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ABSTRACT: 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.
Journal of affective disorders 03/2013; · 3.76 Impact Factor
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ABSTRACT: OBJECTIVE: To analyze the interface between borderline personality disorder (BPD) and bipolarity in depressed patients comorbid with BPD. METHODS: As part of National Multi-site Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1month apart, 19 (3.9%) had comorbid BPD (BPD+), whereas 474 (96.1%) did not manifest this comorbidity (BPD-). RESULTS: Compared to BPD (-), BPD (+) patients displayed higher rates of bipolar (BP) disorders and temperaments, an earlier age at onset with a family history of affective illness, more comorbidity, more stressors before the first episode which was more often depressive or mixed, as well as a greater number and severity of affective episodes. CONCLUSIONS: The hypothesis which fitted at best our findings was to consider BPD as a contributory factor in the development of BP disorder, which could have favoured the progression from unipolar major depression to BP disorder. We could not however exclude that some features of BP disorder may have contributed to the development of BPD.
European Psychiatry 02/2013; · 2.77 Impact Factor
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R Belzeaux,
A Bergon,
V Jeanjean,
B Loriod,
C Formisano-Tréziny,
L Verrier,
A Loundou,
K Baumstarck-Barrau,
L Boyer,
V Gall,
J Gabert,
C Nguyen, J-M Azorin,
J Naudin,
E C Ibrahim
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ABSTRACT: To date, it remains impossible to guarantee that short-term treatment given to a patient suffering from a major depressive episode (MDE) will improve long-term efficacy. Objective biological measurements and biomarkers that could help in predicting the clinical evolution of MDE are still warranted. To better understand the reason nearly half of MDE patients respond poorly to current antidepressive treatments, we examined the gene expression profile of peripheral blood samples collected from 16 severe MDE patients and 13 matched controls. Using a naturalistic and longitudinal design, we ascertained mRNA and microRNA (miRNA) expression at baseline, 2 and 8 weeks later. On a genome-wide scale, we detected transcripts with roles in various biological processes as significantly dysregulated between MDE patients and controls, notably those involved in nucleotide binding and chromatin assembly. We also established putative interactions between dysregulated mRNAs and miRNAs that may contribute to MDE physiopathology. We selected a set of mRNA candidates for quantitative reverse transcriptase PCR (RT-qPCR) to validate that the transcriptional signatures observed in responders is different from nonresponders. Furthermore, we identified a combination of four mRNAs (PPT1, TNF, IL1B and HIST1H1E) that could be predictive of treatment response. Altogether, these results highlight the importance of studies investigating the tight relationship between peripheral transcriptional changes and the dynamic clinical progression of MDE patients to provide biomarkers of MDE evolution and prognosis.
Translational psychiatry. 01/2012; 2:e185.
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ABSTRACT: Compared to healthy individuals, schizophrenic patients suffer from sensorimotor disorders including problems when tracking moving targets and perceiving biological motion. Recent advances in embodied cognition and social coordination dynamics have emphasized the important role played by bodily information exchange (e.g. facial expressions, posture, and movements) in the way people interact with and mutually influence each other. These experimental studies on healthy participants provide data on sensorimotor performances of a patient that are recorded at high temporal and spatial resolutions. They should therefore be considered in studies on schizophrenic patients. These functional, quantitive and dynamic aspects of sensorimotor coordination abilities, may offer promising perspectives and could lead to a better understanding of sensorimotor disorders in schizophrenia. The purpose of this article is to introduce a new experimental paradigm in schizophrenia inspired by the field of coordination dynamics, a theoretical and experimental approach born more than 30 years ago that has recently expanded to interpersonal interactions, the so-called social coordination dynamics. In our study, we hypothesize that the sensorimotor deficits associated with schizophrenia in social interaction may be, at least partially, due to a failure to properly pick up information about the movements of other people. We therefore designed a study where healthy individuals and schizophrenic patients were asked to intentionally track the oscillations of visual targets of various social relevance using hand movements. Four different rhythmic visual stimuli varying in degree of biological relevance (form and motion) are used: [1] an oscillating dot; [2] a computer generated hand moving up and down continuously driven by a sine function; [3] pre-recorded oscillatory movements of a real hand; and [4] the hand of a real individual (behind a curtain that occluded vision of the rest of the body). Two distinct dependent variables are computed to quantify the coordination between the movements of the participants and the visual stimuli: the relative phase and the power spectrum overlap between their own movements. In this preliminary study, analyses of kinematic data revealed that schizophrenic patients had trouble synchronizing to (the more) "biological" target unlike control healthy individuals. These results suggest that patients with schizophrenia may suffer from sensorimotor coordination disabilities with socially relevant visual stimuli. The novel paradigm we introduce in research on schizophrenia should allow for a better understanding of the troubles these patients encounter when interacting with other people thanks to an approach rooted and building on social coordination dynamics as well as motor and social cognition.
