An evolutionary timeline of the oxytocin signaling pathway.

Oxytocin is a neuropeptide associated with both psychological and somatic processes like parturition and social bonding. Although oxytocin homologs have been identified in many species, the evolutionary timeline of the entire oxytocin signaling gene pathway has yet to be described. Using protein sequence similarity searches, microsynteny, and phylostratigraphy, we assigned the genes supporting the oxytocin pathway to different phylostrata based on when we found they likely arose in evolution. We show that the majority (64%) of genes in the pathway are 'modern'. Most of the modern genes evolved around the emergence of vertebrates or jawed vertebrates (540 - 530 million years ago, 'mya'), including OXTR, OXT and CD38. Of those, 45% were under positive selection at some point during vertebrate evolution. We also found that 18% of the genes in the oxytocin pathway are 'ancient', meaning their emergence dates back to cellular organisms and opisthokonta (3500-1100 mya). The remaining genes (18%) that evolved after ancient and before modern genes were classified as 'medium-aged'. Functional analyses revealed that, in humans, medium-aged oxytocin pathway genes are highly expressed in contractile organs, while modern genes in the oxytocin pathway are primarily expressed in the brain and muscle tissue.

Conduct disorder - a comprehensive exploration of comorbidity patterns, genetic and environmental risk factors.

Conduct disorder (CD), a common mental disorder in children and adolescents, is characterized by antisocial behavior. Despite similarities with antisocial personality disorder (ASPD) and possible diagnostic continuity, CD has been shown to precede a range of adult-onset mental disorders. Additionally, little is known about the putative shared genetic liability between CD and adult-onset mental disorders and the underlying gene-environment interplay. Here, we interrogated comorbidity between CD and other mental disorders from the Norwegian Mother, Father and Child Cohort Study (n = 114 500) and investigated how polygenic risk scores (PRS) for mental health traits were associated with CD/CD traits in childhood and adolescence. Gene-environment interplay patterns for CD was explored with data on bullying and parental education. We found CD to be comorbid with several child and adult-onset mental disorders. This phenotypic overlap corresponded with associations between PRS for mental disorders and CD. Additionally, our findings support an additive gene-environment model. Previously conceptualized as a precursor of ASPD, we found that CD was associated with polygenic risk for several child- and adult-onset mental disorders. High comorbidity of CD with other psychiatric disorders reflected on the genetic level should inform research studies, diagnostic assessments and clinical follow-up of this heterogenous group.

Lipid Biomarker Research in Bipolar Disorder: A Scoping Review of Trends, Challenges, and Future Directions.

Bipolar disorder (BD) is a disabling disorder with heterogeneous symptom profiles and trajectories. Like many other neuropsychiatric disorders, clinical decision making related to diagnoses and choice of treatment is based on clinical assessments alone, and risk prediction for treatment success or resistance at an individual level remains sparse. An enormous effort to add biological markers to this risk prediction is ongoing. The role of lipids in normal brain functioning is well established, and several hypotheses about the role of lipids in the pathogenesis of neuropsychiatric disorders, including BD, have been made. The frequent comorbidity between neuropsychiatric disorders and cardiovascular disease, the genetic overlap of risk genes for severe mental disorders and genes involved in lipid regulation, and the lipid-altering effects of antipsychotics and mood stabilizers indicate that lipids could hold promise as biomarkers for neuropsychiatric disorders, including BD. To date, reviews of lipid biomarkers in schizophrenia and major depression have noted caveats for future investigations, while reviews of lipid biomarker research in BD is missing. In the current scoping review, we present a comprehensive overview of trends in previous research on lipid biomarkers in BD. The current literature varies greatly in the phenotypes investigated and study designs, leading to divergent findings. Small sample size; potential confounders related to physical activity, nutritional status, and medication use; and cross-sectional designs were frequently reported limitations. Future research may benefit from pivoting toward utilization of newer laboratory techniques such as lipidomics, but consistent use of study methods across cohorts is also needed.

