Protocol-based assessment and management of first episode psychosis: Comparison of short and medium-term outcomes in psychopathology, quality of life, functioning and family burden across two sites in India.

BACKGROUND: Standard assessment and management protocols exist for first episode psychosis (FEP) in high income countries. Due to cultural and resource differences, these need to be modified for application in low-and middle-income countries. AIMS: To assess the applicability of standard assessment and management protocols across two cohorts of FEP patients in North and South India by examining trajectories of psychopathology, functioning, quality of life and family burden in both. METHOD: FEP patients at two sites (108 at AIIMS, North India, and 115 at SCARF, South India) were assessed using structured instruments at baseline, 3, 6 and 12 months. Standard management protocols consisted of treatment with antipsychotics and psychoeducation for patients and their families. Generalised estimating equation (GEE) modelling was carried out to test for changes in outcomes both across and between sites at follow-up. RESULTS: There was an overall significant improvement in both cohorts for psychopathology and other outcome measures. The trajectories of improvement differed between the two sites with steeper improvement in non-affective psychosis in the first three months at SCARF, and affective symptoms in the first three months at AIIMS. The reduction in family burden and improvement in quality of life were greater at AIIMS than at SCARF during the first three months. CONCLUSIONS: Despite variations in cultural contexts and norms, it is possible to implement FEP standard assessment and management protocols in North and South India. Preliminary findings indicate that FEP services lead to significant improvements in psychopathology, functioning, quality of life, and family burden within these contexts.

Cell cycle abnormality is a cellular phenotype in OCD.

Abnormal indices of cell cycle regulation have been reported in multiple psychiatric disorders. Though reports specific to Obsessive Compulsive Disorder (OCD) are scant, numerous studies have highlighted partly common underlying biology in psychiatric disorders, cell cycle regulation being one such process. In this study, we therefore aimed to explore cell cycle in OCD. To the best of our knowledge, this is the first study to investigate these effects in OCD. We also evaluated the effect of in vitro fluoxetine, commonly used serotonin reuptake inhibitor (SRI) in OCD patients, on cell cycle regulation. The effects of both disease (OCD) and treatment (SRI) were assessed using lymphoblastoid cell lines (LCLs), derived from OCD patients and healthy controls, as a model system. LCLs were treated with 10µM of fluoxetine for 24 h, and the percentage of cells in each phase of the cell cycle was determined by flow cytometry. We observed a lower proportion of cells in the G2/M phase in OCD cases than controls. The findings suggest that cell cycle dysregulation could be peripheral cellular phenotype for OCD. Among cases, all of whom had been systematically characterized for SRI treatment response, LCLs from non-responders to SRI treatment had a lower proportion of cells in G2/M phase than responders.

Association of SLC1A1 gene polymorphism with obsessive compulsive disorder in a sample from southern India.

The glutamate transporter gene SLC1A1 has been shown to have an association with obsessive-compulsive disorder (OCD), and serotonin reuptake inhibitor (SRI) treatment response. One polymorphism (rs3056) in SLC1A1 has been associated with altered brain volumes in OCD. We investigated the association of this polymorphism with OCD and its relationship with various clinical parameters, including age of onset, disease severity, insight, factor analyzed symptom dimensions of OCD, and SRI treatment response. Three hundred seventy seven OCD patients (DSM-IV) aged between 18 to 60 years were recruited from a specialty OCD clinic. To study the association with SRI treatment response, we analyzed full responders (≥35% reduction in the Yale Brown Obsessive Compulsive Scale [YBOCS] and the Clinical Global Impression-Improvement [CGI-I] score of 1 or 2) to any SRI (n = 187) and nonresponders (<25% reduction in the YBOCS and the CGI-I score >4) to adequate trials of at least two SRIs for a duration of 12 weeks (n = 91). Healthy controls (n = 333) were recruited and evaluated using the Mini-International Neuropsychiatric Interview-Plus (MINI-Plus). All subjects were from southern India, and were genotyped for the SLC1A1 polymorphism (rs3056). Genotype frequencies did not deviate significantly from the Hardy-Weinberg equilibrium. Case-control association analysis revealed that the "GG" genotype was significantly more frequent in OCD cases than the controls (p = .04). No association was found with the age of onset, symptom severity, insight, and symptom dimensions. No significant association was found between genotype/allele frequencies with treatment response. To conclude, although there was a significant association between the SLC1A1 rs3056 polymorphism and OCD, there were no significant associations with other clinical parameters or treatment response. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

BDNF gene and obsessive compulsive disorder risk, symptom dimensions and treatment response.

