Multivariate Genetic Correlates of the Auditory Paired Stimuli-Based P2 Event-Related Potential in the Psychosis Dimension From the BSNIP Study.

OBJECTIVE: The complex molecular etiology of psychosis in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is not well defined, presumably due to their multifactorial genetic architecture. Neurobiological correlates of psychosis can be identified through genetic associations of intermediate phenotypes such as event-related potential (ERP) from auditory paired stimulus processing (APSP). Various ERP components of APSP are heritable and aberrant in SZ, PBP and their relatives, but their multivariate genetic factors are less explored. METHODS: We investigated the multivariate polygenic association of ERP from 64-sensor auditory paired stimulus data in 149 SZ, 209 PBP probands, and 99 healthy individuals from the multisite Bipolar-Schizophrenia Network on Intermediate Phenotypes study. Multivariate association of 64-channel APSP waveforms with a subset of 16 999 single nucleotide polymorphisms (SNPs) (reduced from 1 million SNP array) was examined using parallel independent component analysis (Para-ICA). Biological pathways associated with the genes were assessed using enrichment-based analysis tools. RESULTS: Para-ICA identified 2 ERP components, of which one was significantly correlated with a genetic network comprising multiple linearly coupled gene variants that explained ~4% of the ERP phenotype variance. Enrichment analysis revealed epidermal growth factor, endocannabinoid signaling, glutamatergic synapse and maltohexaose transport associated with P2 component of the N1-P2 ERP waveform. This ERP component also showed deficits in SZ and PBP. CONCLUSIONS: Aberrant P2 component in psychosis was associated with gene networks regulating several fundamental biologic functions, either general or specific to nervous system development. The pathways and processes underlying the gene clusters play a crucial role in brain function, plausibly implicated in psychosis.

Effects of hydrochlorothiazide on kidney stone therapy with extracorporeal shock wave lithotripsy.

OBJECTIVE: The aim of this investigation was to assess the efficacy of hydrochlorothiazide as a hypocalciuric diuretic on stone-free rate of renal pelvic calculi after extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: A double-blind, placebo-controlled randomized clinical trial was conducted and 52 patients with renal pelvic calculi (diameter ≤2 cm) were enrolled from February 2010 to September 2010. ESWL protocol was performed by 2,500 shocks per session. The patients were randomized into two groups: (1) 26 patients who were given 25 mg hydrochlorothiazide twice daily; and (2) 26 patients who received placebo. The stone-free rate was defined as residual calculus size ≤4 mm in controlled ultrasound on 2(nd) week, 1 month and 3 months after ESWL. RESULTS: 19 (78%) of the first group and 9 (42.9%) of the second group were stone-free after one session of ESWL (P = 0.02). 88% of the group 1 and 47.8% of the group 2 were stone-free on 1 month after ESWL (P = 0.003); however, this effect of hydrochlorothiazide was not related to the patients' body mass index, age and gender. The accessory treatment procedures were applied in 24% of the group 1 compared with 19% of the group 2 during 3 months (P = 0.68). All patients in both groups were stone-free on 3 months following lithotripsy. CONCLUSIONS: Hydrochlorothiazide did not impact on the stone-free rate and using accessory procedure within 3 months; however, it decreased duration of stone-free status and number of ESWL sessions.

Early intervention and the treatment of prodrome in schizophrenia: a review of recent developments.

OBJECTIVE: Strategies for preventing the development of schizophrenia are in their infancy but are associated with much hope and potential. The relatively long prodrome in schizophrenia allows for indicated prevention as an effective intervention. "High-risk" individuals have subtle symptoms and, without intervention, a third would develop psychosis within 1 year, and many will have poor functional outcomes, even in the absence of psychosis. Research in this area is preliminary but encouraging. METHODS: A literature search was performed using databases including PubMed, PsychInfo, and Cochrane, as well as a search of individual journals through cross-referencing. The search used the following key words: schizophrenia, psychosis, psychotic disorders, first episode, early, prodrome, prodromal, prevention, ultra high risk, at risk, and intervention. RESULTS: Strategies for preventing the development of schizophrenia are divided into universal, selective, and indicated levels of prevention. The common preventive methods include treatment with antipsychotic medications and psychotherapy. Early intervention helps at risk individuals with symptom reduction and appears to delay conversion to full blown psychosis. However, the criteria for identifying at risk individuals have low predictive value, which raises concerns about unnecessary and potentially harmful interventions. CONCLUSION: Although a range of interventions appear to be effective in reducing rates of transition to psychosis, they are inadequately differentiated and require further study. Current data suggest that clinicians take an individualized approach to intervention, considering the risk-benefit ratio on a case-by-case basis.

The DEX/CRH test for major depression: a potentially useful diagnostic test.

The dexamethasone/corticotropin-releasing hormone (DEX/CRH) test has been proposed as a potential diagnostic test for major depressive disorder (MDD). A previously proposed four-step approach assesses the stage of development for a biological finding into a clinically useful diagnostic test. Using this approach, we evaluated the progress of the DEX/CRH test using meta-analysis as a part of step 1. A literature review identified 15 studies of the DEX/CRH test in patients with MDD and healthy controls. Meta-analysis estimated the effect size, heterogeneity, and confidence intervals using random effects models. Studies consistent with any step of the four-step approach were identified, and their characteristics were presented. Eleven studies reported significantly higher cortisol levels with the DEX/CRH test in patients with MDD, compared with the healthy controls (step 1). Eight eligible studies were included in meta-analysis, and had an effect size of 1.34 (95% confidence interval: 0.70-1.97). Most studies were step-1 studies (comparison of patients and healthy controls), and no step-4 studies (multicenter trials) were found. This review emphasizes that despite appearing as a promising test, the DEX/CRH has not been adequately studied for the required stages of development into a clinically useful laboratory test. Particularly, additional step-3 and step-4 studies are necessary.

Self-rated assessment of needs for mental health care: a qualitative analysis.

This study explored perceived mental health-related needs and barriers to meeting them in primary and mental health care settings. Fifty-one participants completed the Perceived Need for Care Questionnaire and an interview to qualitatively explore the meanings behind self-identified needs for medication, information, counselling, practical help, and skills development. Qualitative content analysis indicated perceived needs for care are multifaceted. Dissatisfaction with taking medication may coexist with perceiving medication needs as met; information needs predominantly concerned wanting to better understand one's illness; and communication was the main perceived barrier to meeting these needs. Counselling-related needs included being listened to, supported or assisted with problem-solving, with service attitudes, staff expertise or cost seen as limiting access. Needs for practical help and skills development were described as unmet or addressed by family, and help-seeking for these needs constrained by efforts to self-manage, insufficient information, and affordability. Collaborative care and information-sharing appear important to better meet mental health-related perceived needs.