Journal of psychiatry and brain science最新文献

{"title":"Phenotypic Effects of Polygenic Risk for Schizophrenia: What Have We Learned So Far?","authors":"U. Heilbronner","doi":"10.20900/jpbs.20190019","DOIUrl":"https://doi.org/10.20900/jpbs.20190019","url":null,"abstract":"The results of large genome-wide association studies of schizophrenia (SZ) can be used to calculate an individual’s polygenic risk for SZ (e.g., [1]). This polygenic risk score (PRS) is a weighted sum of SZ risk alleles, and thus holds promise to be used in clinical care someday, e.g., in prevention, diagnosis and treatment of mental disorders (e.g., [2]). It can be used to uncover other phenotypes, such as behavioral traits or disorders, that are influenced by SZ-PRS, and this issue of the Journal of Psychiatry and Brain Science aims to summarize some of the knowledge that has emerged to this regard. Three reviews and two original research articles are contained in this Virtual Special Issue. Schaupp, Schulze and Budde [3] provide an excellent summary of studies researching the associations of SZ-PRS and cognition. Their finding of inconsistent results, both in patients and the general population, albeit characteristic for a developing field, points to a need for larger sample sizes when studying the genetics of cognition, and highlights further methodological problems. Adorjan and Papiol [4] review the relationship of cannabis consumption, SZ, and the SZ-PRS, and discuss accumulating evidence that a high polygenic risk for SZ may be predisposing individuals to cannabis abuse. Thus, consumption of cannabis may not only be understood as an environmental risk factor for SZ, but also as a type of gene-environment correlation/interaction. The last review article of Bengesser and Reininghaus [5] highlights the interesting finding that the SZ-PRS may be used to delineate bipolar disorder patients that respond to lithium from those who do not [6], and can be understood to emphasize the need for biologically-based diagnosis of mental disorders. The original research article of Yasmeen, Papiol, Falkai, Schulze, & Bickeböller [7] researches effects of SZ-PRS in correlated target phenotypes, using both in-silico and empirical data of the PsyCourse study [8]. Results of empirical analyses show that the addition of SZ-PRS to statistical models explaining psychosocial functioning (the Global Assessment of Functioning score) improves model fit, which is further increased when current symptom status is additionally taken into account. Finally, the neuroimaging study of Eberle et al. [9] demonstrates that polygenic scores for SZ can be used to gain a more fundamental understanding of gene-environment interactions. In this study, the authors researched connectivity of the nucleus accumbens, a major component of the brain’s reward circuitry. In healthy individuals, polygenic risk for SZ was associated with a shift towards SZ-like Open Access","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45174911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Risk of Psychosis in Relation to Cannabis Use: Findings from Polygenic Risk Score Approaches","authors":"K. Adorjan, S. Papiol","doi":"10.20900/jpbs.20190018","DOIUrl":"https://doi.org/10.20900/jpbs.20190018","url":null,"abstract":"A psychotic disorder is a multifactorial phenomenon in which not only environmental influences but also genetic factors play an important role. Evidence indicates that psychotic disorders are characterized by a complex mode of inheritance with high polygenicity, in which a large number of common genetic variants with small effects are relevant. One way to measure this polygenic risk is the calculation of polygenic risk scores (PRS). These reflect the complex multifactorial interaction of coding and regulatory DNA variants in the development of mental illness. It is known that the use of cannabis in patients with schizophrenia (SCZ) is much higher than in the general population. Although an exact clinical prognosis based on PRS is not possible at the present, the results found by PRS investigations so far are quite promising. Initial results suggest that people with SCZ and an increased polygenic risk of schizophrenia are more likely to use cannabis. According to these results, the connection between mental illnesses and cannabis use could therefore not simply be seen as an environmental risk, but rather explained as a gene-environment correlation.","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47064092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Historical Perspective on Psychiatric Genetics, the International Society of Psychiatric Genetics and the Role of Elliot Gershon","authors":"L. DeLisi","doi":"10.20900/jpbs.20190015","DOIUrl":"https://doi.org/10.20900/jpbs.20190015","url":null,"abstract":"Psychiatric Genetics is a relatively new field that was defined by groups of researchers interested in the familial aggregation of psychiatric disorders, and spurred on by the escalating new field of molecular genetics beginning in the 1980s. This manuscript contributes to a special issue honoring the career of Elliot S. Gershon, a true pioneer and critical thinker, who contributed substantially to the development of this field and also its stimulating meetings that brought colleagues together to discuss the latest research findings. It details the role Dr. Gershon played in establishing the precursor of the International Society of Psychiatric Genetics (ISPG) and how he remains in a leadership role on its Board of Directors and was honored with one of the ISPG Lifetime Achievement Awards.","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67610439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endophenotype Potential of Nucleus Accumbens Functional Connectivity: Effects of Polygenic Risk for Schizophrenia Interacting with Childhood Adversity","authors":"C. Eberle, Y. Peterse, Filip Jukic, B. Müller-Myhsok, D. Czamara, Jade Martins, Vanessa Schmoll, M. Czisch, E. Binder, P. Sämann","doi":"10.20900/JPBS.20190011","DOIUrl":"https://doi.org/10.20900/JPBS.20190011","url":null,"abstract":"Epidemiological and genetic studies suggest that schizophrenia (SCZ) is associated with both polygenic and environmental risk factors. Little is known if these factors project on common functional circuits relevant to the pathophysiology of SCZ. Here we focussed on resting state functional MRI (rsfMRI) as a biological measure to investigate if genetic and environmental factors for SCZ risk affect the same circuits in healthy controls as well as patients. For this, we compared the effects of a polygenic risk score for SCZ (PGRS), childhood adversity (CA) and their interaction on functional connectivity density (FCD) mapping and nucleus accumbens (NAcc) seed connectivity between 23 patients with SCZ or schizoaffective disorder and 253 healthy subjects. Patients demonstrated strong FCD increases compared with healthy controls mainly in subcortical nuclei including the NAcc, replicating previous reports. In healthy subjects, FCD of the NAcc was positively correlated with both the PGRS and the PGRS-CA-interaction. Both for high PGRS and PGRS-CA-interaction, fine-mapping revealed higher connectivity between the NAcc and visual association cortices. In conclusion, polygenic risk for SCZ shifted global and regionally specific connectivity of the NAcc in healthy subjects into the direction of the connectivity pattern observed in SCZ, and this shift was intensified by higher levels of CA.","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43079032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ULK4 Genetic Variants Have Pleiotropic Effect on Risk of Autism, Associated with Brain mRNA Expression and Antipsychotic Treatment Response","authors":"J. Ou, Kuokuo Li, Hui Guo, K. Xia, Zhengmao Hu, Jingping Zhao, Fengyu Zhang","doi":"10.20900/JPBS.20190010","DOIUrl":"https://doi.org/10.20900/JPBS.20190010","url":null,"abstract":"Background: ULK4 genetic variants have been implicated for adult-onset psychiatric disorders, and common variants are associated with hematologic and cardiologic disorders at genome-wide significance. This study aimed to examine the pleiotropic effect of ULK4 on the risk of autism, cis-association with mRNA and impact on antipsychotic treatment response in humans. Methods: The clinical genetic data comprised one cohort of autism case-parent triad sample in the Han Chinese and three cohorts of family-based samples in the European ancestry, from Autism Genetic Research Exchange, the Autism Genome Project and the Simons Foundation for Autism Research Initiative; mRNA expression in postmortem human prefrontal cortex across the lifespan and different brain regions of postmortem human brain and other tissues from two independent datasets were used for examining the cis-association with ULK4 variants. Antipsychotic treatment response data were from the Clinical Antipsychotic Trials in Intervention Effectiveness in patients with chronic schizophrenia. Transmission disequilibrium test was used to examine the genetic association with autism. General linear regression analysis was performed for cis-association with mRNA expression. The Cox proportion hazard model was used to analyze the primary outcome, the time to discontinued use of antipsychotics. Results: Multiple functional SNPs including rs2272007 in strong linkage disequilibrium at ULK4 were associated with autism in the Han Chinese sample (minimum p < 0.00071) which survived the Bonferroni correction for multiple testing. SNP rs2272007 and other SNPs were significantly associated with ULK4 expression in postmortem human prefrontal cortex in subjects across the lifespan and multiple brain areas in two independent datasets. In addition, two SNPs rs7651623 (Hazard Ratio, HR = 16.33; p = 5.00 × 10−4) and rs2030431 (HR = 17.25; p = 3.00 × 10−4) in strong LD were associated with the risk of discontinuing use of antipsychotic medications in the patients with schizophrenia. SNP rs2272007, perfect LD with rs7651623, was associated with treatment response in olanzapine only (HR = 4.22; p = 0.0034). Conclusion: We provide evidence at multiple layers for ULK4 