Development Of Psychotic Disorders Research Articles

Prevalence and risk of psychiatric disorders in young people: prospective cohort study exploring the role of childhood trauma (the HUNT study).

Better knowledge about childhood trauma as a risk factor for psychiatric disorders in young people could help strengthen the timeliness and effectiveness of prevention and treatment efforts. To estimate the prevalence and risk of psychiatric disorders in young people following exposure to childhood trauma, including interpersonal violence. This prospective cohort study followed 8199 adolescents (age range 12-20 years) over 13-15 years, into young adulthood (age range 25-35 years). Data about childhood trauma exposure from adolescents participating in the Trøndelag Health Study (HUNT, 2006-2008) were linked to data about subsequent development of psychiatric disorders from the Norwegian Patient Registry (2008-2021). One in four (24.3%) adolescents were diagnosed with a psychiatric disorder by young adulthood. Regression analyses showed consistent and significant relationships between childhood exposure to both interpersonal violence and other potentially traumatic events, and subsequent psychiatric disorders and psychiatric comorbidity. The highest estimates were observed for childhood exposure to two or more types of interpersonal violence (polyvictimisation), and development of psychotic disorders (odds ratio 3.41, 95% CI 1.93-5.72), stress and adjustment disorders (odds ratio 4.20, 95% CI 3.05-5.71), personality disorders (odds ratio 3.98, 95% CI 2.70-5.76), alcohol-related disorders (odds ratio 3.28, 95% CI 2.06-5.04) and drug-related disorders (odds ratio 4.67, 95% CI 2.87-7.33). These findings emphasise the importance of integrating knowledge about childhood trauma as a potent risk factor for psychopathology into the planning and implementation of services for children, adolescents and young adults.

A Matched Case-Control Study of the Serum Level and Gene Expression of IL-6 and IL-12 in Patients with Schizophrenia Spectrum Disorder: An Azeri Acute Phase/Recent-Onset Psychosis Survey (ARAS) Study

Background: The causes of schizophrenia spectrum disorders are believed to be multifactorial, with both genetic and environmental factors, as well as gene-environment interactions, influencing the course of this disorder. Research suggests that immunological factors may play a role in the development of psychotic disorders. Objectives: The aim of this study is to evaluate and compare the serum levels of interleukin-6 (IL-6) and interleukin-12 (IL-12), as well as the expression levels of IL-6 and IL-12 genes, between an Iranian Azeri population of patients with first-episode psychosis and healthy controls. Methods: Forty patients who had recently experienced first-episode non-affective psychosis were allocated to the patient group. Forty healthy volunteers, matched for age and gender, were also recruited as controls. The study was conducted in 2020 in Tabriz, Iran. Peripheral blood samples were collected (using the Ficoll-Paque process) and assessed to determine the expression levels of IL-6 and IL-12 mRNA (using real-time Polymerase Chain Reaction-PCR- system), as well as the serum levels of IL-6 and IL-12 (with a sandwich ELISA kit). GraphPad Prism Version 6.0 was used for all statistical analyses. Results: Each group consisted of 40 participants in this study. Patients had significantly higher levels of IL-6 mRNA expression compared to the healthy controls (P < 0.0001), while no significant difference was found between the two groups in terms of IL-12 mRNA expression (P = 0.5697). A similar pattern was reported for the serum levels of IL-6 (P < 0.0001) and IL-12 (P = 0.0777). The area under the curve (AUC), which indicates the accuracy of the predictive model, was 0.9669 for the level of IL-6 mRNA expression (P < 0.0001). This Area (AUC) was 0.9584 for the serum concentration of IL-6 (P < 0.0001). The levels of IL-6 or IL-12 were not correlated with the severity of symptoms, gender, or age of the patients. Conclusions: The expression level of IL-6 mRNA and the serum concentration of IL-6 were altered in patients with first-episode non-affective psychosis. This finding supports the role of inflammatory pathways in the pathogenesis of psychosis. According to our results, measurement of the circulating level of IL-6 may be useful in distinguishing patients with first-episode psychosis from healthy individuals.

