Risk For Psychosis Research Articles

COVID-19 and New-Onset Psychosis: A Comprehensive Review.

Psychosis is a multifactorial condition that typically involves delusions, hallucinations, and disorganized thought, speech or behavior. The observation of an association between infectious epidemics and acute psychosis dates back to the last century. Recently, concerns have been expressed regarding COVID-19 and the risk for the development of new-onset psychosis. This article reviewed the current evidence of a possible link between SARS-CoV-2 and risk of psychosis as an acute or post-infectious manifestation of COVID-19. We here discuss potential neurobiological and environmental factors as well as a number of challenges in ascribing a causal pathogenic relationship between SARS-CoV-2 infection and new-onset psychosis.

Negative Symptom Trajectories in Individuals at Clinical High Risk for Psychosis: Differences Based on Deficit Syndrome, Persistence, and Transition Status.

Negative symptom trajectory in clinical high risk (CHR) for psychosis is ill defined. This study aimed to better characterize longitudinal patterns of change in negative symptoms, moderators of change, and differences in trajectories according to clinical subgroups. We hypothesized that negative symptom course will be nonlinear in CHR. Clinical subgroups known to be more severe variants of psychotic illness-deficit syndrome (DS), persistent negative syndrome (PNS), and acute psychosis onset-were expected to show more severe baseline symptoms, slower rates of change, and less stable rates of symptom resolution. Linear, curvilinear, and stepwise growth curve models, with and without moderators, were fitted to negative symptom ratings from the NAPLS-3 CHR dataset (N = 699) and within clinical subgroups. Negative symptoms followed a downward curvilinear trend, with marked improvement 0-6 months that subsequently stabilized (6-24 months), particularly among those with lower IQ and functioning. Clinical subgroups had higher baseline ratings, but distinct symptom courses; DS vs non-DS: more rapid initial improvement, similar stability of improvements; PNS vs non-PNS: similar rates of initial improvement and stability; transition vs no transition: slower rate of initial improvement, with greater stability of this rate. Continuous, frequent monitoring of negative symptoms in CHR is justified by 2 important study implications: (1) The initial 6 months of CHR program enrollment may be a key window for improving negative symptoms as less improvement is likely afterwards, (2) Early identification of clinical subgroups may inform distinct negative symptom trajectories and treatment needs.

Can we interrogate public databases to fill critical gaps in mental health epidemiology? Testing the association between cannabis and psychosis in the UK as an example.

The psychoactive properties of cannabis have been known forever. Since 1987, several prospective studies have suggested an increased risk of psychosis among cannabis users, with alternative explanations failing to account for such an effect. A cause-effect relationship has thus been implied. Further evidence has indicated that there is a dose-response relationship, and high-potency cannabis varieties confer the greatest risk of psychosis. As cannabis use has become more common over the last decades, one would expect a related increase in the number of schizophrenia cases. However, evidence in this regard remains equivocal for several reasons, including relying on databases that are not primarily designed to address such question and the issue that solid information regarding the incidence of schizophrenia is a relatively recent acquisition. Recent years have seen the development of online web publications, such as Google Trends and "Our World in Data", where data are explorable and interactable for tracking and comparing trends over specific periods and world regions. By using such databases, we believe that the question whether changes in cannabis use are associated with changes in schizophrenia rates can be answered, at least partly. Therefore, we tested these tools by evaluating trends in cannabis use and both cases and prevalence of schizophrenia in the United Kingdom, one of the countries where the incident rates for psychotic disorder have been suggested to be particularly increased by cannabis consumption. Crossing data from these tools revealed that interest in cannabis has been growing at the country level for over 10 years, with a parallel overlapping raise in psychosis cases and prevalence. Following up on this example, let us think of how many public health opportunities these public resources may offer. The question now is whether public health interventions for the benefit of the general population will follow suit.

Adherence to mediterranean diet in children and adolescents at psychosis risk and transition to psychosis: the capris study

Adherence to mediterranean diet in children and adolescents at psychosis risk and transition to psychosis: the capris study

Linguistic markers and basic self-disturbances among adolescents at risk of psychosis. A qualitative study.

Language impairments are key features of schizophrenia spectrum disorders, and have also been suggested to signal enhanced psychosis risk. Incoherence, derailment, and monotonous speaking are however closely related to psychosis onset, and thus not very early markers. Recent phenomenologic-psychiatric studies claim that basic self-disturbance (BSD) may represent more useful early markers. We searched for distinctive irregular linguistics of 30 CHR outpatient adolescents, aged 12-18 years. Standard instruments established psychosis risk and BSD. Participants chose three personal and well manifested BSD phenomena. Ninety verbatim statements were analyzed and grouped into higher order clusters of linguistic irregularities. We identified five clusters of irregular language features: distinctive words, describing an atmosphere of unreality; irregular use of prepositions, indicating experiential detachment; shifts of personal pronouns, indicating identity confusion; near-literal use of metaphors and conjunctions indicating existential insecurity, and idiosyncratic use of adjectives indicating perceptual transcendence. The adolescents provided naturalistic descriptions of experiences that were markedly twisted and almost ineffable. This unique irregular "BSD -language" was highly meaningful in its proper context, expressing informative characteristics of first-personal experiential alterations, essential for early detection. The features may additionally represent precursors of psychosis transition, useful for clinical decision-making. Foundation Dam, Oslo, Norway (Grant Number 2017/FO143368).

Hippocampal Glutamate, Resting Perfusion and the Effects of Cannabidiol in Psychosis Risk.

Preclinical and human data suggest that psychosis onset involves hippocampal glutamatergic dysfunction, driving hyperactivity and hyperperfusion in a hippocampal-midbrain-striatal circuit. Whether glutamatergic dysfunction is related to cerebral perfusion in patients at clinical high risk (CHR) for psychosis, and whether cannabidiol (CBD) has ameliorative effects on glutamate or its relationship with perfusion remains unknown. Using a double-blind, parallel-group design, 33 CHR patients were randomized to a single 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Proton magnetic resonance spectroscopy was used to measure glutamate concentrations in left hippocampus. We examined differences relating to CHR status (controls vs placebo), effects of CBD (placebo vs CBD), and linear between-group effects, such that placebo>CBD>controls or controls>CBD>placebo. We also examined group × glutamate × cerebral perfusion (measured using Arterial Spin Labeling) interactions. Compared to controls, CHR-placebo patients had significantly lower hippocampal glutamate (P =.015) and a significant linear relationship was observed across groups, such that glutamate was highest in controls, lowest in CHR-placebo, and intermediate in CHR-CBD (P =.031). Moreover, there was a significant interaction between group (controls vs CHR-placebo), hippocampal glutamate, and perfusion in the putamen and insula (P FWE =.012), with a strong positive correlation in CHR-placebo vs a negative correlation in controls. Our findings suggest that hippocampal glutamate is lower in CHR patients and may be partially normalized by a single dose of CBD. Furthermore, we provide the first in vivo evidence of an abnormal relationship between hippocampal glutamate and perfusion in the striatum and insula in CHR.

Juvenile depression as at-risk state for psychotic disorders

To establish the risk of psychotic disorders in juvenile depression and to study the role of negative symptoms in its formation. Seventy-four in-patients (19.6±2.3 years old), who were hospitalized for the first time in the clinic for a depressive episode, were examined. Psychometric scales HDRS, SOPS, SANS were used. The risk of manifestation of psychotic disorders was established in the presence of attenuated positive symptoms (APS) with values of at least one of the points P1, P2, P3 and P4 of the corresponding SOPS subscale more or equal to 3. The overall risk of schizophrenia spectrum disorders was established in the presence of attenuated negative symptoms (ANS) with values of at least one of the points H1-H6 of the negative SOPS subscale is more than or equal to 5. Statistical analysis was carried out using the Statistica 12 program. During the psychometric assessment of patients at admission, four groups were identified based on the presence of APS and ANS: group 1 (APS+ANS), group 2 (APS), group 3 (ANS) and a comparison group without APS/ANS. It was found that the presence of APS and ANS in the structure of depression increased its severity (U=109.0; p=0.009). Assessment of the ANS severity on the negative subscale of SOPS and on the SANS demonstrated quantitative differences with the highest representation of negative symptoms in the corresponding groups (APS+ANS and ANS) with significant differences in total scores in the comparison group (U=93.0; p=0.004 and U=85.0; p=0.002). When studying the structure of negative symptoms according to the SANS subscales, patients with APS differed in a lower degree of severity of negative symptoms only according to the «Avolition-Apathy» subscale (U=141.5; p=0.028). Patients from the comparison group, despite significant differences in other psychopathological symptoms, showed lower values only for the SANS subscales «Affective flattening» (U=112.0; p=0.02) and, to a greater extent, «Avolition-Apathy» (U=84.0; p=0.002). Based on the presence of prodromal symptoms in the structure of juvenile depression and their dynamics during therapy, one can assume not only a different degree of risk of endogenous psychoses, but also their nosological affiliation.

Polygenic risk scores for psychiatric disorders in children and adolescents with high risk and first episode for psychosis

Polygenic risk scores for psychiatric disorders in children and adolescents with high risk and first episode for psychosis

Development and Validation of Predictive Model for a Diagnosis of First Episode Psychosis Using the Multinational EU-GEI Case-control Study and Modern Statistical Learning Methods.

It is argued that availability of diagnostic models will facilitate a more rapid identification of individuals who are at a higher risk of first episode psychosis (FEP). Therefore, we developed, evaluated, and validated a diagnostic risk estimation model to classify individual with FEP and controls across six countries. We used data from a large multi-center study encompassing 2627 phenotypically well-defined participants (aged 18-64 years) recruited from six countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions study. To build the diagnostic model and identify which of important factors for estimating an individual risk of FEP, we applied a binary logistic model with regularization by the least absolute shrinkage and selection operator. The model was validated employing the internal-external cross-validation approach. The model performance was assessed with the area under the receiver operating characteristic curve (AUROC), calibration, sensitivity, and specificity. Having included preselected 22 predictor variables, the model was able to discriminate adults with FEP and controls with high accuracy across all six countries (rangesAUROC = 0.84-0.86). Specificity (range = 73.9-78.0%) and sensitivity (range = 75.6-79.3%) were equally good, cumulatively indicating an excellent model accuracy; though, calibration slope for the diagnostic model showed a presence of some overfitting when applied specifically to participants from France, the UK, and The Netherlands. The new FEP model achieved a good discrimination and good calibration across six countries with different ethnic contributions supporting its robustness and good generalizability.

Patient-Reported Outcome Measures in Clinical High Risk for Psychosis: A Systematic Review.

A key issue in both research and clinical work with youth at clinical high risk (CHR) of psychosis is that there are clearly heterogenous clinical outcomes in addition to the development of psychosis. Thus, it is important to capture the psychopathologic outcomes of the CHR group and develop a core outcomes assessment set that may help in dissecting the heterogeneity and aid progress toward new treatments. In assessing psychopathology and often poor social and role functioning, we may be missing the important perspectives of the CHR individuals themselves. It is important to consider the perspectives of youth at CHR by using patient-reported outcome measures (PROMs). This systematic review of PROMs in CHR was conducted based on a comprehensive search of several databases and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Sixty-four publications were included in the review examining PROMs for symptoms, functioning, quality of life, self-perceptions, stress, and resilience. Typically, PROMs were not the primary focus of the studies reviewed. The PROMs summarized here fit with results published elsewhere in the literature based on interviewer measures. However, very few of the measures used were validated for CHR or for youth. There are several recommendations for determining a core set of PROMs for use with CHR.

The Role of Cannabis in the Development of Psychosis.

Cannabis is known to cause psychotic disorders, and the increasing use of cannabis constitutes an important health problem. Growing evidence that cannabis causes the development of psychosis has led to an increase in the number of studies in this field. This review aims to clarify the role of cannabis use in the development of psychosis, discuss the current literature about the underlying neurobiological mechanisms. For this purpose PubMed was searched for the keywords "cannabis use, psychosis, schizophrenia, endocannabinoid system, pathophysiology, neurobiology"; the articles published in the last 10 years were reviewed. Epidemiological studies showed that cannabis use starting at an earlier age is associated with an increased risk of psychosis, this risk is more pronounced in people with genetic predisposition and increases with heavy and high potency cannabis use. Studies showed that the endocannabinoid system, which plays a role in nervous system development and functions as a homeostatic regulator in physiological processes, is affected by cannabis use during critical periods of development like adolescence; cannabis use affects physiological processes such as synaptic pruning due to the effects of this system on neurotransmitters like glutamate and dopamine leading to long-term behavioral and psychological consequences. Additionally, evidence that dysfunctions in the endocannabinoid system play a role in the etiology of schizophrenia suggests that cannabis affects the disease process by worsening existing dysfunctions in this system. Understanding the relationship between cannabis use and the development of psychosis and underlying neurobiological mechanisms will help to identify new treatment targets, and develop appropriate preventive approaches. Keywords: Cannabis Abuse, Psychotic Disorders, Schizophrenia, Endocannabinoids, Neurobiology.

Structural features of the brain in individuals with youth depression at a clinical risk for psychosis

To establish the structural features of the brain (cortical and subcortical) in depressive patients at clinical risk for psychosis. Nineteen right-handed male patients with youth depression, who were assessed for high risk of psychotic manifestation, and 20 healthy controls underwent MRI and clinical examination. T1-weighted images were processed in FreeSurfer 7.1.1. For each subject average values for the cortex thickness and area, volumes of subcortical structures, and separately volumes of the amygdala nuclei were obtained. Intergroup comparisons and correlations with clinical scales (SOPS, HDRS) were calculated. Patients showed decreased gray matter thickness in the left (p=0.002) and right (p=0.003) postcentral gyri and increased thickness in the right posterior cingulate cortex (p=0.003) and rostral anterior cingulate cortex (p=0.001). These findings may reflect cortical changes at early stages of the psychotic process, including the gray matter loss in some areas and the opposite phenomena in others (it cannot be ruled out that the latter may be the result of altered ontogenesis and/or certain compensatory changes).

Using Transcranial Alternating Current Stimulation to enhance working memory in youths at genetic risk for psychosis

Using Transcranial Alternating Current Stimulation to enhance working memory in youths at genetic risk for psychosis

Lifetime cannabis use and childhood trauma associated with CNR1 genetic variants increase the risk of psychosis: findings from the STREAM study.

Gene-environment interactions increase the risk of psychosis. The objective of this study was to investigate gene-gene and gene-environment interactions in psychosis, including single nucleotide variants (SNVs) of dopamine-2 receptor (D2R), N-methyl-d-aspartate receptor (NMDAR), and cannabinoid receptor type 1 (CB1R), lifetime cannabis use, and childhood trauma. Twenty-three SNVs of genes encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898) were genotyped in 143 first-episode psychosis patients (FEPp) and 286 community-based controls by Illumina HumanCoreExome-24 BeadChip. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software. Single-locus analyses among the 23 SNVs for psychosis and gene-gene interactions were not significant (p > 0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p < 0.001). Moreover, gene-environment interactions were significant for an SNV in CNR1 and cannabis use. The best-performing model was the combination of CNR1 rs12720071 and lifetime cannabis use (p < 0.001), suggesting an increased risk of psychosis. Our study supports the hypothesis of gene-environment interactions for psychosis involving T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use.

Exposure to childhood trauma and social cognition in individuals at clinicial high risk for psychosis and first-episode psychoses

Exposure to childhood trauma and social cognition in individuals at clinicial high risk for psychosis and first-episode psychoses

Effects of cannabidiol on brain activation during verbal learning in individuals at clinical high risk for psychosis: an fMRI-MRS study

Effects of cannabidiol on brain activation during verbal learning in individuals at clinical high risk for psychosis: an fMRI-MRS study

Effect of diazepam on brain glutamatergic metabolites in individuals at clinical high risk for psychosis

Effect of diazepam on brain glutamatergic metabolites in individuals at clinical high risk for psychosis

Change in neurocognitive functioning in children and adolescents at clinical high risk for psychosis:a systematic review

Change in neurocognitive functioning in children and adolescents at clinical high risk for psychosis:a systematic review

The heterogeneity of attenuated and brief limited psychotic symptoms: association of contents with age, sex, country, religion, comorbidities, and functioning.

The Attenuated Psychosis Symptoms (APS) syndrome mostly represents the ultra-high-risk state of psychosis but, as does the Brief Intermittent Psychotic Symptoms (BIPS) syndrome, shows a large variance in conversion rates. This may be due to the heterogeneity of APS/BIPS that may be related to the effects of culture, sex, age, and other psychiatric morbidities. Thus, we investigated the different thematic contents of APS and their association with sex, age, country, religion, comorbidity, and functioning to gain a better understanding of the psychosis-risk syndrome. A sample of 232 clinical high-risk subjects according to the ultra-high risk and basic symptom criteria was recruited as part of a European study conducted in Germany, Italy, Switzerland, and Finland. Case vignettes, originally used for supervision of inclusion criteria, were investigated for APS/BIPS contents, which were compared for sex, age, country, religion, functioning, and comorbidities using chi-squared tests and regression analyses. We extracted 109 different contents, mainly of APS (96.8%): 63 delusional, 29 hallucinatory, and 17 speech-disorganized contents. Only 20 contents (18.3%) were present in at least 5% of the sample, with paranoid and referential ideas being the most frequent. Thirty-one (28.5%) contents, in particular, bizarre ideas and perceptual abnormalities, demonstrated an association with age, country, comorbidity, or functioning, with regression models of country and obsessive-compulsive disorders explaining most of the variance: 55.8 and 38.3%, respectively. Contents did not differ between religious groups. Psychosis-risk patients report a wide range of different contents of APS/BIPS, underlining the psychopathological heterogeneity of this group but also revealing a potential core set of contents. Compared to earlier reports on North-American samples, our maximum prevalence rates of contents were considerably lower; this likely being related to a stricter rating of APS/BIPS and cultural influences, in particular, higher schizotypy reported in North-America. The various associations of some APS/BIPS contents with country, age, comorbidities, and functioning might moderate their clinical severity and, consequently, the related risk for psychosis and/or persistent functional disability.

Risk factors for the development of psychotic disorders associated with synthetic cathinones usage

To identify risk factors and predictors of the development of psychotic disorders in patients who used synthetic cathinones (SKat). The study included 176 patients who used SKat, which was toxicologically confirmed. One hundred and eleven (63.1%) were male and 65 (36.9%) were female. The median age was 27 years (22-32 (Q1-Q3)). Patients were divided into main and control groups depending on the presence of a psychotic disorder. The main group (those who developed psychosis) consisted of 98 patients, the control groupincluded 78 participants. Clinical-psychopathological, parametric and statistical methods were performed to study predictors and risk factors for the development of psychotic disorders associated with the use of SKat. The study established factors influencing the incidence of psychosis. Older patients were more likely to develop psychosis (p=0.002). Patients who used SKat for more than 21 consecutive days developed psychoses more often (p=0.048). The use of α-pvp (α-pyrrolidinovalerophenone, alpha-pvp) more often led to the development of psychosis (p<0.001). Patients undergoing rehabilitation were less likely to experience the development of psychosis (p=0.009). The resulting regression model is statistically significant (p<0.001). Based on the value of the Nigelkirk coefficient of determination, the model explains 30.9% of the observed group variance. It has been established that the combination of the following factors increases the chances of developing psychosis: female gender, age, duration of daily use, the presence of signs of mental infantilism, fear of the dark in childhood. In turn, the experience of undergoing rehabilitation and any pathology of the mother's pregnancy reduces the risk of psychosis. The results are consistent with other studies of substance-induced psychoses. The observed patterns demonstrate that this is a special group of disorders that requires the attention of specialists. The results allow us to outline the field for further study, and may also be useful in the development of therapeutic and preventive recommendations.