AIM: Genetic etiology of Obsessive Compulsive Disorder (OCD) has been investigated extensively, with mixed results across candidate gene studies. The dimensional subtypes of OCD are shown to better correlate with brain imaging endophenotypes and thus could potentially enhance the power of genetic association. In this study, we perform a case control analysis of association of a single nucleotide polymorphism rs6265(Val66Met) in Brain Derived Neurotrophic Factor gene, that has been previously implicated in a variety of psychiatric syndromes, and examine its association with symptom dimensions of OCD. METHODS: Individuals diagnosed to have OCD (n=377) and controls (n=449) of South Indian origin were genotyped for polymorphism rs6265 (196G/A, Val66Met). Detailed phenotypic assessment of the cases were carried out in the cases using structured instruments. The genotypic association was tested for clinical variables such as age of onset, gender, family history, co-morbidity, treatment response, and factor analyzed OCD symptom dimensions. RESULTS: The allele 'A' frequency was found to be significantly higher in the controls, as compared to cases suggesting a protective effect. The contamination/washing symptom dimension score was significantly lower in carriers of 'A' allele which remained significant even after testing for confounding effects on linear regression. CONCLUSIONS: Our results support findings from previous studies on a possible protective effect of the 'Met' allele at the Val66Met locus in OCD. Its association with lower scores on the contamination/washing dimension is a novel finding of this study.

Benzodiazepine and "Z-Drug" Dependence: Data From a Tertiary Care Center.

OBJECTIVE: To examine the clinical characteristics and course of benzodiazepine and �Z-drug� dependence in patients presenting to a tertiary deaddiction center in southern India. METHODS: Case files of 950 inpatients admitted between January 2007 and January 2014 who reported benzodiazepine or Z-drug use were reviewed. Patients (n = 170) with an ICD-10 diagnosis of mental and behavioral disorders due to the use of sedatives or hypnotics-dependence syndrome currently using substance (F13.24) were included in this study. RESULTS: Alprazolam (n = 86, 50.6%), nitrazepam (n = 40, 23.5%), and zolpidem (n = 19, 11.2%) were the most commonly reported drugs of abuse. Alcohol dependence was present in 37 subjects (21.8%) and opioid dependence in 41 subjects (24.1%). Comorbid psychiatric illness was diagnosed in 67 patients (39.0%). Only 28 patients (16.5%) had sedative dependence with no other substance use disorder. CONCLUSION: High comorbidity occurs in this group of patients. Outcome varies significantly (P < .05) between sedative-dependent only and multiple-substance�dependent patients. High attrition should be addressed through follow-up and tracking mechanisms.

Correlates of Baclofen Effectiveness in Alcohol Dependence.

Alcohol dependence is a global concern. Baclofen has shown promise as an anti-craving agent but its efficiency remains to be settled. We reviewed 549 male cases diagnosed with alcohol dependence who received Acamprosate (201) or Baclofen (348). 'Time to first drink' was compared between two groups and multiple regression analysis was done in baclofen group to identify correlates of effectiveness. There was a significant difference in outcome measure between Baclofen (M = 4.44, SD = 3.75) and Acamprosate group (M = 3.73, SD = 2.19); t (547) = 2.45, P = 0.01. Initial regression analysis with six predictor variables (average daily alcohol units, current age, age at onset of dependence, family history, duration of dependence and dose of baclofen in mg/day) showed significant correlation of outcome variable with only two predictor variables - dose of baclofen and average daily intake. Using the hierarchical method it was found that 'dose of baclofen' and 'average alcohol intake' explain a significant amount of variance in 'time to first drink'. [F (1, 345) = 182.8, P < 0.001, R2 = 0.52, R2adjusted = 0.51]. This information can be used to select patients in long term longitudinal studies and may explain variable results seen in clinical trials of baclofen done earlier.