Neural dysfunction underlying working memory processing at different stages of the illness course in schizophrenia: a comparative meta-analysis.

Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.

N400 event-related brain potential index of semantic processing and two-year clinical outcomes in persons at high risk for psychosis: A longitudinal study.

The N400 event-related brain potential (ERP) semantic priming effect reflects greater activation of contextually related versus unrelated concepts in long-term semantic memory. Deficits in this measure have been found in persons with schizophrenia and those at clinical high risk (CHR) for this disorder. In CHR patients, we previously found that these deficits predict poorer social functional outcomes after 1 year. In the present study, we tested whether these deficits predicted greater psychosis-spectrum symptom severity and functional impairment over 2 years. We measured N400 semantic priming effects at baseline in CHR patients (n = 47) who viewed prime words each followed by a related/unrelated target word at stimulus-onset asynchronies (SOAs) of 300 or 750 ms. We measured psychosis-spectrum symptoms using the Structured Interview for Prodromal Symptoms and role and social functioning with the Global Functioning: Role and Social scales, at baseline, 1 (n = 29) and 2 years (n = 25). There was a significant interaction between the N400 semantic priming effect at the 300-ms SOA and time on GF:Role scores, indicating that, contrary to expectations, smaller baseline N400 semantic priming effects were associated with more improvement in role functioning from baseline to Year 1, but baseline N400 priming effects did not predict role functioning at Year 2. N400 priming effects were not significantly associated with different trajectories in psychosis-spectrum symptoms or social functioning. Thus, CHR patients' N400 semantic priming effects did not predict clinical outcomes over 2 years, suggesting that this ERP measure may have greater value as a state or short-term prognostic neurophysiological biomarker.

Network Meta-Analysis Indicates Superior Effects of Omega-3 Polyunsaturated Fatty Acids in Preventing the Transition to Psychosis in Individuals at Clinical High-Risk.

BACKGROUND: The efficacy of pharmacological and nutritional interventions in individuals at clinical high risk for psychosis (CHR-P) remains elusive. This study aims to investigate the efficacy of pharmacological and nutritional interventions in CHR-P and whether these interventions can enhance the efficacy of psychological treatments. METHODS: We systematically reviewed data from 5 databases until July 24, 2021: PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, and WanFang Data. The primary outcome was the transition to psychosis. Network meta-analyses were conducted at 3 time points (6, 12, and ≥24 months) considering both pharmacological/nutritional interventions alone and its combination with psychotherapy. RESULTS: Out of 11 417 identified references, 21 studies were included, comprising 1983 participants. CHR-P participants receiving omega-3 polyunsaturated fatty acids treatment were associated with a lower probability of transition compared with placebo/control at 6 months (odds ratio [OR] = 0.07, 95% confidence interval [CI] = .01 to .054), 12 months (OR = 0.14, 95% CI = .03 to .66), and ≥24 months (OR = 0.16, 95% CI = .05 to .54). Moreover, risperidone plus psychotherapy was associated with a lower likelihood of transition at 6 months compared with placebo/control plus psychotherapy, but this result was not sustained over longer durations. CONCLUSION: Omega-3 polyunsaturated fatty acids helped in preventing transitions to psychosis compared with controls. PROSPERO REGISTRATION NUMBER: CRD42021256209.

Improving prediction of psychosis in youth at clinical high-risk: pre-baseline symptom duration and cortical thinning as moderators of the NAPLS2 risk calculator.

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.

Assessing evidence supporting cannabis harm reduction practices for adolescents at clinical high-risk for psychosis: a review and clinical implementation tool.

Cannabis use is consistently associated with both increased incidence of frank psychotic disorders and acute exacerbations of psychotic symptoms in healthy individuals and people with psychosis spectrum disorders. Although there is uncertainty around causality, cannabis use may be one of a few modifiable risk factors for conversion to psychotic disorders in individuals with Clinical High Risk for Psychosis (CHR-P) syndromes, characterized by functionally impairing and distressing subthreshold psychotic symptoms. To date, few recommendations beyond abstinence to reduce adverse psychiatric events associated with cannabis use have been made. This narrative review synthesizes existing scientific literature on cannabis' acute psychotomimetic effects and epidemiological associations with psychotic disorders in both CHR-P and healthy individuals to bridge the gap between scientific knowledge and practical mental health intervention. There is compelling evidence for cannabis acutely exacerbating psychotic symptoms in CHR-P, but its impact on conversion to psychotic disorder is unclear. Current evidence supports a harm reduction approach in reducing frequency of acute psychotic-like experiences, though whether such interventions decrease CHR-P individuals' risk of conversion to psychotic disorder remains unknown. Specific recommendations include reducing frequency of use, lowering delta-9-tetrahydrocannabinol content in favor of cannabidiol-only products, avoiding products with inconsistent potency like edibles, enhancing patient-provider communication about cannabis use and psychotic-like experiences, and utilizing a collaborative and individualized therapeutic approach. Despite uncertainty surrounding cannabis' causal association with psychotic disorders, cautious attempts to reduce acute psychosis risk may benefit CHR-P individuals uninterested in abstinence. Further research is needed to clarify practices associated with minimization of cannabis-related psychosis risk.

The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis.

BACKGROUND: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. METHODS: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. RESULTS: SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. CONCLUSIONS: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.

Linking enlarged choroid plexus with plasma analyte and structural phenotypes in clinical high risk for psychosis: A multisite neuroimaging study.

BACKGROUND: Choroid plexus (ChP) enlargement exists in first-episode and chronic psychosis, but whether enlargement occurs before psychosis onset is unknown. This study investigated whether ChP volume is enlarged in individuals with clinical high-risk (CHR) for psychosis and whether these changes are related to clinical, neuroanatomical, and plasma analytes. METHODS: Clinical and neuroimaging data from the North American Prodrome Longitudinal Study 2 (NAPLS2) was used for analysis. 509 participants (169 controls, 340 CHR) were recruited. Conversion status was determined after 2-years of follow-up, with 36 psychosis converters. The lateral ventricle ChP was manually segmented from baseline scans. A subsample of 31 controls and 53 CHR had plasma analyte and neuroimaging data. RESULTS: Compared to controls, CHR (d = 0.23, p = 0.017) and non-converters (d = 0.22, p = 0.03) demonstrated higher ChP volumes, but not in converters. In CHR, greater ChP volume correlated with lower cortical (r = -0.22, p < 0.001), subcortical gray matter (r = -0.21, p < 0.001), and total white matter volume (r = -0.28,p < 0.001), as well as larger lateral ventricle volume (r = 0.63,p < 0.001). Greater ChP volume correlated with makers functionally associated with the lateral ventricle ChP in CHR [CCL1 (r = -0.30, p = 0.035), ICAM1 (r = 0.33, p = 0.02)], converters [IL1ß (r = 0.66, p = 0.004)], and non-converters [BMP6 (r = -0.96, p < 0.001), CALB1 (r = -0.98, p < 0.001), ICAM1 (r = 0.80, p = 0.003), SELE (r = 0.59, p = 0.026), SHBG (r = 0.99, p < 0.001), TNFRSF10C (r = 0.78, p = 0.001)]. CONCLUSIONS: CHR and non-converters demonstrated significantly larger ChP volumes compared to controls. Enlarged ChP was associated with neuroanatomical alterations and analyte markers functionally associated with the ChP. These findings suggest that the ChP may be a key an important biomarker in CHR.

Plasma complement and coagulation proteins as prognostic factors of negative symptoms: An analysis of the NAPLS 2 and 3 studies.

INTRODUCTION: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. METHODS: In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. RESULTS: Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (ß: 0.501, 95 % CI: 0.160, 0.842; ß: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (ß: 0.501, 95 % CI: -0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (ß: 0.442, 95 % CI: 0.127, 0.757). CONCLUSION: The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk.

Diminished differentiation of rewards in individuals at clinical high-risk for psychosis.

Reward processing is impaired in people with schizophrenia, which may begin in the clinical high-risk (CHR) for psychosis period. The Monetary Incentive Delay (MID) task has been important in understanding the neural correlates of reward processing deficits in various psychiatric disorders. Previous research has found that CHR individuals have an imprecise mental representation of rewards, which leads to a diminished differentiation between rewards, though this has not been observed behaviorally. A total of 19 CHR individuals and 20 controls were given a novel variant of the MID task, designed to examine how modulating reward context may impact responses to reward cues, a process often referred to as "adaptive coding." Both groups appeared to update their behavior in response to the rewards available in this adaptive task. However, when compared to controls who showed a more graded decrease in response time to increasing reward contexts, CHR individuals appeared to have a sharp decrease in response time in the low reward context that is nearly stable across higher reward contexts. This is largely driven by the exponential component of the response time distribution, which is often interpreted to be more cognitively or effortfully influenced. Response times are related to negative symptoms, but not positive symptoms, disorganized symptoms, or estimated intelligence. Although an adaptive coding effect was not observed, these results provide novel insight into the reward processing mechanisms and volitional processes in the CHR population, as this was the first study to observe the diminished differentiation of rewards behaviorally.

