Social psychiatry and psychiatric epidemiology functional impairment among people with severe and enduring mental disorder in rural Ethiopia: a cross-sectional study

Purpose: Evidence regarding functional impairment in people with severe mental disorders (SMD) is sparse in low and middle-income countries. The aim of this study was to identify factors associated with functional impairment in people with enduring SMD in a rural African setting. Methods: A cross-sectional study was conducted at the baseline of a health service intervention trial. A total of 324 participants were recruited from an existing communityascertained cohort of people with SMD (n= 218), and attendees at the Butajira General Hospital psychiatric clinic (n= 106). Inclusion criteria defined people with SMD who had ongoing need for care: those who were on psychotropic medication, currently symptomatic or had a relapse in the preceding two years. The World Health Organization Disability Assessment schedule (WHODAS-2.0) and the Butajira Functioning Scale (BFS), were used to assess functional impairment. Multivariable negative binomial regression models were fitted to investigate the association between demographic, socio-economic and clinical characteristics, and functional impairment. Results: Increasing age, being unmarried, rural residence, poorer socio-economic status, symptom severity, continuous course of illness, medication side effects and internalized stigma were associated with functional impairment across self reported and caregiver responses for both the WHODAS and the BFS. Diagnosis per se was not associated consistently with functional impairment. Conclusion: To optimize functioning in people with chronic SMD in this setting, services need to target residual symptoms, poverty, medication side effects and internalized stigma. Testing the impact of community interventions to promote recovery will be useful. Advocacy for more tolerable treatment options is warranted

Characterization of an Alkali- and Halide-Resistant Laccase Expressed in E. coli: CotA from <i>Bacillus clausii</i>

The limitations of fungal laccases at higher pH and salt concentrations have intensified the search for new extremophilic bacterial laccases. We report the cloning, expression, and characterization of the bacterial cotA from Bacillus clausii, a supposed alkalophilic ortholog of cotA from B. subtilis. Both laccases were expressed in E. coli strain BL21(DE3) and characterized fully in parallel for strict benchmarking. We report activity on ABTS, SGZ, DMP, caffeic acid, promazine, phenyl hydrazine, tannic acid, and bilirubin at variable pH. Whereas ABTS, promazine, and phenyl hydrazine activities vs. pH were similar, the activity of B. clausii cotA was shifted upwards by ~0.5-2 pH units for the simple phenolic substrates DMP, SGZ, and caffeic acid. This shift is not due to substrate affinity (K(M)) but to pH dependence of catalytic turnover: The k(cat) of B. clausii cotA was 1 s⁻¹ at pH 6 and 5 s⁻¹ at pH 8 in contrast to 6 s⁻¹ at pH 6 and 2 s⁻¹ at pH 8 for of B. subtilis cotA. Overall, k(cat)/K(M) was 10-fold higher for B. subtilis cotA at pH(opt). While both proteins were heat activated, activation increased with pH and was larger in cotA from B. clausii. NaCl inhibited activity at acidic pH, but not up to 500-700 mM NaCl in alkaline pH, a further advantage of the alkali regime in laccase applications. The B. clausii cotA had ~20 minutes half-life at 80°C, less than the ~50 minutes at 80°C for cotA from B. subtilis. While cotA from B. subtilis had optimal stability at pH~8, the cotA from B. clausii displayed higher combined salt- and alkali-resistance. This resistance is possibly caused by two substitutions (S427Q and V110E) that could repel anions to reduce anion-copper interactions at the expense of catalytic proficiency, a trade-off of potential relevance to laccase optimization

Bipolar disorder comorbid with alcohol use disorder: focus on neurocognitive correlates

Bipolar disorder (BD) and alcohol use disorders (AUDs) are usually comorbid, and both have been associated with significant neurocognitive impairment. Patients with the BD-AUD comorbidity (dual diagnosis) may have more severe neurocognitive deficits than those with a single diagnosis, but there is paucity of research in this area. To explore this hypothesis more thoroughly, we carried out a systematic literature review through January 2015. Eight studies have examined the effect of AUDs on the neurocognitive functioning of BD patients. Most studies found that BD patients with current or past history of comorbid AUDs show more severe impairments, especially in verbal memory and executive cognition, than their non-dual counterparts. Greater neurocognitive dysfunction is another facet of this severe comorbid presentation. Implications for clinical practice and research are discussed. Specifically, the application of holistic approaches, such as clinical staging and systems biology, may open new avenues of discoveries related to the BD-AUD comorbidity

Outcome prediction with a social cognitive battery: a multicenter longitudinal study

The interest in social cognition in schizophrenia is justified by the relationship between deficits in these skills and negative functional outcomes. Although assessment batteries have already been described, there is no consensus about which measures are useful in predicting patient functioning or quality of life (QoL). We investigated a set of five measures of recognition of facial emotions, theory of mind (ToM), and empathy in a cohort of 143 patients with schizophrenia or schizoaffective disorder at inclusion and, amongst whom 79 were reassessed 1 year later. The distribution was satisfactory for the TREF (Facial Emotion Recognition Task), V-SIR (Versailles-Situational Intention Reading), and QCAE (Questionnaire of Cognitive and Affective Empathy). Internal consistency was satisfactory for the TREF, V-SIR, V-Comics (Versailles Intention Attribution Task), and QCAE. Sensitivity to change was acceptable for the TREF. The TREF and V-SIR showed a cross-sectional relationship with functioning beyond the clinical symptoms of schizophrenia but not beyond neurocognition. Moreover, the TREF and V-SIR at inclusion could not predict functioning one year later, whereas most neurocognitive and clinical dimensions at inclusion could. Finally, only affective QCAE showed a significant cross-sectional, but not longitudinal, association with QoL. In conclusion, the TREF had satisfactory psychometric properties and showed a cross-sectional, but not longitudinal, association with objective outcome measures, thus appearing to be reliable in clinical practice and research. The V-SIR also showed promising psychometric properties, despite a possible weakness to detect change. However, these measures should be interpreted within the context of the good predictive power of the neurocognitive and clinical status on the outcome.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte