Background: The insights and experiential knowledge of individuals with lived experience of bipolar disorder represent a valuable yet underutilized resource for informing clinical practice and guiding research. We conducted an online survey asking people with bipolar disorder what they want from clinicians and which research topics they find important. Method: The online survey "Wish list to clinicians and researchers in bipolar disorder" was distributed by the Norwegian Centre for Mental Disorders Research and the Norwegian Bipolar Association. Participants were asked to select 1-3 topics from a list of 16 predefined treatment targets and rate the importance of 20 research topics on a 5-point Likert scale. Results: A total of 415 individuals with bipolar disorder responded. The three most frequent wishes to clinicians were 1) "Stabilization of depression, mania and suicidal thoughts" 2) "Teach me to cope with and stabilize my emotions" and 3) "Help me to process trauma". The three highest rated research topics were 1) "The association between bipolar disorder and cognitive functions" 2) "More effective medication with less side effects" and 3) "What has been helpful to those who have recovered" Conclusion: Participants' wishes for clinical help go beyond established guidelines by underscoring treatment of trauma and affect regulation in daily life. Their wishes for research highlight the importance of reducing medication side-effects, and broader dissemination of knowledge about cognitive impairments in addition to research findings that provide hope for recovery and a satisfying life.

BackgroundIndividuals with bipolar disorder (BD) often experience unstable mood beyond mood episodes, which appears to be more prominent in BD II than in BD I. It is unclear whether the mood instability and associated sleep- and substance use patterns are different between BD subtypes and also present in the first treatment phase of the disorder. In this study, we compared the degree of instability of mood, sleep characteristics, and use of nicotine and alcohol across BD I and II.MethodsWe recruited 40 patients with BD in their first treatment phase (BD I n = 15, BD II n = 22 and BD Not Otherwise Specified n = 3) at Oslo University Hospital in Norway. The “MinDag” (MyDay) app was used to collect daily self-reports of mood (sadness, irritability, mood elevation and anxiety), sleep (length and quality) and weekly reports of alcohol and nicotine use for up to six months (mean no. of weeks = 18.5, a total of up to 740 weeks). To compare the degree of instability in the time-series across the two BD subtypes we used Root Mean Squared Successive Differences (rMSSD), representing the time domain, and power spectral density (PSD), representing the frequency domain. Cumulative difference periodogram (CDP) was used for group comparison.ResultsSignificant differences were found between BD I and BD II in the mean levels of irritability and mean hours of sleep throughout the follow-up period. The trends for higher instability in anxiety (.029) and irritability (.058) in BD II compared to BD I did not survive Bonferroni correction. Similarly, the variability of sleep length and quality and the use of nicotine and alcohol was comparable across the two groups.ConclusionApplying longitudinal app-based self-monitoring and time-series analyses, our study did not replicate previous findings of more mood instability in BD II versus BD I. The pattern of similar instability across the groups also applied to sleep characteristics and nicotine and alcohol use. Larger samples are needed to investigate how BD subtypes can explain the instability of mood and other illness-related features, which could support the development of more personalized treatment.

BACKGROUND:The prevalence of substance use disorders in bipolar disorder (BD) is high. Exploring potential interactions between mood and the use of common substances such as alcohol and nicotine may contribute to a better understanding of the mechanisms underlying such comorbidities. Digital tools now allow for continuous monitoring and data collection of both symptoms and behavior. This enables time-series analyses to explore such associations with greater precision. METHODS:Thirty-two individuals in the early phases of BD registered their mood daily and their use of substances weekly in the MinDag (MyDay) app for up to 6 months. We explored temporal relationships between the use of alcohol and nicotine and the levels of depressed, elevated, irritable, and anxious mood using Vector Autoregressive Models and Granger causality tests. RESULTS:We found indications that mood influenced alcohol- and nicotine use, and vice versa. Significant temporal relationships (Granger causality) were found in 55% (11 out of 20) of the participants for alcohol and 70% (7 out of 10) for nicotine use, and with high proportions of the variance explained by the one time-series on the other. The associations were consistent with causal effects in one or both directions, but with no adjustment for confounding. CONCLUSION:Our findings indicate that mood influences alcohol- and nicotine use and vice versa in individuals with BD, although caution should be taken due to the exploratory approach. Larger samples are needed to further disentangle these relationships to provide insight for better prevention and treatment of BD and comorbid substance use disorders.