Persistent negative symptoms in young people at clinical high risk of psychosis treated with an Italian early intervention program: a longitudinal study.

Negative symptoms in CHR-P people are generally not responsive to treatments and commonly related to poorer functional outcome. However, less research attention has been dedicated to Persistent Negative Symptoms (PNS), defined as clinically stable negative symptoms of moderate severity evident for at least 6 months. This study aims to (a) determine the prevalence of PNS in a sample of young people at CHR-P; (b) investigate any association of PNS with functioning and clinical features; (c) examine longitudinal course of PNS across 2 years of follow-up and changes in PNS severity levels with specialized treatments. One Hundred Eighty CHR-P participants were recruited and were divided into CHR-P/PNS + and CHR-P/PNS- subgroups. The clinical assessments were based on the PANSS and the GAF and were conducted at baseline and every 12 months during the follow-up. Twenty four participants showed PNS at entry. Of them, 21 concluded the 2-year follow-up period. At baseline, the CHR-P/PNS + participants showed more educational and employment deficits, and more social and functioning impairment. During the follow-up, the CHR-P/PNS + subgroup had a significant longitudinal decrease in negative symptoms, which was specifically related to antidepressant treatment. CHR-P/PNS + subjects also showed a higher incidence of new hospitalization and a lower functional recovery over time. Our findings support that the persistence of negative symptoms in CHR-P people is longitudinally related to worse daily functioning and more severe clinical conditions that are at higher risk of hospitalization and are less responsive to specialized treatments.

Disorganization in individuals at clinical high risk for psychosis: psychopathology and treatment response.

Disorganization is a nuclear dimension of psychosis, especially in schizophrenia. Despite its relevant association with poor prognosis and negative outcomes, it is still under-investigated compared to positive and negative symptoms, in particular at the onset of illness. This study explored disorganization in youth at Clinical High Risk for Psychosis (CHR-P) over a 2-year period. A sample of 180 CHR-P participants (50% males; 51.1% with baseline second-generation antipsychotic medication) recruited within a specialized CHR-P service completed the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Across the follow-up, we examined key associations of disorganization with other domains of psychopathology, functioning, and treatment response using Spearman's rank correlation coefficients and linear regression analyses. Our results showed a significant longitudinal reduction in disorganization severity levels across the follow-up. This decrease was significantly associated with improvements in negative symptoms and daily functioning, with a shorter duration of untreated psychiatric symptoms, and with baseline equivalent dose of antipsychotic medication. No significant longitudinal associations with other treatment component of the PARMS program were found. Our findings suggest a longitudinal improvement in disorganization dimension in CHR-P individuals, especially in the context of early interventions targeting reduction in the duration of untreated psychiatric symptoms and favoring a prompt antipsychotic therapy.

Fronto-temporal cortical grey matter thickness and surface area in the at-risk mental state and recent-onset schizophrenia: a magnetic resonance imaging study.

BACKGROUND: Studies to date examining cortical thickness and surface area in young individuals At Risk Mental State (ARMS) of developing psychosis have revealed inconsistent findings, either reporting increased, decreased or no differences compared to mentally healthy individuals. The inconsistencies may be attributed to small sample sizes, varying age ranges, different ARMS identification criteria, lack of control for recreational substance use and antipsychotic pharmacotherapy, as well as different methods for deriving morphological brain measures. METHODS: A surfaced-based approach was employed to calculate fronto-temporal cortical grey matter thickness and surface area derived from magnetic resonance imaging (MRI) data collected from 44 young antipsychotic-naïve ARMS individuals, 19 young people with recent onset schizophrenia, and 36 age-matched healthy volunteers. We conducted group comparisons of the morphological measures and explored their association with symptom severity, global and socio-occupational function levels, and the degree of alcohol and cannabis use in the ARMS group. RESULTS: Grey matter thickness and surface areas in ARMS individuals did not significantly differ from their age-matched healthy counterparts. However, reduced left-frontal grey matter thickness was correlated with greater symptom severity and lower function levels; the latter being also correlated with smaller left-frontal surface areas. ARMS individuals with more severe symptoms showed greater similarities to the recent onset schizophrenia group. The morphological measures in ARMS did not correlate with the lifetime level of alcohol or cannabis use. CONCLUSIONS: Our findings suggest that a decline in function levels and worsening mental state are associated with morphological changes in the left frontal cortex in ARMS but to a lesser extent than those seen in recent onset schizophrenia. Alcohol and cannabis use did not confound these findings. However, the cross-sectional nature of our study limits our ability to draw conclusions about the potential progressive nature of these morphological changes in ARMS.