Epidemiological overview of major depressive disorder in Scandinavia using nationwide registers.

Background: Major depressive disorder (MDD) is a common psychiatric disorder associated with a high disease burden. This study gives a comprehensive overview of the prevalence, outcomes, treatment, and genetic epidemiology of MDD within and across the Scandinavian countries. Methods: This study has aimed to assess and compare across Norway, Denmark, and Sweden 1) the prevalence and trajectories of MDD and comorbidity, 2) outcomes and treatment, and 3) heritability (Denmark and Sweden only). The analyses leveraged data on 272,944 MDD cases (and 6.2 million non-cases) from Norway, Sweden, and Denmark in specialist care in national longitudinal health registers covering 1975-2013. Relying on harmonized public data global comparisons of socioeconomic and health metrics were performed to assess to what extent findings are generalizable. Findings: MDD ranked among the most prevalent psychiatric disorders. For many cases, the disorder trajectory was severe, with varying proportions experiencing recurrence, developing comorbid disorders, requiring inpatient treatment, or dying of suicide. Important country differences in specialist care prevalence and treatment were observed. Heritability estimates were moderate (35-48%). In terms of socioeconomic and health indices, the Scandinavian nations were comparable to one another and grouped with other Western nations. Interpretation: The Scandinavian countries were similar with regards to MDD epidemiological measures, but we show that differences in health care organization need to be taken into consideration when comparing countries. This study demonstrates the utility of using comprehensive population-wide registry data, outlining possibilities for other applications. The findings will be of use to policy makers for developing better prevention and intervention strategies. Funding: Swedish Research Council (Vetenskapsrådet, award D0886501 to PFS), US National Institutes of Mental HealthR01 MH123724 (to PFS), European Union's Horizon 2020 Research and Innovation Program (847776 and 964874, to OA) and European Research Council grant (grant agreement ID 101042183, to YL).

Associations Between Symptoms of Premenstrual Disorders and Polygenic Liability for Major Psychiatric Disorders.

Importance: Premenstrual disorders are heritable, clinically heterogenous, with a range of affective spectrum comorbidities. It is unclear whether genetic predispositions to affective spectrum disorders or other major psychiatric disorders are associated with symptoms of premenstrual disorders. Objective: To assesss whether symptoms of premenstrual disorders are associated with the genetic liability for major psychiatric disorders, as indexed by polygenic risk scores (PRSs). Design, Setting, and Participants: Women from the Norwegian Mother, Father and Child Cohort Study were included in this genetic association study. PRSs were used to determine whether genetic liability for major depression, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder, and autism spectrum disorder were associated with the symptoms of premenstrual disorders, using the PRS for height as a somatic comparator. The sample was recruited across Norway between June 1999 and December 2008, and analyses were performed from July 1 to October 14, 2022. Main Outcomes and Measures: The symptoms of premenstrual disorders were assessed at recruitment at week 15 of pregnancy with self-reported severity of depression and irritability before menstruation. Logistic regression was applied to test for the association between the presence of premenstrual disorder symptoms and the PRSs for major psychiatric disorders. Results: The mean (SD) age of 56 725 women included in the study was 29.0 (4.6) years. Premenstrual disorder symptoms were present in 12 316 of 56 725 participants (21.7%). The symptoms of premenstrual disorders were associated with the PRSs for major depression (ß = 0.13; 95% CI, 0.11-0.15; P = 1.21 × 10-36), bipolar disorder (ß = 0.07; 95% CI, 0.05-0.09; P = 1.74 × 10-11), attention deficit/hyperactivity disorder (ß = 0.07; 95% CI, 0.04-0.09; P = 1.58 × 10-9), schizophrenia (ß = 0.11; 95% CI, 0.09-0.13; P = 7.61 × 10-25), and autism spectrum disorder (ß = 0.03; 95% CI, 0.01-0.05; P = .02) but not with the PRS for height. The findings were confirmed in a subsample of women without a history of psychiatric diagnosis. Conclusions: The results of this genetic association study show that genetic liability for both affective spectrum disorder and major psychiatric disorders was associated with symptoms of premenstrual disorders, indicating that premenstrual disorders have overlapping genetic foundations with major psychiatric disorders.

Sex differences in antipsychotic-related triglyceride levels are associated with metabolic hormone differences in patients with severe mental disorders.

BACKGROUND: Adverse effects of antipsychotics (AP) contribute to cardiovascular disease (CVD) risk in patients with severe mental disorders (SMD). We investigated sex differences in AP-related CVD risk factors and the role of metabolic hormones. METHODS: Patients with SMD (N = 1791) receiving AP with different CVD risk were recruited and grouped into olanzapine and/or clozapine (N = 532), other APs (N = 744) or no use of APs (N = 515). Associations between CVD risk factor (total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), body mass index (BMI), glucose, blood pressure), sex and AP groups were tested in multiple linear regression with interactions, controlling for diagnostic group, lifestyle factors, polypharmacy, age and ethnicity. Next, we tested associations between sex differences in AP-related CVD risk factors and metabolic regulatory hormones. RESULTS: AP groups and male sex were significantly associated with higher levels of LDL-C, TG and BMI, and lower levels of HDL-C. Significant interaction between AP groups and sex were found for TG (p = 0.017), with larger increase in males. Serum adiponectin, insulin, cortisol, leptin, testosterone, free thyroxine and thyroid-stimulating hormone (TSH) were associated with TG levels (all p ≤ 0.001), and a significant interaction with sex for insulin (p = 0.005), cortisol (p = 0.016), leptin (p < 0.001) and TSH (p = 0.001). CONCLUSIONS: We found more severe AP-related CVD risk factors in male patients with SMD. The male-dependent increase in TG levels was associated with leptin, insulin, cortisol and TSH levels. Clinicians treating patients with SMD should be aware of increased vulnerability for AP-related lipid abnormalities in males.

Limited association between infections, autoimmune disease and genetic risk and immune activation in severe mental disorders.

BACKGROUND: Low-grade inflammation may be part of the underlying mechanism of schizophrenia and bipolar disorder. We investigated if genetic susceptibility, infections or autoimmunity could explain the immune activation. METHODS: Seven immune markers were selected based on indicated associations to severe mental disorders (IL-1Ra, sIL-2R, IL-18, sgp130, sTNFR-1, APRIL, ICAM-1) and measured in plasma of patients with schizophrenia (SCZ, N = 732) and bipolar spectrum disorders (BD, N = 460) and healthy controls (HC, N = 938). Information on rate of infections and autoimmune diseases were obtained from Norwegian national health registries for a twelve-year period. Polygenic risk scores (PRS) of SCZ and BD were calculated from genome-wide association studies. Analysis of covariance were used to test effects of infection rate, autoimmune disease and PRS on differences in immune markers between patients and HC. RESULTS: Infection rate differed between all groups (BD > HC > SCZ, all p < 0.001) whereas autoimmune disease was more frequent in BD compared to SCZ (p = 0.004) and HC (p = 0.003). sIL-2R was positively associated with autoimmune disease (p = 0.001) and negatively associated with PRS of SCZ (p = 0.006) across SCZ and HC; however, associations represented only small changes in the difference of sIL-2R levels between SCZ and HC. CONCLUSION: There were few significant associations between rate of infections, autoimmune disease or PRS and altered immune markers in SCZ and BD, and the detected associations represented only small changes in the immune aberrations. The findings suggest that most of the low-grade inflammation in SCZ and BD is explained by other factors than the underlying PRS, autoimmunity and infection rates.

Immune marker levels in severe mental disorders: associations with polygenic risk scores of related mental phenotypes and psoriasis.

Several lines of evidence implicate immune abnormalities in the pathophysiology of severe mental disorders (SMD) and comorbid mental disorders. Here, we use the data from genome-wide association studies (GWAS) of autoimmune diseases and mental phenotypes associated with SMD to disentangle genetic susceptibilities of immune abnormalities in SMD. We included 1004 patients with SMD and 947 healthy controls (HC) and measured plasma levels of IL-1Ra, sIL-2R, gp130, sTNFR-1, IL-18, APRIL, and ICAM-1. Polygenic risk scores (PRS) of six autoimmune disorders, CRP, and 10 SMD-related mental phenotypes were calculated from GWAS. General linear models were applied to assess the association of PRS with immune marker abnormalities. We found negative associations between PRS of educational attainment and IL-1Ra (P = 0.01) and IL-18 (P = 0.01). There were nominal positive associations between PRS of psoriasis and sgp130 (P = 0.02) and PRS of anxiety and IL-18 (P = 0.03), and nominal negative associations between PRS of anxiety and sIL-2R (P = 0.02) and PRS of educational attainment and sIL-2R (P = 0.03). Associations explained minor amounts of the immune marker plasma-level difference between SMD and HC. Different PRS and immune marker associations in the SMD group compared to HC were shown for PRS of extraversion and IL-1Ra ([interaction effect (IE), P = 0.002), and nominally for PRS of openness and IL-1Ra (IE, P = 0.02) and sTNFR-1 (IE, P = 0.04). Our findings indicate polygenic susceptibilities to immune abnormalities in SMD involving genetic overlap with SMD-related mental phenotypes and psoriasis. Associations might suggest immune genetic factors of SMD subgroups characterized by autoimmune or specific mental features.

Oxytocin-pathway polygenic scores for severe mental disorders and metabolic phenotypes in the UK Biobank.

Oxytocin is a neuromodulator and hormone that is typically associated with social cognition and behavior. In light of its purported effects on social cognition and behavior, research has investigated its potential as a treatment for psychiatric illnesses characterized by social dysfunction, such as schizophrenia and bipolar disorder. While the results of these trials have been mixed, more recent evidence suggests that the oxytocin system is also linked with cardiometabolic conditions for which individuals with severe mental disorders are at a higher risk for developing. To investigate whether the oxytocin system has a pleiotropic effect on the etiology of severe mental illness and cardiometabolic conditions, we explored oxytocin's role in the shared genetic liability of schizophrenia, bipolar disorder, type-2 diabetes, and several phenotypes linked with cardiovascular disease and type 2 diabetes risk using a polygenic pathway-specific approach. Analysis of a large sample with about 480,000 individuals (UK Biobank) revealed statistically significant associations across the range of phenotypes analyzed. By comparing these effects to those of polygenic scores calculated from 100 random gene sets, we also demonstrated the specificity of many of these significant results. Altogether, our results suggest that the shared effect of oxytocin-system dysfunction could help partially explain the co-occurrence of social and cardiometabolic dysfunction in severe mental illnesses.

Telomeres are shorter and associated with number of suicide attempts in affective disorders.

BACKGROUND: Shorter telomere length is a putative biomarker of accelerated aging and has been associated with affective disorders and mortality. Psychological factors and behaviors associated with telomere shortening are yet to be clarified. Here, we investigate the association between history of suicide attempts and telomere length in patients with affective disorders. METHODS: Leucocyte telomere length was determined by quantitative real-time Polymerase Chain Reaction (qPCR) in patients with affective disorders (n = 248) including bipolar disorders type I (n = 159), type II (n = 67), major depressive disorder (n = 22), and healthy controls (n = 401). Diagnosis, duration of illness, and age at onset were assessed using the Structural Clinical Interview for DSM-IV (SCID-I). Number of lifetime suicide attempts were based on self-reports. Effect size was calculated using Cohen's d. RESULTS: Telomere length was reduced in patients with affective disorders relative to healthy controls (d = 0.18, F = 5.26, p = 0.02). Among patients, a higher number of suicide attempts was associated with shorter telomere length (ß = -0.24, t = -3.83, CI = -0.44 to -0.14, p < 0.001), also when controlling for duration of illness and age at onset (ß = -.23, CI = -.42 to -.12, p = 0.001). Multiple suicide attempts were associated with telomere length reduction comparable to eight years lifespan, adjusted for demographic and clinical characteristics. CONCLUSIONS: While longitudinal data are needed to clarify the temporal course, previous suicide attempts and related distress may accelerate telomere shortening and aging in patients with affective disorders.