Anomalous self-experiences and neurocognitive functioning in adolescents at risk for psychosis: Still no significant associations found between these two vulnerability markers

BackgroundAnomalous self-experiences (ASEs) and neurocognitive impairments are considered essential domains of vulnerability for developing psychotic disorders. However, little research exists of possible associations between ASEs and neurocognitive functions in individuals at-risk for psychosis. The interconnections between ASEs and neurocognitive impairments should therefore be clarified as much as possible, especially in young individuals at risk. No previous studies have investigated these two fundamental domains in non-help-seeking adolescents at risk for developing psychosis. MethodsThis study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). Adolescents (N = 48, 94% females, mean age = 15.3) were invited to participate after completing a 14-year-old survey distributed by MoBA. At-risk adolescents were selected based on the 0.4% highest scores on 19 items assessing both psychotic-like experiences and ASEs. Five specifically selected and formulated items measuring ASEs were computed to an ASEs total score. Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery. ResultsRegression analyses revealed no significant relationships between ASEs and any neurocognitive domain. ConclusionsWe did not find any significant associations between ASEs and neurocognitive functions in non-help-seeking adolescents at risk for psychotic disorders, which is in line with reports from other types of cohorts. Thus, ASEs and neurocognitive functions may be understood as two relatively separate domains that co-exist in at-risk states. These results underline the need for a wider scope when making predictions about future trajectories, e.g. the development of psychotic disorders. Including both ASEs and neurocognitive functioning in at-risk populations may increase the specificity of vulnerability criteria in this population and enhance our understanding of early psychosis psychopathology.

Does antipsychotic therapy prevent the development of chronic psychotic disorders in people addicted to ilegal psychoactive substances

IntroductionAcute psychotic disorders are increasingly being diagnosed in people addicted to PASA part of these patients develops chronic psychotic disorders for reasons that still insufficently known.ObjectivesThe aim of the study was to determine preventive potential of antipsychotics in the development of chronic psychotic disorders as well as possible side effects of theur use.MethodsThe prospective retrospective qualitative study conducted in the period Septmeber 2017-September 2022.Data from medical records and electronic databases were used in the study.A structured questionnare for conductin research,a clinnical psychatic inteview,MMPI 202,tests to determine of ilegal PAS in body flluids.ResultsAccording to the results of the study adequate treatment of the underlying desease,fewer or complete abscence of relapses,social and psychoteraapeutic support had the greater effects.In the group of opiate addicts an adequate dose of supstitution therapy it often played a crucial role.ConclusionsIn experimental conditions the hypotesis about the preventive effect of antipsychotics on the development of psychotic disorders in peoplle addicted to PAS.On the contrary a whole series of new questions has beenopened.Disclosure of InterestNone Declared

Relationship between the Polymorphism of the AKT1 Gene and the Consumption of Cannabis in the Appearance of Psychosis

Introduction: Psychotic disorders are a mental illness that affect 3% of the world’s population. The external (cannabis) and internal vulnerability factors (polymorphisms of the AKT1 gene, the COMT gene and the DAT1 gene) acquire special relevance in the appearance of psychosis; this is known as the vulnerability–stress model. Objective: To analyze the scientific evidence that reflects the relationship between the polymorphism of the AKT1 gene and the consumption of cannabis in the appearance of psychosis. Material and Methods: The bibliographic search was made using databases such as Scopus, WoS, Cochrane Library, TRIP Database, PubPsych and PubMed. The criteria of the “MeSH” terminology and the inclusion and exclusion criteria were followed, obtaining a total of 22 articles that comprises this narrative review. Results: The presence of genetic variation in the locus rs2494732 of the AKT1 gene in a cannabis user raises the risk of the appearance of psychosis, especially if homozygous with the C allele. Likewise, consumption entails a slowdown in the functionality of the AKT1 gene, releasing a greater amount of dopamine in the striatum through the involvement of indirect mechanisms. Similarly, the COMT gene and the interaction of the AKT1 gene with the DAT1 gene raise the risk of developing psychotic disorder. Conclusion: The genetic polymorphism rs2494732 of AKT1 is the main factor responsible for the appearance of psychosis, although polymorphisms of the COMT and DAT1 gene are also implicated. Regarding the AKT1 gene, subjects with two copies of the C allele have a higher risk of developing psychosis compared to subjects with two copies of the T allele. It should also be noted that the muscarinic receptors rs115455482 and rx74722579 are related to a greater vulnerability to psychosis and the development of psychotic disorders.

The influence of childhood aspirations on the risk of developing psychotic disorders, substance use disorders, and dual diagnosis in adulthood based on the Metropolit 1953 Danish Male Birth Cohort.

Thestudy aims to investigate the association of aspiration for future occupation, socioeconomic position, and intellectual abilities with risk of dual diagnosis, psychosis, substance use disorder (SUD) in later life, and to explore if social and intellectual disadvantage modify any effect of childhood aspirations on outcomes. The study included 7177 Danish boys born in 1953. We investigated childhood aspirations (preference regarding future occupation), socioeconomic position (paternal social group), and intellectual abilities (Härnquist intelligence score) on outcomes with dual diagnosis, psychotic disorder, or SUD in Danish registers. Combinations of variables were used for a two-way and three-way analysis (high and low levels of exposure variables). Cox regression with age as the underlying time scale was used for analysis. The separate analysis showed no associations between childhood aspirations and outcomes. Boys with low intelligence scores had an increased risk of developing psychotic disorders (aHR 1.5, 95% CI 1.1-2.1) and SUD (aHR 1.8, 95% CI 1.5-2.1) compared to high intelligence scores. The interaction analyses showed that individuals with a combination of low intelligence score, high aspirations, and/or high paternal social group might have an increased risk of developing dual diagnosis, psychotic disorders, or SUD in later life. This result should be interpreted with caution as interaction variables were not overall significant with the outcome of dual diagnosis or psychotic disorder. The findings suggest that childhood abilities and social position could be associated with the development of psychotic disorders and SUD in later life, however, further studies are needed to address the temporality of the association to gain an understanding of the underlying mechanism of the association.

The association between social deprivation and the rate of identification of individuals at Ultra-High Risk for psychosis and transition to psychosis.

There is a higher incidence of psychotic disorders in neighbourhoods of greater social deprivation. However, it is not known whether this represents a causal relationship, as the stage at which social deprivation exerts its influence on the development of psychotic disorders is yet to be elucidated. We aimed to investigate the association between neighbourhood-level social deprivation and the rate of identification of individuals at Ultra-High Risk for psychosis (UHR), as well as the risk of transition to psychosis in UHR individuals. The cohort included all young people aged 15 to 24 identified as UHR attending an Early Intervention clinic in northwestern Melbourne over a 5-year period (2012-2016). Australian census data were used to obtain the at-risk population and social deprivation information according to the postcode of residence. Levels of social deprivation were arranged into quartiles. Poisson regression was used to calculate rate ratios and Cox regression analysis determined hazard ratios. Of the 461 young people identified as UHR, 11.1% (n = 49) lived in the most affluent neighbourhoods (Quartile 1) compared to 36.7% (n = 162) in the most deprived neighbourhoods (Quartile 4). There was a 35% higher rate of identification of young people who were UHR from the most deprived neighbourhoods (aIRR = 1.35, 95% CI [0.98, 1.86]). Over a median follow-up of approximately 10 months (308 days (IQR: 188-557), 17.5% (n = 77) were known to have transitioned to a full-threshold psychotic disorder. Residing in a neighbourhood of above average deprivation had a hazard ratio of 2.05 (95% CI [0.88, 4.80]) for risk of transition, when controlling for age, sex and substance use. These findings provide more support that EI services should be funded as per the expected incidence of psychotic disorders.

Dynamics of ideas about the concept of epileptic psychosis

Introduction: psychosis in epilepsy is more common than in the general population. The frequency of psychotic mental disorders varies from 0,5% to 10%. The article presents the dynamics of the development of the concept of epileptic psychosis, depending on the evolutionary approaches to the study of the problem of mental disorders in epilepsy. Materials and methods: the analysis of Russian—and English language articles in scientific databases on keywords from 1971 to 2011 was carried out. Results: the first systematic descriptions of mental disorders occurring in epilepsy date back to the 19th century. The contribution of foreign and domestic authors to the study of the problem is described. There are six main periods of the concept formation, including the definitions of the concept of epileptic psychosis, the dynamics of clinical manifestations, the role of the influence of biological, personal and social factors in the genesis and development of psychotic disorders in epilepsy. The following risk factors for the development of psychosis are considered: the form of epilepsy; age of onset of seizures, lateralization of the epileptic focus, gender, and drug therapy. Variants of classification approaches to the problem are presented. The article discusses the differences in the systematization of «endoform» syndromes, as well as the parallels between schizophrenia and psychoses in epilepsy. The dynamics of scientific views on the interest in the formation of epileptic psychoses in various parts of the brain: the temporal lobe (amygdala, hippocampus, paralimbic zones and parahippocampal bend), as well as GABA-ergic neurons of the upper tubercles of the quadriplegic, posterior hypothalamus and serotonergic neurons of the dorsal suture and noradrenergic neurons of the blue spot are reflected. The association of psychopathological manifestations with neurophysiological, biochemical, genetic and morphofunctional correlates is noted. The authors‘ interest in psychoses associated with the use of antiepileptic drugs is emphasized. Conclusion: despite all attempts to systematize these conditions, the factors that provoke the development of psychoses in patients with epilepsy, their structure and prognosis remain poorly predictable and require further in-depth study.

Early Detection and Prevention of Schizophrenic Psychosis-A Review.

Psychotic disorders often run a chronic course and are associated with a considerable emotional and social impact for patients and their relatives. Therefore, early recognition, combined with the possibility of preventive intervention, is urgently warranted since the duration of untreated psychosis (DUP) significantly determines the further course of the disease. In addition to established diagnostic tools, neurobiological factors in the development of schizophrenic psychoses are increasingly being investigated. It is shown that numerous molecular alterations already exist before the clinical onset of the disease. As schizophrenic psychoses are not elicited by a single mutation in the deoxyribonucleic acid (DNA) sequence, epigenetics likely constitute the missing link between environmental influences and disease development and could potentially serve as a biomarker. The results from transcriptomic and proteomic studies point to a dysregulated immune system, likely evoked by epigenetic alterations. Despite the increasing knowledge of the neurobiological mechanisms involved in the development of psychotic disorders, further research efforts with large population-based study designs are needed to identify suitable biomarkers. In conclusion, a combination of blood examinations, functional imaging techniques, electroencephalography (EEG) investigations and polygenic risk scores should be considered as the basis for predicting how subjects will transition into manifest psychosis.

Stimulant treatment effectiveness, safety and risk for psychosis in individuals with 22q11.2 deletion syndrome.

This study aimed to retrospectively evaluate an association between stimulant treatment for attention-deficit/hyperactivity disorder (ADHD) in individuals with 22q11.2DS and the development of psychotic disorders, to evaluate long-term effectiveness and safety of stimulant treatment in individuals with 22q11.2DS compared to individuals with idiopathic ADHD, and to explore effects of catechol-O-methyltransferase (COMT) genotype on 22q11.2DS response to stimulants and risk of side effects. Rates of stimulant use and methylphenidate equivalent exposure were compared among individuals with 22q11.2DS, between 51 with psychotic disorders and a control group of 57 22q11.2DS without psychotic disorders, from Tel Aviv and Geneva. In addition, 44 individuals with 22q11.2DS and ADHD from Tel Aviv who initiated stimulants before age 18years were compared to a control group of 35 age- and sex-matched controls with idiopathic ADHD, for treatment effectiveness (Clinical Global Impression Scale-Improvement), and rates of side effects. Stimulant use history and methylphenidate equivalent exposure did not differ among individuals with 22q11.2DS, between those with and without psychotic disorders. The long-term retrospective follow-up (5.3 ± 4.1years) of stimulant-treated individuals with 22q11.2DS showed a higher rate of significant clinical improvement of ADHD symptoms, compared to idiopathic ADHD individuals (p = 0.013), and similar side effect rates. There was no effect of the COMT genotype on response to stimulants or on any side effects. This preliminary long-term retrospective analysis suggests that stimulant treatment in 22q11.2DS is apparently safe in terms of psychosis conversion and rates of side effects, and that it is effective in alleviating ADHD symptoms.

Связь между потреблением каннабиса и психозами – современный взгляд на проблему. Повествовательный обзор литературы

Cannabis continues to be the most widely used drug worldwide. Recently, there has been two trends in the field: a liberalization of cannabis-related legislation in a number of countries, as well as an increase in the content of the psychoactive component in cannabis plant – tetrahydrocannabinol. The review covers a topic that has been little studied in Russian addiction science – cannabis use and associated psychotic disorders. Research materials: publications in the Pubmed and RSCI databases. Topics addressed include: cannabis use and psychotic disorders; alternative views on the causal relationship between cannabis use and psychotic disorders; gender specifics in the development of psychotic disorders; genetic predisposition to the development of psychotic disorders in cannabis users; problems with cannabis use in adolescence; possible reasons for using cannabis; suicidal behavior of cannabis users; relationship between cannabis and tobacco use; clinical aspects of treating cannabis users with psychotic disorders; promising areas of future studies. In the absence of domestic research on these topics, such a brief review may help addiction doctors to get a general idea of the modern state of the problem.

Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 2

Introduction: at the end of the last century, the macrophage-T-lymphocyte theory of the development of mental disorders was formulated. It underlines the important role of monocytes/macrophages and cytokines produced by them in the pathogenesis of schizophrenia, bipolar affective disorder (BAD) and depression. The first part of our review is dedicated to the analysis of the mechanisms of cellular and molecular interactions of activated monocytes/macrophages synthesizing proinflammatory CD16 receptors with endothelial cells, platelets, and microglia cells in the pathogenesis of systemic immune inflammation, including CNS as a result of violation of the integrity of the blood-brain barrier (BBB), activate microglia and cause the development of neuroinflammation in patients.The aim of work: to analyze and summarize the results of the main scientific publications for the role of cell-molecular mechanisms of the monocyte-macrophage immunity link activation in the pathogenesis of schizophrenia, BAD and depression. Material and methods: keywords “proinflammatory monocytes, cytokines, chemokines, molecules of cell adhesion, microglia, neuroinflammation, mental disorders” were used to search for data published over the past 20 years in domestic and foreign studies in PubMed, eLIBRARY, Science direct and EMBASE.Conclusion: the present review is dedicated to the analysis of the latest research data concerning an increase in the number of active circulating monocytes/macrophages and an increased level of proinflammatory cytokines, chemokines and receptors for them produced by monocytes in patients with schizophrenia, BAD and depression, what allows to associate these disorders with systemic immune inflammation. The data reasearches on cellular and molecular mechanisms of proinflammatory monocytes/macrophages interaction with microglia cells that initiate neuroinflammation in the CNS and lead to destabilization of brain function and the development of psychotic disorders are presented. The association of high levels of proinflammatory cytokines with somatic comorbidity, including metabolic syndrome, diabetes, atherosclerosis and other systemic diseases is shown in patients with mental disorders.Findings: the presented review of the research data allows us to better understand the cellular and molecular aspects of activation of the monocyte-macrophage immunity link in the development of neuroinflammation and cognitive decline in the pathogenesis of mental disorders, as well as helps in the search for informative biomarkers of the positive treatment of these disorders and the new approaches in the treatment of patients, based on the complex use of psychotropic and anti-inflammatory drugs.

