First-episode Psychosis Participants Research Articles

Glutamatergic neurotransmission in schizophrenia: A systematic review and quantitative synthesis of proton magnetic resonance spectroscopy studies across schizophrenia spectrum disorders.

Studies using proton magnetic resonance spectroscopy reveal substantial inconsistencies in the levels of brain glutamate, glutamine and glutamate + glutamine across schizophrenia spectrum disorders. This systematic review employs qualitative and quantitative methods to analyse the patterns and relationships between glutamatergic metabolites, schizophrenia spectrum disorders and brain regions. A literature search was conducted using various databases with keywords including glutamate, glutamine, schizophrenia, psychosis and proton magnetic resonance spectroscopy. Inclusion criteria were limited to case-control studies that reported glutamatergic metabolite levels in adult patients with a schizophrenia spectrum disorder diagnosis - i.e. first-episode psychosis, schizophrenia, treatment-resistant schizophrenia and/or ultra-treatment-resistant schizophrenia - using proton magnetic resonance spectroscopy at 3 T or above. Pooled study data were synthesized and analysed. A total of 92 studies met the inclusion criteria, including 2721 healthy controls and 2822 schizophrenia spectrum disorder participants. Glu levels were higher in the basal ganglia, frontal cortex and medial prefrontal of first-episode psychosis participants, contrasting overall lower levels in schizophrenia participants. For Gln, strong differences in metabolite levels were evident in the basal ganglia, dorsolateral prefrontal cortex and frontal cortex, with first-episode psychosis showing significantly higher levels in the basal ganglia. In glutamate + glutamine, higher metabolite levels were found across schizophrenia spectrum disorder groups, particularly in the basal ganglia and dorsolateral prefrontal cortex of treatment-resistant schizophrenia participants. Significant relationships were found between metabolite levels and medication status, clinical measures and methodological variables. The review highlights abnormal glutamatergic metabolite levels throughout schizophrenia spectrum disorders and in specific brain regions. The review underscores the importance of standardized future research assessing glutamatergic metabolites using proton magnetic resonance spectroscopy due to considerable literature heterogeneity.

Diagnostic shift in first episode psychosis: Results from the 2-year follow-up of the “Parma Early Psychosis” program

PurposeAlthough the stability of current diagnostic criteria for people with First Episode Psychosis (FEP) is essential for treatment, it still remains poorly investigated. As its examination necessarily requires a prospective evaluation of diagnostic trajectories, the aims of the current longitudinal investigation were: (a) to assess diagnostic changes in an Italian FEP population treated within an “Early Intervention in Psychosis” service during a 2-year follow-up period, and (b) to identify potential sociodemographic and clinical moderators of diagnostic instability at entry. MethodsAll participants were FEP individuals, aged 12–35 years. Their primary diagnosis was formulated both at baseline and at the end of the follow-up. At entry, they also completed the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. As measure of diagnostic stability, the Kappa statistic was first calculated. The associations of diagnostic shift with baseline sociodemographic and clinical characteristics were then analyzed using a logistic model with the diagnostic change as dependent variable. Finally, a propensity score was calculated, based on logistic analysis results. Results221 (50.1 %) FEP participants changed their initial diagnosis. The highest prospective diagnostic stability was found for initial diagnosis of schizophrenia (93.9 %) and affective spectrum psychoses (92.4 %). Diagnostic instability was high for initial diagnosis of brief psychotic disorder (100 %), schizophreniform disorder (100 %) and psychotic disorder not otherwise specified (92.1 %). The best predictors of diagnostic change were previous contact with neuropsychiatry services, shorter duration of untreated psychosis and higher baseline levels of disorganization. ConclusionsDiagnostic stability is crucial for treatment and clinical decision making. Addressing instability in FEP diagnoses and detecting its moderators at entry are important challenges for future diagnostic development of early psychosis.

Borderline personality disorder vs. schizophrenia spectrum disorders in young people recruited within an "Early Intervention in Psychosis" service: clinical and outcome comparisons.

Borderline Personality Disorder (BPD) is under-recognized in First-Episode Psychosis (FEP) and its psychotic manifestations are difficult to differentiate from Schizophrenia Spectrum Disorders (SSD). The aim of this investigation was to compare clinical, sociodemographic, and outcome characteristics between FEP patients with BPD vs. FEP subjects with SSD both at baseline and across a 2-year follow-up period. Participants completed the Health of the Nation Outcome Scale (HoNOS), the Positive And Negative Syndrome Scale (PANSS), and the Global Assessment of Functioning (GAF) scale both at entry and every 12months during the follow-up. A mixed-design ANOVA model was conducted to investigate the temporal stability of clinical scores within and between the two subgroups. Among 356 FEP participants, 49 had a BPD diagnosis. Compared to FEP/SSD (n = 307), FEP/BPD patients showed higher prevalence of employment, current substance use, and past attempted suicide. They had a lower equivalent dose of antipsychotic medication at entry and lower levels of negative symptoms. Finally, they had a higher 2-year drop-out rate and a significant improvement in psychopathological scores limited to the first year of treatment. BPD as categorical entity represents a FEP subgroup with specific clinical challenges. Appropriate treatment guidelines for this FEP subgroup are thus needed.

Sociodemographic and clinical characteristics of patients with borderline personality disorder enrolled for a first episode psychosis within a specialized “early intervention” service

Borderline Personality Disorder (BPD) is under-recognized in First Episode Psychosis (FEP). The aims of this investigation were: (a) to examine the prevalence of BPD in FEP patients enrolled within an Italian “Early Intervention in Psychosis” (EIP) service; (2) to compare sociodemographic, clinical and treatment characteristics at entry between FEP individuals with and without BPD; and (3) to compare their drop-out rates along a 2-year follow-up period. BPD was assessed using the Structured Clinical Interview for DSM-IV axis II personality disorders. All participants also completed the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Forty-nine (9.6%) FEP participants showed a BPD diagnosis. FEP individuals with BPD had a higher baseline prevalence of substance misuse, a lower baseline equivalent dose of antipsychotic medication, lower baseline levels of negative symptoms, and higher baseline levels of anxious-depressive features. They also had a higher 2-year drop-out rate. In conclusion, BPD is present in 10% of FEP patients. This FEP subgroup has peculiar clinical challenges (e.g. high substance misuse at entry, high drop-out rate) and additional comorbidities (e.g. high levels of depressive symptoms at entry), which would require appropriate treatment guidelines.

A good life with psychosis: rate of positive outcomes in first-episode psychosis at 10-year follow-up.

More knowledge about positive outcomes for people with first-episode psychosis (FEP) is needed. An FEP 10-year follow-up study investigated the rate of personal recovery, emotional wellbeing, and clinical recovery in the total sample and between psychotic bipolar spectrum disorders (BD) and schizophrenia spectrum disorders (SZ); and how these positive outcomes overlap. FEP participants (n = 128) were re-assessed with structured clinical interviews at 10-year follow-up. Personal recovery was self-rated with the Questionnaire about the Process of Recovery-15-item scale (total score ⩾45). Emotional wellbeing was self-rated with the Life Satisfaction Scale (score ⩾5) and the Temporal Experience of Pleasure Scale (total score ⩾72). Clinical recovery was clinician-rated symptom-remission and adequate functioning (duration minimum 1 year). In FEP, rates of personal recovery (50.8%), life satisfaction (60.9%), and pleasure (57.5%) were higher than clinical recovery (33.6%). Despite lower rates of clinical recovery in SZ compared to BD, they had equal rates of personal recovery and emotional wellbeing. Personal recovery overlapped more with emotional wellbeing than with clinical recovery (χ2). Each participant was assigned to one of eight possible outcome groups depending on the combination of positive outcomes fulfilled. The eight groups collapsed into three equal-sized main outcome groups: 33.6% clinical recovery with personal recovery and/or emotional wellbeing; 34.4% personal recovery and/or emotional wellbeing only; and 32.0% none. In FEP, 68% had minimum one positive outcome after 10 years, suggesting a good life with psychosis. This knowledge must be shared to instill hope and underlines that subjective and objective positive outcomes must be assessed and targeted in treatment.

Exercise behaviours and motivation after a first psychotic episode: A digital intervention.

Research has demonstrated that participation in aerobic exercise can have significant beneficial effects across both physical and mental health domains for individuals who are in the early phase of schizophrenia. Despite these notable benefits of exercise, deficits in motivation and a lack of methods to increase engagement are significant barriers for exercise participation, limiting these potentially positive effects. Fortunately, digital health tools have the potential to improve adherence to an exercise program. The present study examined the role of motivation for exercise and the effects of an automated digital text messaging program on participation in an aerobic exercise program. A total of 46 first-episode psychosis participants from an ongoing 12-month randomized clinical trial (Enhancing Cognitive Training through Exercise Following a First Schizophrenia Episode (CT&E-RCT)) were included in an analysis to examine the efficacy of motivational text messaging. Personalized motivational text message reminders were sent to participants with the aim of increasing engagement in the exercise program. We found that participants with higher levels of intrinsic motivation to participate in a text messaging program and in an exercise intervention completed a higher proportion of individual, at-home exercise sessions. In a between groups analysis, participants who received motivational text messages, compared to those who did not, completed a higher proportion of at-home exercise sessions. These results indicate the importance of considering a person's level of motivation for exercise and the potential utility of using individualized and interactive mobile text messaging reminders to increase engagement in aerobic exercise in the early phase of psychosis. We emphasize the need for understanding how individualized patient preferences and needs interplay between intrinsic motivation and digital health interventions for young adults.

Peripheral and central biomarkers associated with inflammation in antipsychotic naïve first episode psychosis: Pilot studies

BackgroundElevated serum pro-inflammatory molecules have been reported in early psychosis. What is not known is whether peripheral inflammatory biomarkers are associated with CNS biomarkers. In the brain, release of pro-inflammatory molecules by microglial hyperactivity may lead to neuronal apoptosis seen in neurodegenerative disorders and account for loss of brain tissue observed in psychotic disorders. Neurochemical changes, including elevated glutamate levels, are also associated with neuroinflammation, present in early psychosis and change with antipsychotic treatment. MethodsAntipsychotic naïve patients with first episode psychosis (FEP) were studied as part of a collaborative project of neuroinflammation. In Study 1 we explored associations between plasma inflammatory molecules and neurometabolites in the dorsal caudate using magnetic resonance spectroscopy (1H-MRS) in N = 13 FEP participants. Study 2 examined the relationship between inflammatory molecules in the Plasma and CSF in N = 20 FEP participants. ResultsIn Study 1, the proinflammatory chemokine MDC/CCL22 and IL10 were significantly positively correlated with Glutamate and Glx (glutamate + glutamine) levels in the dorsal caudate. In Study 2, plasma inflammatory molecules (MIP1β/CCL4, MCP1/CCL2, Eotaxin-1/CCL11 and TNFα) were significantly correlated with CSF MIP1β/CCL4, IL10, MCP1/CCL2 and Fractalkine/CX3CL1 and symptoms ratings. DiscussionPlasma inflammatory biomarkers are elevated in early psychosis, associated with neurochemical markers as well as CSF inflammatory molecules found in neurodegenerative disorders. Future studies are needed that combine both peripheral and central biomarkers in both FEP and HC to better understand a potential neuroinflammatory subtype of psychosis likely to respond to targeted interventions.

Borderline personality disorder vs. mood disorders: clinical comparisons in young people treated within an “Early Intervention” service for first episode psychosis

Background and ObjectiveBorderline Personality Disorder (BPD) is under-investigated in First Episode Psychosis (FEP). BPD psychotic manifestations and mood changes are also difficult to differentiate from first episode affective psychosis. The aim of this study was to compare sociodemographic and clinical features between FEP patients with BPD vs. Bipolar Disorder (BD) or Major Depressive Disorder (MDD) both at baseline and across a 2-year follow-up period. Methods224 FEP participants (49 with BPD, 93 with BD and 82 with MDD) completed the Health of the Nation Outcome Scale (HoNOS), the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Psychiatric diagnosis was reformulated at the end of our follow-up. Inter-group comparisons were analyzed using the Kruskal-Wallis or the Chi-square test. A mixed-design ANOVA model was also performed to assess the temporal stability of clinical scores within and between the 3 subgroups. ResultsCompared to FEP/BD subjects at baseline, FEP/BPD patients showed higher depressive symptom severity and lower excitement severity. Compared to FEP/MDD at entry, they had a higher prevalence rate of substance abuse, a lower interpersonal impairment and a shorter DUP. Finally, they had a lower treatment response on HoNOS “Psychiatric Symptoms” subscale scores across the follow-up in comparison with both FEP/BD and FEP/MDD individuals. ConclusionBPD as categorical entity represents a FEP subgroup with specific clinical features and treatment response. Appropriate treatment guidelines for this FEP subgroup are thus needed.

Clinical characteristics of people presenting with first episode psychosis pre- and during the COVID-19 pandemic in KwaZulu-Natal Province, South Africa.

The COVID-19 pandemic and the lockdown experience may have not only precipitated or exacerbated mental illness but also influenced access to care and the nature and content of the psychotic symptomatology of people with psychosis. This study aimed to evaluate the association of the COVID-19 pandemic and lockdown experience on clinical presentation and quality of life of people (QOL) with first episode psychosis (FEP). Two first episode psychosis cohorts from the same epidemiological area collected prior to, and during the COVID-19 pandemic and lockdown were compared in terms of clinical symptomatology, substance use and QOL. All adult in- and outpatients with FEP at five clinical units in KwaZulu-Natal, South Africa, aged between 18 and 45 years, were assessed with the MINI interview for psychosis, Positive and Negative Symptoms Scale, WHO Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the WHO QOL scales. Eighty-eight FEP participants were recruited between 2019 and 2020 (cohort 1) before the pandemic. Study recruitment was suspended in March 2020 due to the pandemic. On study resumption from November 2020 to November 2022, 95 new participants (cohort 2) were recruited. There were no sociodemographic differences between the two cohorts, except unemployment status (57% vs. 65%) and household income. The cohort presenting post-COVID-19 pandemic onset had significantly more positive psychotic symptoms (21.9 vs. 23.7), lower PANSS domain depressive score, more lifetime use of tobacco, cannabis and alcohol. However, they reported improved QOL (196 vs. 239). Following the pandemic and lockdown experience participants presented with more severe psychotic symptoms and concomitant substance use but improved perceived QOL. This suggests the need to explore individual and social factors that may influence the clinical presentation.

Treated incidence of first episode psychosis in Sinop, Turkey: results of a 4-year admission-based study - SINOPsy.

The incidence of psychotic disorders varies in different geographic areas. As there has been no report from Turkey, this study aimed to provide the treated incidence rate of first-episode psychosis (FEP) in a defined area. All individuals, aged 15-64 years, presenting with FEP (ICD-10 F20-29, F30-33) to mental health services in a defined catchment-area in Sinop which is located in the Black Sea region of the northern Turkey were recorded over a 4-year period (2009 to 2012). Incidence rates of psychotic disorders and their 95% confidence intervals (CIs) were estimated. Poisson regression was applied to estimate the differences in incidence rate ratio (IRR) by age, sex, and urbanicity. One hundred and fifteen FEP participants were identified during the 4 years. Crude incidence rates of all psychoses, schizophrenia, other psychotic disorders, and affective psychotic disorders were respectively 38.5 (95% CI 27.1-49.9), 10.7 (95% CI 6.6-14.8), 10.0 (95% CI 5.7-14.3) and 17.7 (95% CI 11.3-24.2) per 100 000 person-years. After age-sex standardisation the rates increased slightly. There were no gender differences in the incidence rates. IRR of any psychotic disorder was highest in the youngest age group (15-24 years) compared to the oldest age group (55-64 years), 7.9 (95% CI 2.8-30.5). In contrast with previous studies, the incidence rate of any psychotic disorder was not significantly increased in urban areas compared with rural areas. The current study, the first of its kind from Turkey, indicates that the risk of schizophrenia and other psychotic disorders in a lowly urbanised area of Turkey is comparable to those reported in Western European cities.

Suicide risk among individuals at Ultra-High Risk (UHR) of psychosis in a developing North African country: A 12-month naturalistic prospective cohort study from the TRIP project

BackgroundThe limited studies that focused on suicidality in individuals at Ultra-High Risk (UHR) of psychosis were predominantly cross-sectional, emerging from Western countries. We aimed to examine suicide risk among Tunisian UHR and First Episode Psychosis (FEP) patients at baseline, and to evaluate the evolution and correlates of suicidal ideation over a 12-month period in the UHR group exclusively. Methods35 UHR (aged 22.8 ± 4.0 years, 45.7% male) and 33 FEP (aged 27.3 ± 4.8 years, 63.6% male) participants were included. The Comprehensive Assessment of at Risk Mental States, the Positive and Negative Syndrome Scale (PANSS), The Rosenberg Self-Esteem Scale, and The Multidimensional Scale of Perceived Social Support were used. ResultsNo significant differences were found between the UHR and the FEP groups with regard to levels of suicidal ideation at baseline. Suicidal ideation scores showed a significant decrease over time in UHR participants (p=.014; η2=0.242). An increase in total PANSS scores at 1 year (Beta=0.03; p=.048; 95%CI 0.001, 0.060; η2=0.182) significantly increased suicidal ideation scores at 1 year in the UHR group. ConclusionOur findings contribute to the limited body of evidence on this topic by providing new prospective data from a population, country and region that has never been researched previously.

Executively-mediated language skills are related to performance-based social functioning in the early psychosis spectrum

Social impairment is a core deficit in psychotic spectrum disorders (PSDs). Prior work shows that language abnormalities can predict psychosis onset and are related to social outcomes in PSDs. Few studies have investigated nuanced relationships between language/verbal abilities and social functioning in the early psychosis spectrum, including at-risk (schizotypy) and first episode of psychosis (FEP) individuals. This study aimed to examine the relationship to between language/verbal performance and performance-based and examiner-rated social functioning. We also aimed to replicate prior models that demonstrate neurocognition is related to social functioning through negative symptoms and social cognition. Low schizotypy (n = 42), high schizotypy (n = 44), and FEP (n = 15) participants completed a battery of language/verbal, social cognition, and social functioning measures. Regression analyses revealed that Proverb Test performance was uniquely and significantly associated with performance-based but not examiner-rated social functioning. Other language/verbal measures were not significantly related to social functioning. In mediational analyses, language/verbal performance was indirectly related to social functioning through negative traits, and also through social cognition. Findings extend support for negative symptom and social cognitive intervention in the early psychosis spectrum, and uniquely suggest that executively-mediated language skills may be an additional target to improve social functioning.

Individual psychotherapy may help to reduce suicidal ideation in first episode psychosis: results from a 2-year Italian follow-up study

IntroductionSuicidal thinking is relevant in patients with First Episode Psychosis (FEP). However, longitudinal studies specifically examining treatment response for suicidal ideation in FEP are still relatively scarce, especially with long-term design and in real-world clinical settings.ObjectivesThe aims of this research were (A) to longitudinally assess suicidal thoughts in people with FEP along a 2-year follow-up period and (B) to overtime investigate any significant association of suicidal ideation levels with the specific treatment components of an ‘Early Intervention in Psychosis’ (EIP) protocol along the 2 years of follow-up.MethodsAt entry, 232 FEP participants (aged 12–35 years) completed the Brief Psychiatric Rating Scale (BPRS), including a ‘Suicidality’ item subscore. Multiple linear regression analysis was then performed.ResultsAcross the follow-up, FEP subjects showed a relevant decrease in suicidal thinking levels overtime. This was specifically predicted by the total number of individual psychotherapy sessions offered within the 2-year EIP protocol and antidepressant dose (at least as regards the first year of our intervention).Image:ConclusionsSuicidal ideation is clinically relevant in FEP but seems to improve overtime together with the provision of specific, patient-tailored and integrated EIP treatments, especially individual psychotherapy.Disclosure of InterestNone Declared

Correlates of substance use in a large naturalistic cohort of young people with early and emerging psychosis

BackgroundSubstance use remains a barrier to recovery for young people accessing early intervention services for psychosis. While correlates of use have been explored in populations experiencing a first episode of psychosis (FEP), sample sizes have been small and less research assesses cohorts at ultrahigh risk of psychosis (UHR).MethodsThis study uses data from a naturalistic cohort including UHR and FEP participants (N = 1252) to elucidate clinical correlates of use in the past 3 months of any illicit substance, amphetamine-type stimulants (ATS), cannabis, and tobacco. Moreover, network analysis based on use of these substances and additionally alcohol, cocaine, hallucinogens, sedatives, inhalants, and opioids was completed.ResultsYoung people with FEP used substances at significantly higher rates than those at UHR. High concurrence of use was seen between substances. In the FEP group, participants who had used any illicit substance, ATS, and/or tobacco had increased positive symptoms and decreased negative symptoms. Young people with FEP who used cannabis had increased positive symptoms. In the UHR group, participants who had used any illicit substance, ATS, and/or cannabis in the past 3 months showed decreased negative symptoms compared to those who had not.ConclusionA distinct clinical picture of more florid positive symptoms and alleviated negative symptoms seen in those who use substances in the FEP group appears muted in the UHR cohort. Treating young people at UHR in early intervention services represents the earliest opportunity to address substance use early to improve outcomes.

Predictors of treatment attrition of cognitive health interventions in first episode psychosis.

Dropping out of psychological interventions is estimated to occur in up to a third of individuals with psychosis. Given the high degree of attrition in this population, identifying predictors of attrition is important to develop strategies to retain individuals in treatment. We observed a particularly high degree of attrition (48%) in a recent randomized controlled study assessing cognitive health interventions for first-episode psychosis participants with comorbid social anxiety. Due to the importance of developing interventions for social anxiety in first episode psychosis, the aim of the present study was to identify putative predictors of attrition through a secondary analysis of data. Participants (n= 96) with first episode psychosis and comorbid social anxiety were randomized to receive cognitive behavioural therapy for social anxiety or cognitive remediation. Differences between completers and non-completers (<50% intervention completed) were compared using t-tests or chi-square analyses; statistically significant variables were entered into a multivariate logistic regression model. Non-completers tended to be younger, had fewer years of education and had lower levels of social anxiety compared to completers. Lower baseline social anxiety and younger age were statistically significant predictors of non-completion in the logistic regression model. Age and social anxiety were predictors of attrition in cognitive health interventions in first episode psychosis populations with comorbid social anxiety. In the ongoing development of social anxiety interventions for this population, future studies should investigate specific engagement strategies, intervention formats and outcome monitoring to improve participant retention in treatment.

Early identification of treatment non-response in first-episode psychosis.

Approximately one-third of patients with psychotic disorders does not respond to standard antipsychotic treatments. Consensus criteria for treatment resistance (TR) may aid the identification of non-response and subsequent tailoring of treatments. Since consensus criteria require stability of clinical status, they are challenging to apply in first-episode psychosis (FEP). This study aims to investigate (a) if an adaptation of consensus criteria can be used to identify FEP patients with early signs of TR (no early clinical recovery-no-ECR) after 1year in treatment and (b) to what extent differences in antipsychotic treatments differentiate between outcome groups. Participants with FEP DSM-IV schizophrenia spectrum disorders were recruited during their first treatment. A total of 207 participated in the 1-year follow-up. Remission and recovery definitions were based on adaptations of the "Remission in Schizophrenia Working Group" criteria and TR on adaptations of the "Treatment Response and Resistance in Psychosis" (TRRIP) working group criteria. 97 participants (47%) could be classified as no-ECR, 61 (30%) as ECR, and 49 (23%) as with partial ECR (P-ECR). Statistically significant baseline predictors of no-ECR matched previously identified predictors of long-term TR. Only 35 no-ECR participants had two adequate treatment trials and met the full TRRIP criteria. 21 no-ECR participants were using the same medication over the follow-up year despite the lack of significant effects. The difference in the percentage of FEP participants classified as no-ECR versus TR indicates that we may underestimate the prevalence of early TR when using consensus criteria.

Large-Scale Thalamocortical Triple Network Dysconnectivities in Patients With First-Episode Psychosis and Individuals at Risk for Psychosis.

Aberrant thalamocortical connectivity and large-scale network interactions among the default mode network (DMN), salience network (SN), and executive control network (ECN) (ie, triple networks) have been regarded as critical in schizophrenia pathophysiology. Despite the importance of network properties and the role of the thalamus as an integrative hub, large-scale thalamocortical triple network functional connectivities (FCs) in different stages of the psychotic disorder have not yet been reported. Thirty-nine first-episode psychosis (FEP) patients, 75 individuals at clinical high risk (CHR) for psychosis, 46 unaffected relatives (URs) of schizophrenia patients with high genetic loading, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Modular community detection was used to identify cortical and thalamic resting-state networks, and thalamocortical network interactions were compared across the groups. Thalamic triple networks included higher-order thalamic nuclei. Thalamic SN-cortical ECN FC was greater in the FEP group than in the CHR, UR, and HC groups. Thalamic DMN-cortical DMN and thalamic SN-cortical DMN FCs were greater in FEP and CHR participants. Thalamic ECN-cortical DMN and thalamic ECN-cortical SN FCs were greater in FEP patients and URs. These results highlight critical modulatory functions of thalamic triple networks and the shared and distinct patterns of thalamocortical triple network dysconnectivities across different stages of psychotic disorders. The current study findings suggest that large-scale thalamocortical triple network dysconnectivities may be used as an integrative biomarker for extending our understanding of the psychosis pathophysiology and for targeting network-based neuromodulation therapeutics.

Facial affect recognition in first-episode psychosis is impaired but not associated with psychotic symptoms

IntroductionSocial dysfunction is a key feature of psychotic disorders such as schizophrenia linked to disability. Less is known about social functioning in the early stages of the disorder and if there is an association to psychotic symptoms. AimsInvestigate if antipsychotic drug-naïve or briefly medicated individuals with first-episode psychosis (FEP), have impaired facial affect recognition (FAR) compared to control participants and if psychotic symptoms are associated with the FAR ability. MethodIndividuals with FEP (n = 67) and control participants (n = 51) performed a computer-aided FAR task on basic emotions. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Group performances were compared using age and gender as covariates. The associations between FAR and performance on the subscales of PANSS were analyzed. ResultsCompared to control participants, individuals with FEP were impaired in general FAR (Beta = -2.04 [95 % conf: -3.75/-1.62], p < 0.001) and FAR of negative emotions (Beta = -1.74 [95 % conf: -3.08/-1.22], p < 0.001), driven by difficulties in recognition of anger and disgust. In both groups, there was a pattern of mistaking negative emotions for other negative emotions. There were no significant group differences in FAR of happiness. No significant associations between FAR and psychotic symptoms were observed. DiscussionThe results indicate that FAR, an underlying mechanism of social functioning is impaired early in the course of psychotic disorders. Current findings do not support the hypothesis that misinterpretation of facial expressions in individuals with FEP underlies or contributes to symptoms of psychosis.

Cognitive insight in individuals at ultra-high risk for psychosis compared to patients with first-episode psychosis and non-psychotic help-seeking youths

Defective insight is a hallmark of schizophrenia. Less is known about insight in emerging psychosis. In this study a widely used measure of cognitive insight, the Beck Cognitive Insight Scale (BCIS), has been applied to a sample including patients with first-episode psychosis (FEP), at ultra-high risk (UHR) for psychosis, and help-seeking youths without psychotic symptoms. The Comprehensive Assessment of At-Risk Mental State (CAARMS) interview was used to classify patients. Enrolled patients were assessed with the General Health Questionnaire-12 (GHQ-12), the Prodromal Questionnaire-16 (PQ-16), the Social and Occupational Functioning Assessment Scale (SOFAS), and the BCIS. The sample included 212 participants (58%) with non-psychotic mental distress, 131 participants (36%) were UHR, and 22 (6%) were with FEP. Males and females were in equal proportion, mean age was 19.2±2.6 years old (range: 15-25 years). Reliability (Cronbach's alpha) was good for clinical scales (>0.7) and acceptable (around 0.6) for the two BCIS subscales. The self-certainty subscale of the BCIS was more reproducible in factor analysis than the self-reflectiveness scale. Youths devoid of psychotic symptoms scored lower than UHR and FEP participants on the GHQ-12 and the PQ-16 and had better psychosocial functioning as measured by the SOFAS. Levels of cognitive insight did not differ between groups. People in the early stages of psychosis may be still accessible to self-reflectiveness and more hesitant about the certainty of their beliefs than patients at more advanced stages of the illness, as those with fully displayed schizophrenia.

Altered White Matter Integrity at Illness Onset in Adolescents With a First Episode of Psychosis.

BackgroundDisruption in white matter integrity has been consistently observed in individuals with psychosis. However, whether such abnormalities are already present at illness onset or are related to downstream processes remains elusive. The study of adolescents with a recent onset of psychosis provides the opportunity to evaluate white matter integrity proximally to disease onset.MethodsTwenty-six adolescents (aged 15.9 ± 1.3 years) with a first episode of psychosis (FEP) (less than 6 months duration) were compared with 26 age and sex-matched healthy controls (HC) (16.8 ± 2 years). In participants with a FEP, clinical diagnoses were confirmed after a minimum of 1 year follow-up (main categories: schizophrenia, bipolar disorder, or schizoaffective disorder). Anatomical images and diffusion tensor sequences were acquired using a 1.5T scanner. Whole brain, voxel-wise group differences in fractional anisotropy (FA) were investigated between participants with a FEP and controls.ResultsRelative to HC, FEP participants displayed decreased FA in the right posterior cingulate gyrus, encompassing the right superior and posterior corona radiata, and the right parahippocampal gyrus, including the cingulum and fornix. FEP patients showed no areas of increased FA relative to HC. The results remained significant after controlling for medication, cannabis use and intelligence.ConclusionOur findings indicate that adolescents with recent onset of psychotic disorders show decreased white matter integrity in circuits implicated in cognitive functions and emotion regulation.