The app “MinDag” (MyDay) was developed as a tool for monitoring mood, symptoms and illness-relevant behaviour in the initial treatment of bipolar disorder. Digital self-monitoring may provide patients and clinicians with valuable data for tailoring treatment interventions. This study aims to evaluate the practical use and clinical implications of integrating MinDag in the early treatment of bipolar disorder from the perspectives of both patients and clinicians. The MinDag app includes six content modules covering mood, sleep, functioning/activities, substance use, emotional reactivity, and psychotic symptoms. Patients were asked to use the app for six months, and automated feedback based on the app registrations was delivered to the patients’ clinicians biweekly. The study involved quantitative evaluations completed by patients (n = 20), as well as interviews with patients (n = 7) and clinicians (n = 2). Overall, the patients reported that they felt that MinDag was safe, relevant and easy to use, although technical difficulties such as too many automated reminders and need for reinstallations were reported. The patients appreciated the potential for increased awareness of their mental health, but expressed a desire for direct access to their data. Clinicians found the visual reports and feedback useful for tailoring treatment, even though the alert system for high-risk variables needed refinement. The quantitative evaluations indicated a positive general reception, with suggestions for improvement in usability and accessibility. The MinDag app shows promise as a tool for enhancing the treatment of bipolar disorder by facilitating self-monitoring and providing actionable data to clinicians. However, technical issues and the need for direct patient access to data must be addressed. Development of digital tools to support the treatment of bipolar disorder and other mental health conditions is resource demanding, and there is a need to clarify criteria to establish proof of concept to guide the selection of tools for upscaling and implementation.

Background Shared decision-making between clinicians and service users is crucial in mental health care. One significant barrier to achieving this goal is the lack of user-centered services. Integrating digital tools into mental health services holds promise for addressing some of these challenges. However, the implementation of digital tools, such as mobile apps, remains limited, and attrition rates for mental health apps are typically high. Design thinking can support the development of tools tailored to the needs of service users and clinicians. Objective This study aims to develop and beta test a digital tool designed for individuals with severe mental disorders or substance use disorders to facilitate shared decision-making on treatment goals and strategies within mental health services. Methods We used a user-centered design approach to develop iTandem, an app facilitating collaborative treatment between service users and clinicians. Through qualitative interviews and workshops, we engaged 6 service users with severe mental disorders or substance use disorders, 6 clinicians, and 1 relative to identify and design relevant app modules. A beta test of iTandem was conducted to refine the app and plan for a pilot trial in a clinical setting. After 6 weeks of app use, 5 clinicians and 4 service users were interviewed to provide feedback on the concept, implementation, and technical issues. Safety and ethical considerations were thoroughly discussed and addressed. Results To avoid overload for the service users, we applied a pragmatic take on module content and size. Thus, iTandem includes the following 8 modules, primarily based on the needs of service users and clinicians: Sleep (sleep diary), Medication (intake and side effects), Recovery (measures, including well-being and personal recovery, and exercises, including good things and personal strengths), Mood (mood diary and report of daily feelings), Psychosis (level of positive symptoms and their consequences and level of negative symptoms), Activity (goal setting and progress), Substance use (weekly use, potential triggers or strategies used to abstain), and Feedback on therapy (of individual sessions and overall rating of the past week). For the beta testing, service users and clinicians collaborated in choosing 2-3 modules in iTandem to work with during treatment sessions. The testing showed that the app was well received by service users, and that facilitation for implementation is crucial. Conclusions iTandem and similar apps have the potential to enhance treatment outcomes by facilitating shared decision-making and tailoring treatment to the needs of service users. However, successful implementation requires thorough testing, iterative development, and evaluations of both utility and treatment effects. There is a critical need to focus on how technology integrates into clinical settings—from development to implementation—and to conduct further research on early health technology assessments to guide these processes.

PurposePsychotropic and somatic medications are both used in treating severe mental disorders (SMDs). Realistic estimates of the prevalence of use across medication categories are needed. We obtained this in a clinical cohort of patients with SMD and healthy controls (HCs).Materials and methodsPrescriptions filled at Norwegian pharmacies the year before and after admittance to the Thematically Organized Psychosis (TOP) study were examined in 1406 patients with SMD (mean age 32.5 years, 48.2% women) and 920 HC (34.1 years, 46.2% women). Using data from the Norwegian Prescription Database (NorPD), the number of users in different anatomical therapeutic chemical (ATC) categories was compared using logistic regression. Population estimates were used as reference data.ResultsUse of antipsychotics (N05A), antiepileptics (N03A), antidepressants (N06A), anxiolytics (N05B), hypnotics and sedatives (N05C), anticholinergics (N04A), psychostimulants, attention deficit hyperactivity disorder and nootropic agents (N06B) and drugs for addiction disorders (N07B) was significantly more prevalent in patients with SMD than HC. Use of diabetes treatment (A10), antithrombotic drugs (B01), beta blockers (C07), lipid modifiers (C10), and thyroid and endocrine therapeutics (H03) was also more prevalent in patients with SMD, but with two exceptions somatic medication use was comparable to the general population. Among HC, there was low prevalence of use for most medication categories.ConclusionPatients were using psychiatric medications, but also several types of somatic medications, more often than HC. Still, somatic medication use was mostly not higher than in the general population. The results indicate that HC had low use of most medication types.