common genetic variants associated with the risk of autism. This may have clinical implication for translational research and precision psychiatry","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46454523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What We Know and Still Need to Know about Gender Aspects of Delusional Disorder: A Narrative Review of Recent Work","authors":"A. González-Rodríguez, M. Estève, A. Álvarez, A. Guàrdia, J. Monreal, D. Palao, J. Labad","doi":"10.20900/JPBS.20190009","DOIUrl":"https://doi.org/10.20900/JPBS.20190009","url":null,"abstract":"While gender differences in the psychopathology and clinical course of schizophrenia have been extensively reported, the potential for analogous differences in delusional disorder has been understudied. Our aim in this paper is to focus on the recent literature on delusional disorder and to explore gender aspects. This is a non-systematic, narrative and critical review. The review is divided into the following main sections: gender differences in epidemiology, symptomatology, phenotypic factor analyses, psychiatric comorbidity, response and adherence to medications, and clinical trajectories. Culture-bound delusional syndromes are also addressed, and potential causes for gender differences and their treatment are critically discussed. Although DMS-5 reports no gender differences in the frequency of delusional disorder or in delusional content, several studies have found erotomania to be more frequent in women. There seem also to be gender differences in affective and substance abuse comorbidity, which may prove clinically important. The loss of the neuroprotection conferred by estrogens during the reproductive period in women may trigger depressive symptoms after menopause. The interaction of age and gender has been insufficiently studied as is also the case for selective cultural pressures on men and women and their impact on the content of delusions. Studies designed to focus on gender differences in response to treatment are currently needed in delusional disorder","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43152411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D Levels Are Not Associated with Hippocampal-Dependent Learning in Young Adult Male C57BL/6J Mice: A Negative Report","authors":"K. Jaeschke, D. Blackmore, Natalie J. Groves, M. Al-Amin, S. Alexander, T. Burne","doi":"10.20900/jpbs.20190008","DOIUrl":"https://doi.org/10.20900/jpbs.20190008","url":null,"abstract":"It is well established that vitamin D is essential in calcium homeostasis and bone metabolism. Recent evidence has exposed further roles of vitamin D in adult brain function, specifically indicating that low vitamin D levels during adulthood may be related to cognitive impairment. We have recently shown that adult vitamin D (AVD) deficiency disrupts hippocampal-dependent learning and structural brain connectivity in BALB/c mice. The BALB/c mouse strain is more vulnerable to social stress compared with other resilient mouse strains, such as C57BL/6J mice. Therefore, the primary aim of this research was to examine C57BL/6J mice exposed to varying levels of vitamin D (0, 1500 and 15,000 IU/vitamin D3/kg referred to as deficient, control and elevated, respectively) for 10 weeks. The mice were assessed for hippocampal-dependent learning using the active place avoidance (APA) task. Mice were tested for behaviours that could alter performance on the APA task, and hippocampal tissue was analysed for catecholamine and protein expression. Vitamin D status did not affect spatial learning and memory, general behavioural domains, or catecholamine or protein expression in C57BL/6J mice. Overall, these results indicate that, in contrast to BALB/c mice, vitamin D status does not impact on hippocampal-dependent behaviour in young and healthy, adult male C57BL/6J mice","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43744111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Cannabidiol on Psychosis-like Behaviour Induced by Methamphetamine and MK-801 in Mice: A Negative Report","authors":"E. Jaehne, M. Buuse","doi":"10.20900/JPBS.20190006","DOIUrl":"https://doi.org/10.20900/JPBS.20190006","url":null,"abstract":"Background: Cannabis is a widely used illicit substance but may also have medicinal properties. Cannabidiol (CBD), one of the main compounds of interest in the cannabis plant, has been suggested to have beneficial effects in various psychiatric disorders including anxiety and psychosis. Drug-induced locomotor hyperactivity is a commonly used animal model of psychosis-like behaviour and to show antipsychotic drug action. Several genetic and developmental animal models of psychosis show differences in locomotor hyperactivity. The aim of the present study was to investigate the effect of pretreatment with CBD on psychosis-like behaviour in mice. Methods: The animals underwent 5 sessions of locomotor activity testing each, with 3–4 days between tests to allow washout of acute drug challenge. Groups of mice (n = 8 male mice and n = 8 female mice combined) were pretreated