Evidence for Reduced Long-Term Potentiation-Like Visual Cortical Plasticity in Schizophrenia and Bipolar Disorder.

Several lines of research suggest that impairments in long-term potentiation (LTP)-like synaptic plasticity might be a key pathophysiological mechanism in schizophrenia (SZ) and bipolar disorder type I (BDI) and II (BDII). Using modulations of visually evoked potentials (VEP) of the electroencephalogram, impaired LTP-like visual cortical plasticity has been implicated in patients with BDII, while there has been conflicting evidence in SZ, a lack of research in BDI, and mixed results regarding associations with symptom severity, mood states, and medication. We measured the VEP of patients with SZ spectrum disorders (n = 31), BDI (n = 34), BDII (n = 33), and other BD spectrum disorders (n = 2), and age-matched healthy control (HC) participants (n = 200) before and after prolonged visual stimulation. Compared to HCs, modulation of VEP component N1b, but not C1 or P1, was impaired both in patients within the SZ spectrum (χ 2 = 35.1, P = 3.1 × 10-9) and BD spectrum (χ 2 = 7.0, P = 8.2 × 10-3), including BDI (χ 2 = 6.4, P = .012), but not BDII (χ 2 = 2.2, P = .14). N1b modulation was also more severely impaired in SZ spectrum than BD spectrum patients (χ 2 = 14.2, P = 1.7 × 10-4). N1b modulation was not significantly associated with Positive and Negative Syndrome Scale (PANSS) negative or positive symptoms scores, number of psychotic episodes, Montgomery and Åsberg Depression Rating Scale (MADRS) scores, or Young Mania Rating Scale (YMRS) scores after multiple comparison correction, although a nominal association was observed between N1b modulation and PANSS negative symptoms scores among SZ spectrum patients. These results suggest that LTP-like plasticity is impaired in SZ and BD. Adding to previous genetic, pharmacological, and electrophysiological evidence, these results implicate aberrant synaptic plasticity as a mechanism underlying SZ and BD.

Heart rate variability is associated with disease severity in psychosis spectrum disorders.

While a growing literature links cardiac autonomic dysregulation to a variety of psychiatric disorders, the relationship between cardiac autonomic functioning and specific symptoms in schizophrenia (SZ) and bipolar disorder (BD) remains elusive. Thus, we investigated heart rate variability (HRV), a proxy for vagal activity, as a biological marker for symptom severity in patients with SZ and BD. HRV was calculated in 35 patients with SZ and 52 patients with BD, as well as in 149 healthy controls. In the patient groups, symptom severity and function were measured by the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Results showed that HRV was significantly lower in both clinical groups compared to the healthy controls, with no significant HRV differences between patient groups. PANSS general psychopathology scores, GAF symptom scores, and GAF function scores showed statistically significant associations with HRV across groups. These results suggest that disease severity is associated with autonomic dysfunction and that HRV may provide a potential biomarker of disease severity in SZ and BD.

Indicated association between polygenic risk score and treatment-resistance in a naturalistic sample of patients with schizophrenia spectrum disorders.

