[Show abstract][Hide abstract] ABSTRACT: Background:
Mood disorders are frequently characterized by uncertain prognosis and studying mRNA expression variations in blood cells represents a promising avenue of identifying biomarkers for mood disorders. State-dependent gene expression variations have been described during a major depressive episode (MDE), in particular for SLC6A4 mRNA, but how this transcript varies in relation to MDE evolution remains unclear. In this study, we prospectively assessed time trends of SCL6A4 mRNA expression in responder and nonresponder patients.
We examined SLC6A4 mRNA expression in blood samples from 13 patients treated for severe MDE and their matched controls by reverse transcription and quantitative PCR. All subjects were followed for 30 weeks. Patients were classified as either responders or nonresponders based on improvement of depression according to the 17-item Hamilton Depression Rating Scale. Using a longitudinal design, we ascertained mRNA expression at baseline, 2, 8, and 30 weeks and compared mRNA expression between responder and nonresponder patients, and matched controls.
We observed a decrease of SLC6A4 mRNA expression in responder patients across a 30-week follow-up, while nonresponder patients exhibited up-regulated SLC6A4 mRNA.
Peripheral SLC6A4 mRNA expression could serve as a biomarker for monitoring and follow-up during an MDE and may help to more appropriately select individualized treatments.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder.
Within the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and 'suicide attempts' or 'suicide', was conducted, and data extracted for analysis from all eligible articles. Demographic and clinical variables for which ≥ 3 studies with usable data were available were meta-analyzed using fixed or random-effects models for association with suicide attempts and suicide deaths. There was considerable heterogeneity in the methods employed by the included studies.
Variables significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use, comorbid cluster B/borderline personality disorder, and first-degree family history of suicide. Suicide deaths were significantly associated with male gender and first-degree family history of suicide.
This paper reports on the presence and magnitude of the correlates of suicide attempts and suicide deaths in bipolar disorder. These findings do not address causation, and the heterogeneity of data sources should limit the direct clinical ranking of correlates. Our results nonetheless support the notion of incorporating diagnosis-specific data in the development of models of understanding suicide in bipolar disorder.
[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) and its components in a cohort of French patients with bipolar disorder; determine correlations with sociodemographic, clinical, and treatment-related factors; and investigate the gap between optimal care and effective care of the treated patients.
654 bipolar disorder patients from the FACE-BD cohort were included from 2009 to 2012. Sociodemographic and clinical characteristics, lifestyle information, and data on antipsychotic treatment and comorbidities were collected, and a blood sample was drawn. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to confirm the diagnosis of bipolar disorder. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria.
18.5% of individuals with bipolar disorder met criteria for MetS. Two-thirds of bipolar disorder patients did not receive adequate treatment for MetS components. Multivariate analysis showed that risk of MetS in men was nearly twice that in women (OR = 1.9; 95% CI, 1.0-3.8), and older patients had a 3.5 times higher risk (95% CI, 1.5-7.8) of developing MetS than patients under the age of 35 years. Moreover, patients receiving antipsychotic treatment had a 2.3 times increased risk (95% CI, 1.2-3.5) of having MetS, independent of other potential confounders.
The prevalence of MetS is high in bipolar disorder patients, and there was considerable undertreatment of the components of MetS in this population. The prevention and treatment of cardiovascular diseases in these patients should be assessed systematically. The findings highlight the need for integrated care, with more interaction and coordination between psychiatrists and primary care providers.
The Journal of Clinical Psychiatry 10/2014; 75(10):1078-85. DOI:10.4088/JCP.14m09038 · 5.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
Deficit in facial affect recognition is a well-documented impairment in schizophrenia, closely connected to social outcome. This deficit could be related to psychopathology, but also to a broader dysfunction in processing facial information. In addition, patients with schizophrenia inadequately use configural information-a type of processing that relies on spatial relationships between facial features. To date, no study has specifically examined the link between symptoms and misuse of configural information in the deficit in facial affect recognition.
Unmedicated schizophrenia patients (n = 30) and matched healthy controls (n = 30) performed a facial affect recognition task and a face inversion task, which tests aptitude to rely on configural information. In patients, regressions were carried out between facial affect recognition, symptom dimensions and inversion effect.
Patients, compared with controls, showed a deficit in facial affect recognition and a lower inversion effect. Negative symptoms and lower inversion effect could account for 41.2% of the variance in facial affect recognition.
This study confirms the presence of a deficit in facial affect recognition, and also of dysfunctional manipulation in configural information in antipsychotic-free patients. Negative symptoms and poor processing of configural information explained a substantial part of the deficient recognition of facial affect. We speculate that this deficit may be caused by several factors, among which independently stand psychopathology and failure in correctly manipulating configural information.
[Show abstract][Hide abstract] ABSTRACT: This review traces the history of negative symptom profiles in neuropsychiatry from their earliest emergence in the 19th century to the current psychiatric concepts and therapeutic approaches. Recent investigations performing exploratory and confirmatory factor analysis have suggested that negative symptoms are multidimensional, including evidence for at least two distinct negative symptom subdomains: diminished expression and amotivation. Preliminary studies have demonstrated the clinical validity of this distinction. Several potential pathophysiological validating factors based on brain imaging analysis of emotional experiences and expressions in individuals with schizophrenia are examined. Finally, the potential of different treatment strategies, including medications and various psychotherapeutic techniques, to most favorably treat each of these subdomains is discussed.
[Show abstract][Hide abstract] ABSTRACT: Background: Previous studies have shown that major depressive patients may differ in several features according to gender, but the existence of a specific male depressive syndrome remains controversial. 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, 125 (27.7%) were of male gender, whereas 317 (72.3%) were female, after exclusion of bipolar I patients. Results: Compared to women, men were more often married, had more associated mixed features, with more bipolar disorder NOS, more hyperthymic temperaments, and less depressive temperaments. Women had an earlier age at onset of depression, more depressive episodes and suicide attempts. A higher family loading was shown in men for bipolar disorder, alcohol use disorder, impulse control disorders and suicide, whereas their family loading for major depressive disorder was lower. Men displayed more comorbidities with alcohol use, impulse control, and cardiovascular disorders, with lower comorbidities with eating, anxiety and endocrine/metabolic disorders. The following independent variables were associated with male gender: hyperthymic temperament (+), alcohol use disorder (+), impulse control disorders (+), and depressive temperament (-). Limitations: The retrospective design and the lack of specific tools to assess the male depressive syndrome. Conclusion: Study findings may lend support to the male depression syndrome concept and draw attention to the role of hyperthymic temperament, soft bipolarity as well as comorbidities as determinants of this syndrome. The latter could help recognize an entity which is probably underdiagnosed, but conveys a high risk of suicide and cardiovascular morbidity.
[Show abstract][Hide abstract] ABSTRACT: Adjunctive use of methylphenidate, a central stimulant, has been considered as a potential therapeutic choice for patients with refractory unipolar, geriatric, or bipolar depression, and depression secondary to medical illness. We present a case of bipolar depression in which the patient responded significantly to augmentation with methylphenidate, without any side effects, after failure of adjunctive repetitive transcranial magnetic stimulation and electroconvulsive therapy. Mr U, a 56-year-old man with bipolar I disorder, had melancholic symptoms during his sixth episode of bipolar depression. After failure of repetitive transcranial magnetic stimulation and electroconvulsive therapy, he was treated with fluoxetine 80 mg/day, duloxetine 360 mg/day, mirtazapine 60 mg/day, and sodium valproate 1,000 mg/day, with no improvement. We added methylphenidate at a dose of 10 mg/day for one week, which resulted in mild clinical improvement, and then methylphenidate extended-release 20 mg/day for one week, with significant clinical improvement. He tolerated his medications well. His clinical recovery was stable over one year. The patient's antidepressants and methylphenidate were gradually tapered and finally discontinued after one year with no withdrawal syndrome. To date, he remains well on sodium valproate as monotherapy and is being followed up at our bipolar department. This case suggests that methylphenidate augmentation might be a therapeutic option when treating highly treatment-resistant patients with bipolar depression, even if they had not responded to adjunctive neuromodulation. In these clinical situations, physicians might be interested in prescribing methylphenidate because of its efficacy and safety.
[Show abstract][Hide abstract] ABSTRACT: Thought and language disturbances are crucial clinical features in Bipolar Disorders (BD), and constitute a fundamental basis for social cognition. In BD, clinical manifestations such as disorganization and formal thought disorders may play a role in communication disturbances. However, only few studies have explored language disturbances in BD at a neurophysiological level. Two main Event-Related brain Potentials (ERPs) have been used in language comprehension research: the N400 component, elicited by incongruous word with the preceding semantic context, and the Late Positive Component (LPC), associated with non-specifically semantic and more general cognitive processes. Previous studies provided contradictory results regarding N400 in mood disorders, showing either preserved N400 in depression or dysthymia, or altered N400 in BD during semantic priming paradigm. The aim of our study was to explore N400 and LPC among patients with BD in natural speech conditions.