Xiaoyaosan regulates depression-related behaviors with physical symptoms by modulating Orexin A/OxR1 in the hypothalamus.

The functional regulation of the orexin system in the central nervous system is closely related to the occurrence and development of psychotic disorders. Abnormal changes in the lateral region of the hypothalamus are associated with the comorbidity of depression and physical symptoms, and how the traditional Chinese formula Xiaoyaosan regulates these changes may reveal aspects of the pathogenesis of depression. This study aimed to establish a rat model of depression in order to examine changes in Orexin A/OxR1 expression in the lateral region of the hypothalamus and the effects of Xiaoyaosan. Sixty specific pathogen-free (SPF) male healthy Sprague-Dawley (SD) rats were used in the experiment and randomly divided into the control group, the model group, the Xiaoyaosan group and the fluoxetine group. The depression model was established by 21-day chronic immobilization stress (CIS). Food intake and body weight were recorded, and the sucrose preference test (SPT) and open field test (OFT) were used to evaluate the model. Then, the expression of Orexin A/OxR1 in the hypothalamus was measured by ELISA, Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression of Orexin A and OxR1 in the lateral hypothalamic area was significantly down regulated in the model group, compared with the control group. Xiaoyaosan significantly reversed these changes with obvious curative effects. Abnormal changes in Orexin A/OxR1 in the lateral hypothalamic area of rats with depression caused by chronic stress are closely related to the pathogenesis of depression accompanied by physical symptoms. Xiaoyaosan can improve depression accompanied by physical symptoms by regulating Orexin A/OxR1.

Implementation of a collaborative smoking cessation referral process in a psychiatric setting

Abstract Background Tobacco use is more prevalent in persons with psychotic disorders than in the United States adult population. Tobacco use is associated with an increased risk for the development of psychotic disorders. Tobacco also alters medication pharmacodynamics increasing the likelihood of non-therapeutic doses. Tobacco treatment specialists (TTS) are healthcare personnel trained to counsel patients on smoking cessation. Purpose The aim of the quality improvement project was to create a standardized smoking cessation referral process for inpatients and outpatients at Vanderbilt Psychiatric Hospital and educate about available TTS resources. Method A patient list was created and select providers were granted access to add patients to the list. Pre-intervention and post-intervention questionnaires allowed for analysis of provider tendencies and opinions. Results The pre-intervention questionnaire indicated providers were unfamiliar with TTS availability. After provider education on TTS and implementation of the referral process, 69 patients were referred in 16 weeks. Provider familiarity with TTS and listing of “smoking” on the problem list increased, though there was no statistically significant change in provider view of smoking cessation importance. Conclusions The standardized referral process was successful in increasing referrals to TTS and was more effective in the inpatient setting than the outpatient setting. Continued education on smoking cessation resources is required.

Migrant status and identification as ultra-high risk for psychosis and transitioning to a psychotic disorder.