BACKGROUND: One third of people diagnosed with schizophrenia fail to respond adequately to antipsychotic medication, resulting in persisting disabling symptoms, higher rates of hospitalization and higher costs for society. In an effort to better understand the mechanisms behind resistance to antipsychotic treatment in schizophrenia, we investigated its potential relationship to the genetic architecture of the disorder. METHODS: Patients diagnosed with a schizophrenia spectrum disorder (N = 321) were classified as either being treatment-resistant (N = 108) or non-treatment-resistant (N = 213) to antipsychotic medication using defined consensus criteria. A schizophrenia polygenic risk score based on genome-wide association studies (GWAS) was calculated for each patient and binary logistic regression was performed to investigate the association between polygenetic risk and treatment resistance. We adjusted for principal components, batch number, age and sex. Additional analyses were performed to investigate associations with demographic and clinical variables. RESULTS: High levels of polygenic risk score for schizophrenia significantly predicted treatment resistance (p = 0.003). The positive predictive value of the model was 61.5% and the negative predictive value was 71.7%. The association was significant for one (p = 0.01) out of five tested SNP significance thresholds. Season of birth was able to predict treatment-resistance in the regression model (p = 0.05). CONCLUSIONS: The study indicates that treatment-resistance to antipsychotic medication is associated with higher polygenetic risk of schizophrenia, suggesting a link between antipsychotics mechanism of action and the genetic underpinnings of the disorder.

Vitamin D Deficiency Associated With Cognitive Functioning in Psychotic Disorders.

BACKGROUND: Cognitive dysfunctions are core features of psychotic disorders with substantial impact on daily functioning. Vitamin D deficiency has been found to be related to cognitive dysfunctions, but the associations between vitamin D deficiency and cognition in persons with a psychotic disorder are largely unknown. METHODS: This cross-sectional study included 225 patients with a DSM-IV psychotic disorder consecutively recruited from 2003 to 2014 and 159 randomly selected healthy controls, assessed by a cognitive test battery, a clinical protocol (including Structured Clinical Interview for DSM-IV Axis I Disorders and Positive and Negative Syndrome Scale), and a physical examination including vitamin D measurements. Multiple regression models were performed to evaluate the effect of vitamin D deficiency (defined serum 25-hydroxyvitamin D [25(OH)D] < 25 nmol/L) on key cognitive domains: processing speed, verbal learning, verbal memory, and executive functioning. RESULTS: Vitamin D deficiency was significantly associated with decreased processing speed (ie, Digit Symbol Coding) (t = -2.6, P = .01; total model: adjusted R² = 0.40, F6, 374 = 43.8, P < .001) and decreased fluency (ie, verbal fluency) (t = -2.1, P = .04; total model: adjusted R² = 0.35, F6, 373 = 34.2, P < .001) when the results were controlled for age, ethnicity, IQ, patient versus control status, and substance or alcohol abuse. Additional analyses indicated that negative symptoms diluted the association between vitamin D deficiency and processing speed (t = -1.72, P = .09) and verbal fluency (t = -1.35, P = .18) in patients. CONCLUSION: The associations between vitamin D deficiency and processing speed and verbal fluency are good arguments for planning large-scale randomized controlled studies in target populations so conclusions can be made about the potential beneficial effect of vitamin D on cognition in psychotic disorders.

Contribution of oxytocin receptor polymorphisms to amygdala activation in schizophrenia spectrum disorders.