L Encéphale 12/2011; 37 Suppl 2:S100-9. · 0.63 Impact Factor
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ABSTRACT: Abnormalities involving the prefrontal cortex (PFC) have long been postulated to underpin the pathophysiology of schizophrenia. Investigations of PFC integrity have focused mainly on the dorsolateral PFC (DLPFC) and abnormalities in this region have been extensively documented. However, defects in schizophrenia may extend to other prefrontal regions, including the ventromedial PFC (VMPFC), and evidence of VMPFC abnormalities comes from neuropathological, structural and functional studies. Patients with acquired brain injury to the VMPFC display profound disruption of social behaviour and poor judgment in their personal lives. The Iowa Gambling Task (IGT) was developed to assess decision-making in these neurological cases : it presents a series of 100 choices from four card decks that differ in the distribution of rewarding and punishing outcomes. Whilst healthy volunteers gradually develop a preference for the two "safe" decks over the course of the task, patients with VMPFC lesions maintain a preference for the two "risky" decks which are associated with high reinforcement in the short term, but significant long-term debt. Interestingly, damage to VMPFC may cause both poor performance on the IGT and lack of insight concerning the acquired personality modification. Recently, our group reported a trait-related decisionmaking impairment in the three phases of bipolar disorder. In a PET study, VMPFC dysfunction was shown in bipolar manic patients impaired on a decision-making task and an association between decision-making cognition and lack of insight was described in mania. A quantitative association between grey matter volume of VMPFC and memory impairment was previously reported in schizophrenia. Research suggests that lack of insight is a prevalent feature in schizophrenia patients, like auditory hallucinations, paranoid or bizarre delusions, and disorganized speech and thinking. Because schizophrenia is associated with significant social or occupational dysfunction, previous research assessed decision-making function but indicates conflicting results. Thirteen studies have reported impaired IGT performance in patients with schizophrenia and, in seven reports, no significant differences in IGT performance between patient and healthy control groups were found. Those discrepancies may relate to multiple factors. First, most of the studies included small sample size and negative findings may be due to the large variance of net scores. Second, as suggested by Rodríguez-Sánchez et al., there is a wide disparity in performance by control subjects across studies. Third, intelligence quotient (IQ) score and level of education may be correlated with IGT performance, which may explain IGT performance differences in studies that did not control for educational or IQ score. Fourth, only two studies have systematically controlled for substance use disorder, a potential confounder. Fifth, only two studies assessed the impact of antipsychotic (AP) class on performance. Sixth, to our knowledge, no study assessed the impact of AP dosage on decision-making ability, while AP dose-reduction and dopamine increase, might lead to improvements, in cognitive functions in schizophrenia and in IGT performance in bipolar disorder, respectively. Finally, discrepancies between studies may be related to the heterogeneity of diagnostic groups. Two of the negative studies included schizophrenia and schizoaffective disorder while positive studies have generally included only patients with schizophrenia. Nevertheless, some studies that included only patients with schizophrenia failed to find differences between groups. Thus, further research should assess decision-making in schizophrenia by testing a large group of patients with homogeneity of diagnostic, in comparison with a large group of control subjects. Authors should control for IQ or level of education, substance use disorder and smoking status. While it is now accepted that DLPFC defects in schizophrenia may extend to VMPFC, future investigations should test for an association between memory, insight ability and IGT performance and assess the impact of antipsychotic dosage upon performance.