Certain migrant groups are more likely to develop a psychotic disorder compared to the native-born populations, and a younger age at migration is associated with greater risk. However, it is not known at which stage migration has an effect on the development of psychotic disorders. We examined whether migrants were more likely to be identified as ultra-high risk for psychosis (UHR) compared to native-born young people and whether migrant status was associated with the risk of transition to a full-threshold psychotic disorder. The cohort included all young people aged 15-24 who were identified as UHR at a specialist clinic over a five-year period (2012-16). Australian census data were used to obtain the at-risk population. Poisson regression was used to calculate rate ratios and Cox regression analysis determined hazard ratios. 467 young people were identified as UHR, of which 13.5% (n=63) were born overseas. First-generation migrants were 2.6-fold less likely to be identified as UHR compared to Australian-born young people (IRR=0.39, 95% CI [0.30, 0.51], P<0.001). There was no difference between migrant and native-born young people in their risk of transitioning to a psychotic disorder (HR=0.90, 95% CI [0.39, 2.08], P=0.81). UHR first-generation migrants may be under-accessing mental health services.

Uncharted Waters: Treating Trauma Symptoms in the Context of Early Psychosis.

Psychosis is conceptualized in a neurodevelopmental vulnerability-stress framework, and childhood trauma is one environmental factor that can lead to psychotic symptoms and the development of psychotic disorders. Higher rates of trauma are associated with higher psychosis risk and greater symptom frequency and severity, resulting in increased hospitalization rates and demand on outpatient primary care and mental health services. Despite an estimated 70% of individuals in the early stages of psychosis reporting a history of experiencing traumatic events, trauma effects (post-traumatic anxiety or depressive symptoms) are often overlooked in psychosis treatment and current interventions typically do not target commonly comorbid post-traumatic stress symptoms. We presented a protocol for Trauma-Integrated Cognitive Behavioral Therapy for Psychosis (TI-CBTp), an approach to treating post-traumatic stress symptoms in the context of early psychosis care. We provided a brief summary of TI-CBTp as implemented in the context of Coordinated Specialty Care and presented preliminary data supporting the use of TI-CBTp in early psychosis care. The preliminary results suggest that individuals with comorbid psychosis and post-traumatic stress symptoms can be appropriately and safely treated using TI-CBTp within Coordinated Specialty Care.

Autoimmune Diseases and Psychotic Disorders.

The notion of immunological pathways playing a role in the etiology of a subset of psychotic disorders has received increased interest in the last decades. One of the findings that has spiked interest herein, is an apparent link between autoimmune diseases and psychotic disorders. This is supported by genetic findings associating immune-related genetic markers with schizophrenia and clinical studies finding increased levels of inflammatory markers in patients with psychosis. Several large-scale epidemiologic studies have found positive associations between autoimmune diseases and psychosis. Particularly, autoimmune diseases as multiple sclerosis and lupus are known to have higher frequencies of neuropsychiatric symptoms, including psychosis, compared to healthy controls. Cross sectional studies have found higher prevalence of psychiatric diagnoses among those with autoimmune diseases, and longitudinal studies have shown bidirectional associations between several autoimmune diseases and increased risks associated with schizophrenia. Moreover, a family history of autoimmune diseases has been shown to be associated with an increased risk of psychotic disorders and vice versa. In this review we will summarize the epidemiologic evidence on associations between autoimmune diseases and psychosis. Possible mechanisms accountable for the association will be discussed, amongst others the probable role of shared genetic risk factors, the impact of infections on both autoimmunity and the development of psychotic disorders, and the potential role of the microbiome. We discuss the findings on and influence of autoantibodies and dysregulation of T- and B-cells in both disease categories, and why further research hereon is needed. In addition to the potential importance of autoimmunity in etiological mechanisms of psychotic disorders, the association also brings important attention to somatic comorbidity in patients with psychotic disorders.

Attention deficit hyperactivity disorder symptoms as antecedents of later psychotic outcomes in 22q11.2 deletion syndrome

Individuals with 22q11.2 Deletion Syndrome (22q11.2DS) are at substantially heightened risk for psychosis. Thus, prevention and early intervention strategies that target the antecedents of psychosis in this high-risk group are a clinical priority. Attention Deficit Hyperactivity Disorder (ADHD) is one the most prevalent psychiatric disorders in children with 22q11.2DS, particularly the inattentive subtype. The aim of this study was to test the hypothesis that ADHD inattention symptoms predict later psychotic symptoms and/or psychotic disorder in those with 22q11.2DS. 250 children and adolescents with 22q11.2DS without psychotic symptoms at baseline took part in a longitudinal study. Assessments were performed using well-validated structured diagnostic instruments at two time points (T1 (mean age = 11.2, SD = 3.1) and T2 (mean age = 14.3, SD = 3.6)). Inattention symptoms at T1 were associated with development of psychotic symptoms at T2 (OR:1.2, p = 0.01) but weak associations were found with development of psychotic disorder (OR:1.2, p = 0.15). ADHD diagnosis at T1 was strongly associated with development of psychotic symptoms at T2 (OR:4.5, p < 0.001) and psychotic disorder (OR:5.9, p = 0.02). Our findings that inattention symptoms and the diagnosis of ADHD are associated with subsequent psychotic outcomes in 22q11.2DS have important clinical implications. Future studies examining the effects of stimulant and other ADHD treatments on individuals with 22q11.2DS are warranted.

Decreased use of active coping styles contributes to elevated allostatic load index in first-episode psychosis

Accumulating evidence indicates that stress plays an important role in the development of psychotic disorders. Recent studies have revealed that patients with first-episode psychosis (FEP) present systemic biological dysregulations related to stress-exposure in terms of elevated allostatic load (AL) index. However, the mechanisms underlying this observation remain unknown. Therefore, in this study we aimed to investigate the AL index with respect to stress coping strategies in 36 FEP patients and 31 matched controls. We found significantly higher AL index in FEP patients compared to controls after co-varying for potential confounding factors. Patients with FEP were less likely to use active and task-focused coping. Lower odds of using these coping styles, planning as well as positive reinterpretation and growth were related to higher AL index in FEP patients, but not in controls. Depressive symptoms were associated with lower likelihood of using task-focused coping as well as positive reinterpretation and growth. Additionally, depressive symptoms were related to higher AL index. Finally, depressive symptoms mediated the effects of task-focused coping as well as positive reinterpretation and growth on the AL index. Our results confirm systemic biological dysregulation indexed as AL in FEP patients. Lower odds of using active coping styles might contribute to higher AL index via the mediating effect of depressive symptoms in patients with FEP. Longitudinal studies are required to establish causal inferences between coping styles, depressive symptoms and the AL index in early psychosis.

Interaction between childhood adversity and functional polymorphisms in the dopamine pathway on first-episode psychosis

BackgroundThere is consistent evidence of a cumulative relationship between childhood adversity and psychosis, with number of adversities experienced increasing the probability of psychosis onset. It is possible that genetic factors moderate the association between childhood adversity and psychosis, potentially by influencing how an individual reacts biologically and/or psychologically following exposure to adversity, in such a way as to set them off on the path to psychosis. However, identifying the specific genetic variants involved and how they interact with childhood adversity remains challenging. We examined whether the association between cumulative exposure to childhood adversity and development of psychotic disorder was moderated by the COMT Val158Met, AKT1 rs2494732 or DRD2 rs1076560 polymorphisms, known to affect dopamine levels. MethodsParticipants were 285 first-presentation psychosis cases and 256 geographically-matched controls drawn from the Genetics and Psychosis (GAP) study. Childhood adversity was assessed using the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and blood- and cheek-derived genotype data were collected. ResultsOur findings revealed no main effect of COMT Val158Met, AKT1 rs2494732 and DRD2 rs1076560 polymorphisms on psychosis case status or reports of childhood adversity. Individuals reporting a history of multiple adversities were more likely to be psychosis patients than controls, regardless of their genetic risk. There was no evidence of candidate genotype by childhood adversity interactions in relation to psychosis onset. ConclusionThese findings did not provide evidence of a possible role of COMT Val158Met, AKT1 rs2494732 or DRD2 rs1076560 genotypes in modifying the association between childhood adversity and onset of psychosis.