BACKGROUND: Oxytocin has been proposed to mediate amygdala dysfunction associated with altered emotion processing in schizophrenia, but the contribution of oxytocin pathway genes is yet to be investigated. AIMS: To identify potential different contributions of three oxytocin receptor polymorphisms (rs53576, rs237902 and rs2254298) between patients with schizophrenia spectrum disorders (SCZ), affective spectrum disorders (AD) and healthy controls (HC). METHOD: In a total of 346 participants (104 with SCZ, 100 with AD, and 142 HC) underwent genotyping and functional magnetic resonance imaging (fMRI) during an emotional faces matching paradigm. Genetic association analyses were performed to test the possible effects on task-induced BOLD amygdala response to fearful/angry faces. RESULTS: In participants with SCZ, the rs237902 G allele was associated with low amygdala activation (left hemisphere: b=-4.99, Bonferroni corrected P=0.04) and interaction analyses showed that this association was disorder specific (left hemisphere: Bonferroni corrected P=0.003; right hemisphere: Bonferroni corrected P=0.03). There were no associations between oxytocin polymorphisms and amygdala activation in the total sample, among AD patients or HC. CONCLUSIONS: Rs237902 was associated with amygdala activation in response to fearful/angry faces only in patients with SCZ. Our findings indicate that the endogenous oxytocin system could serve as a contributing factor in biological underpinnings of emotion processing and that this contribution is disorder specific. DECLARATION OF INTEREST: O.A.A. received speaker's honoraria from GSK, Otsuka, Lundbeck. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Resting-state high-frequency heart rate variability is related to respiratory frequency in individuals with severe mental illness but not healthy controls.

Heart rate variability (HRV) has become central to biobehavioral models of self-regulation and interpersonal interaction. While research on healthy populations suggests changes in respiratory frequency do not affect short-term HRV, thus negating the need to include respiratory frequency as a HRV covariate, the nature of the relationship between these two variables in psychiatric illness is poorly understood. Therefore, the aim of this study was to investigate the association between HRV and respiratory frequency in a sample of individuals with severe psychiatric illness (n = 55) and a healthy control comparison group (n = 149). While there was no significant correlation between HF-HRV and respiration in the control group, we observed a significant negative correlation in the psychiatric illness group, with a 94.1% probability that these two relationships are different. Thus, we provide preliminary evidence suggesting that HF-HRV is related to respiratory frequency in severe mental illness, but not in healthy controls, suggesting that HRV research in this population may need to account for respiratory frequency. Future work is required to better understand the complex relationship between respiration and HRV in other clinical samples with psychiatric diseases.

Association between Genetic Variation in the Oxytocin Receptor Gene and Emotional Withdrawal, but not between Oxytocin Pathway Genes and Diagnosis in Psychotic Disorders.

Social dysfunction is common in patients with psychotic disorders. Oxytocin is a neuropeptide with a central role in social behavior. This study aims to explore the relationship between oxytocin pathway genes and symptoms related to social dysfunction in patients with psychotic disorders. We performed association analyses between four oxytocin pathway genes (OXT, OXTR, AVP, and CD38) and four areas of social behavior-related psychopathology as measured by Positive and Negative Syndrome Scale. For this purpose, we used both a polygenic risk score (PGRS) and single OXTR candidate single nucleotide polymorphism previously reported in the literature (rs53576, rs237902, and rs2254298). A total of 734 subjects with DSM-IV psychotic spectrum disorders and 420 healthy controls were included. Oxytocin pathway PGRSs were calculated based on the independent Psychiatric Genomics Consortium study sample. There was a significant association between symptom of Emotional Withdrawal and the previously reported OXTR risk allele A in rs53576. No significant associations between oxytocin pathway gene variants and a diagnosis of psychotic disorder were found. Our findings indicate that while oxytocin pathway genes do not appear to contribute to the susceptibility to psychotic disorders, variations in the OXTR gene might play a role in the development of impaired social behavior.

Migrant background and ethnic minority status as predictors for duration of untreated psychosis.

AIM: The aim of the study was to explore if patients with migration and/or ethnic minority background have longer duration of untreated psychosis (DUP) than patients from the reference population, and in case to what extent this was best explained by ethnic minority status or migration background, including age at migration. METHODS: Four hundred sixty-two first-episode patients were included. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders was used for diagnostic purposes. Patients were interviewed about migration history and ethnicity using structured questionnaires. RESULTS: Being part of an ethnic minority group had a trend-level significance, and migration after the age of 6 had a statistically significant association with prolonged DUP. CONCLUSIONS: Age at migration has a moderate, but statistically significant effect on DUP. The findings indicate migrating after school start is associated with a longer DUP in immigrant populations.