ERPs from 19 bipolar type I patients with manic or hypomanic symptomatology and 19 healthy controls were recorded. Participants were asked to listen to congruous and incongruous complete sentences and to judge the match between the final word and the sentence context. Behavioral results and ERPs data were analyzed.
At the behavioral level, patients with BD show worst performances than healthy participants. At the electrophysiological level, our results show preserved N400 component in BD. LPC elicited under natural speech conditions shows preserved amplitude but delayed latency in difference waves.
Small size of samples, absence of schizophrenic group and medication status.
In contrast with the only previous N400 study in BD that uses written semantic priming, our results show a preserved N400 component in ecological and natural speech conditions among patients with BD. Possible implications in terms of clinical specificity are discussed.
[Show abstract][Hide abstract] ABSTRACT: Although psychiatric disorders are frequently characterized by clinical heterogeneity, high recurrence, and unpredictable prognosis, studies of mRNA expression variations in blood cells from psychiatric patients constitute a promising avenue to establish clinical biomarkers. We report here, to our knowledge, the first genetic monitoring of a major depressive episode (MDE).
The subject is a 51-year-old male, who was healthy at baseline and whose blood mRNA was monitored over 67 weeks for expression variations of 9 candidate genes. At week 20 the subject experienced a mild to moderate unexpected MDE, and oral antidepressant treatment was initiated at week 29. At week 36, the patient recovered from his MDE. After 6 months, antidepressant treatment was discontinued and the subject remained free of depressive symptoms. Genetic monitoring revealed that mRNA expression of SLC6A4/5HTT increased with the emergence of a depressive state, which later returned to basal levels after antidepressant treatment and during MDE recovery. PDLIM5, S100A10 and TNF mRNA showed also an interesting pattern of expression with regards to MDE evolution.
This case demonstrated the applicability of peripheral mRNA expression as a way to monitor the natural history of MDE.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to describe the phenomenology of mania and depression in bipolar patients experiencing a manic episode with mixed features as defined in the new Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
In this multicenter, international on-line survey (the IMPACT study), 700 participants completed a 54-item questionnaire on demographics, diagnosis, symptomatology, communication of the disease, impact on life, and treatment received. Patients with a manic episode with or without DSM-5 criteria for mixed features were compared using descriptive and inferential statistics.
Patients with more than 3 depressive symptoms were more likely to have had a delay in diagnosis, more likely to have experienced shorter symptom-free periods, and were characterized by a marked lower prevalence of typical manic manifestations. All questionnaire items exploring depressive symptomatology, including the DSM-5 criteria defining a manic episode as "with mixed features", were significantly overrepresented in the group of patients with depressive symptoms. Anxiety associated with irritability/agitation was also more frequent among patients with mixed features.
Retrospective cross-sectional design, sensitive to recall bias. Two of the 6 DSM-5 required criteria for the specifier "with mixed features" were not explored: suicidality and psychomotor retardation.
Bipolar disorder patients with at least 3 depressive symptoms during a manic episode self-reported typical symptomatology. Anxiety with irritability/agitation differentiated patients with depressive symptoms during mania from those with "pure" manic episodes. The results support the use of DSM-5 mixed features specifier and its value in research and clinical practice.
[Show abstract][Hide abstract] ABSTRACT: Antipsychotic drug side effects are common and can cause stigmatisation, decreased quality of life, poor adherence, and secondary morbidity and mortality. Systematic assessment of anticipated side effects is recommended as part of good clinical care, but is uncommon in practice and patients may not spontaneously report side effects. We aimed to develop a simple patient-completed checklist to screen systematically for potential antipsychotic side effects.
The SMARTS checklist was developed over a series of group meetings by an international faculty of 12 experts (including psychiatrists, a general physician and a psychopharmacologist) based on their clinical experience and knowledge of the literature. The emphasis is on tolerability (i.e. assessment of side effects that 'trouble' the patient) as subjective impact of side effects is most relevant to medication adherence. The development took account of feedback from practising psychiatrists in Europe, the Middle East and Africa, a process that contributed to face validity.
The SMARTS checklist assesses whether patients are currently 'troubled' by 11 well-established potential antipsychotic side effects. Patients provide their responses to these questions by circling relevant side effects. An additional open question enquires about any other possible side effects. The checklist has been translated into Italian and Turkish.
The SMARTS checklist aims to strike a balance between brevity and capturing the most common and important antipsychotic side effects. It is appropriate for completion by patients prior to a clinical consultation, for example, in the waiting room. It can then form the focus for a more detailed clinical discussion about side effects. It can be used alone or form part of a more comprehensive assessment of antipsychotic side effects including blood tests and a physical examination when appropriate. The checklist assesses current problems and can be used longitudinally to assess change.