with CBD (10 mg/kg) or its vehicle, followed 1 h later with either saline, the dopamine releaser, methamphetamine (1 or 3 mg/kg), or the NMDA receptor antagonist, MK-801 (0.1 or 0.25 mg/kg). Results: There was no significant effect of CBD on its own on locomotor activity. Pretreatment with CBD had no effect on the hyperlocomotion induced by either dose of methamphetamine. There was also no effect of CBD on MK-801 induced hyperlocomotion following the 0.25 mg/kg dose, while 0.1 mg/kg MK-801 did not induce hyperactivity. Conclusions: These results do not support an antipsychotic action of CBD","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48413685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thermoregulatory Fear of Harm Mood Disorder: In Depth Exploration of a Unique Juvenile-Onset Phenotype That Provides a Parsimonious Clinical Description of Certain Youths with Highly Comorbid Treatment Refractory Psychiatric Disorders","authors":"D. Papolos, S. Mattis, H. Lachman, Martin H. Teicher","doi":"10.20900/JPBS.20190004","DOIUrl":"https://doi.org/10.20900/JPBS.20190004","url":null,"abstract":"Among aggressive youths with severe mood lability who frequently fail to benefit from mood stabilizers and antipsychotics there is a discrete subtype called ‘Thermoregulatory Fear of Harm Mood Disorder’ (FOH). This disorder is characterized by an underlying thermoregulatory deficit, a specific prodromal sequence and a unique constellation of symptoms. The underlying problem appears to be a deficit in thermoregulation resulting in excessive heat that manifests as thermal discomfort in neutral ambient temperatures and moderate to extreme cold tolerance, and produces REM sleep-related problems and parasomnias, such as night-terrors and hypnogogic hallucinations. Clinically, FOH is associated with the advent in childhood of frequent, recurrent, vivid nightmares with themes of pursuit and abandonment. The apparent psychological sequelae of exposure to this frightening imagery is fear sensitization and auto-traumatization. A developmental sequence of fear based defensive behaviors arises and includes obsessive bedtime rituals, fear of the dark, separation anxiety, contamination fears, hypervigilance, perfectionism, misperception of neutral stimuli as threatening, as well as reactive aggression in response to limit setting and perceived threat or loss. Ketamine, chosen as a potential treatment because of its effectiveness in reducing fear sensitization and dose-dependent lowering of body temperature in preclinical studies, has been associated with sustained improvement in otherwise refractory youths. We present a detailed description of this heritable disorder, link its clinical features to a potential disturbance in brain derived neurotropic factor (BDNF) and orexin, and indicate how ketamine rapidly affects BDNF through multiple mechanisms, to produce a dramatic beneficial response in youths with this disorder","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43996820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic Risk for Schizophrenia and Global Assessment of Functioning—A Comparison with In-Silico Data","authors":"S. Yasmeen, S. Papiol, P. Falkai, T. Schulze, H. Bickeböller","doi":"10.20900/JPBS.20190003","DOIUrl":"https://doi.org/10.20900/JPBS.20190003","url":null,"abstract":"In psychiatry, polygenic risk scores (PRSs) have recently been exploited to uncover the shared genetic components in distinct psychiatric disorders. Summary data of large-scale discovery genome-wide association studies (GWASs) on traits such as schizophrenia (SZ) are available. In addition, clinical deep phenotyping includes several correlated phenotypes for psychosocial functioning such as the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). PANSS evaluates acute symptom severity, thus adjusting for this effect when measuring overall assessment and progression of patients with the GAF. A far-reaching understanding of the properties of PRS in such phenotypes is critical to interpreting such analyses, especially when the intermediate phenotype limits sample size. We conducted a simulation study to investigate the performance of PRS in the correlated target phenotypes using sample sizes n = 200, 500, and 1000 (100 replicates) in terms of explained variance in the simulated target phenotypes. We investigated performance of SZ-PRS in the PsyCourse study involving 653 patients (psychotic n = 387, affective \u0000n = 266), in which SZ-PRS was derived from the results of a large GWAS of schizophrenia by the Psychiatric Genomics Consortium. Our simulation results reveal that decreasing correlation between target phenotypes indicates a definable decrease in shared genetic burden with the discovery phenotype. However, with a small sample size, there is already a loss in retrieved R2 with an identical generation model. Our PsyCourse results portrayed that for all patients and for psychotic subgroup, SZ-PRS explained 1% R2 for GAF","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48193154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}