Emotional hyper-reactivity and cardiometabolic risk in remitted bipolar patients: a machine learning approach.

OBJECTIVE: Remitted bipolar disorder (BD) patients frequently present with chronic mood instability and emotional hyper-reactivity, associated with poor psychosocial functioning and low-grade inflammation. We investigated emotional hyper-reactivity as a dimension for characterization of remitted BD patients, and clinical and biological factors for identifying those with and without emotional hyper-reactivity. METHOD: A total of 635 adult remitted BD patients, evaluated in the French Network of Bipolar Expert Centers from 2010-2015, were assessed for emotional reactivity using the Multidimensional Assessment of Thymic States. Machine learning algorithms were used on clinical and biological variables to enhance characterization of patients. RESULTS: After adjustment, patients with emotional hyper-reactivity (n = 306) had significantly higher levels of systolic and diastolic blood pressure (P < 1.0 × 10-8 ), high-sensitivity C-reactive protein (P < 1.0 × 10-8 ), fasting glucose (P < 2.23 × 10-6 ), glycated hemoglobin (P = 0.0008) and suicide attempts (P = 1.4 × 10-8 ). Using models of combined clinical and biological factors for distinguishing BD patients with and without emotional hyper-reactivity, the strongest predictors were: systolic and diastolic blood pressure, fasting glucose, C-reactive protein and number of suicide attempts. This predictive model identified patients with emotional hyper-reactivity with 84.9% accuracy. CONCLUSION: The assessment of emotional hyper-reactivity in remitted BD patients is clinically relevant, particularly for identifying those at higher risk of cardiometabolic dysfunction, chronic inflammation, and suicide.

Ethical considerations in bipolar disorders.

The implications of biomedical ethics principles extend to both medical care and biomedical research. They are particularly relevant for psychiatry in which pathologies are often chronic and disabling. Bipolar disorders impact the ability to make judgements and to take decisions during mood episodes and remain a stigmatised condition. Early interventions, even those in the prodromal phase, pose ethical questions for both clinicians and researchers. The degree of patients' autonomy in their clinical care must also now be considered from a biomedical ethics perspective.

The "psychomicrobiotic": Targeting microbiota in major psychiatric disorders: A systematic review.

The gut microbiota is increasingly considered as a symbiotic partner in the maintenance of good health. Metagenomic approaches could help to discover how the complex gut microbial ecosystem participates in the control of the host's brain development and function, and could be relevant for future therapeutic developments, such as probiotics, prebiotics and nutritional approaches for psychiatric disorders. Previous reviews focused on the effects of microbiota on the central nervous system in in vitro and animal studies. The aim of the present review is to synthetize the current data on the association between microbiota dysbiosis and onset and/or maintenance of major psychiatric disorders, and to explore potential therapeutic opportunities targeting microbiota dysbiosis in psychiatric patients.

Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review.

OBJECTIVE: To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders]. METHOD: Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open-labelled clinical and randomized controlled trials (RCTs). RESULTS: Four major classes of anti-inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta-analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta-analysis indicated that COX-2 specific inhibitors showed effectiveness in schizophrenia. Anti-TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia. CONCLUSION: Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side-effects, they may be reasonable therapeutic alternatives for resistant symptomatology.

Interaction between SLC6A4 promoter variants and childhood trauma on the age at onset of bipolar disorders.

Age at onset (AAO) of bipolar disorders (BD) could be influenced both by a repeat length polymorphism (5HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) and exposure to childhood trauma. We assessed 308 euthymic patients with BD for the AAO of their first mood episode and childhood trauma. Patients were genotyped for the 5HTTLPR (long/short variant) and the rs25531. Genotypes were classified on functional significance (LL, LS, SS). A sample of 126 Brazilian euthymic patients with BD was used for replication. In the French sample, the correlation between AAO and trauma score was observed only among 'SS' homozygotes (p = 0.002) but not among 'L' allele carriers. A history of at least one trauma decreased the AAO only in 'SS' homozygotes (p = 0.001). These results remained significant after correction using FDR. Regression models suggested an interaction between emotional neglect and 'SS' genotype on the AAO (p = 0.009) and no further interaction with other trauma subtypes. Partial replication was obtained in the Brazilian sample, showing an interaction between emotional abuse and 'LS' genotype on the AAO (p = 0.02). In conclusion, an effect of childhood trauma on AAO of BD was observed only in patients who carry a specific stress responsiveness-related SLC6A4 promoter genotype.

Stigma experiences in bipolar patients: the impact upon functioning.

The aim of this study was to investigate the impact of self-rated stigma and functioning in patients with bipolar disorder in South Brazil. This is a cross-sectional study. Sixty participants with bipolar disorder were recruited from an outpatient Bipolar Disorder Program. Experiences with and impact of perceived stigma were evaluated using the Inventory of Stigmatizing Experiences. Functional impairment was assessed with the Functioning Assessment Short Test (FAST). Higher scores of self-perceived stigma were correlated with higher FAST scores, indicating more disability. After linear correlation analysis, current depressive symptoms, age at onset of treatment, age at diagnosis and functioning were correlated with self-perceived stigma. The study demonstrated a correlation between stigma and poor functioning in bipolar disorder. Perceived stigma is really important to individuals with bipolar disorder, both to how they experience their illness and to its results on functioning. Potential consequences of such results for mental health care professionals are discussed. Differential clinical features, sociocultural factors and the sample size limit the generalization of the present findings.

Case Report. Disseminated aspergillosis complicating pregnancy.

We report a case of disseminated aspergillosis in a hitherto healthy 24-year-old woman during her 24th week of pregnancy. Relevant findings at autopsy revealed innumerable septate, dichotomously branched (45 degrees ) hyphae compatible with Aspergillus in lung and liver tissues. Cerebral histology showed cerebral vessels occluded by hyphae causing cerebral infarction. There was no evidence of invasive aspergillosis in the placenta and fetal tissues. Aspergillus sp. was confirmed by amplification of a specific 357-base-pair amplicon from a paraffin block containing lung tissue. This case illustrates a previously uncharacterized spectrum of disseminated aspergillosis, indicating the need for a heightened awareness that Aspergillus species are opportunistic agents for invasive and disseminated infection in pregnancy.