L Encéphale 12/2011; 37 Suppl 2:S110-6. · 0.63 Impact Factor
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ABSTRACT: In social cognition, the notion of Theory of Mind (ToM) is widely studied among people with schizophrenia to give an account for intersubjective disturbances. ToM is classically defined as the ability to make inferences about other persons'mental states, as beliefs, thoughts or intentions. However, ToM is not understood or explored as a homogeneous notion. First, this review briefly describes main theoretical models, as well as experimental tasks of ToM. Second, clinical results strongly suggest that patients with schizophrenia present impaired ToM performances. However, the presence of a robust relationship between ToM and schizophrenic symptomatology, or clinical course, is still controversial. Third, we highlight main findings from functional brain imaging studies based on ToM. Finally and in a more critical perspective, we suggest a few theoretical and experimental limitations regarding impaired ToM as a core feature of schizophrenic disturbances in social interactions.
L Encéphale 12/2011; 37 Suppl 2:S117-22. · 0.63 Impact Factor
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ABSTRACT: Schizophrenia is a complex illness whose mechanisms are still largely unknown. Functional brain imaging, by making the link between psyche and brain, has recently become an indispensable tool to study in vivo the neural bases underlying cognitive dysfunction in this disease. But despite the proliferation of data coming from this approach, the exact impact of functional imaging on our understanding of the disease remains blurry. In general, studies of the brain functioning of patients with schizophrenia found activation abnormalities which vary in nature and localization depending of the cognitive paradigm used. However, it appears that neurofunctional abnormalities observed in patients cannot be reduced to a simple well-localized deficit. It would be rather an alteration of the dynamics of the interactions between different brain regions that underlie the cognitive disturbances encountered in the disease. Functional brain imaging now offers new perspectives to clarify the dynamics of the brain networks, and particularly those involved in high-level cognitive functions, such as cognitive control or social cognition which seem to play a crucial role in the disease. The characterization of these features is an important issue not only to develop new hypotheses on the pathophysiology of the disorder, but also more pragmatically to identify potential therapeutic targets.
L Encéphale 12/2011; 37 Suppl 2:S123-6. · 0.63 Impact Factor
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ABSTRACT: Schizophrenia is a complex and heritable disorder. Nevertheless, molecular genetics of schizophrenia remains inconclusive. By developing the concept of endophenotype for the disorder, it is easier to define an association between a phenotype and genetic variants or physiopathological processes. Cognitive disorders could be useful endophenotypes for schizophrenia. For example, the val(158)/met COMT polymorphism has been associated with executive function or working memory. Therefore, several cognitive dysfunctions were proposed as endophenotypes and were investigated in the context of different genetic polymorphisms. Genome-wide association studies and epistatic studies demonstrated the complexity of the mechanisms underlying cognitive disturbance. However, meta-analysis remains inconclusive. Altogether, the study of endophenotypes is an attractive approach to solve the complex mechanisms causing schizophrenia vulnerability. Nevertheless, several limitations exist and include the lack of reproducibility, the discordant results between healthy subjects and patients, the exclusion of the many rare variants.
