of schizophrenia and substance-related disorders is common in psychiatric practice. Epidemiologic studies and report have established that the risk of a substance-related disorder was 4 to 5 times higher in a population of psychiatric patients than in the general population. However, little is known on the reason of this relationship and the treatments required. Its well known that a family history of psychosis is a risk factor of schizophrenia. Similarly a family history of substance use disorders increases the risk of using substances. Because the two disorders often occurred together, it could be hypothesized that a genetic risk factor is common. However, recent studies did not confirm this hypothesis and it seems that their genetic risks factor would be unrelated. Evidence now exists describing the different profiles of patients whether they used substance or not. Concerning negative symptoms clinical studies and meta-analyses have described fewer symptoms in schizophrenia patients with a substance use disorder. Among the different explanations that have been addressed, it seems that a lower capability of obtaining the substance could partly explain this relationship. Perhaps because patients with social withdrawal have more difficulties to find and spend the time required to obtain abused substances. At the opposite some products such as cocaine may relieve some symptoms especially anhedonia and alogia. However the link between substance-related disorders and negative symptoms is weak and decreases in more recent studies, probably because negative symptoms as well as addiction disorders are better characterized. Considering that treating psychiatric symptoms may not always lead to a decrease in the substance-related disorders but that patients who give up substances improve their psychotic symptoms, a therapeutic strategy should be planned for these dual disorders patients combining psychiatry and addiction interventions.Dual diagnosis of schizophrenia and substance-related disorders is common in psychiatric practice. Epidemiologic studies and report have established that the risk of a substance-related disorder was 4 to 5 times higher in a population of psychiatric patients than in the general population. However, little is known on the reason of this relationship and the treatments required. Its well known that a family history of psychosis is a risk factor of schizophrenia. Similarly a family history of substance use disorders increases the risk of using substances. Because the two disorders often occurred together, it could be hypothesized that a genetic risk factor is common. However, recent studies did not confirm this hypothesis and it seems that their genetic risks factor would be unrelated. Evidence now exists describing the different profiles of patients whether they used substance or not. Concerning negative symptoms clinical studies and meta-analyses have described fewer symptoms in schizophrenia patients with a substance use disorder. Among the different explanations that have been addressed, it seems that a lower capability of obtaining the substance could partly explain this relationship. Perhaps because patients with social withdrawal have more difficulties to find and spend the time required to obtain abused substances. At the opposite some products such as cocaine may relieve some symptoms especially anhedonia and alogia. However the link between substance-related disorders and negative symptoms is weak and decreases in more recent studies, probably because negative symptoms as well as addiction disorders are better characterized. Considering that treating psychiatric symptoms may not always lead to a decrease in the substance-related disorders but that patients who give up substances improve their psychotic symptoms, a therapeutic strategy should be planned for these dual disorders patients combining psychiatry and addiction interventions.

Troubles affectifs et troubles des conduites alimentaires

Resume Les etudes epidemiologiques montrent une comorbidite frequente entre troubles affectifs et troubles des conduites alimentaires. La prevalence d’un de ces troubles chez les patients souffrant de l’autre trouble se revele bien superieure a la prevalence observee dans la population generale. Plusieurs causes pourraient expliquer cette comorbidite elevee. En premier lieu, l’origine iatrogene est detaillee. En effet, l’emploi de psychotropes, et notamment les regulateurs de l’humeur, entraine frequemment des modifications des conduites alimentaires. Par ailleurs, troubles affectifs et troubles des conduites alimentaires partagent plusieurs caracteristiques semiologiques communes. Ces similarites pourraient non seulement etre a l’origine de meprises dans le diagnostic differentiel, mais aussi temoigner de mecanismes physiopathologiques partages entre ces deux troubles. Les donnees genetiques et biologiques sont toutefois pour l’instant trop eparses pour pouvoir appuyer cette hypothese. Il est cependant important de noter que la comorbidite aggrave le pronostic du patient, et se voit associee a des formes de troubles affectifs severes marquees par un âge de debut de la maladie plus precoce, un nombre plus eleve d’episodes thymiques ainsi qu’une plus grande suicidalite. Enfin, les traitements pharmacologiques generalement utilises dans les troubles affectifs sont revus afin de determiner leur preuve d’efficacite dans les troubles des conduites alimentaires, dans l’optique d’etablir la meilleure option therapeutique en cas de comorbidite.

Fonctionnement neurocognitif dans la manie pure et la manie mixte

Neurocognitive dysfunction is increasingly recognized as a prominent feature of bipolar disorder. Cognitive function seems to be impaired across different states of bipolar illness. Nervertheless, research that studies neuropsychological functioning in acute phases is scarce. Acutely ill patients have shown dysfunctions in several cognitive areas. We reviewed the literature on neuropsychological studies of acute phases to highlight neurocognitive deficits in mixed and pure mania. The results show dysfunctions in sustained attention that are significantly more important in mixed mania rather than in pure mania. Impulsive pattern of responding seems to characterize pure manic state. We also found impairments in processing speed, verbal and spatial learning/memory and executive functions, including cognitive flexibility, inhibitory control, conceptual reasoning, planning and problem solving. Disturbance in executive functioning seems to be more important in pure mania rather than mixed mania.