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Background: Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders. Methods: The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration. Results: Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006). Conclusions: Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis. [ABSTRACT FROM AUTHOR]

The reading the mind in the eyes test (RMET) – which assesses the theory of mind component of social cognition – is often used to compare social cognition between patients with schizophrenia and healthy controls. There is, however, no systematic review integrating the results of these studies. We identified 198 studies published before July 2020 that administered RMET to patients with schizophrenia or healthy controls from three English-language and two Chinese-language databases. These studies included 41 separate samples of patients with schizophrenia (total n = 1836) and 197 separate samples of healthy controls (total n = 23 675). The pooled RMET score was 19.76 (95% CI 18.91–20.60) in patients and 25.53 (95% CI 25.19–25.87) in controls (z = 12.41, p < 0.001). After excluding small-sample outlier studies, this difference in RMET performance was greater in studies using non-English v. English versions of RMET (Chi [Q] = 8.54, p < 0.001). Meta-regression analyses found a negative association of age with RMET score and a positive association of years of schooling with RMET score in both patients and controls. A secondary meta-analysis using a spline construction of 180 healthy control samples identified a non-monotonic relationship between age and RMET score – RMET scores increased with age before 31 and decreased with age after 31. These results indicate that patients with schizophrenia have substantial deficits in theory of mind compared with healthy controls, supporting the construct validity of RMET as a measure of social cognition. The different results for English versus non-English versions of RMET and the non-monotonic relationship between age and RMET score highlight the importance of the language of administration of RMET and the possibility that the relationship of aging with theory of mind is different from the relationship of aging with other types of cognitive functioning. [ABSTRACT FROM AUTHOR]

Background: Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models. Methods: Participants from both the NAPLS2 and NAPLS3 samples were classified as either 'long' or 'short' symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis. Results: The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78). Conclusions: These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Social cognition has not previously been assessed in treatment-naive patients with chronic schizophrenia, in patients over 60 years of age, or in patients with less than 5 years of schooling. Methods: We revised a commonly used measure of social cognition, the Reading the Mind in the Eyes Test (RMET), by expanding the instructions, using both self-completion and interviewer-completion versions (for illiterate respondents), and classifying each test administration as 'successfully completed' or 'incomplete'. The revised instrument (RMET-CV-R) was administered to 233 treatment-naive patients with chronic schizophrenia (UT), 154 treated controls with chronic schizophrenia (TC), and 259 healthy controls (HC) from rural communities in China. Results: In bivariate and multivariate analyses, successful completion rates and RMET-CV-R scores (percent correct judgments about emotion exhibited in 70 presented slides) were highest in HC, intermediate in TC, and lowest in UT (adjusted completion rates, 97.0, 72.4, and 49.9%, respectively; adjusted RMET-CV-R scores, 45.4, 38.5, and 34.6%, respectively; all p < 0.02). Stratified analyses by the method of administration (self-completed v. interviewer-completed) and by education and age ('educated-younger' v. 'undereducated-older') show the same relationship between groups (i.e. NC>TC>UT), though not all differences remain statistically significant. Conclusions: We find poorer social cognition in treatment-naive than in treated patients with chronic schizophrenia. The discriminant validity of RMET-CV-R in undereducated, older patients demonstrates the feasibility of administering revised versions of RMET to patients who may otherwise be considered ineligible due to education or age by changing the method of test administration and carefully assessing respondents' ability to complete the task successfully. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment. Our objective was to apply a risk calculator (RC) to identify people that would benefit from antipsychotics. Methods: Drawing on 400 CHR individuals recruited between 2011 and 2016, 208 individuals who received antipsychotic treatment were included. Clinical and cognitive variables were entered into an individualized RC for psychosis; personal risk was estimated and 4 risk components (negative symptoms-RC-NS, general function-RC-GF, cognitive performance-RC-CP, and positive symptoms-RC-PS) were constructed. The sample was further stratified according to the risk level. Higher risk was defined based on the estimated risk score (20% or higher). Results: In total, 208 CHR individuals received daily antipsychotic treatment of an olanzapine-equivalent dose of 8.7 mg with a mean administration duration of 58.4 weeks. Of these, 39 (18.8%) developed psychosis within 2 years. A new index of factors ratio (FR), which was derived from the ratio of RC-PS plus RC-GF to RC-NS plus RC-CP, was generated. In the higher-risk group, as FR increased, the conversion rate decreased. A small group (15%) of CHR individuals at higher-risk and an FR >1 benefitted from the antipsychotic treatment. Conclusions: Through applying a personal risk assessment, the administration of antipsychotics should be limited to CHR individuals with predominantly positive symptoms and related function decline. A strict antipsychotic prescription strategy should be introduced to reduce inappropriate use. [ABSTRACT FROM AUTHOR]

Background: Antisaccade tasks can be used to index cognitive control processes, e.g. attention, behavioral inhibition, working memory, and goal maintenance in people with brain disorders. Though diagnoses of schizophrenia (SZ), schizoaffective (SAD), and bipolar I with psychosis (BDP) are typically considered to be distinct entities, previous work shows patterns of cognitive deficits differing in degree, rather than in kind, across these syndromes. Methods: Large samples of individuals with psychotic disorders were recruited through the Bipolar-Schizophrenia Network on Intermediate Phenotypes 2 (B-SNIP2) study. Anti- and pro-saccade task performances were evaluated in 189 people with SZ, 185 people with SAD, 96 people with BDP, and 279 healthy comparison participants. Logistic functions were fitted to each group's antisaccade speed-performance tradeoff patterns. Results: Psychosis groups had higher antisaccade error rates than the healthy group, with SZ and SAD participants committing 2 times as many errors, and BDP participants committing 1.5 times as many errors. Latencies on correctly performed antisaccade trials in SZ and SAD were longer than in healthy participants, although error trial latencies were preserved. Parameters of speed-performance tradeoff functions indicated that compared to the healthy group, SZ and SAD groups had optimal performance characterized by more errors, as well as less benefit from prolonged response latencies. Prosaccade metrics did not differ between groups. Conclusions: With basic prosaccade mechanisms intact, the higher speed-performance tradeoff cost for antisaccade performance in psychosis cases indicates a deficit that is specific to the higher-order cognitive aspects of saccade generation. [ABSTRACT FROM AUTHOR]

Background: The ability to manage emotions is an important social-cognitive domain impaired in schizophrenia and linked to functional outcome. The goal of our study was to examine the impact of cognitive enhancement therapy (CET) on the ability to manage emotions and brain functional connectivity in early-course schizophrenia. Methods: Participants were randomly assigned to CET (n = 55) or an enriched supportive therapy (EST) control group (n = 45). The resting-state functional magnetic resonance imaging scans and measures of emotion management performances were collected at baseline, 9, and 18 months follow-up. The final sample consisted of 37 CET and 25 EST participants, including 19 CET and 12 EST participants with imaging data. Linear mixed-effects models investigated the impact of treatment on emotion management and functional connectivity from the amygdala to ventrolateral and dorsolateral prefrontal cortex (dlPFC). Results: The CET group showed significant improvement over time in emotion management compared to EST. Neither functional connectivity changes nor main group differences were observed following treatment. However, a significant between-group interaction showed that improved emotion management ability was associated with increased functional connectivity between the left amygdala and the left dlPFC in the CET group exclusively. Conclusion: Our results replicate the previous work demonstrating that CET is effective at improving some aspects of social cognition in schizophrenia. We found evidence that improvement in emotion management may be associated with a change in amygdala-dlPFC connectivity. This fronto-limbic circuit may provide a mechanistic link between the biology of emotion management processes that can be enhanced in individuals with schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits. Participants and Methods: Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%). Results: A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2). Conclusions: Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes. [ABSTRACT FROM AUTHOR]