Epidemiology of DSM-5 psychiatric disorders in Kenyan Youth with Low and High Psychosis Risk.

INTRODUCTION: There are few psychiatric epidemiology studies among Kenyan youth and fewer among those at high psychosis risk (HR). METHODS: This study assessed the epidemiology of DSM-5 psychiatric disorders in HR and low-risk (LR) individuals to inform research and mental health services. 567 participants (aged 15-25) in HR (n = 246) and LR (n = 260) groups based on Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen scores. Diagnostic Interview Schedule, version 5 (DIS-5) assessed DSM-5 psychiatric disorder prevalence. Diagnostic comorbidity and demographic relationships were investigated. RESULTS: A higher prevalence was observed for all DSM-5 disorders in the HR group, significantly for gambling disorder (13% vs. 5.8%), major depressive disorder (9.8% vs. 3.8%), antisocial personality disorder (5.7% vs. 2.3%), general anxiety disorder (4.9% vs. 0.4%), oppositional defiant disorder (3.3% vs. 0.4%), panic disorder (2.8% vs. 0.8%), and anorexia nervosa (2.8% vs. 0%). Gambling disorder was the most prevalent and showed significant gender effects (males>females). DISCUSSION: Psychiatric disorders occur at increased rates among HR compared to LR. Prevalence rates found are lower than in US studies, except for gambling disorder which was highly prevalent. Large-population-based epidemiology studies in Africa are needed to estimate rates, particularly of disorders such as schizophrenia, accurately.

Screening for psychosis risk in primary mental health care services - Implementation, prevalence and recovery trajectories.

OBJECTIVES: Early interventions improve outcomes for people at high risk of psychosis and are likely to be cost saving. This group tends to seek help for emotional problems - depression and anxiety - via primary care services, where early detection methods are poor. We sought to determine prevalence rates of high risk for psychosis in UK primary care mental health services and clinical outcomes following routinely delivered psychological therapies. METHODS: We used a brief screen designed for settings with low base rates and significant time constraints to determine prevalence of high risk for psychosis in UK 'Talking Therapies' services. We examined socio-demographic characteristics, presenting problems and recovery trajectories for this group, compared with people not at risk of psychosis. RESULTS: A 2-item screen selected for specificity yielded a prevalence rate of 3% in primary care mental health services. People at elevated risk of psychosis were younger and more likely to report at least one long-term physical condition. This group presented with higher levels of depression, anxiety and trauma symptoms at assessment and were less likely to have recovered at the end of treatment, compared to people not at risk. CONCLUSIONS: Very brief screening tools can be implemented in busy health care settings. The 3% of referrals to UK primary care psychological therapies services at elevated risk of psychosis typically present with more severe symptoms and greater levels of comorbidity and may require augmented interventions to recover fully.

Exploring the acceptability, barriers, and facilitators to psychosis screening in the integrated behavioral health primary care setting: a qualitative study.

BACKGROUND: A longer duration of untreated psychosis (DUP) is associated with poorer treatment outcomes. Screening for psychosis spectrum disorders in the primary care setting could help support the earlier detection and treatment of individuals in need. However, the acceptability of screening for psychosis in this setting as part of routine care is currently unknown. METHODS: We conducted a qualitative interview study with providers and service users who participated in an early psychosis screening program conducted in an integrated behavioral health primary care (IBH-PC) setting. Interviews were recruited from one of eight WellSpace Federally Qualified Health Center IBH-PC clinics in the Sacramento, CA area. Transcripts of the recorded interviews were analyzed using thematic analysis. RESULTS: In total, 12 providers and eight service users participated in the interviews. Most service user and provider participants were supportive of psychosis screening in an IBH-PC setting, but not as part of the general practitioner consultation due to the brief, non-behavioral health nature of many of the appointments, and the expected low prevalence of psychosis in this population. The support of leadership, adequate training and support, staff turnover, and organizational changes were all seen to impact the successful implementation of the program. Different barriers and facilitators were considered important at each stage of the process from introducing the screening procedures to service users; to determining when, where, and how to screen; and how to effectively manage the referral and post-referral stages. CONCLUSIONS: Despite the additional challenges of screening in an IBH-PC setting relative to secondary mental health services, the process was considered acceptable and feasible to providers and service users. Services that plan to conduct psychosis screening in their clinics need to consider the challenges and their potential solutions to implementation at each stage of the screening process.

