Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Heritability and polygenic predictionIn the EUR sample, the SNP-based heritability (h 2 SNP ) (that is, the proportion of variance in liability attributable to all measured SNPs)
Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.
Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic “risk” and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke’s R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P < .001), patients from siblings (OR = 1.58, P < .001), and siblings from controls (OR = 1.21, P = .001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome.
Both lithium and valproate may be associated with immediate verbal memory impairment, sparing other cognitive functions. Presence of a similar verbal memory deficit in the lithium and valproate groups suggests that this deficit might be intrinsic to BD or that the 2 medications influence immediate verbal memory similarly. Larger samples of remitted bipolar patients on monotherapy should be studied for more precise conclusions.
This is a comparison study that is aimed to investigate and compare the frequency and severity of secondary social anxiety disorder (SAD) in patients with hyperkinesias, which is associated with a significant sense of disfigurement and compromised social interaction. Patients with hemifacial spasm (n = 20), cervical dystonia (n = 20), and essential tremor (n = 20) were evaluated by SCID-I, Liebowitz Social Anxiety Scale, Hamilton Anxiety and Depression Rating Scales, and Sheehan Disability Scale. The DSM-IV H criterion excluding social anxiety related to a medical condition was disregarded for the diagnosis of secondary SAD. The control group (n = 60) consisted of matched healthy subjects. The frequency of the diagnosis and severity of symptoms were compared and associations with sociodemographic and clinical factors were explored. There was no difference between three patient groups in terms of the frequency or the severity of secondary SAD. Younger age and depressive symptoms were associated with the severity of secondary SAD, while severity or duration of the movement disorder or social disability was not. This study revealed a high frequency of secondary SAD in hyperkinesias, emphasizing the need for psychiatric assessment, especially for younger and depressed patients, who seem to be at greater risk.
An association of suicidality and depersonalization with akathisia has been reported, but it is not clear whether these phenomena are specific to akathisia or are nonspecific manifestations of distress. The authors used the Barnes Akathisia Rating Scale, Brief Psychiatric Rating Scale, and Hamilton Rating Scale for Depression (Ham-D) to examine the relationships between suicidality, depersonalization, dysphoria, and akathisia in 68 patients with schizophrenia or schizophreniform disorder. Akathisia was associated with higher scores on the Ham-D ratings of suicidality, depersonalization, and agitation. In a logistic regression model, depressive mood and subjective awareness of akathisia appeared to be the only predictors of suicidality and depersonalization, respectively. These findings support the association between akathisia and both suicidality and depersonalization. However, these symptoms appear to be nonspecific responses to accompanying depressive mood and the subjective awareness of the akathisia syndrome, respectively.
Previous research highlights the presence of social anxiety disorder related to disfiguring diseases, although DSM-IV precludes the diagnosis of social anxiety disorder related to a medical condition. The present study investigated the frequency and severity of social anxiety disorder in patients with Parkinson's disease (n=50) and comparison subjects (n=50). Social anxiety was diagnosed in 16% of patients with Parkinson's disease and 2% of the comparison subjects. Regression analysis revealed younger age and depression as predictive factors of social anxiety. This study supported the likelihood of social anxiety disorder as a comorbid condition in Parkinson's disease. Revision of the criteria for social anxiety disorder in future diagnostic systems is necessary for the detection and management of these patients.
Neuroleptic-induced acute akathisia (NIA) is a distressing condition and an important clinical problem because it is associated with treatment noncompliance and suicidal or impulsive behavior. Anticholinergics are among the treatment options; however, a review of the literature fails to identify a double-blind, randomized, placebo-controlled study of these medications in NIA. In a randomized, double-blind, placebo-controlled design, we studied the effectiveness of intramuscular biperiden (n = 15) or isotonic saline (n = 15) in the treatment of NIA diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Injections were repeated up to 3 times unless akathisia was completely treated (scored 0 for global akathisia with the Barnes Akathisia Rating Scale). Patients were assessed for akathisia, other movement disorders, and psychiatric symptoms at baseline and 3 times after the first injection at 2-hour intervals. Response was defined as at least a 2-point decline in the global akathisia score. The numbers of responders in the 2 groups were not significantly different (7 and 5 in the biperiden and placebo groups, respectively). The courses of individual items on the Barnes Akathisia Rating Scale were also similar. Our results suggest that intramuscular biperiden should not be considered as a first-line treatment of NIA.
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