Background: Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program. Method: In total, 400 CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Syndromes. In the first phase of 300 CHR individuals, 196 subjects (65.3%) who completed neurocognitive assessments and had at least a 2-year follow-up assessment were included in the construction of an RC for psychosis. In the second phase of the SHARP sample of 100 subjects, 93 with data integrity were included to validate the performance of the SHARP-RC. Results: The SHARP-RC showed good discrimination of subsequent transition to psychosis with an AUC of 0.78 (p < 0.001). The individualized risk generated by the SHARP-RC provided a solid estimation of conversion in the independent validation sample, with an AUC of 0.80 (p = 0.003). A risk estimate of 20% or higher had excellent sensitivity (84%) and moderate specificity (63%) for the prediction of psychosis. The relative contribution of individual risk components can be simultaneously generated. The mobile app-based SHARP-RC was developed as a convenient tool for individualized psychosis risk appraisal. Conclusions: The SHARP-RC provides a practical tool not only for assessing the probability that an individual at CHR will develop full psychosis, but also personal risk components that might be targeted in early intervention. [ABSTRACT FROM AUTHOR]

Background: Despite significant advancements in healthcare technology, digital health solutions – especially those for serious mental illnesses – continue to fall short of their potential across both clinical practice and efficacy. The utility and impact of medicine, including digital medicine, hinges on relationships, trust, and engagement, particularly in the field of mental health. This paper details results from Phase 1 of a two-part study that seeks to engage people with schizophrenia, their family members, and clinicians in co-designing a digital mental health platform for use across different cultures and contexts in the United States and India. Methods: Each site interviewed a mix of clinicians, patients, and their family members in focus groups (n = 20) of two to six participants. Open-ended questions and discussions inquired about their own smartphone use and, after a demonstration of the mindLAMP platform, specific feedback on the app's utility, design, and functionality. Results: Our results based on thematic analysis indicate three common themes: increased use and interest in technology during coronavirus disease 2019 (COVID-19), concerns over how data are used and shared, and a desire for concurrent human interaction to support app engagement. Conclusion: People with schizophrenia, their family members, and clinicians are open to integrating technology into treatment to better understand their condition and help inform treatment. However, app engagement is dependent on technology that is complementary – not substitutive – of therapeutic care from a clinician. [ABSTRACT FROM AUTHOR]

Background: Neurological Examination Abnormalities (NES) are quantified by measuring subtle, partially localizable (cerebello-thalamo-prefrontal cortical circuit) and heritable neurological signs comprising sensory integration, motor coordination and complex motor sequencing that are associated with first-episode psychosis (FEP). A few studies have evaluated NES longitudinally and as a predictor for diagnostic and response classification, but these studies have been confounded, underpowered and divergent. We examined (1) baseline and longitudinal NES differences between diagnostic and year 1 response groups; (2) if NES predicts diagnostic and response groups and (3) relationships between clinical variables and NES measures in antipsychotic-naïve FEP. Methods: NES and clinical measures were obtained for FEP-schizophrenia (FEP-SZ, n = 232), FEP non-schizophrenia (FEP-NSZ, n = 117) and healthy controls (HC, n = 204). Response groups with >25% improvement in average year 1 positive and negative symptomatology scores were classified as responsive (n = 97) and <25% improvement as non-responsive (n = 95). Analysis of covariance, NES trajectory analysis and logistic regression models assessed diagnostic and response group differences. Baseline and longitudinal NES relationships with clinical variables were performed with Spearman correlations. Data were adjusted for age, sex, race, socioeconomic status and handedness. Results: Cognitive perceptual (COGPER) score was better than repetitive motor (REPMOT) at differentiating FEP-SZ from FEP-NSZ and distinguishing responders from non-responders. We identified significant group-specific associations between COGPER and worse GAF, positive and negative symptomatology and some of these findings persisted at 1-year assessment. Conclusion: NES are an easy to administer, bedside-elicited, endophenotypic measure and could be a cost-effective clinical tool in antipsychotic-naïve FEP. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD) and schizophrenia are neurodevelopmental disorders which share substantial overlap in cognitive deficits during adulthood. However, treatment evaluation in ASD and treatment comparisons across ASD and schizophrenia are limited by a dearth of empirical work establishing the validity of a standard cognitive battery across ASD and schizophrenia. Promisingly, the MATRICS Consensus Cognitive Battery (MCCB) has been validated in schizophrenia and encompasses cognitive domains that are impacted in ASD. Thus, this study aimed to establish MCCB's generalizability from schizophrenia to ASD. Methods: Community-residing adults with schizophrenia (N = 100) and ASD (N = 113) underwent MCCB assessment. Using multigroup confirmatory factor analysis, MCCB's transdiagnostic validity was evaluated by examining whether schizophrenia and ASD demonstrate the same configuration, magnitude, and directionality of relationships within and among measures and their underlying cognitive domains. Results: Across schizophrenia and ASD, the same subsets of MCCB measures inform three cognitive domains: processing speed, attention/working memory, and learning. Except for group means in category fluency, continuous performance, and spatial span, both groups show vastly comparable factor structures and characteristics. Conclusions: To our knowledge, this study is the first to establish the validity of a standard cognitive battery in adults with ASD and furthermore the first to establish a cognitive battery's comparability across ASD and schizophrenia. Cognitive domain scores can be compared across new samples using weighted sums of MCCB scores resulting from this study. These findings highlight MCCB's applicability to ASD and support its utility for standardizing treatment evaluation of cognitive outcomes across the autism-schizophrenia spectrum. [ABSTRACT FROM AUTHOR]

Improving understanding of and outcomes for early-course psychosis (ECP) is a recognised global mental health priority. We argue digital health technologies can advance care for ECP by better accounting for clinical heterogeneity, offering better predictive models, increasing access to early interventions and enhancing existing treatment options.Declaration of interestL.M.T. owns shares in Safari Health Inc - a digital health technology company. [ABSTRACT FROM AUTHOR]

Given the substantial overlap in cognitive dysfunction between bipolar disorder (BD) and schizophrenia (SZ), we examined the utility of the MATRICS Consensus Cognitive Battery (MCCB)—developed for use in SZ—for the measurement of cognition in patients with BD with psychosis (BDP) and its association with community functioning. The MCCB, Multnomah Community Ability Scale, and measures of clinical symptoms were administered to participants with BDP (n=56), SZ (n=37), and healthy controls (HC) (n=57). Groups were compared on clinical and cognitive measures; linear regressions examined associations between MCCB and community functioning. BDP and SZ groups performed significantly worse than HC on most neurocognitive domains; BDP and HC did not differ on Social Cognition. Patients with BDP performed better than patients with SZ on most cognitive measures, although groups only differed on social cognition, working memory, verbal memory, and the composite after controlling for clinical variables. MCCB was not associated with community functioning. The MCCB is an appropriate measure of neurocognition in BDP but does not appear to capture social cognitive deficits in this population. The addition of appropriate social cognitive measures is recommended. (JINS, 2015, 21, 468–472) [ABSTRACT FROM AUTHOR]

In this paper, we review the history of the concept of neuroplasticity as it relates to the understanding of neuropsychiatric disorders, using schizophrenia as a case in point. We briefly review the myriad meanings of the term neuroplasticity, and its neuroscientific basis. We then review the evidence for aberrant neuroplasticity and metaplasticity associated with schizophrenia as well as the risk for developing this illness, and discuss the implications of such understanding for prevention and therapeutic interventions. We argue that the failure and/or altered timing of plasticity of critical brain circuits might underlie cognitive and deficit symptoms, and may also lead to aberrant plastic reorganization in other circuits, leading to affective dysregulation and eventually psychosis. This “dysplastic” model of schizophrenia can suggest testable etiology and treatment-relevant questions for the future. [ABSTRACT FROM AUTHOR]

Objective: Olfactory identification deficits (OIDs) are seen in schizophrenia, but it is unclear whether they are state- or trait-related. Methods: We examined the prevalence of OIDs, as assessed by the University of Pennsylvania Smell Identification Test (UPSIT), and their correlations with prodromal symptoms in young relatives at risk for schizophrenia or schizoaffective disorder (HR-S). Results: UPSIT scores were lower in HR- S than in healthy controls, but were non-significant after covarying the effects of age, gender and IQ. OID deficits in HR-S were correlated, after covarying out the effects of age and IQ, with prodromal disorganisation. Conclusion: The potential value of OID deficits as markers of psychopathological vulnerability in young relatives at risk for schizophrenia deserves further investigation. [ABSTRACT FROM AUTHOR]

We describe a patient with marked elevations of creatine kinase following institution of clozapine treatment. The enzyme levels promptly subsided with discontinuation of clozapine. The clinical features did not meet any of the published criteria for neuroleptic malignant syndrome. [ABSTRACT FROM AUTHOR]

The authors look at the correlation between involuntary movements (IMs) and first-episode psychoses. They stress that IMs are often manifested in medication-naïve patients and that it is still unclear whether IMs are medication-induced phenomena or a phenotypic-trait related features of schizophrenia. The authors discuss the findings of their study on the relationship between IMs in medication-free first-episode psychosis patients and positive and negative symptoms and executive function.

The article considers the capacity of an elephant for self-reflection and mentalize, based of observation at an elephant training camp in Chiang Mai, Thailand. It is suggested that functional magnetic resonance imaging can be used in determining the neural networks governing this capacity to mentalize. A discussion on metacognition and the concept of the theory of the mind is presented.

The article offers a look at the contribution of two German psychiatrists, Karl Ludwig Kahlbaum and Ewald Hecker, to the field of psychiatry. Kahlbaum has identified the important aetiological role of parenting upbringing, with reference to schizophrenia as juvenile madness. Meanwhile, Hecker has expounded hebephrenia and described a disorganised form of chronic idiopathic psychosis that arose in youth.

Caudate nuclei are smaller in drug-naive people with schizophrenia but larger in antipsychotic-treated patients. In this magnetic resonance imaging study we found volume reduction of right and left caudate by 8.9 and 8.1% respectively in 50 offspring without psychosis of patients with schizophrenia compared with 53 age- and gender-matched controls, providing new evidence that caudate volume reduction may be a trait-related abnormality in schizophrenia. [ABSTRACT FROM AUTHOR]

The article offers information on psychiatrists Emil Kraepelin and Adolf Meyer. Both Kraepelin and Meyer believed that understanding of psychological problems was best achieved through consideration of life circumstances. Kraepelin introduced the first widely accepted systematic classification of psychiatric disorders, while Meyer introduced both Kraepelins' classificatory system and Sigmund Freud's ideas into mainstream American psychiatry.

Background: Despite significant advancements in healthcare technology, digital health solutions - especially those for serious mental illnesses - continue to fall short of their potential across both clinical practice and efficacy. The utility and impact of medicine, including digital medicine, hinges on relationships, trust, and engagement, particularly in the field of mental health. This paper details results from Phase 1 of a two-part study that seeks to engage people with schizophrenia, their family members, and clinicians in co-designing a digital mental health platform for use across different cultures and contexts in the United States and India., Methods: Each site interviewed a mix of clinicians, patients, and their family members in focus groups ( n = 20) of two to six participants. Open-ended questions and discussions inquired about their own smartphone use and, after a demonstration of the mindLAMP platform, specific feedback on the app's utility, design, and functionality., Results: Our results based on thematic analysis indicate three common themes: increased use and interest in technology during coronavirus disease 2019 (COVID-19), concerns over how data are used and shared, and a desire for concurrent human interaction to support app engagement., Conclusion: People with schizophrenia, their family members, and clinicians are open to integrating technology into treatment to better understand their condition and help inform treatment. However, app engagement is dependent on technology that is complementary - not substitutive - of therapeutic care from a clinician., Competing Interests: None., (© The Author(s) 2021.)

Background: Social cognition has not previously been assessed in treatment-naive patients with chronic schizophrenia, in patients over 60 years of age, or in patients with less than 5 years of schooling., Methods: We revised a commonly used measure of social cognition, the Reading the Mind in the Eyes Test (RMET), by expanding the instructions, using both self-completion and interviewer-completion versions (for illiterate respondents), and classifying each test administration as 'successfully completed' or 'incomplete'. The revised instrument (RMET-CV-R) was administered to 233 treatment-naive patients with chronic schizophrenia (UT), 154 treated controls with chronic schizophrenia (TC), and 259 healthy controls (HC) from rural communities in China., Results: In bivariate and multivariate analyses, successful completion rates and RMET-CV-R scores (percent correct judgments about emotion exhibited in 70 presented slides) were highest in HC, intermediate in TC, and lowest in UT (adjusted completion rates, 97.0, 72.4, and 49.9%, respectively; adjusted RMET-CV-R scores, 45.4, 38.5, and 34.6%, respectively; all p < 0.02). Stratified analyses by the method of administration (self-completed v. interviewer-completed) and by education and age ('educated-younger' v. 'undereducated-older') show the same relationship between groups (i.e. NC>TC>UT), though not all differences remain statistically significant., Conclusions: We find poorer social cognition in treatment-naive than in treated patients with chronic schizophrenia. The discriminant validity of RMET-CV-R in undereducated, older patients demonstrates the feasibility of administering revised versions of RMET to patients who may otherwise be considered ineligible due to education or age by changing the method of test administration and carefully assessing respondents' ability to complete the task successfully.

Background: Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment. Our objective was to apply a risk calculator (RC) to identify people that would benefit from antipsychotics., Methods: Drawing on 400 CHR individuals recruited between 2011 and 2016, 208 individuals who received antipsychotic treatment were included. Clinical and cognitive variables were entered into an individualized RC for psychosis; personal risk was estimated and 4 risk components (negative symptoms-RC-NS, general function-RC-GF, cognitive performance-RC-CP, and positive symptoms-RC-PS) were constructed. The sample was further stratified according to the risk level. Higher risk was defined based on the estimated risk score (20% or higher)., Results: In total, 208 CHR individuals received daily antipsychotic treatment of an olanzapine-equivalent dose of 8.7 mg with a mean administration duration of 58.4 weeks. Of these, 39 (18.8%) developed psychosis within 2 years. A new index of factors ratio (FR), which was derived from the ratio of RC-PS plus RC-GF to RC-NS plus RC-CP, was generated. In the higher-risk group, as FR increased, the conversion rate decreased. A small group (15%) of CHR individuals at higher-risk and an FR >1 benefitted from the antipsychotic treatment., Conclusions: Through applying a personal risk assessment, the administration of antipsychotics should be limited to CHR individuals with predominantly positive symptoms and related function decline. A strict antipsychotic prescription strategy should be introduced to reduce inappropriate use.

Background: Symptoms of serious mental illness are multidimensional and often interact in complex ways. Generative models offer value in elucidating the underlying relationships that characterise these networks of symptoms., Aims: In this paper we use generative models to find unique interactions of schizophrenia symptoms as experienced on a moment-by-moment basis., Method: Self-reported mood, anxiety and psychosis symptoms, self-reported measurements of sleep quality and social function, cognitive assessment, and smartphone touch screen data from two assessments modelled after the Trail Making A and B tests were collected with a digital phenotyping app for 47 patients in active treatment for schizophrenia over a 90-day period. Patients were retrospectively divided up into various non-exclusive subgroups based on measurements of depression, anxiety, sleep duration, cognition and psychosis symptoms taken in the clinic. Associated transition probabilities for the patient cohort and for the clinical subgroups were calculated using state transitions between adjacent 3-day timesteps of pairwise survey domains., Results: The three highest probabilities for associated transitions across all patients were anxiety-inducing mood (0.357, P < 0.001), psychosis-inducing mood (0.276, P < 0.001), and anxiety-inducing poor sleep (0.268, P < 0.001). These transition probabilities were compared against a validation set of 17 patients from a pilot study, and no significant differences were found. Unique symptom networks were found for clinical subgroups., Conclusions: Using a generative model using digital phenotyping data, we show that certain symptoms of schizophrenia may play a role in elevating other schizophrenia symptoms in future timesteps. Symptom networks show that it is feasible to create clinically interpretable models that reflect the unique symptom interactions of psychosis-spectrum illness. These results offer a framework for researchers capturing temporal dynamics, for clinicians seeking to move towards preventative care, and for patients to better understand their lived experience.

Background: As mental healthcare expands to smartphone apps and other technologies that may offer therapeutic interventions without a therapist involved, it is important to assess the impact of non-traditional therapeutic relationships.AimsTo determine if there were any meaningful data regarding the digital therapeutic alliance in smartphone interventions for serious mental illnesses., Method: A literature search was conducted in four databases (PubMed, PsycINFO, Embase and Web of Science)., Results: There were five studies that discuss the therapeutic alliance when a mobile application intervention is involved in therapy. However, in none of the studies was the digital therapeutic alliance the primary outcome. The studies looked at different mental health conditions, had different duration of technology use and used different methods for assessing the therapeutic alliance., Conclusions: Assessing and optimising the digital therapeutic alliance holds the potential to make tools such as smartphone apps more effective and improve adherence to their use. However, the heterogeneous nature of the five studies we identified make it challenging to draw conclusions at this time. A measure is required to evaluate the digital therapeutic alliance.

In this paper, we review the history of the concept of neuroplasticity as it relates to the understanding of neuropsychiatric disorders, using schizophrenia as a case in point. We briefly review the myriad meanings of the term neuroplasticity, and its neuroscientific basis. We then review the evidence for aberrant neuroplasticity and metaplasticity associated with schizophrenia as well as the risk for developing this illness, and discuss the implications of such understanding for prevention and therapeutic interventions. We argue that the failure and/or altered timing of plasticity of critical brain circuits might underlie cognitive and deficit symptoms, and may also lead to aberrant plastic reorganization in other circuits, leading to affective dysregulation and eventually psychosis. This "dysplastic" model of schizophrenia can suggest testable etiology and treatment-relevant questions for the future.

Background: Prefrontal cortical dysfunctions, including disturbances in adaptive context-specific behavior, have been reported in neuropsychological and brain imaging studies of schizophrenia. Some data suggest that treatment with antipsychotic medications may ameliorate these deficits., Method: We investigated antisaccade performance in 39 antipsychotic-naive, first-episode schizophrenia patients who were re-evaluated 6 weeks after treatment initiation. A group of matched healthy subjects were examined at similar time-points. Patients and healthy individuals available for longer-term testing were re-assessed 26 and 52 weeks after initial testing., Results: Before treatment, patients showed elevated rates of response suppression errors and prolonged latencies of correct antisaccades. Increased rates of antisaccade errors were associated with faster response latencies during a separate, visually guided saccade task, but only prior to treatment. Throughout the 1-year follow-up, patients progressively improved in their ability to voluntarily suppress context-inappropriate behavior. Although treatment assignment was by clinician choice, results of exploratory analyses revealed that patients treated with risperidone progressively planned and initiated correct antisaccades more quickly than patients receiving haloperidol., Conclusions: Deficits in the voluntary control of spatial attention are exaggerated during acute episodes of illness, but remain an enduring aspect of prefrontal dysfunction in schizophrenia even after treatment. During acute illness, speeded sensorimotor transformations may compound these deficits and contribute to the heightened distractibility associated with acute psychosis. Continued improvement in task performance throughout the 1-year follow-up suggests that partial normalization of prefrontal cognitive functions resulting from antipsychotic treatment may have a longer and more gradual time course than the reduction of acute psychotic symptoms.

Studies on schizophrenia (SZ) have documented an increased presence of cavum septi pellucidi (CSP) in individuals suffering from the illness. Moreover, the presence of CSP has been cited in support of the early neurodevelopmental hypothesis in SZ. Our objective was to assess the magnetic resonance imaging (MRI) scans of first-episode patients and healthy controls to evaluate the frequency of CSP. The presence and the size of CSP were visually assessed on the MRI scans of 40 first-episode SZ patients, 19 nonpsychotic child and high-risk adolescent offspring of patients with SZ or schizoaffective disorder, and 59 controls. Our analysis revealed an absence of statistically significant differences in the occurrence of CSP between SZ patients, high-risk subjects, and controls. Even when the analysis was restricted to large CSP, no differences were found. Furthermore, no association between CSP and sex or handedness was observed. The absence of CSP abnormalities in first-episode SZ subjects might indicate that SZ is not characterized by developmentally mediated alterations in CSP. Also, family history of SZ might not increase likelihood for CSP.