Investigation of Siblings of Patients Diagnosed with Substance-Induced Psychotic Disorder in terms of Cognitive Functions and Clinical High-Risk State for Psychosis.

OBJECTIVE: This study aimed to investigate the influence of familial predisposition on substance-induced psychosis among healthy siblings of patients diagnosed with substance-induced psychotic disorder, who themselves lack any family history of psychotic disorders. Additionally, the study aimed to explore clinical high-risk states for psychosis, schizotypal features, and neurocognitive functions in comparison to a healthy control group. METHOD: The study compared healthy siblings of 41 patients diagnosed with substance-induced psychotic disorder with 41 healthy volunteers without a family history of psychotic disorders, matching age, gender, and education. Sociodemographic and clinical characteristics of participants were obtained using data collection forms. The Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Structured Interview for Schizotypy-Revised Form (SIS-R) scales were utilized to assess clinical high risk for psychosis. Neurocognitive functions were evaluated with digit span test (DST), trail making test part A-B (TMT), verbal fluency test (VFT), and Stroop test (ST). RESULTS: Analysis using the CAARMS scale revealed that 39% of siblings and 7.3% of the control group were at clinically high risk for psychosis, indicating a significant difference in rates of psychotic vulnerability. Comparison between siblings and the control group showed significant differences in mean SIS-R subscale scores, including social behavior, hypersensitivity, referential thinking, suspiciousness, illusions, and overall oddness, as well as in mean neurocognitive function scores, including errors in TMT-A, TMT-B, and VFT out-of-category errors, with siblings exhibiting poorer performance. CONCLUSION: Our study suggests that healthy siblings of patients with substance-induced psychosis exhibit more schizotypal features and have a higher risk of developing psychosis compared to healthy controls. Additionally, siblings demonstrate greater impairment in attention, response inhibition, and executive functions compared to healthy controls, indicating the potential role of genetic predisposition in the development of substance-induced psychotic disorder.

Clinical and neurodevelopmental predictors of psychotic disorders in children and adolescents at clinical high risk for psychosis: the CAPRIS study.

BACKGROUND: The neurodevelopmental hypothesis of schizophrenia represents the disorder as an expression of an alteration during the brain development process early in life. Neurodevelopmental variables could become a trait marker, and the study of these variables in children and adolescents at clinical high risk for psychosis (CHR) could identify a specific cluster of patients who later developed psychosis. The aim of this study is to describe clinical and neurodevelopment predictors of transition to psychosis in child and adolescent participants at CHR. Naturalistic longitudinal two-center study of 101 CHR and 110 healthy controls (HC) aged 10-17. CHR participants were children and adolescents aged 10-17, meeting one or more of the CHR criteria assessed at baseline and at 18 months' follow-up. Neurodevelopmental variables assessed were obstetric complications, delay in principal development milestones, and presence of a neurodevelopment diagnosis. Pairwise comparisons, linear regressions, and binary logistic regression were performed.A transition rate of 23.3% at 1.5 years was observed. Participants who developed psychosis (CHR-P) showed higher rates of grandiosity and higher proportions of antipsychotic medication intake at baseline compared to participants who did not develop a psychotic disorder (CHR-NP). In terms of neurodevelopment alterations, CHR-P group showed a higher proportion of participants reporting delay in language development than the CHR-NP and HC groups. The odds of psychosis increased by 6.238 CI 95% [1.276-30.492] for a one-unit increase in having a positive score in grandiosity; they increased by 4.257 95% CI [1.293-14.023] for a one-unit increase in taking antipsychotic medication, and by 4.522 95% [1.185-64.180] for showing language development delay. However, the p-values did not reach significance after adjusting for multiple comparisons.A combination of clinical and neurodevelopmental alterations could help predict the transition to psychotic disorder in a CHR child and adolescent sample. Our results suggest the potential utility of collecting information about neurodevelopment and using these variable multifactorial models to predict psychosis disorders.

Clinical utility of the at-risk for psychosis state beyond transition: A multidimensional network analysis.

To be relevant to healthcare systems, the clinical high risk for psychosis (CHR-P) concept should denote a specific (i.e., unique) clinical population and provide useful information to guide the choice of intervention. The current study applied network analyses to examine the clinical specificities of CHR-P youths compared to general help-seekers and non-CHR-P youth. 146 CHR-P (mean age = 14.32 years) and 103 non-CHR-P (mean age = 12.58 years) help-seeking youth were recruited from a neuropsychiatric unit and assessed using the Structured Interview for Psychosis-Risk Syndromes, Children's Depression Inventory, Multidimensional Anxiety Scale for Children, Global Functioning: Social, Global Functioning: Role, and Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale. The first network structure comprised the entire help-seeking sample (i.e., help-seekers network), the second only CHR-P patients (i.e., CHR-P network), and the third only non-CHR-P patients (i.e., non-CHR-P network). In the help-seekers network, each variable presented at least one edge. In the CHR-P network, two isolated "archipelagos of symptoms" were identified: (a) a subgraph including functioning, anxiety, depressive, negative, disorganization, and general symptoms; and (b) a subgraph including positive symptoms and the intelligence quotient. In the non-CHR-P network, positive symptoms were negatively connected to functioning, disorganization, and negative symptoms. Positive symptoms were less connected in the CHR-P network, indicating a need for specific interventions alongside those treating comorbid disorders. The findings suggest specific clinical characteristics of CHR-P youth to guide the development of tailored interventions, thereby supporting the clinical utility of the CHR-P concept.

Cognitive predictors of transition and remission of psychosis risk syndrome in a child and adolescent sample: longitudinal findings from the CAPRIS study.

Cognitive impairments are proposed as predictors in the differentiation between subjects with psychosis risk syndrome (PRS) who will develop a psychotic disorder (PRS-P) and those who will not (PRS-NP). More in-depth study of the PRS-NP group could contribute to defining the role of cognitive alterations in psychosis. This study aims to analyze cognition of children and adolescents with PRS in terms of their clinical outcome at 18-month follow-up (psychosis, remission, and non-remission) and of determinate predictors of transition to psychosis and remission of PRS. The method is two-site, naturalistic, longitudinal study design, with 98 help-seeking adolescents with PRS and 64 healthy controls (HC). PRS-P (n = 24) and PRS-NP (n = 74) participants were clinically and cognitively assessed at baseline, and when full-blown psychotic disorder had developed or at 18-month follow-up. PRS-P subjects showed lower scores at baseline in processing speed, visuospatial memory, attention, and executive function (cognitive flexibility/processing speed) compared to HC. PRS-NP subjects showed lower baseline scores in verbal working memory and verbal fluency compared to HC. This deficit is also observed in the PRS group of participants still presenting attenuated psychotic symptoms at 18-month follow-up, while PRS subjects in remission showed a similar cognitive profile to HC subjects. Baseline score on processing speed, measured with a coding task, appeared to be a predictive variable for the development of a psychotic disorder. Performance in verbal working memory was predictive of remission in the PRS-NP. Post hoc comparisons indicate the need for careful interpretation of cognitive markers as predictors of psychosis. Cognitive impairments are present in both PRS-P and PRS-NP. Those individuals who recover from PRS show baseline cognitive performance comparable to the HC group. Together with sociodemographic variables, this observation could help in the differentiation of a variety of PRS trajectories in children and adolescents.

Debate: The prevention of psychosis in child and adolescent mental health services.

Psychopathological conditions in adolescence and young adulthood often result from an altered neurodevelopment already phenotypically expressed in childhood. Child and adolescent mental health services are ideally placed to intercept in the developmental trajectories of younger adolescents and contribute to the early detection of a risk for psychosis, as proposed by Salazar de Pablo and Arango (2023, Child and Adolescent Mental Health), opening a debate to which we contribute. The early detection of a specific risk for psychosis and of a broader risk for severe mental illness requires an understanding of the clinical staging of psychosis, neurodevelopmental antecedents of severe mental illness and of heterotypic trajectories between childhood phenotypes and adult disorders.