L Encéphale 12/2011; 37 Suppl 2:S127-32. · 0.63 Impact Factor
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ABSTRACT: Accumulating evidence supports the hypothesis of abnormal neurodevelopment in schizophrenia. According to this hypothesis, schizophrenia is the consequence of prenatal abnormalities resulting from the interaction of genetic and environmental factors. In line with this hypothesis, several studies indicate that pregnancy and birth complications are risk factors for developing schizophrenia. At the clinical level, multiple cognitive deficits can be found in schizophrenic patients before illness onset. The neurodevelopmental hypothesis considers these cognitive deficits as the expression of early abnormalities on the central nervous system development. Consistently, brain imaging data show early structural abnormalities and abnormal progressive brain changes in schizophrenia. Finally, genetic and histological data indicate that genes associated with schizophrenia are involved in brain development.
L Encéphale 12/2011; 37 Suppl 2:S133-6. · 0.63 Impact Factor
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ABSTRACT: The robust and specific associations between cognitive abilities and the functional prognosis of patients suffering from schizophrenia lead to a major concern for cognitive impairment in this disorder. Among the strategies considered to correct or enhance cognition in schizophrenia, drugs hold a pivotal place. Evidently, antipsychotic drugs, which are inextricable from patients' management, have generated considerable scrutiny in this topic. This paper first aims to outline the current views on the impact of antipsychotic drugs in schizophrenia. The distinction between conventional and atypical drugs is reminded in order to more precisely review existing data comparing the impact of these two types of molecules on cognitive impairment. More specifically, an elementary framework is proposed to facilitate the recognition of methodological flaws and offer a critical examination of previous findings. It emerges subsequently that differences between atypical and conventional drugs appear far less contrasted than initially suggested. Also, atypical antipsychotics compose a disparate pharmacological class and much clarification could be obtained by differentiating the individual effects of these molecules rather than considering them as a group. Finally, the relevance of these cognitive measures is also considered. In particular, we address alternative measures closer to real life situations as well as the growing interest in the broad field of social cognition. A last part of this article deals with strategies relying on adjunctive therapies. The fairly modest results obtained with these approaches is evoked and briefly reviewed.
L Encéphale 12/2011; 37 Suppl 2:S137-42. · 0.63 Impact Factor
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ABSTRACT: Patients with schizophrenia often become non-adherent following negative treatment experiences as antipsychotics'side-effects. The objective of this study was to propose an alternative measure of patients'perception of atypical antipsychotics'side-effects on weight, as weight is a major concern reported by patients.
We used a computer-assisted method called Alceste, which is a pragmatic analysis of speech. We selected three groups of ten patients respectively treated by three different atypical antipsychotics: aripiprazole, olanzapine and risperidone. Participants were administered an interview. All speeches were retranscribed and structured in a set of texts, called a corpus. Regarding antipsychotic treatment, we constituted three corpuses of ten speeches. We analyzed separately the three corpuses with the software Alceste.
Our findings revealed the presence of a specific class dealing with treatment and illness in the speech of patients, regardless of their treatment. We found weight-related words in all three-treatment groups. The examination of the context of use showed this notion was differently employed in each treatment group: if weight was statistically associated with the notion of loss in the aripiprazole group, the reverse was found (notion of gain) in the two other treatment groups.
Our findings are valuable because they contribute to validate this speech analysis method. Actually our results, which are mathematically obtained through speech analysis, are convergent with those objectively observed by clinicians. Thus we hypothesize the Alceste-software is a relevant tool to evaluate the perceptions of antipsychotic side-effects.
L Encéphale 12/2011; 37 Suppl 2:S143-50. · 0.63 Impact Factor
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ABSTRACT: Cognitive impairment among patients suffering from schizophrenia is closely linked to psychoeducation and therapeutic education. First, this cognitive impairment requires specific communication strategy and special cognitive and behavioral techniques, which make possible for the patients to improve their trainability. Some of these tools are detailed, such as solving problems, communication skills, role plays, repetition, rewarding, and motivational support. Second, functional and social impairment, and outcome, are partly consequences of these cognitive problems. Cognitive remediation targets elementary cognitive impairment, mostly with repetitive cognitive tasks, and studies show an improvement in these specific tasks, but without positive effect on functional and social aspects of the illness. Overall approaches, such as psychoeducation or therapeutic education, obtain real gains in quality of life for the patients, autonomy and clinical improvement. It's not yet possible to know if these positive results underlie improvement in elementary cognitive impairment. The combination between remediation and psychoeducation seems to be promising.