Cognitive impairment is a major determinant of functional outcomes in schizophrenia, however, understanding of the biological mechanisms underpinning cognitive dysfunction in the disorder remains incomplete. Here, we apply Genomic Structural Equation Modelling to identify latent cognitive factors capturing genetic liabilities to 12 cognitive traits measured in the UK Biobank. We identified three broad factors that underly the genetic correlations between the cognitive tests. We explore the overlap between latent cognitive factors, schizophrenia, and schizophrenia symptom dimensions using a complementary set of statistical approaches, applied to data from the latest schizophrenia genome-wide association study (Ncase = 53,386, Ncontrol = 77,258) and the Thematically Organised Psychosis study (Ncase = 306, Ncontrol = 1060). Global genetic correlations showed a significant moderate negative genetic correlation between each cognitive factor and schizophrenia. Local genetic correlations implicated unique genomic regions underlying the overlap between schizophrenia and each cognitive factor. We found substantial polygenic overlap between each cognitive factor and schizophrenia and biological annotation of the shared loci implicated gene-sets related to neurodevelopment and neuronal function. Lastly, we show that the common genetic determinants of the latent cognitive factors are not predictive of schizophrenia symptoms in the Norwegian Thematically Organized Psychosis cohort. Overall, these findings inform our understanding of cognitive function in schizophrenia by demonstrating important differences in the shared genetic architecture of schizophrenia and cognitive abilities.

BackgroundThe rate of suicide attempts by patients with bipolar disorder is high. In addition to patient and country specific factors, environmental factors may contribute to suicidal behavior. Sunlight has multiple diverse impacts on human physiology and behavior. Solar insolation is defined as the electromagnetic energy from the sun striking a surface area on earth. We previously found that a large change in solar insolation between the minimum and maximum monthly values was associated with an increased risk of suicide attempts in patients with bipolar I disorder.MethodsThe association between solar insolation and a history of suicide attempts in bipolar disorder was again investigated using an international database with 15% more data and more sites at diverse locations and countries.ResultsData were available from 5641 patients with bipolar I disorder living at a wide range of latitudes in 41 countries in both hemispheres. A large change in solar insolation between the minimum and maximum monthly values was associated with a history of suicide attempts in patients with bipolar I disorder, a replication of our prior analysis. The estimated model also associated state sponsored religion in the onset country, female gender, a history of alcohol or substance abuse, and being part of a younger birth cohort with a history of suicide attempts.ConclusionsA large change between the minimum and maximum monthly values of solar insolation was associated with a history of suicide attempts in bipolar I disorder, replicating our prior research. Physicians should be aware that daylight has wide ranging physiological and psychiatric impacts, and that living with large changes in solar insolation may be associated with an increased suicide risk.

BACKGROUND: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. METHODS: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). RESULTS: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. CONCLUSIONS: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.

Cases with schizophrenia (SCZ) and healthy controls show differences in white blood cell (WBC) counts and blood inflammation markers. Here, we investigate whether time of blood draw and treatment with psychiatric medications are related to differences in estimated WBC proportions between SCZ cases and controls. DNA methylation data from whole blood was used to estimate proportions of six subtypes of WBCs in SCZ patients ( n = 333) and healthy controls ( n = 396). We tested the association of case-control status with estimated cell-type proportions and the neutrophil-to-lymphocyte ratio (NLR) in 4 models: with/without adjusting for time of blood draw, and then compared results from blood samples drawn during a 12-h (07:00–19:00) or 7-h (07:00-14:00) period. We also investigated WBC proportions in a subgroup of medication-free patients ( n = 51). Neutrophil proportions were significantly higher in SCZ cases (mean=54.1%) vs. controls (mean=51.1%; p = <0.001), and CD8 + T lymphocyte proportions were lower in SCZ cases (mean=12.1%) vs. controls (mean=13.2%; p = 0.001). The effect sizes in the 12-h sample (07:00–19:00) showed a significant difference between SCZ vs. controls for neutrophils, CD4 + T, CD8 + T, and B-cells, which remained significant after adjusting for time of blood draw. In the samples matched for time of blood draw during 07.00–14.00, we also observed an association with neutrophils, CD4 + T, CD8 + T, and B-cells that was unaffected by further adjustment for time of blood draw. In the medication-free patients, we observed differences that remained significant in neutrophils ( p = 0.01) and CD4 + T ( p = 0.01) after adjusting for time of day. The association of SCZ with NLR was significant in all models (range: p < 0.001 to p = 0.03) in both medicated and unmedicated patients. In conclusion, controlling for pharmacological treatment and circadian cycling of WBC is necessary for unbiased estimates in case-control studies. Nevertheless, the association of WBC with SCZ remains, even after adjusting for the time of day.

IntroductionCognitive impairments are common in bipolar disorder (BD), but the long-term course remains understudied. Longitudinal data on cognitive functioning from the start of the first treatment could help clarify pathophysiological processes that shape the illness outcome. We here aim to investigate the 10-year cognitive course in BD compared to healthy controls (HC) and the effects of clinical symptoms on cognitive trajectories. MethodsFifty-six BD participants recruited within their first year of treatment and 108 HC completed clinical and cognitive assessments at baseline and 10-year follow-up. We derived eight cognitive domain scores and a cognitive composite score, which were further investigated using linear mixed model analyses. Correlation analyses were used to assess associations between the composite score and depressive, manic and psychotic symptoms. ResultsBD participants performed poorer than HCs in all domains except mental speed and verbal fluency. Verbal learning and memory, verbal fluency and the composite score improved over time in both BD participants and HC, while short-term memory, mental speed, psychomotor speed and working memory were stable. We found no significant correlations between cognition and symptom level at either time point in BD participants. ConclusionsWe found evidence of long-term cognitive stability or improvement in BD participants from first treatment to 10-year follow-up. Though the BD group was impaired in all domains except mental speed and verbal fluency, the change in cognitive functioning was parallel to that of HCs. These findings are not consistent with the notion of neuroprogression in BD.

Abstract Background Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. Methods Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. Results The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. Conclusion UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

There is substantial cognitive heterogeneity among patients with schizophrenia (SZ) and bipolar disorders (BD). More knowledge about the magnitude and clinical correlates of performance variability could improve our understanding of cognitive impairments. Using double generalized linear models (DGLMs) we investigated cognitive mean and variability differences between patients with SZ (n = 905) and BD spectrum disorders (n = 522), and healthy controls (HC, n = 1170) on twenty-two variables. The analysis revealed significant case-control differences on 90% of the variables. Compared to HC, patients showed larger intra-individual (within subject) variability across tests and larger inter-individual (between subject) variability in measures of fine-motor speed, mental processing speed, and inhibitory control (SZ and BD), and in verbal learning and memory and intellectual functioning (SZ). In SZ, we found that lager intra -and inter (on inhibitory control and speed functions) individual variability, was associated with lower functioning and more negative symptoms. Inter-individual variability on single measures of memory and intellectual function was additionally associated with disorganized and positive symptoms, and use of antidepressants. In BD, there were no within-subject associations with symptom severity. However, greater inter-individual variability (primarily on inhibitory control and speeded functions) was associated with lower functioning, more negative -and disorganized symptoms, earlier age at onset, longer duration of illness, and increased medication use. These results highlight larger individual differences in patients compared to controls on various cognitive domains. Further investigations of the causes and correlates of individual differences in cognitive function are warranted.

Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies of the Big 5 personality traits and cognitive function on our multivariate findings, boosting genetic discovery in other personality traits and improving polygenic prediction. These findings advance our understanding of the polygenic architecture of these complex mental traits, indicating a prominence of pleiotropic genetic effects across higher order domains of mental function such as personality and cognitive function. Hindley et al. used multivariate statistical genetics tools to examine the genetic underpinnings of cognitive and personality traits and find they are shared across higher order domains of mental functioning.

Background Intellectual functioning (IQ) is lower in schizophrenia patients compared to healthy controls, with bipolar patients intermediate between the two. Declines in IQ mark the onset of schizophrenia, while stability is generally found post-onset. There are to date few studies on long-term IQ development in bipolar disorder. This study presents 10-year follow-up data on IQ, including premorbid IQ estimates, to track the developmental course from pre-onset levels to long-term outcomes in both patient groups compared to healthy controls. Methods We included 139 participants with schizophrenia, 76 with bipolar disorder and 125 healthy controls. Mixed model analyses were used to estimate developmental slopes for IQ scores from estimated premorbid level (NART IQ) through baseline (WASI IQ) measured within 12 months post-onset, to 10-year follow-up (WASI IQ), with pairwise group comparisons. The best fit was found using a model with a breakpoint at baseline assessment. Results Only the schizophrenia group had significant declines from estimated premorbid to baseline IQ levels compared to controls. When comparing patient groups, schizophrenia patients had steeper declines than the bipolar group. Increases in IQ were found in all groups over the follow-up period. Conclusions Trajectories of IQ from premorbid level to 10-year follow-up indicated declines from estimated premorbid level to illness onset in both patient groups, followed by increases during the follow-up period. Schizophrenia patients had a steeper decline than bipolar patients. During follow-up, increases indicate developmental improvement for both patient groups, but with a maintained lag compared to healthy controls due to lower premorbid levels.

Background The relationship between psychotic disorders and cannabis use is heavily debated. Shared underlying genetic risk is one potential explanation. We investigated the genetic association between psychotic disorders (schizophrenia and bipolar disorder) and cannabis phenotypes (lifetime cannabis use and cannabis use disorder). Methods We used genome-wide association summary statistics from individuals with European ancestry from the Psychiatric Genomics Consortium, UK Biobank, and International Cannabis Consortium. We estimated heritability, polygenicity, and discoverability of each phenotype. We performed genome-wide and local genetic correlations. Shared loci were identified and mapped to genes, which were tested for functional enrichment. Shared genetic liabilities to psychotic disorders and cannabis phenotypes were explored using causal analyses and polygenic scores, using the Norwegian Thematically Organized Psychosis cohort. Findings Psychotic disorders were more heritable than cannabis phenotypes and more polygenic than cannabis use disorder. We observed positive genome-wide genetic correlations between psychotic disorders and cannabis phenotypes (range 0 center dot 22-0 center dot 35) with a mixture of positive and negative local genetic correlations. Three to 27 shared loci were identified for the psychotic disorder and cannabis phenotype pairs. Enrichment of mapped genes implicated neuronal and olfactory cells as well as drug-gene targets for nicotine, alcohol, and duloxetine. Psychotic disorders showed a causal effect on cannabis phenotypes, and lifetime cannabis use had a causal effect on bipolar disorder. Of 2181 European participants from the Norwegian Thematically Organized Psychosis cohort applied in polygenic risk score analyses, 1060 (48 center dot 6%) were females and 1121 (51 center dot 4%) were males (mean age 33 center dot 1 years [SD 11 center dot 8]). 400 participants had bipolar disorder, 697 had schizophrenia, and 1044 were healthy controls. Within this sample, polygenic scores for cannabis phenotypes predicted psychotic disorders independently and improved prediction beyond the polygenic score for the psychotic disorders. Interpretation A subgroup of individuals might have a high genetic risk of developing a psychotic disorder and using cannabis. This finding supports public health efforts to reduce cannabis use, particularly in individuals at high risk or patients with psychotic disorders. Identified shared loci and their functional implications could facilitate development of novel treatments. Copyright (c) 2023 Elsevier Ltd. All rights reserved.

Introduction:The Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnostic category "Psychotic disorder not otherwise specified" (PNOS) is seldom investigated, and we lack knowledge about long-term outcomes. We examined long-term symptom severity, global functioning, remission/recovery rates, and diagnostic stability after the first treatment for PNOS. Methods:Participants with first-treatment PNOS (n = 32) were reassessed with structured interviews after 7 to 10 years. The sample also included narrow schizophrenia spectrum disorders (SSD, n = 94) and psychotic bipolar disorders (PBD, n = 54). Symptomatic remission was defined based on the Remission in Schizophrenia Working Group criteria. Clinical recovery was defined as meeting the criteria for symptomatic remission and having adequate functioning for the last 12 months. Results:Participants with baseline PNOS or PBD had lower symptom severity and better global functioning at follow-up than those with SSD. More participants with PNOS and PBD were in symptomatic remission and clinical recovery compared to participants with SSD. Seventeen (53%) PNOS participants retained the diagnosis, while 15 participants were diagnosed with either SSD (22%), affective disorders (19%), or substance-induced psychotic disorders (6%). Those rediagnosed with SSD did not differ from the other PNOS participants regarding baseline clinical characteristics. Conclusions:Long-term outcomes are more favorable in PNOS and PBD than in SSD. Our findings confirm diagnostic instability but also stability for a subgroup of participants with PNOS. However, it is challenging to predict diagnostic outcomes of PNOS based on clinical characteristics at first treatment.