Familial risk of psychosis in obsessive-compulsive disorder: Impact on clinical characteristics, comorbidity and treatment response.

BACKGROUND: Family studies in obsessive-compulsive disorder (OCD) indicate higher rates of psychosis among their first-degree relatives (FDRs). However, the etiological and clinical relationships between the two disorders remain unclear. We compared the clinical characteristics and pharmacological treatment response in patients diagnosed with OCD with a family history of psychosis (OCD-FHP), with a family history of OCD (OCD-FHO) and those with sporadic OCD (OCD-S). METHODS: A total of 226 patients who met DSM-IV criteria for OCD (OCD-FHP = 59, OCD-FHO = 112, OCD-S = 55) were included for analysis. All patients were evaluated using the Mini International Neuropsychiatric Interview (MINI 6.0.0), Yale-Brown Obsessive-Compulsive Scale (YBOCS), and the Family Interview for Genetic Studies (FIGS). Treatment response was characterized over naturalistic follow-up. RESULTS: The three groups did not differ across any demographic or clinical variables other than treatment response. Patients in the OCD-FHP group were found to have received a greater number of trials with serotonin reuptake inhibitors (SRI) [F (2,223) = 7.99, p < 0.001], were more likely to have failed ≥2 trials of SRIs (χ2 = 8.45, p = 0.014), and less likely to have attained remission (χ2 = 6.57, p = 0.037) CONCLUSIONS: We observed that having a relative with psychosis may predispose to treatment resistance in OCD. Further research on the influence of genetic liability to psychosis on treatment response in OCD may offer novel translational leads.

Neurocognition and its association with adverse childhood experiences and familial risk of mental illness.

Environmental factors such as adverse childhood experiences (ACEs) may affect neurocognition, an endophenotype for several mental illnesses. This study examines the effect of ACEs on neurocognitive performance in first-degree relatives (FDRs) of patients with severe mental illness to determine whether familial risk has a moderating effect on the relationship between ACEs and neurocognition. Unaffected FDRs from multiplex families with severe mental illnesses (schizophrenia, bipolar disorder, obsessive-compulsive disorder, or alcohol use disorder) (n = 324) and healthy controls (with no familial risk) (n = 188) underwent neurocognitive tests for processing speed, new learning, working memory and Theory of Mind. ACEs were measured using the WHO ACE-International Questionnaire (ACE-IQ). Regression models were done to predict each neurocognitive domain by the effect of familial risk, ACE-IQ Score and their interaction (familial risk*ACE-IQ score). The main effect of familial risk predicted poor performance in all domains of neurocognition (p < 0.01), and the interaction had a negative association with global neurocognition (ß = -0.093, p = 0.009), processing speed (ß = -0.109, p = 0.003) and working memory (ß = -0.092, p = 0.01). Among the ACEs sub-domains, only maltreatment (specifically the main effect of physical neglect and the interaction effect of sexual abuse with familial risk) predicted poorer neurocognition. In FDRs of schizophrenia and bipolar disorder, only the main effects of familial risk were significantly associated with poorer neurocognition. We conclude that there is a relationship between ACEs (especially maltreatment) and neurocognitive functioning, which is moderated by the familial risk of mental illnesses. Genetic/familial vulnerability may have a stronger association with neurocognition in schizophrenia and bipolar disorder.

A Comparative Study of the Efficacy of Levosulpiride versus Paroxetine in Premature Ejaculation.

BACKGROUND: Premature ejaculation (PME) can be defined as a lack in the normal voluntary control over ejaculation. It is the most common sexual dysfunction encountered by the male populace. In general, these patients presents with distress. Hence, a novel treatment to eliminate their problem is required. Although the role of SSRI has already been established, the high discontinuation rate and other types of sexual dysfunctions associated with SSRIs reduce their efficacy in controlling this menace. Levosulpiride is a new drug indicated in treatment of PE. AIMS AND OBJECTIVES: The objective is to study the efficacy of levosulpiride; paroxetine and their comparison in patients of PE. METHODOLOGY: Index of premature ejaculation (IPE) and intravaginal ejaculation latency time (IELT) were used. A total of 36 patients (18 in each group) were included. The patients were assessed at baseline; at 4 weeks' and at 8 weeks' interval. RESULTS: On comparison the score of IPE in domains of ejaculation control, sexual satisfaction, and the total score of IPE were statistically significant on all the three visits. However, the distress score of IPE and the IELT score were statistically not significant between the two groups. CONCLUSION: No doubt both agents are efficacious in patients of PME but paroxetine is more efficacious than levosulpiride. At the same time, levosulpiride is a lesser studied and used drug hence more research should be done for it.

Effect of prefrontal tDCS on resting brain fMRI graph measures in Alcohol Use Disorders: A randomized, double-blind, sham-controlled study.

OBJECTIVES: Transcranial Direct Current Stimulation (tDCS) is a promising new adjuvant approach in the treatment of Alcohol Use Disorders (AUDs) that has the potential to ameliorate the aberrations secondary to chronic alcohol use. In this study, using a randomized, double-blind, sham-controlled, parallel-arm design, we examined the effects of prefrontal tDCS on resting-state functional magnetic resonance imaging (rsfMRI) and its correlates with impulsivity and time to first lapse in subjects with AUDs. METHODS: Patients with AUD as per DSM-5 criteria were randomly allocated to receive a five-day course of either verum-tDCS (n = 12) or sham-tDCS (n = 12). Of them, 21 patients (verum/sham = 11/10) participated in both baseline and post-intervention 10-min rsfMRI sessions. Outside the scanner, subjects also performed the Stop-Signal Task at two time-points (baseline and post-intervention), which provided a measure of changes in impulsivity following tDCS. After completion of the post-intervention scan, all subjects were discharged and were followed-up for 90 days post-discharge or until lapse to first alcohol use. RESULTS: Graph theoretical analysis of rsfMRI data revealed that verum-tDCS (but not sham) resulted in a significant increase in the global efficiency of brain networks with a concurrent significant reduction in global clustering; network-based statistical analysis identified a significant increase in the functional connectivity of a specific sub-network involving prefrontal regions. Furthermore, increased global efficiency of brain networks following verum tDCS predicted a significantly reduced likelihood of relapse. In addition, a reduction in the global clustering had a significant positive correlation with a reduction in the measure of impulsivity. CONCLUSIONS: The present study adds further support to the increasing evidence base for the clinical utility of tDCS in AUDs. Importantly, we observed improvement in both whole-brain network efficiency as well as inter-regional connectivity within a specific local prefrontal sub-network that is relevant to the neurobiology of AUDs. Replication and extension of these promising leads from the present study can facilitate clinical translation of tDCS, given its advantages (i.e. safety, cost-effectiveness, administration ease with potential for remotely-supervised / home-based application) for treating patients with AUDs.

Tolerance of transcranial direct current stimulation in psychiatric disorders: An analysis of 2000+ sessions.

Transcranial direct current stimulation (tDCS), a non-invasive, neuromodulatory technique, is being increasingly applied to several psychiatric disorders. In this study, we describe the side-effect profile of repeated tDCS sessions (N = 2005) that were administered to 171 patients (156 adults and 15 adolescents) with different psychiatric disorders [schizophrenia [N = 109], obsessive-compulsive disorder [N = 28], alcohol dependence syndrome [N = 13], mild cognitive impairment [N = 10], depression [N = 6], dementia [N = 2] and other disorders [N = 3]]. tDCS was administered at a constant current strength of 2 mA with additional ramp-up and ramp-down phase of 20 s each at the beginning and end of the session, respectively. Other tDCS protocol parameters were: schizophrenia and obsessive-compulsive disorder: 5-days of twice-daily 20-min sessions with an inter-session interval of 3-h; Mild cognitive impairment/dementia and alcohol dependence syndrome: at least 5-days of once-daily 20-min session; Depression: 10-days of once-daily 30 min session. At the end of each tDCS session, any adverse event observed by the administrator and/or reported by the patient was systematically assessed using a comprehensive questionnaire. The commonly reported adverse events during tDCS included burning sensations (16.2%), skin redness (12.3%), scalp pain (10.1%), itching (6.7%), and tingling (6.3%). Most of the adverse events were noted to be mild, transient and well-tolerated. In summary, our observations suggest that tDCS is a safe mode for therapeutic non-invasive neuromodulation in psychiatric disorders in adults as well as the adolescent population.

Treatment of Catatonia in Parkinson's Disease with Electroconvulsive Therapy.

Parkinson's disease (PD) is known to have associated nonmotor manifestations including psychiatric symptoms such as depression and psychosis. Catatonia has been reported extremely rarely in patients of PD. The case described here is a rare example of catatonia in a patient with PD with psychosis. Treatment with electroconvulsive therapy (ECT) brought improvement in symptoms of both PD and catatonia. ECT appears to be an effective treatment option in patients of PD, especially with psychiatric manifestations.