L Encéphale 12/2011; 37 Suppl 2:S151-4. · 0.63 Impact Factor
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ABSTRACT: Cognitive deficits are routinely evident in schizophrenia, and are of sufficient magnitude to influence functional outcomes in work, social functioning and illness management. Cognitive remediation is an evidenced-based non-pharmacological treatment for the neurocognitive deficits seen in schizophrenia. Narrowly defined, cognitive remediation is a set of cognitive drills or compensatory interventions designed to enhance cognitive functioning, but from the vantage of the psychiatric rehabilitation field, cognitive remediation is a therapy which engages the patient in learning activities that enhance the neurocognitive skills relevant to their chosen recovery goals. Cognitive remediation programs vary in the extent to which they reflect these narrow or broader perspectives but a metaanalytic study reports moderate range effect sizes on cognitive test performance, and daily functioning. Reciprocal interactions between baseline ability level, the type of instructional techniques used, and motivation provide some explanatory power for the heterogeneity in patient response to cognitive remediation. Recent studies indicate that intrinsic motivation mediates the relationship between neurocognition and functional outcomes. Results of these studies suggest that intrinsic motivation should be a viable treatment target in cognitive remediation intervention. In this perspective, NEAR (Neuropsychological Educational Approach to Remediation) program was created to enhance intrinsic motivation by employing more engaging and interesting software packages for cognitive practice, involving consumers in choosing the focus of training and having the NEAR leader serve as a coach to engage the consumers in active guidance of their own treatment program.
L Encéphale 12/2011; 37 Suppl 2:S155-60. · 0.63 Impact Factor
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L Encéphale 12/2011; 37 Suppl 2:S93-4. · 0.63 Impact Factor
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ABSTRACT: Schizophrenia affects 1% of the general population. In addition to disabling clinical symptoms, cognitive deficits have also been updated. It has further been proposed that the well-known diversity of schizophrenia in terms of functional outcome and recovery from acute episode is best characterized by cognitive deficits, but not by its classical symptoms. DSM-V acknowledges the importance of cognition in schizophrenia, and could recommend a formal neuropsychological assessment in individuals with psychosis. Schizophrenic patient's cognitive functioning has been studied extensively in the domain of memory and executive control. To date, the studies highlight important deficits in both of these domains. However, within the memory systems, some of them remain unaffected. Altogether, the data invalidate the hypothesis of a global damage and are in favor of specific cognitive deficits. The observed deficits would depend on the dominant symptoms and pre-morbid functioning. The interest of these results was to give impulse to the development of comprehensive assessment battery designed to evaluate the cognitive profiles of each patient and develop a personalized program of cognitive remediation.
L Encéphale 12/2011; 37 Suppl 2:S95-9. · 0.63 Impact Factor
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ABSTRACT: To check whether the presence or not of free intervals between episodes could help differentiate subtypes of bipolar disorder, as suggested by the seminal controversy between Falret and Baillarger.
From 1090 bipolar I patients included in a French national study, 981 could be classified as with or without free intervals and assessed for demographic and illness characteristics.
Compared with patients with free intervals (n=722), those without (n=259) had an earlier age at onset, more episodes, suicide attempts, cyclothymic and irritable temperaments. The following independent variables were associated with no free intervals: being single or divorced, delay to mood stabilizer treatment, multiple hospitalizations, incongruent psychotic features, panic and generalized anxiety disorder.
"Folie à double forme" (without free intervals) and "folie circulaire" (with free intervals) may actually refer to early and later onset bipolar subtypes, insofar as most differences we found between them were previously evidenced between the latter two. We cannot, however, exclude that they might simply be two separate subtypes, whose main characteristics could be accounted for by different explanatory factors.
European Psychiatry 09/2011; 26(6):375-80. · 2.77 Impact Factor
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ABSTRACT: The clinical picture of schizophrenia is frequently worsened by manifestations of impulsivity. However, the neural correlates of impulsivity in this disorder are poorly known. Although impulsivity has been related to disturbances of the neural processes underlying response inhibition, no studies have yet examined the relationship between these processes and psychometric measures of impulsivity in schizophrenia. This was the aim of the current investigation.
Event-related functional magnetic resonance imaging in conjunction with a Go/NoGo task was employed to probe the neural activity associated with response inhibition in 26 patients with schizophrenia and 30 healthy comparison subjects. All participants also completed the Barratt Impulsiveness Scale - version 11 (BIS-11). Voxel-wise regression analyses were used to examine the relationship between the BIS-11 score and brain activation during response inhibition in each group.
Patients with schizophrenia were more impulsive than healthy subjects, as indicated by higher BIS-11 scores. Patients, but not healthy subjects, were found to display a positive correlation between these scores and cerebral activation associated with response inhibition. This correlation involves a unique cluster localized within the right ventrolateral prefrontal cortex (VLPFC), a key node of the brain network subserving response inhibition.
We evidenced in patients with schizophrenia that greater BIS-11 scores are associated with greater activation within the right VLPFC during response inhibition. This finding suggests that the efficiency of this brain region to process inhibitory control is reduced in the more impulsive patients.
Psychological Medicine 02/2011; 41(2):291-9. · 6.16 Impact Factor
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ABSTRACT: OBJECTIVE: To identify some of the main features of bipolar disorder for both first-episode (FE) mania and the preceding prodromal phase, in order to increase earlier recognition. METHODS: One thousand and ninety manic patients (FE=81, multiple-episodes [ME]=1009) were assessed for clinical and temperamental characteristics. RESULTS: Compared to ME, FE patients reported more psychotic and less depressive symptoms but were comparable with respect to temperamental measures and comorbid anxiety. The following independent variables were associated with FE mania: a shorter delay before correct diagnosis, greater substance use, being not divorced, greater stressors before current mania, a prior diagnosis of an anxiety disorder, lower levels of depression during index manic episode, and more suicide attempts in the past year. CONCLUSION: In FE patients, the diagnosis of mania may be overlooked, as they present with more psychotic symptoms than ME patients. The prodromal phase is characterised by high levels of stress, suicide attempts, anxiety disorders and alcohol or substance abuse. Data suggest to consider these prodromes as harmful consequences of temperamental predispositions to bipolar disorder that may concur to precipitate mania onset. Their occurrence should therefore incite clinicians to screen for the presence of such predispositions, in order to identify patients at risk of FE mania.
European Psychiatry 02/2011; · 2.77 Impact Factor
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Annales médico-psychologiques. 01/2011;
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ABSTRACT: Good news on chronobiological models of affective disorders are coming from a therapeutic innovation in the field of antidepressive action. Coming back to fundamentals by reconsidering the importance of the role of biological rhythms impairment in dysthymic pathology, a new interest bored on studies exploring short periodicities, so-called "ultradian" ones, on the basis of pharmacodynamics in the concept of therapeutic "window" of administration. The priority of circadian rhythms due to the major external biological desynchronization in depression, as well as the importance of sleep and alertness pathology, the spectacular relief of the depressive mood upon sleep deprivation, and the strong reduction of sleep need in mania, delayed exploration of ultradian exaltation of harmonic circadian components, marking a "buzz" of rhythmic structure and calling a "chronobiotic compound" which would be able to apply a "reset" to the temporal organisation. Another return to the origin leads to the experimental genomics, informing nor the "depressivity" but manic pathogenesis, in a mouse gene model which queries on the share of addictive and affective disorders.
L Encéphale 12/2010; 36 Suppl 6:S157-66. · 0.63 Impact Factor
