Impaired flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives: The effect of genetic loading

We previously reported familial aggregation in flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives. However, little is known about whether this abnormal skin response is associated with genetic loading for schizophrenia. This study compared the niacin flush response in subjects from families with only one member affected with schizophrenia (simplex families) with those from families having a sib-pair with schizophrenia (multiplex families). Subjects were patients with schizophrenia and their nonpsychotic first-degree relatives from simplex families (176 probands, 260 parents, and 80 siblings) and multiplex families (311 probands, 180 parents, and 52 siblings) as well as 94 healthy controls. Niacin patches of 3 concentrations (0.001M, 0.01M, and 0.1M) were applied to forearm skin, and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. More attenuated flush response to topical niacin was shown in schizophrenia probands and their relatives from multiplex families than in their counterparts from simplex families, and the differentiation was better revealed using 0.1M concentration of niacin than 0.01M or 0.001M. For the highest concentration of 0.1M and the longest time lag of 15 minutes, a subgroup of probands (23%), parents (27%), and siblings (19%) still exhibited nonflush response. Flush response to niacin skin patch is more impaired in schizophrenia patients and their relatives from families with higher genetic loading for schizophrenia, and this finding has implications for future genetic dissection of schizophrenia. © 2008 The Authors.published_or_final_versio

Using an Uncertainty-Coding Matrix in Bayesian Regression Models for Haplotype-Specific Risk Detection in Family Association Studies

Haplotype association studies based on family genotype data can provide more biological information than single marker association studies. Difficulties arise, however, in the inference of haplotype phase determination and in haplotype transmission/non-transmission status. Incorporation of the uncertainty associated with haplotype inference into regression models requires special care. This task can get even more complicated when the genetic region contains a large number of haplotypes. To avoid the curse of dimensionality, we employ a clustering algorithm based on the evolutionary relationship among haplotypes and retain for regression analysis only the ancestral core haplotypes identified by it. To integrate the three sources of variation, phase ambiguity, transmission status and ancestral uncertainty, we propose an uncertainty-coding matrix which combines these three types of variability simultaneously. Next we evaluate haplotype risk with the use of such a matrix in a Bayesian conditional logistic regression model. Simulation studies and one application, a schizophrenia multiplex family study, are presented and the results are compared with those from other family based analysis tools such as FBAT. Our proposed method (Bayesian regression using uncertainty-coding matrix, BRUCM) is shown to perform better and the implementation in R is freely available

Regional differences in psychiatric disorders in Chile

BACKGROUND: Psychiatric epidemiological surveys in developing countries are rare and are frequently conducted in regions that are not necessarily representative of the entire country. In addition, in large countries with dispersed populations national rates may have low value for estimating the need for mental health services and programs. METHODS: The Chile Psychiatric Prevalence Study using the Composite International Diagnostic Interview was conducted in four distinct regions of the country on a stratified random sample of 2,978 people. Lifetime and 12-month prevalence and service utilization rates were estimated. RESULTS: Significant differences in the rates of major depressive disorder, substance abuse disorders, non-affective psychosis, and service utilization were found across the regions. The differential prevalence rates could not be accounted by socio-demographic differences between sites. CONCLUSIONS: Regional differences across countries may exist that have both implications for prevalence rates and service utilization. Planning mental health services for population centers that span wide geographical areas based on studies conducted in a single region may be misleading, and may result in areas with high need being underserved

An ongoing process: A qualitative study of how the alcohol-dependent free themselves of addiction through progressive abstinence

<p>Abstract</p> <p>Background</p> <p>Most people being treated for alcoholism are unable to successfully quit drinking within their treatment programs. In few cases do we know the full picture of how abstinence is achieved in Taiwan. We tracked processes of abstinence in alcohol-dependency disorders, based on study evidence and results. This research explores the process of recovery from the viewpoint of the alcohol-dependent.</p> <p>Methods</p> <p>Semi-structured interviews were conducted in two different settings, using purpose sampling, during 2003-2004. The data were analyzed using content analysis. Participants were 32 adults, purposefully selected from an Alcoholics Anonymous group and a psychiatric hospital in North Taiwan.</p> <p>Results</p> <p>We found that the abstinence process is an ongoing process, in which the alcohol-dependent free themselves of addiction progressively. This process never ends or resolves in complete recovery. We have identified three stages in the struggle against alcoholism: the Indulgence, Ambivalence and Attempt (IAA) cycle, in which the sufferer is trapped in a cycle of attempting to give up and failing; the Turning Point, in which a Personal Nadir is reached, and the Ongoing Process of abstinence, in which a constant effort is made to remain sober through willpower and with the help of support groups. We also discuss Influencing Factors that can derail abstinence attempts, pushing the sufferer back into the IAA cycle.</p> <p>Conclusion</p> <p>This study provides important points of reference for alcohol and drug service workers and community healthcare professionals in Taiwan, casting light on the abstinence process and providing a basis for intervention or rehabilitation services.</p

A Nationwide Population-Based Cohort Study: Will Anxiety Disorders Increase Subsequent Cancer Risk?

BACKGROUND: The aim of this study was to evaluate a possible association between malignancy and anxiety disorders (AD) in Taiwan. METHODS: We employed data from the National Health Insurance system of Taiwan. The AD cohort contained 24,066 patients with each patient randomly frequency matched according to age and sex with 4 individuals from the general population without AD. Cox's proportional hazard regression analysis was conducted to estimate the influence of AD on the risk of cancer. RESULTS: Among patients with AD, the overall risk of developing cancer was only 1% higher than among subjects without AD, and the difference was not significant (hazard ratio [HR] = 1.01, 95% confidence interval [95% CI] = 0.95-1.07). With regard to individual types of cancer, the risk of developing prostate cancer among male patients with AD was significantly higher (HR = 1.32, 95% CI = 1.02-1.71). On the other hand, the risk of cervical cancer among female patients with AD was marginally significantly lower than among female subjects without AD (HR = 0.72, 95% CI = 0.51-1.03). LIMITATIONS: One major limitation is the lack of information regarding the life style or behavior of patients in the NHI database, such as smoking and alcohol consumption. CONCLUSIONS: Despite the failure to identify a relationship between AD and the overall risk of cancer, we found that Taiwanese patients with AD had a higher risk of developing prostate cancer and a lower risk of developing cervical cancer

Mutation screening of NOS1AP gene in a large sample of psychiatric patients and controls

<p>Abstract</p> <p>Background</p> <p>The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (<it>NOS1AP</it>) is located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Previous genetic and functional studies explored the role of <it>NOS1AP </it>in these psychiatric conditions, but only a limited number explored the sequence variability of <it>NOS1AP</it>.</p> <p>Methods</p> <p>We analyzed the coding sequence of <it>NOS1AP </it>in a large population (n = 280), including patients with schizophrenia (n = 72), ASD (n = 81) or OCD (n = 34), and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93).</p> <p>Results</p> <p>Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions.</p> <p>Conclusions</p> <p>Coding variations of <it>NOS1AP </it>are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human <it>NOS1AP </it>gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders.</p

Chinese beliefs in luck are linked to gambling problems via strengthened cognitive biases:A mediation test

10.1007/s10899-017-9690-6Journal of gambling studies3341325-133

Rare coding variants in ten genes confer substantial risk for schizophrenia

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3–50, P < 2.14 × 10−6) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-d-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders1, epilepsy and severe neurodevelopmental disorders2, although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk3, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach