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Background: There is limited evaluation of approaches to identify patients with new onset bipolar affective disorder (BPAD) when using administrative datasets., Methods: Using the Massachusetts All-Payer Claims Database (APCD), we identified individuals with a 2016 diagnosis of bipolar disorder with mania and examined patterns of psychiatric and medical care over the preceding 48 months., Results: Among 4806 individuals aged 15-35 years with a 2016 BPAD with mania diagnosis, 3066 had 48 months of historical APCD data, and of those, 75 % involved information from ≥2 payors. After excluding individuals with historical BPAD or mania diagnoses, there were 583 individuals whose 2016 BPAD with mania diagnosis appeared to be new (i.e., 34 new diagnoses per 100,000 individuals aged 15-35 years). Most individuals received medical care, e.g., 98 % had outpatient visits, 76 % had Emergency Department (ED) visits, and 50 % had mental health-related ED visits during the 48 months prior to their first mania diagnosis. One-third (37.2 %) had a depressive episode before their initial BPAD with mania diagnosis., Limitations: Study was conducted in one state among insured individuals. We used administrative data, which permits evaluation of large populations but lacks rigorous, well-validated claims-based definitions for BPAD. There could be diagnostic uncertainty during illness course, and clinicians may differ in their diagnostic thresholds., Conclusions: Careful examination of multiple years of patient history spanning all payors is essential for identifying new onset BPAD diagnoses presenting with mania, which in turn is critical to estimating population rates of new disease and understanding the early course of disease., Competing Interests: Declaration of competing interest Dr. Benson reports volunteering for the Epic Behavioral Health Specialty Steering Board. Dr. Smoller is a member of the Scientific Advisory Board of Sensorium Therapeutics (with options), and has received grant support from Biogen, Inc. He is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments. Dr. Hsu consults for Cambridge Health Alliance, Brandeis University, University of Southern California, and Columbia University, and has received compensation for keynote speeches from the University of South Carolina and Invitrx., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Psychosis symptom assessment instruments are rarely used in US mental health community clinical practice despite the advantages of measurement-based care. Barriers include the length of typical scales and that data for scale evaluation often come from researcher and not clinician raters., Study Design: The 12-item COMPASS symptom assessment was designed for the RAISE-ETP study of early phase psychosis. Ratings were done by community facility clinicians. COMPASS psychometric properties were examined with a Mokken scale analysis. Subsequently, Mokken analyses were done on 10-item COMPASS data from the ESPRITO learning health system., Study Results: 3600 RAISE-ETP COMPASS assessments were examined. The COMPASS 12-item version fulfilled Mokken scale criteria for unidimensionality (H = 0.329 (SE:0.007)) as did a derived reduced 10-item version (H = 0.359 (SE:0.007)) and 5-item version (H = 0.396 (SE = 0.009)). The 12-item version showed one significant monotonicity violation; no significant violations were found in the reduced item versions. Of the reduced item versions, clinicians preferred the 10-item over the 5-item version. In the ESPRITO data, both the 10-item and 5-item versions met unidimensionality criteria (H = 0.458 (SE:0.030) and 0.478 (0.034) respectively) with no monotonicity violations., Conclusions: The COMPASS scale offers clinicians versions with varying lengths for assessment of individuals with first episode psychotic disorders in community settings. COMPASS can also facilitate data collection for large scale initiatives; the 10-item version is a symptom assessment option in the US national EPINET project., Competing Interests: Declaration of competing interest Dr. Robinson has been a consultant to Acadia, Advocates for Human Potential, Amalyx, American Psychiatric Association, C4 Innovations, Costello Medical Consulting, Health Analytics, Innovative Science Solutions, Janssen, Lundbeck, Neurocrine, Neuronix, Otsuka, Teva and US WorldMeds. Dr. Robinson provides training and consultation about implementing NAVIGATE treatment that can include compensation. Drs. John and Miller report no conflicts. Dr. Schooler has consulted or served on Advisory Boards for Alkermes, Boerhinger Ingelheim Lundbeck and Otsuka. Dr. Kane has been a consultant to or received honoraria for lectures from Alkermes, Allergan, Boerhinger Ingelheim, Cerevel, Dainippon Sumitomo, Intracellular Therapies, Janssen, Karuna, LB Pharma, Lundbeck, Merck, Neurocrine, Newron, Otsuka, Pierre Fabre, Reviva, Roche, Saladax, Sunovion, and Teva. He has received grant support from Janssen, Lundbeck, Otsuka and Sunovion. He is a shareholder of The Vanguard Research Group and LB Pharma., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Treating the early phase of schizophrenia is crucial for preventing further episodes and improving quality of life, functioning, and social inclusion. Pharmacotherapies are first-line treatments, but have limitations. There is consensus on the need for non-pharmacological interventions for individuals in the early phase of schizophrenia. Several psychological interventions have shown promising effects; however, their comparative effectiveness remains largely unknown. To address this issue, a network meta-analysis will be performed. We aim to develop a hierarchy of existing psychological treatments concerning their efficacy and tolerability, which will inform treatment guidelines., Protocol: Randomized controlled trials (RCTs) investigating psychological interventions for first-episode psychosis, first-episode schizophrenia, or early phase schizophrenia will be included. The primary outcome will be overall schizophrenia symptoms (measured up to 6 and 12 months, and at the longest follow-up) and relapse as a co-primary outcome. Secondary outcomes are premature discontinuation; change in positive, negative, and depressive symptoms of schizophrenia; response; quality of life; overall functioning; satisfaction with care; adherence; adverse events; and mortality. The study selection and data extraction are performed by two independent reviewers. We will assess the risk of bias of each study using the Cochrane Risk of Bias tool 2 and evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). Subgroup and sensitivity analyses will be conducted to explore heterogeneity and assess the robustness of our findings., Discussion: This systematic review and network meta-analysis aims to compare multiple existing psychological interventions, establishing which are best for symptom reduction, relapse prevention, and other important outcomes in early phase schizophrenia. Our results may provide practical guidance concerning the most effective psychological intervention to reduce symptom severity and the societal burden associated with the disorder., Competing Interests: Competing interests: In the last three years SL has received honoraria for advising/consulting and/or for lectures and/or for educational material from Angelini, Boehringer Ingelheim, Eisai, Ekademia, GedeonRichter, Janssen, Karuna, Kynexis, Lundbeck, Medichem, Medscape, Mitsubishi, Neurotorium, Otsuka, NovoNordisk, Recordati, Rovi, Teva; JP from uniQure. The other authors declare that they have no competing interests. MH is a part-time employee of Get.On Institut für Gesundheitstrainings GmbH/HelloBetter., (Copyright: © 2024 Feber L et al.)

Suicide is a critical public health concern among individuals with schizophrenia spectrum disorders (SSDs). Still, significant gaps remain in understanding relationships between suicide outcomes and both demographic and clinical characteristics. Data were examined from 57 adults of a psychological autopsy study who had psychosis symptoms and died between 1989 and 2017 in the Midwestern United States. This study compared demographic and clinical characteristics of those who died by suicide (n = 26) to those who died by natural (n = 26) or accidental (n = 5) causes. Those who died by suicide were more often younger, white/Caucasian, more educated, and more often employed than those who died by natural or accidental causes (p < .05). Furthermore, symptoms of depression, recurrent suicidal ideation, history of suicide attempt, and being in a first episode of psychosis were experienced significantly more by those who died by suicide in comparison to natural or accidental causes (p < .05). Findings highlight the need to consider depression in suicide risk for psychosis populations, intervene in early stages of psychosis illness, and implement suicide prevention strategies tailored to individuals with psychosis and SSDs. Implications point towards the need for tailored interventions to mitigate risk for suicide death in this vulnerable population., Competing Interests: Declaration of competing interest LAB and NB employed by the University of Michigan. CB is employed by the University of Michigan and the VA Center for Clinical Management Research in Ann Arbor, MI. JO is employed by Case Western Reserve University. CAS is employed by the University of Mississippi Medical Center., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study investigated the impact of prior antidepressant and stimulant exposure on the age at onset (AAO) of first episode mania (FEM) or psychosis (FEP). Patients with FEP and FEM born after 1985 in Olmsted County, Minnesota, were identified using the Rochester Epidemiology Project. Duration and peak dose of antidepressant and stimulant exposure were quantified by review of the electronic health record. Peak doses were converted to defined daily dose (DDD), and cumulative exposure was calculated as DDD multiplied by treatment duration. Linear models were used to assess relationships between AAO with any exposures, and cumulative antidepressant and stimulant exposures. A total of 190 FEM/FEP patients (mean AAO=20.8 ± 3.7 years) were included. There was no significant difference in AAO with vs. without exposure to antidepressants or stimulants. Cumulative antidepressant exposure correlated with a later AAO in overall sample (r = 0.28, p < 0.001), and in FEP (r = 0.33, p < 0.001). No significant correlation emerged between cumulative stimulant exposure and AAO. Multivariable modeling confirmed that cumulative antidepressant exposure (Estimate=2.42, 95 %CI=1.66-3.18, p < 0.001), but not cumulative stimulant exposure (Estimate=-0.04, 95 %CI=-1.10-1.02, p = 0.94), was associated with later AAO. Antidepressant and stimulant exposures were not associated with earlier AAO. However, cumulative antidepressant exposure was associated with later AAO. Limitations include retrospective design and relatively small sample size. Our findings may inform adolescent treatment recommendations when assessing risk for psychotropic-related adverse events. Further risk modeling investigations of antidepressants and stimulants with larger sample sizes are needed to explore the role of antidepressant and stimulant exposure in the trajectory leading to FEM/FEP., Competing Interests: Declaration of competing interest JLVV has received grant-in-kind support for supplies and genotyping from Assurex Health. MAF received grant support from Assurex Health and Mayo Foundation, received CME travel and honoraria from Carnot Laboratories and American Physician Institute, and has Financial Interest/Stock ownership/Royalties from Chymia LLC. No other declaration of interests from other authors., (Copyright © 2024. Published by Elsevier B.V.)

Background: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. When atrial fibrillation is first diagnosed, it tends to be permanent and associated with significant morbidity and mortality. We aimed to study the management of a first episode of atrial fibrillation in a group of patients in Yaounde, Cameroon., Methods: We conducted a retrospective study with data collected from the Cardiology department of Yaounde Central Hospital and the internal medicine department of Yaounde General Hospital over five years (January 2017 to December 2021), for a duration of 4 months, from February 2022 to May 2022. All patients older than 15 years with a first episode of atrial fibrillation were included, and all patients with incomplete medical records were excluded. The association between different variables was assessed using a χ² test and logistic regression method with a significance threshold of p < 0.05., Results: Of the 141 patients recruited, the mean age was 68.5 ± 10.6 years. The sex ratio (M/F) was 0.7. The main associated factors and co-morbidities were hypertension in 70.2% (99) patients, heart failure in 36.9% (52) patients and a sedentary lifestyle in 33.3% (47) patients. The most common anticoagulant treatment was AntiVitamin K, used in 64.5% (91) of patients. Heart rate control was the most commonly used symptom control strategy in 85.1% (120) patients, mainly with beta-blockers in 52.5% (74). We found 1.4% (2) participants who were not treated with antithrombotics as recommended. Treatment of arrhythmia due to co-morbidities was not always recommended. The complication rate was 94.3% (133) patients. Control of the bleeding risk due to antithrombotic therapy and monitoring of anticoagulant therapy were not optimal. The heart rate control strategy had a higher success rate, and the sinus rhythm maintenance rate at one year was 61.7% (37) participants., Conclusion: The management of a first episode of atrial fibrillation at Yaoundé's Central and General Hospitals is not always performed according to current recommendations and is far from optimal. However, nearly two out of three patients maintained sinus rhythm for one year., (© 2024. The Author(s).)

Hallucinations are a core feature of psychosis, and their severity during the acute phase of illness is associated with a range of poor outcomes. Various clinical and sociodemographic factors may predict hallucinations and other positive psychotic symptoms in first episode psychosis (FEP). Despite this, the precise factors associated with hallucinations at first presentation to an early intervention service have not been extensively researched. Through detailed interviews and chart reviews, we investigated sociodemographic and clinical predictors in 636 minimally-medicated patients who entered PEPP-Montréal, an early intervention service for FEP, between 2003 and 2018. Hallucinations were measured using the Scale for the Assessment of Positive Symptoms (SAPS), while negative symptoms were assessed using the Scale for the Assessment of Negative symptoms (SANS). Depressive symptoms were evaluated through the Calgary Depression Scale for Schizophrenia (CDSS), and anxiety symptoms via the Hamilton Rating Scale for Anxiety (HAS). A majority (n = 381, 59.9 %) of the sample presented with clinically significant hallucinations (SAPS global hallucinations score ≥ 3) at program entry. These patients had an earlier age at onset, fewer years of education, and a higher severity of delusions, depression and negative symptoms than those without clinical-level hallucinations. These results suggest that individuals with clinically significant hallucinations at admission tend to be younger and have a greater overall symptom burden. This makes it especially important to monitor hallucinations alongside delusions, depression and negative symptoms in order to identify who might benefit from targeted interventions. The implications of these findings for early intervention and person-centered care are discussed., Competing Interests: Declaration of competing interest A.M. reports no funding from industry in >3 years. R. J. reports no funding from industry in >3 years. M.L. reports grants from Otsuka Lundbeck Alliance and personal fees from Otsuka Canada, Lundbeck Canada, and MedAvante-Prophase, as well as grants and personal fees from Janssen. These interests had no relation to the present study. Other co-authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: Clinical studies following a first episode of psychosis (FEP) have increasingly exposed the complexity of identifying predictive outcome variables. We aimed to explore the utility of NEET status (not in education, employment or training) at FEP onset in predicting high threshold clinical remission (absence of positive symptoms and off antipsychotic medication for 6 months) at 3 years following treatment with an early intervention for psychosis service., Methods: We studied an established retrospective naturalistic cohort of 354 patients with FEP (the S1P cohort)., Results: Baseline NEET status was identified in 172 patients (49%) and was significantly associated with mean duration of untreated psychosis (p = .035). Only 64 (21%) achieved defined remission criteria by 3 years. Multivariate logistic regression analysis revealed baseline NEET status as the only variable significantly associated with remission status (p < .001)., Conclusion: NEET may represent an important predictive variable of symptomatic outcomes which requires prospective evaluation., (© 2024 John Wiley & Sons Australia, Ltd.)

Introduction: Psychotic depression (PD) is characterized by the co-occurrence of emotional dysfunction and psychotic symptoms such as delusions and hallucinations with poor clinical outcomes. TSH may involve in the development of PD. This study aims to explore relationship between TSH and PD., Methods: A total of 1718 outpatients diagnosed as FEDN MDD were recruited in this study. The relationship between PD and TSH was evaluated using multivariable binary logistic regression analysis. To assess the presence of non-linear associations, a two-piecewise linear regression model was employed. Furthermore, interaction and stratified analyses were conducted with respect to sex, education, marital status, comorbid anxiety, and suicide attempt., Results: Multivariable logistic regression analysis revealed that TSH was positively associated with the risk of PD after adjusting for confounders (OR = 1.26, 95% CI: 1.11 to 1.43; p < 0.05). Smoothing plots showed a nonlinear relationship between TSH and PD, with the inflection point of TSH being 4.94 mIU/L. On the right of the inflection point, for each unit increase in serum TSH level on the right side of the inflection point, the probability of PD increased substantially by 47% (OR = 1.47, 95% CI: 1.25 to 1.73, p < 0.001), while no significant association was observed on the left side of the inflection point (OR = 0.87, 95% CI: 0.67 to 1.14, p = 0.32)., Conclusion: Our investigation showed a nonlinear TSH-PD relationship in FEDN MDD patients, thus contributing to effective intervention strategies for psychotic symptoms in depression patients., (© 2024. The Author(s).)

Aim: To explore perceived expressed emotion in the south Asian context for individuals with a first episode of psychosis (FEP)., Method: Semi-structured interviews were conducted with 16 service users experiencing a FEP to understand their experience of expressed emotion (EE) from their caregivers. Interviews were analysed using inductive thematic analysis., Results: Four main categories were identified: connection and support, understanding and awareness, boundaries and independence and context and influence. Factors influencing perceived expressed emotion such as acceptance, acculturation, warmth and expressions of love, communication and family values were identified. Findings highlight south Asian's experiences of being cared for, and their perception of EE, including warmth and connection as a strength and resource., Conclusion: The findings shed light on culturally specific EE within the context of FEP that can be considered when working with south Asian communities within early intervention services. Findings highlight the impact of navigating and negotiating bicultural identities and generational differences in EE in the British south Asian context., (© 2024 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

The stress-vulnerability model has been repeatedly highlighted in relation to the risk, onset and course of psychosis, and has been independently studied in clinical high-risk (CHR) and first-episode psychosis (FEP) populations. Notable in this literature, however, is that there are few studies directly comparing markers of stress response across progressive stages of illness. Here we examined the psychobiological response to the Trier Social Stress Test in 28 CHR (mean age 19.1) and 61 FEP (age 23.0) patients, in order to understand the stage(s) or trajectories in which differences in subjective stress or physiological response occur. The overall clinical sample had greater perceived stress and blunted cortisol (FEP + CHR, n = 89, age 21.7) compared with healthy controls ( n = 45, age 22.9). Additional analyses demonstrated elevated heart rate and systolic blood pressure in FEP compared with CHR, but there were no further differences in physiological parameters (cortisol, heart rate, or blood pressure) between stage- or trajectory-based groups. Together, this suggests that individual stress response markers may differentially emerge at particular stages en route to psychosis - and demonstrates how stage-based analyses can shed light on the emergence and evolution of neurobiological changes in mental illness.

Background: Previous studies have found electroacupuncture could improve the clinical symptoms of first-episode major depressive disorder (MDD), but the exact neural mechanism of action needs to be further elucidated., Methods: Twenty-eight first-episode MDD patients were randomly divided into 14 electro-acupuncture stimulation (EAS) groups and 14 sham-acupuncture stimulation (SAS) groups, and clinical symptoms were assessed and functional magnetic resonance imaging (fMRI) scans were done in both groups. Amplitude of low-frequency fluctuations (ALFF) was used to observe the changes between the pre-treatment and post-treatment in the two groups, and the altered brain areas were selected as region of interest (ROI) to observe the FC changes. Meanwhile, the correlation between the altered clinical symptoms and the altered ALFF and FC of brain regions in the two groups was analyzed., Results: The EAS significantly decreased the HAMD-24 and HAMA-14 scores of MDD than SAS group. The imaging results revealed that both groups were able to increase the ALFF of the left middle temporal gyrus and the left cerebellar posterior lobe. When using the left middle temporal gyrus and the left posterior cerebellar lobe as ROIs, EAS group increased the FC between the left middle temporal gyrus with the left superior frontal gyrus, the left middle frontal gyrus, and the left hippocampus, and decreased the FC between the left posterior cerebellar lobe and the left calcarine gyrus, while SAS group only increased the FC between the left middle temporal gyrus with the left superior frontal gyrus. The alternations in clinical symptoms after EAS treatment were positively correlated with the altered ALFF values in the left middle temporal gyrus and the altered FC values in the left middle temporal gyrus and the left middle frontal gyrus., Conclusion: EA demonstrates modulation of functional activity in the default mode network (DMN), sensorimotor network (SMN), cognitive control network (CCN), limbic system, and visual network (VN) for the treatment of the first-episode MDD. Our findings contribute to the neuroimaging evidence for the efficacy of EAS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Patients with schizophrenia often encounter notable weight gain during their illness, heightening the risk of metabolic diseases. While previous studies have noted a correlation between obesity and cognitive impairment in schizophrenia, many were cross-sectional, posing challenges in establishing a causal relationship between weight gain and cognitive function. The aim of this longitudinal study is to examine the relationship between weight gain and cognitive function in patients with first-episode schizophrenia (FES) during the initial 6-month antipsychotic treatments. Employing linear and logistic regression analyses, the study involved 337 participants. Significantly, baseline scores in processing speed (OR = 0.834, p = 0.007), working memory and attention (OR = 0.889, p = 0.043), and executive function (OR = 0.862, p = 0.006) were associated with clinically relevant weight gain (CRW, defined as an increase in body weight > 7%) at the 6-month endpoint. On the other hand, CRW correlated with improvements in the Brief Visuospatial Memory Test ( p = 0.037). These findings suggest that patients with lower baseline cognitive performance undergo more substantial weight gain. Conversely, weight gain was correlated with cognitive improvements, particularly in the domain of visual learning and memory. This suggested a potential bidirectional relationship between weight gain and cognitive function in first-episode schizophrenia patients.

Introduction: Major depressive disorder (MDD) is a major cause of poor quality of life and disability and is highly prevalent worldwide. Various pathological mechanisms are implicated in MDD, including the reward system. The human brain is equipped with a reward system that is involved in aspects such as motivation, pleasure, and learning. Several studies including a meta-analysis have been reported on the reward system network and MDD. However, to our knowledge, no studies have examined the relationship between the reward system network of drug-naïve, first-episode MDD patients and the detailed symptoms of MDD or age. The fronto-striato network (FSN) is closely related to the reward system network. The present study primarily aimed to elucidate this point., Methods: A total of 89 drug-naïve first-episode MDD patients and 82 healthy controls (HCs) patients were enrolled in the study. The correlation between the FSN and age and the interaction between age and illness in the FSN were investigated in 75 patients in the MDD group and 79 patients in the HC group with available information on the FSN and age. In addition, the association between the FSN and the total scores on the 17-item Hamilton Rating Scale for Depression (HAMD-17) and scores in each symptom item was analyzed in 76 MDD subjects with information on the FSN and HAMD-17. The significance of each result was evaluated according to a p-value of <0.05., Results: Age was inversely correlated with the FSN (p=2.14e-11) in the HC group but not in the MDD group (p=0.79). FSN varied with the presence of MDD and with age, particularly showing an interaction with MDD and age (p=1.04e-08). Specifically, age and the presence or absence of MDD each affected FSN, but the effect of age on FSN changed in the presence of depression. FSN did not correlate with total HAMD-17 scores or scores in each item., Discussion: The reward system may be dysfunctional in patients with MDD. In addition, the effect could be greater in younger patients. Meanwhile, there is no correlation between the function of the reward system and the severity of MDD or the severity of each symptom. Thus, the reward system network may be an important biological marker of MDD, although careful consideration should be given to age and its association with the severity of the disorder., Conclusion: The reward system function is decreased in MDD patients, and this decrease may be more pronounced in younger patients, although further research is still needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kijima, Watanabe, Okamoto, Ikenouchi, Tesen, Kakeda and Yoshimura.)

Background: Age of onset (AOO) influences the prognosis of many diseases and even serves as potential driver. But in Major Depressive Disorder, there is no consensus regarding the effect of AOO on the course., Methods: In this study, a total of 38,671 inpatients were surveyed over 16 years, and 6113 inpatients were eventually included in the statistical analysis after applying rigorous data criteria. Inpatients were divided into four AOO subgroups: adolescent onset, early adult onset, middle adult onset, and late adult onset., Results: In the subset of first hospitalization (n = 4884), the differences in the length of stay between several AOO subgroups were statistically significant (F = 56.852, df 1  = 3, df 2  = 4880, P < 0.001, ω 2  = 0.033). Similarly, this difference was also significant in the subset of relapse hospitalization (n = 1229, F = 5.985, df 1  = 3, df 2  = 1225, P < 0.001, ω 2  = 0.012). The Bonferroni post hoc test suggested a longer length of stay in the adolescent onset group (P < 0.001). Besides, in the adolescent onset subgroup, the proportion with 2 or more relapses hospitalization within one year was higher than those without relapses (6.7 % Vs 2.7 %, χ 2  = 12.685, df = 6, P < 0.001). Logistic regression suggests that patients with adolescent onset are at higher risk for 2 or more relapses hospitalization within one year (B = 0.881, OR = 2.41, 95 % CI 1.37-4.23, P = 0.002)., Limitations: Retrospective design may have recall bias., Conclusions: This is the first large sample size study to examine age at onset and risk of relapse at the individual level in a Chinese population. Our study found that adolescent onset is more susceptible to the chronicity of MDD. These findings will contribute to the accurate typing of MDD, as well as customized individualized prevention and treatment options., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: We aim to compare the psychiatric antecedents of schizophrenia (SZ) and bipolar disorder (BD)., Methods: Using the Rochester Epidemiology Project, we searched for residents of Olmsted County that had a diagnosis of SZ or BD. We confirmed each case using DSM-5 criteria and obtained the psychiatric antecedents., Results: We identified 205 cases with first episode psychosis or mania (SZ = 131; BD = 74). The mean age at first visit for mental health reasons was 12.3 ± 6.3 years for SZ and 13.9 ± 5.6 years for BD. The duration of the initial prodrome (time from first mental health visit to first episode) was similar for both groups (SZ 8.3 ± 6.2 years vs BD 7.3 ± 5.9 years). We found that SZ and BD have overlapping antecedents, but SZ was more common in males and in foreign born and had more learning deficits before the first episode. BD was more common in white population and had higher rates of depressive and adjustment disorders prior to first episode. BD also had more affective symptoms, nightmares, and panic attacks before the first episode. Both groups had similarly high rates of substance use (SZ 74 % vs BD 74.3 %), prescription of antidepressants (SZ 46.6 % vs BD 55.4 %) and stimulants (SZ 30.5 % vs BD 22.9 %)., Conclusions: The psychiatric antecedents of SZ and BD usually start during adolescence, overlap, and present in unspecific ways. The initial prodromes are more alike than distinct. Further studies are encouraged to continue looking for specific factors that distinguish the antecedents of these two disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mark A. Frye received grant support from Assurex Health and Mayo Foundation, received CME travel and honoraria from Carnot Laboratories, and has Financial Interest/Stock ownership/Royalties from Chymia LLC. No other declaration of interests from other authors., (Copyright © 2023. Published by Elsevier B.V.)

Whilst antipsychotic medication reduces risk of relapse following a first episode of psychosis (FEP), some individuals can discontinue medication and remain relapse free. We aimed to identify patient and service-specific factors which influence clinical outcome following antipsychotic discontinuation. The outcomes 'admission to hospital' and 'remaining free from psychotic symptoms', both within one year from discontinuation, were explored retrospectively in an established naturalistic cohort of 354 patients with FEP. Logistic regression analysis was used to explore influence of routinely available baseline and treatment course variables on these outcomes. Seventy-seven individuals (22 %) fully discontinued antipsychotic treatment within a year, at mean 102 days from initiation. Only antipsychotic type had significant association with discontinuation; aripiprazole was discontinued more than olanzapine (p = 0.028). Seventeen individuals required admission to hospital; significantly associated with prior admission at first illness onset (p = 0.004), and prior legal detention to hospital (p = 0.001). Admission was less likely in those discontinuing aripiprazole vs olanzapine (p = 0.044). Twenty-four patients remained psychosis symptom free and were most significantly likely to have received clinician support in discontinuation; this group had no association with either initial duration of untreated psychosis or prior duration of antipsychotic treatment. Future studies exploring outcomes following antipsychotic discontinuation require consistency of choice of outcome measures and sample stratification by vulnerability factors including severity of first illness episode, whether remaining symptom free after first episode, which medication switched from and baseline functioning. The impact and nature of clinician support to discontinue requires further exploration alongside its association with abruptness of discontinuation., Competing Interests: Declaration of competing interest No conflict of interest is recorded for all study authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). Controlling for FH and SZ-PRS did not attenuate the association between childhood maltreatment and IQ in cases or controls. Findings suggest that these expressions of genetic liability cannot account for the lower levels of cognition found among adults maltreated in childhood., (© 2023. The Author(s).)

Background: Evidence has suggested that emotional dysregulation is a transdiagnostic feature in schizophrenia and major affective disorders. However, the relationship between emotional dysregulation and appetite hormone disturbance remains unknown in nonobese adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder., Methods: In total, 22 adolescents with schizophrenia; 31 with bipolar disorder; 33 with major depressive disorder; and 41 healthy age-, sex-, and body mass index (BMI)/BMI percentile-matched controls were enrolled for assessing levels of appetite hormones, namely leptin, ghrelin, insulin, and adiponectin. Emotional regulation symptoms were measured using the parent-reported Child Behavior Checklist-Dysregulation Profile., Results: Adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder exhibited greater emotional dysregulation symptoms than the control group ( P  = .037). Adolescents with bipolar disorder demonstrated higher log-transformed levels of insulin ( P  = .029) and lower log-transformed levels of leptin ( P  = .018) compared with the control group. BMI ( P  < .05) and log-transformed ghrelin levels ( P  = .028) were positively correlated with emotional dysregulation symptoms., Discussion: Emotional dysregulation and appetite hormone disturbance may occur in the early stage of severe mental disorders. Further studies are required to clarify the unidirectional or bidirectional association of emotional dysregulation with BMI/BMI percentile and appetite hormones among patients with severe mental disorder.

Aim: Correct early diagnosis and intervention for schizophrenia is associated with improved outcomes. This study sought to determine the potential value of specialized consultations for individuals thought to have a recent-onset schizophrenia spectrum disorder who were not receiving specialized care., Methods: 121 consecutive one-time consultations were performed in a clinic specializing in recent-onset schizophrenia. Parents of 79 patients were questioned about the process and the value of the consultation., Results: Consultations were perceived by parents as both positive and helpful experiences. 85% of parents were somewhat or very happy with the consultation experience, and 86% found the consultation to be moderately or very helpful. A third of parents viewed the consultation as contributing to the long-term improvement of the patient's condition., Conclusions: The findings demonstrate the potential value of consultations for individuals with possible schizophrenia spectrum disorders not receiving specialized treatment, and provide rationale for comprehensive studies investigating the widespread implementation of such consultations., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background: Recent studies have reported that psychotic symptoms are common in patients with major depressive disorder (MDD). However, few studies have reported the relationship between thyroid function, lipid metabolism and clinical profiles in female MDD patients. Thus, this study aimed to investigate the prevalence of psychotic depression (PD) and its risk factors in first-episode and drug naive (FEDN) depression among the female population in China., Methods: This was a cross-sectional study involving a representative probability sample of 1,130 FEDN female outpatients with MDD (aged 18 years or older) in China. We collected information relating to socio-demographic characteristics, clinical data and blood samples. The Hamilton Depression Rating Scale 17-item version (HAMD-17), Hamilton Anxiety Rating Scale 14-item version (HAMA-14), and Positive and Negative Syndrome Scale (PANSS) were used to evaluate depressive, anxiety, and psychotic symptoms., Results: The prevalence of psychotic symptoms in female MDD patients was 10.97%. The findings revealed significant differences between MDD female patients with psychotic symptoms and non-PD female patients in the following areas: higher HAMD scores, higher HAMA scores, more severe anxiety and an increased risk of suicide attempts. Further logistic regression analysis showed that psychotic symptoms were associated with higher thyroid-stimulating hormone (TSH) levels and an odds ratio of 1.168., Conclusions: Our findings supported the hypothesis that higher TSH levels were correlated with psychotic symptoms in female MDD patients. Therefore, serum TSH levels may be a potential biomarker of PD in female MDD patients. In addition, we found that PD was closely associated with suicide attempts and lipid levels, but did not reach statistical significance., (© 2023. The Author(s).)

Background: Cognitive training (CT) and aerobic exercise both show promising moderate impact on cognition and everyday functioning in schizophrenia. Aerobic exercise is hypothesized to increase brain-derived neurotrophic factor (BDNF) and thereby synaptic plasticity, leading to increased learning capacity. Systematic CT should take advantage of increased learning capacity and be more effective when combined with aerobic exercise., Methods: We examined the impact of a 6-month program of cognitive training & exercise (CT&E) compared to cognitive training alone (CT) in 47 first-episode schizophrenia outpatients. All participants were provided the same Posit Science computerized CT, 4 h/week, using BrainHQ and SocialVille programs. The CT&E group also participated in total body circuit training exercises to enhance aerobic conditioning. Clinic and home-based exercise were combined for a target of 150 min per week., Results: The MATRICS Consensus Cognitive Battery Overall Composite improved significantly more with CT&E than with CT alone ( p = 0.04), particularly in the first 3 months (6.5 v. 2.2 T-score points, p < 0.02). Work/school functioning improved substantially more with CT&E than with CT alone by 6 months ( p < 0.001). BDNF gain tended to predict the amount of cognitive gain but did not reach significance. The cognitive gain by 3 months predicted the amount of work/school functioning improvement at 6 months. The amount of exercise completed was strongly associated with the degree of cognitive and work/school functioning improvement., Conclusions: Aerobic exercise significantly enhances the impact of CT on cognition and functional outcome in first-episode schizophrenia, apparently driven by the amount of exercise completed.

Background: The mechanisms underlying the antipsychotic potential of cannabidiol (CBD) remain unclear but growing evidence indicates that dysfunction in the insula, a key brain region involved in the processing of motivationally salient stimuli, may have a role in the pathophysiology of psychosis. Here, we investigate whether the antipsychotic mechanisms of CBD are underpinned by their effects on insular activation, known to be involved in salience processing., Methods: A within-subject, crossover, double-blind, placebo-controlled investigation of 19 healthy controls and 15 participants with early psychosis was conducted. Administration of a single dose of CBD was compared with placebo in psychosis participants while performing the monetary incentive delay task, an fMRI paradigm. Anticipation of reward and loss were used to contrast motivationally salient stimuli against a neutral control condition., Results: No group differences in brain activation between psychosis patients compared with healthy controls were observed. Attenuation of insula activation was observed following CBD, compared to placebo. Sensitivity analyses controlling for current cannabis use history did not affect the main results., Conclusion: Our findings are in accordance with existing evidence suggesting that CBD modulates brain regions involved in salience processing. Whether such effects underlie the putative antipsychotic effects of CBD remains to be investigated.

Aim: To determine whether thyroid hormone levels are associated with a specific clinical phenotype in patients with first-episode psychosis (FEP)., Methods: Ninety-eight inpatients experiencing FEP and with less than 6 weeks of antipsychotic treatment were included in the study and were followed up for one year. Baseline psychiatric evaluation included assessment of prodromal symptoms, positive and negative symptoms, depressive symptoms, stressful life events and cycloid psychosis criteria. Thyroid function (thyroid-stimulating hormone (TSH) and free thyroxin (FT4)) was determined at admission. Partial correlation analysis was conducted to analyse the correlation between levels of TSH/FT4 and symptoms. Logistic regression was performed to explore the association between psychopathological symptoms, 12-month diagnoses and thyroid hormones while adjusting for covariates., Results: Patients with prodromal symptomatology showed lower baseline FT4 levels (OR = 0.06; p  = 0.018). The duration of untreated psychosis (DUP) was inversely associated with FT4 concentrations ( r  =  - 0.243; p  = 0.039). FEP patients with sudden onset of psychotic symptoms (criteria B, cycloid psychosis) showed higher FT4 levels at admission (OR = 10.49; p  = 0.040). Patients diagnosed with affective psychotic disorders (BD or MDD) at the 12-month follow-up showed higher FT4 levels at admission than patients diagnosed with nonaffective psychosis (schizophrenia, schizoaffective) (OR = 8.57; p  = 0.042)., Conclusions: Our study suggests that higher free-thyroxine levels are associated with a specific clinical phenotype of FEP patients (fewer prodromal symptoms, shorter DUP duration and sudden onset of psychosis) and with affective psychosis diagnoses at the 12-month follow-up., Competing Interests: The authors declare there are no competing interests., (©2023 Gine-Serven et al.)

Objectives: To assess the status at 13 to 17 years follow-up of a cohort of young male traumatic shoulder dislocators., Study Design: Prospective cohort study., Methods: A prospective study of first-time young male traumatic shoulder dislocators, began in 2004. Subjects were evaluated by the apprehension test after completing rehabilitation 6 to 9 weeks post dislocation. Between March 2021 and July 2022, a telephone questionnaire was administered to ascertain their current shoulder status. Subjects were questioned about avoidance of activities of daily living and sport, participation in sports, current instability, and self-assessed shoulder function by the SANE score., Results: 50/53 (94.3%) of the study subjects, mean age 20.4 years, completed a mean follow-up of 181.8 ± 12 months. The non-redislocation survival was 13% for those with a positive apprehension test and 49% for those with a negative test (p = 0.007). SANE scores were 64.3 ± 23.7 for those with a positive apprehension test and 83.7 ± 19.7 for those with a negative test (p = 0.001). In the year before the follow-up, 33.3% of those treated conservatively and 42.9% treated surgically experienced subluxation (p = 0.5). Fifty-seven percent of those who were treated conservatively and 56% of those who underwent surgery avoided some ADL or sports because of their shoulder., Conclusions: For young male first time traumatic shoulder dislocators a positive apprehension test after rehabilitation is associated with a high risk for reoccurrence and poorer long-term results. Most subjects were still dealing with shoulder symptoms at long-term follow-up., Competing Interests: Declaration of interest statement The authors declare that they have no competing interests., (Copyright © 2023 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Objectives: We investigated the differences in serum brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) levels and clinical symptoms with first-episode depression at different ages., Methods: Ninety patients (15-60 years old) diagnosed with first-episode depression were enrolled as the study group, and they were divided into early-onset, adult and late-onset groups. The age-matched control groups were healthy volunteers. Serum BDNF and GDNF concentrations were determined by enzyme-linked immunosorbent assay (ELISA). GraphPad Prism 9 was used for t tests, one-way ANOVAs, chi-square tests, and correlation analyses. p  < 0.05 indicated significant differences., Results: Serum BDNF and GDNF levels were lower in the whole study group and the three subgroups than in the healthy groups. Illness severity, anxiety and education were higher in the early-onset than late-onset patients. Serum BDNF levels were lower in the adult than late-onset patients. Serum BDNF levels were negatively correlated with patient CGI-SI scores. After the LSD test for multiple comparisons, the results were also significant., Conclusions: Low serum BDNF and GDNF levels may be involved in the pathophysiology of first-episode depression, and there were differences in serum BDNF levels at different ages, verifying that serum BDNF and GDNF could serve as potential biomarkers of depression. KEY POINTSDepression is often conceptualised as a systemic illness with different biological mechanisms, but satisfactory explanations have not been provided thus far.The aim of our study was to investigate differences in serum BDNF and GDNF levels and their relationships with clinical symptoms in patients with first-episode depression at different ages.The potential of the neurotrophic factor hypothesis to advance the diagnosis and treatment of depression will be a very exciting new strategy for future research.

Over the past two decades, research and clinical resources on clinical high risk (CHR) for psychosis have both expanded, with goals to better understanding risk and protective factors on the course of illness and inform early intervention efforts. However, some studies have highlighted potential sampling bias among CHR research studies, raising questions about generalizability of findings and inequitable access to early detection and intervention. The current study sought to explore these questions by comparing 94 participants in a CHR longitudinal monitoring study across North America (NAPLS-2) who converted to syndromal psychosis over the course of the study (CHR-CV) to 171 participants who presented for treatment at a localized first-episode psychosis service (FES) after converting. CHR-CV participants were significantly more likely to be White and have a college-educated parent, while FES participants were more likely to be Black and first- or second-generation immigrants. On average, CHR-CV participants were younger at onset of attenuated positive symptoms, had a longer period of attenuated symptoms prior to conversion, and were more likely to be treated with antipsychotics prior to conversion compared to those in FES programs. After controlling for time since conversion, CHR-CV participants had higher global functioning and were less likely to have experienced recent psychiatric hospitalization. Findings suggest that CHR research and FES clinics may be sampling from different populations, although conclusions are limited by inconsistent sampling frames and methods. Integrated early detection that targets defined geographic catchments may deliver more epidemiologically representative samples to both CHR research and FES., Competing Interests: Declaration of competing interest We have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To compare the differences in gut microbiota and short-chain fatty acids (SCFAs; metabolites of gut microbiota) in the serum of patients with first-episode depression and the healthy population and to analyze the relationship between gut microbiota and metabolite SCFAs and the clinical symptoms of major depressive disorder (MDD)., Methods: A total of 45 patients with first-episode depression and 22 healthy volunteers were chosen to complete relevant scale evaluations, and feces samples and venous blood samples were collected. The 16S RNA method was used to analyze the intestinal microflora and the characteristics of serum SCFAs detection by ELISA kit, as well as the intestinal flora, SCFAs content and their correlation with MDD clinical indicators., Results: The abundance of Akkermansia , Megamonas , Prevotellaceae NK3B31 group , and butyrate-producing bacteria, Lachnospira , Subdoligranulum , Blautia , and Dialister , and acetate-producing bacteria, Streptococcus , in the gut microbiota of the MDD group was lower than that in the control (C) group. The abundance of Parasutterella in the MDD group was higher than that in the C group. Dialister negatively correlated with all measured clinical symptoms ( r < 0, P < 0.05). The serum SCFA content in the MDD group was higher than that in the C group, and the content positively correlated with the Hamilton anxiety scale scores ( r = 0.584, P < 0.05)., Conclusion: The results demonstrated that the MDD group differed from the C group in terms of gut microbiota and SCFAs in the serum and that the change in certain intestinal bacteria might participate in the pathogenic mechanism of MDD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Wang, Jing, Wang and An.)

Objective: Cannabis use is increasingly normalized; psychosis is a major adverse health outcome. We reviewed evidence on cannabis use-related risk factors for psychosis outcomes at different stages toward recommendations for risk reduction by individuals involved in cannabis use. Methods: We searched primary databases for pertinent literature/data 2016 onward, principally relying on reviews and high-quality studies which were narratively summarized and quality-graded; recommendations were developed by international expert consensus. Results: Genetic risks, and mental health/substance use problem histories elevate the risks for cannabis-related psychosis. Early age-of-use-onset, frequency-of-use, product composition (i.e., THC potency), use mode and other substance co-use all influence psychosis risks; the protective effects of CBD are uncertain. Continuous cannabis use may adversely affect psychosis-related treatment and medication effects. Risk factor combinations further amplify the odds of adverse psychosis outcomes. Conclusions: Reductions in the identified cannabis-related risks factors-short of abstinence-may decrease risks of related adverse psychosis outcomes, and thereby protect cannabis users' health.

Objective: Sensory gating P50 (SG-P50) may be involved in the pathophysiological mechanisms of impaired cognition in schizophrenia (SCZ). Comorbid depressive symptoms are common in SCZ patients and are also found to be associated with their cognitive impairment. However, it is unclear whether SG-P50 is abnormal in first episode antipsychotics naïve (FEAN) SCZ patients with depressive symptoms. Our aimed to investigate the relationships between SG-P50, depressive symptoms and neurocognition in FEAN-SCZ patients., Methods: We recruited 103 FEAN-SCZ patients (depression: n = 63; non-depression: n = 40) and 55 healthy controls. SG-P50 was measured using the standard auditory dual-click (S1&S2) paradigm. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale-17 (HDRS-17). Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB)., Results: Compared with non-depressive patients, depressive patients had a significantly larger S2 amplitude (p = 0.005) and a higher S2/S1 ratio at trend level (p = 0.075) after corrected. There were significant differences in the scores of CPT-IP and Mazes (NAB) between depressive and non-depressive FEAN-SCZ patients (both p values < 0.05). For all patients, the SG-P50 S2/S1 ratio was significantly correlated with HDRS-17 score (r = 0.23, p = 0.020) and MCCB-Symbol coding (r = -0.16, p = 0.043). For depressive FEAN-SCZ patients, S2 amplitude was an independent predictor of the MCCB-Mazes (NAB) (β = -0.31, t = -2.52, p = 0.015)., Conclusions: SG-P50 deficit may be an informational biomarker for depressive symptoms and neurocognitive impairments in FEAN-SCZ patients., Competing Interests: Conflict of interest There was no conflict of interested reported by any of the authors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Few studies have explored the complex relationship of pro- and anti-inflammatory cytokines with cognitive function in adolescents with first-episode schizophrenia, bipolar disorder, or major depressive disorder., Methods: In total, 26, 35, and 29 adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder, respectively, and 22 age- and sex-matched controls were included in the current study. Cytokines, namely interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP), were assessed. The Wisconsin Card Sorting Test (WCST) and the working memory task were administered to assess cognitive function., Results: Using generalized linear models with adjustment for demographic data and clinical symptoms, patients with bipolar disorder were found to exhibit the highest levels of CRP ( P  = .023), IL-6 ( P  = .022), and TNF-α ( P  = .011), and had the lowest IL-2 levels ( P  = .034) among the four groups. According to the results of the WCST and working memory task, adolescents with schizophrenia exhibited the lowest performance in cognitive function. In addition, among the assessed cytokines, only CRP levels ( P  = .027) were negatively associated with WCST scores., Discussion: Dysregulated pro- and anti-inflammatory cytokines and impaired cognitive functioning were observed in first-episode adolescent-onset schizophrenia, bipolar disorder, and major depressive disorder. The altered cytokine profiles may play important roles in the pathophysiology of schizophrenia, bipolar disorder, and major depressive disorder.

Purpose: While the prevalence of delusional themes appears to be consistent across geographic contexts, little is known about the relative prevalence of such themes within a given setting over periods of time. We therefore investigated delusional themes across 12 years of presentation to a catchment-based early intervention service for first episode psychosis (FEP)., Methods: Systematically collected data from 500 patients at an early intervention service for FEP were analyzed. Four cohorts of 3 years each, from 2006 to 2017, were used to compare the frequency of delusion themes across cohorts. We also integrated into the analysis baseline sociodemographic factors such as gender, age, and highest level of education and clinical factors such as anxiety, depression, suicidality, hallucinations, and primary diagnosis (affective or non-affective psychosis)., Results: Sex and education level were stable across cohorts, while patient age varied (p = 0.047). Clinical anxiety, depression, and suicidality at entry were also stable. Across cohorts, the proportion of patients with affective versus non-affective diagnosis differed (p = 0.050), with no differences in global rating of delusion severity or theme prevalence except for delusions of guilt or sin (p = 0.001). This single theme difference was not correlated with age or diagnosis., Conclusion: Our study suggests relatively stable prevalence of delusion themes across cohorts of individuals experiencing FEP. This demonstrates the potential utility of studying thematic content both for understanding delusions in clinical populations and in research. Future explorations of the relationships between delusion themes and across individual patient episodes should be conducted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Selective attention is impaired in first-episode psychosis (FEP). Selective attention effects can be detected during auditory tasks as increased sensory activity. We previously reported electroencephalography scalp-measured N100 enhancement is reduced in FEP. Here, we localized magnetoencephalography (MEG) M100 source activity within the auditory cortex, making novel use of the Human Connectome Project multimodal parcellation (HCP-MMP) to identify precise auditory cortical areas involved in attention modulation and its impairment in FEP. MEG was recorded from 27 FEP and 31 matched healthy controls (HC) while individuals either ignored frequent standard and rare oddball tones while watching a silent movie or attended tones by pressing a button to oddballs. Because M100 arises mainly in the auditory cortices, MEG activity during the M100 interval was projected to the auditory sensory cortices defined by the HCP-MMP (A1, lateral belt, and parabelt parcels). FEP had less auditory sensory cortex M100 activity in both conditions. In addition, there was a significant interaction between group and attention. HC enhanced source activity with attention, but FEP did not. These results demonstrate deficits in both sensory processing and attentional modulation of the M100 in FEP. Novel use of the HCP-MMP revealed the precise cortical areas underlying attention modulation of auditory sensory activity in healthy individuals and impairments in FEP. The sensory reduction and attention modulation impairment indicate local and systems-level pathophysiology proximal to disease onset that may be critical for etiology. Further, M100 and N100 enhancement may serve as outcome variables for targeted intervention to improve attention in early psychosis., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Aim: To assess central set point of thyroid homeostasis in drug-naïve patients affected by first episode schizophrenia., Methods: This cross-sectional study was conducted in Xinxiang city, Henan, China. Patients were drug-naïve patients affected by first episode schizophrenia, aged 14-50 years old and admitted to the "Second Affiliated Hospital of Xinxiang Medical University" from January 2018 to December 2018. Controls were healthy individuals who underwent annual health from Xinxiang city, a community population of the same age and time period. The parameters of "central set point of thyroid homeostasis" were measured by "thyroid-stimulating hormone (TSH) index" and "thyroid feedback quantile-based index". The parameters were compared between schizophrenia patients and controls. Linear regression models adjusted by age and sex were used to assess the association of schizophrenia with the parameters., Results: A total of 235 patients and 121 controls were included in this study. Patients affected by schizophrenia had significantly higher prevalence of hyperthyroxinemia and levels of free T4, "TSH index", and "thyroid feedback quantile-based index" than controls. After adjusting age and sex, schizophrenia was independently associated with the higher level of "TSH index" (adjusted β 0.33, 95 % confidence interval 0.17, 0.49) and "thyroid feedback quantile-based index" (adjusted β 0.21, 95 % confidence interval 0.12, 0.30). The results with age and sex matched patients and controls were similar to those observed in the overall study population., Conclusion: Higher central set point may be the underlying mechanism of thyroid allostatic load in drug-naïve patients affected first episode schizophrenia., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Hypothesis: A pro-inflammatory phenotype has been related to psychotic disorders. The neutrophil-lymphocyte ratio (NLR) is an accessible biomarker that could be helpful to characterize this systemic inflammation state., Study Design: This study evaluated the NLR in a cohort of 310 subjects with a first episode of psychosis (FEP) and a matched group of 215 healthy controls, recruited in 16 Spanish centers participating in the PEPs Project. We investigated the NLR measures over 2 years in a prospective, naturalistic study., Study Results: At baseline, the FEP group showed a significant higher mean NLR compared to the control group (1.96 ± 1.11 vs 1.72 ± 0.74, P = 0.03). These ratio differences between groups grew at the 24 months follow-up visit (2.04 ± 0.86 vs 1.65 ± 0.65, P < 0.001). Within the FEP group, there were no significant differences in NLR across the follow-up visits, between genders or diagnosis groups (affective vs nonaffective). NLR values did not correlate with the Positive and Negative Symptoms Scale scores. The group of patients who did not reach remission criteria at the end of the study showed a significant higher NLR than those who remitted (2.1896 ± 0.85 vs 1.95 ± 0.87, P = 0.042). A significant correlation between antipsychotic doses and NLR was found at the two-years follow-up visit (r=0.461, P < 0.001)., Conclusions: Our results highlight the existence of an underlying predisposition of FEP patients to present an increased mean NLR. The use of NLR in clinical practice could be helpful to identify this inflammatory imbalance., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The dorsal striatum, comprised of the caudate and putamen, is implicated in the pathophysiology of psychosis spectrum disorders. Given the high concentration of dopamine receptors in the striatum, striatal dopamine imbalance is a likely cause in cortico-striatal dysconnectivity. There is great interest in understanding the relationship between striatal abnormalities in psychosis and antipsychotic treatment response, but few studies have considered differential involvement of the caudate and putamen. This study's goals were twofold. First, identify patterns of dorsal striatal dysconnectivity for the caudate and putamen separately in patients with a psychosis spectrum disorder; second, determine if these dysconnectivity patterns were predictive of treatment response., Methods: Using resting state functional connectivity, we evaluated dorsal striatal connectivity using separate bilateral caudate and putamen seed regions in two cohorts of subjects: a cohort of 71 medication-naïve first episode psychosis patients and a cohort of 42 unmedicated patients with schizophrenia (along with matched controls). Patient and control connectivity maps were contrasted for each cohort. After receiving 6 weeks of risperidone treatment, patients' clinical response was calculated. We used regression analyses to determine the relationship between baseline dysconnectivity and treatment response., Results: This dysconnectivity was also predictive of treatment response in both cohorts., Discussion: These findings suggest that the caudate may be more of a driving factor than the putamen in early cortico-striatal dysconnectivity., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Social isolation is common among individuals with schizophrenia spectrum and other psychotic disorders. Research indicates that social isolation relates to poorer mental health outcomes, depression, and negative symptoms, with less known about its relationship with positive symptoms. This study examined depression as a mediator in the relationships between positive symptoms (i.e., hallucinations and delusions) and social isolation among an early treatment phase sample in the United States. Data were obtained from the Recovery After an Initial Schizophrenia Episode project of the National Institute of Mental Health's Early Treatment Program. Participants ( N = 404) included adults between ages 15 and 40 in a first episode of psychosis. Data were analyzed using structural equation modeling in Mplus (Version 8). The study showed that delusions ( b = .095, SE = 0.04, p < .05) and hallucinations ( b = .076, SE = 0.03, p < .01) were directly related to depression, and that both delusions ( b = .129, SE = 0.06, p < .05) and depression ( b = .254, SE = 0.09, p < .05) were directly related to social isolation. Findings of this study determined that depression functioned as a mediator in the relationships between positive symptoms and social isolation. Targeting psychosis symptomatology and depression in treatment, improving social skills and social support networks, and considering the role of stigma in social isolation are of great importance in the prevention of poorer mental health outcomes., (© 2022 National Association of Social Workers.)

Objectives: We determined whether patients requiring surgery could be identified using pneumothorax volume/size in the first episode of primary spontaneous pneumothorax (PSP) and confirmed which of six different measurement methods of pneumothorax volume/size best predicted surgical indication (prolonged air leak, PAL, or ipsilateral recurrence)., Methods: Between 2013 and 2017, 282 patients with PSP were analysed. The volume of the pneumothorax (%) was calculated using volumetric methods (Collins, Rhea, Kircher, Light), while its size (large or small) was determined using the British Thoracic Society (BTS) and American College of Chest Physicians (ACCP) guidelines for the first PSP episode. The optimal cut-off points of pneumothorax volume in patients requiring surgery were based on the most sensitive and specific scores, calculated using receiver operating characteristic analysis., Results: Surgery was indicated in 162 patients (57.4%) because of PAL (n = 92) or ipsilateral recurrence (n = 70). Kircher's method had a better area under the curve (AUC) value than the others (AUC = 0.731, 95% confidence interval [CI] 0.676-0.782). Comparing the calculated cut-off points for each volumetric method and the known thresholds from the BTS/ACCP, the best predictor for surgical indications (for both PAL and ipsilateral recurrence) was Kircher's method (odds ratio = 5.636, 95% CI 3.338-9.516, p < 0.001). The four volumetric methods were significantly correlated with pneumothorax volume (rho ≥ 0.8, p < 0.001, for all comparisons)., Conclusions: Pneumothorax volume/size calculated in the first PSP episode may help predict surgical candidates, with Kircher's method being the best predictor. There was a correlation between all the volumetric methods of the pneumothorax volume., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Neurotransmitter metabolism plays a critical role in the pathophysiology of major depressive disorder (MDD). However, whether the neurotransmitter metabolism in adolescent MDD is differentiated from adult MDD is still elusive. In the current study, plasma concentrations of monoamine and amino acid neurotransmitters as well as their metabolites, including tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), vanillylmandelic acid (VMA), 3-methoxy-4-hydroxyphenylglycol (MHPG), glutamine (GLN), glutamate (GLU) and gamma-aminobutyric acid (GABA), were measured and compared in two cohorts of subjects (adult cohort: 31 first-episode MDD vs. 35 healthy controls; adolescent cohort: 33 first-episode MDD vs. 30 healthy controls). To assess the effects of antidepressant treatment, we also analyzed the concentrations of these indexes pre- and post-treatment in adult and adolescent cohorts. At baseline, the deficits of neurotransmitter metabolism in adult MDD were manifested in all the neurotransmitter systems. In contrast, for adolescent MDD, the dysregulation of neurotransmission was mainly indicated in the catecholaminergic systems. After antidepressant treatment, adult MDD showed increased TRP, KYN, KYNA and GLU levels, together with decreased levels of 5-HIAA and DOPAC. Adolescent MDD illustrated an increased level of 5-HT and decreased levels of TRP and GABA. The improvements of Hamilton total scores correlated with the changes in plasma TRP and the turnover of KYN/TRP after treatment in all MDD patients. However, these correlations were only manifested in the adult MDD rather than in adolescent MDD patients. The findings highlight the shared and distinguished neurotransmitter pathways in MDD and emphasize the different antidepressant responses between adults and adolescents. Potentially, the neurotransmitters above could serve as diagnostic biomarkers and provide a novel pharmacological treatment strategy for MDD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: Antipsychotic discontinuation has been a long-standing clinical and medicolegal issue. The Asian Network of Early Psychosis developed guidelines for antipsychotic discontinuation in patients who recover from first-episode non-affective psychosis. We reviewed the existing studies and guidelines on antipsychotic discontinuation to develop guidelines for antipsychotic discontinuation in such patients., Methods: We reviewed the relevant studies, reviews, guidelines, and ongoing trials related to antipsychotic discontinuation in patients with first-episode psychosis or schizophrenia. The quality of randomized controlled trials was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach., Results: Most studies had low to very low quality, and 2 had moderate quality. All studies, except 1, advised against antipsychotic discontinuation because of higher relapse rates in the antipsychotic discontinuation group (19%-82% at 1-year follow-up) than the treatment maintenance group compared with the maintenance group. Based on expert opinion and Grading of Recommendations Assessment, Development, and Evaluation evidence of trials, guidelines have been recommended for future discontinuation studies on patients with first-episode schizophrenia spectrum disorders., Conclusions: Currently, there are no recommendations for antipsychotic discontinuation in patients with first-episode schizophrenia spectrum disorders. However, there is a pressing need to conduct more rigorous research in remitted patients using more stringent criteria of full recovery, which can form the basis of guidelines on when and how antipsychotics should be tapered and discontinued. Studies that evaluate the patient characteristics and biomarkers that predict successful antipsychotic discontinuation are also needed., (© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.)

Objective: To provide a qualitative view and quantitative measure of sleep disturbances across and between early stages - clinical ultra high-risk and first episode - of psychotic and bipolar disorders., Methods: Electronic databases (PubMed, Cochrane, Embase, PsychINFO) were searched up to March 2021 for studies comparing sleep measures between individuals with an early stage and controls. Standard mean deviations (Cohen's d effect sizes) were calculated for all comparisons and pooled with random-effects models. Chi-square tests were used for direct between-subgroups (ultra high-risk vs first episode) comparisons of standard mean deviations. The effects of age, sex ratio, symptoms and treatment were examined in meta-regression analyses., Results: A database search identified 13 studies that contrasted sleep measures between individuals with an early stage ( N  = 537) and controls ( N  = 360). We observed poorer subjective sleep quality (standard mean deviation = 1.32; 95% confidence interval, [1.01, 1.62]), shorter total sleep time (standard mean deviation =-0.44; 95% confidence interval, [-0.67, -0.21]), lower sleep efficiency (standard mean deviation = -0.72; 95% confidence interval, [-1.08, -0.36]), longer sleep onset latency (standard mean deviation = 0.75; 95% confidence interval, [0.45, 1.06]) and longer duration of wake after sleep onset (standard mean deviation = 0.49; 95% confidence interval, [0.21, 0.77]) were observed in early stages compared to controls. No significant differences were observed for any of the reported electroencephalographic parameters of sleep architecture. No significant between-subgroups differences were observed. Meta-regressions revealed a significant effect of the age and the antipsychotic status on subjective measures of sleep., Conclusion: The early stage population presents with significant impairments of subjective sleep quality continuity, duration and initiation. Systematic assessments of sleep in early intervention settings may allow early identification and treatment of sleep disturbances in this population.

Aim: Studies using oral glucose tolerance tests (OGTT) have shown that impaired glucose metabolism presents in the early stages of schizophrenia (SCZ). However, there is a lack of studies on changes in glucose metabolism with the stage of the disease. We first explored the features of glucose metabolic pattern at different phases of male SCZ., Methods: We recruited 83 male first episode drug-naïve patients with SCZ (FEDN-SCZ) and 64 male chronic patients with SCZ (CH-SCZ), as well as 14 male healthy controls. The Positive and Negative Syndrome Scale (PANSS) was used to assess the psychopathology of patients. OGTT, fasting plasma glucose and lipid profiles of all participants were examined., Results: While the impaired glucose tolerance (IGT) rate of male SCZ patients was higher than that of HC (P < .05), there was no difference in IGT prevalence between FEDN-SCZ and CH-SCZ. In male FEDN-SCZ, LDL (OR = 2.64, 95% CI = 1.11-6.29, P = .028) and PANSS total score (OR = 1.03, 95% CI = 1.00-1.06, P = .046) were positively correlated with IGT; in male CH-SCZ, BMI (OR = 1.7, 95% CI = 1.08-2.67, P = .023), PANSS total score (OR = 0.82, 95% CI = 0.70-0.96, P = .015) and positive symptoms (OR = 0.45, 95% CI = 0.20-0.99, P = .046) were significantly correlated with IGT., Conclusions: Our findings reflect different glucose metabolism patterns in different stages of SCZ., (© 2021 John Wiley & Sons Australia, Ltd.)

Objectives: Selection bias is a concern in studies on psychotic disorders due to high dropout rates and many eligibility criteria for inclusion. We studied how representative the first-episode psychosis study sample in the Turku Early Psychosis Study (TEPS) was., Methods: We screened 3772 consecutive admissions to the clinical psychiatric services of Turku Psychiatry, Finland, between October 2011 and June 2016. A total of 193 subjects had first-episode psychosis and were suitable for TEPS. Out of 193 subjects, 101 participated (PA) and 92 did not participate (NPA) in TEPS due to refusal or contact problems. We retrospectively used patient register data to study whether NPA and PA groups differed in terms of clinical outcomes during 1-year follow-up., Results: In overall sample, the NPA group had a significantly higher rate of discontinuation of clinical treatment than the PA group (48.9 % vs 29.7 %, p = 0.01). In the hospital-treated subsample chi-square tests did not indicate statistically significant differences between the NPA and PA groups in the rate of involuntary care (69.7 % vs 62.7 %, p = 0.34), coercive measures (36.0 % vs 22.7 %, p = 0.06), and readmissions during the follow-up (41.5 % vs 33.8 %, p = 0.31), respectively., Conclusion: The differences in clinical outcomes and treatment characteristics in the non-participating and participating groups were relatively modest. The results do not support a major sample selection bias that would complicate the interpretation of results in this first-episode psychosis study., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

There is a growing body of evidence highlighting the role of gut microbiota as a biological basis of psychiatric disorders. The existing literature suggest that cognitive and emotional activities can be influenced by microbes through the microbiota-gut-brain axis and implies an association between alterations in the gut microbiome and several psychiatric conditions, such as autism, depression, bipolar disorder and psychosis. The aim of this review is to summarise recent findings and provide concise updates on the latest progress of the role of gut microbiota in the development and maintenance of psychiatric symptoms in schizophrenia and the first episode of psychosis. Despite the lack of consistent findings in regard to specific microbiome changes related to psychosis, the emerging literature reports significant differences in the gut microbiome of schizophrenic subjects compared to healthy controls and increasingly outlines the significance of an altered microbiome composition in the pathogenesis, development, symptom severity and prognosis of psychosis. Further human studies are, however, required, which should focus on identifying the drivers of microbiota changes in psychosis and establish the direction of causality between psychosis and microbiome alterations.

This study sought to investigate the influence of neurocognition on the emotional processing profiles of patients with first-episode schizophrenia, using the 4-branch Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) (Perceiving Emotions; Facilitating Emotions; Understanding Emotions and Managing Emotions). A sample of 78 patients with first-episode schizophrenia and a group of 90 non-psychiatric control subjects were included in this work. The initial results showed that patients had lower scores than controls for the "Understanding Emotions" and "Managing Emotions" MSCEIT branches. However, after controlling for neurocognition, the only deficits were found on the "Managing Emotions" branch of the MSCEIT. This branch can be considered as measuring a more sophisticated level of emotional processing, which may constitute a deficit in itself. In conclusion, patients with first-episode schizophrenia present deficits in social cognition at the highest level that seem to be independent from neurocognition. These findings support the inclusion of the "Managing Emotions" branch of the MSCEIT as part of the MCCB.

Cognitive reserve (CR) has been conceptualized as an individual's ability to optimize or maximize performance through differential recruitment of brain networks. As such, CR may contribute to the heterogeneity of cognitive deficits observed in schizophrenia. This study aimed to assess the relationships between CR, cognition and quality of life in first-episode (FES) patients. A total of 137 patients with either ICD-10 schizophrenia or "acute and transient psychotic disorders" diagnosis, and 62 healthy controls had completed a comprehensive assessment of six cognitive domains: speed of processing, attention, working memory/flexibility, verbal memory, visual memory, and abstraction/executive functioning. CR was calculated from the participants' education, premorbid IQ, and socioeconomic status. The results suggested that in patients, CR was positively related to cognitive performance in all domains, explaining 42.6% of the variance observed in cognition overall. Effects of CR in the control group were limited to three domains: speed of processing, abstraction/executive function and working memory/flexibility. These results suggest that CR largely contributes to cognitive variations present in FES patients. In addition, CR was negatively related to the social construct of patients' quality of life, and positively to symptom severity and general functioning., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Sleep and circadian rhythms disturbances (SCRD) in young people at high risk or with early onset of bipolar disorders (BD) are poorly understood. We systematically searched for studies of self, observer or objective estimates of SCRD in asymptomatic or symptomatic offspring of parents with BD (OSBD), individuals with presentations meeting recognised BD-at-risk criteria (BAR) and youth with recent onset of full-threshold BD (FT-BD). Of 76 studies eligible for systematic review, 35 (46%) were included in random effects meta-analyses. Pooled analyses of self-ratings related to circadian rhythms demonstrated greater preference for eveningness and more dysregulation of social rhythms in BAR and FT-BD groups; analyses of actigraphy provided some support for these findings. Meta-analysis of prospective studies showed that pre-existing SCRD were associated with a 40% increased risk of onset of BD, but heterogeneity in assessments was a significant concern. Overall, we identified longer total sleep time (Hedges g: 0.34; 95% confidence intervals:.1, .57), especially in OSBD and FT-BD and meta-regression analysis indicated the effect sizes was moderated by the proportion of any sample manifesting psychopathology or receiving psychotropic medications. This evolving field of research would benefit from greater attention to circadian rhythm as well as sleep quality measures., (Copyright © 2022. Published by Elsevier Ltd.)