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

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.

Objective: To compare clinical and functional variables among 3 groups of children and adolescents: subjects at clinical high risk for psychosis (CHR-P) who also have obsessive-compulsive symptoms (OCS), CHR-P patients without OCS, and healthy controls (HC).Methods: A total of 128 CHR-P patients and 98 HC between the ages of 10 and 17 years were recruited as part of a multicenter prospective longitudinal study conducted in Spain between January 1, 2011, and December 31, 2018, with diagnoses made for CHR-P using the Scale of Prodromal Symptoms (SOPS). Two groups were obtained based on Leyton Obsessional Inventory-Child Version (LOI-CV) scores: 64 CHR-P patients with OCS (OCS+) and 64 CHR-P patients without OCS (OCS-). Clinical variables were analyzed with a generalized linear model.Results: Overall, 128 CHR-P patients, 64 (50%) with OCS (mean ± SD age = 15.5 ± 1.4 years, 34.4% male), 64 CHR-P patients without OCS (mean ± SD age = 15.1 ± 1.9 years, 34.4% male), and 98 HC (mean ± SD age = 15.5 ± 1.5 years, 42.9% male), of whom 19 (19.5%) had OCS, were included. Generalized linear model analysis revealed significant differences between the groups. The OCS+ group showed more severe prodromal symptoms (P = .007), worse functioning at baseline (P = .044) and during the previous year (P = .004), and more dysmorphophobic symptoms (P < .001) compared to the OCS- group. OCS+ patients were also more frequently treated with antidepressants (P = .004) than were OCS- patients.Conclusions: In our sample, among children and adolescents with CHR-P, the prevalence of OCS was high (50%). OCS+ subjects had a more severe clinical and functional profile than OCS- subjects. Early detection and treatment of these symptoms can lead to better outcomes for these patients.

Deficits in functioning affect people with first-episode psychosis. Deficits in cognitive performance are common in such individuals and appear to be related to functioning. The present study examined the relationship between the domains of cognitive performance and personal and social functioning, as well as evaluating which cognitive domains are the most closely related to personal and social functioning and whether they explain variations once other clinical and sociodemographic aspects are accounted for. Ninety-four people with first-episode psychosis participated in the study; they were assessed with the MATRICS battery. Symptoms were evaluated with the Emsley factors of the positive and negative syndrome scale. Cannabis use, duration of untreated psychosis, suicide risk, perceived stress, antipsychotic doses, and premorbid intelligence quotient was accounted for. Processing speed, attention/vigilance, working memory, visual learning, reasoning and problem solving correlated to personal and social functioning. Processing speed emerged as the strongest predictor of social and personal functioning and underscores the importance of targeting this domain in treatment. Moreover, suicide risk and excited symptoms were also significant variables in functioning. Early intervention, focusing on improvement of processing speed, may be crucial to the improvement of functioning in first-episode psychosis. The relationship of this cognitive domain with functioning in first-episode psychosis should be studied further.

People with a mental disorder have a higher risk of suicidal behavior. Little research has examined the role of childhood trauma in suicide behavior, and even fewer studies have assessed the specific relevance of subtypes of childhood trauma and suicidal behavior in first-episode psychosis (FEP). The aims of the present study were: 1) to compare suicide behavior between FEP and HC; 2) to study the relationship between the five types of ChT and suicide risk in FEP controlling for confounding sociodemographic, clinical, and psychosocial variables. 95 patients diagnosed with FEP and 92 healthy control (HC) were recruited as a part of the PROFEP study. ChT was evaluated using The Childhood Trauma Questionnaire-Short Form (CTQ) and suicide behavior through The Suicide Risk Scale of Plutchik (SRSP). Our results showed that patients with FEP presented more suicide behavior (ideation, attempt, and suicide risk) than HC. Emotional abuse was the most relevant type of ChT in suicide ideation and suicide risk. After controlling for other relevant variables, perceived stress seemed to play an important role in suicide ideations, suicide attempt, and suicide risk. The results highlight the importance of assessing and considering in the clinical practice ChT and the perceived stress.

Importance The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. Objective To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). Design, Setting, and Participants In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020. Main Outcomes and Measures Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group). Results Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001). Conclusions and Relevance This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.

Although psychosocial stress is consistently described as a casual factor for psychosis, the role of recent stressful life events (SLEs) is inconclusive. Studies with subjects with psychosis risk syndrome (PRS), fail to show a large number of SLEs but suggest greater stress sensitivity in these populations. We evaluate the presence of recent SLEs and stress sensitivity, and their relationship with symptoms and functionality in a sample consisting exclusively of help-seeking children and adolescents. Seventy-two 10- to 17-year-old help-seeking subjects who met PRS criteria and forty-two healthy control (HC) subjects participated in a naturalistic multi-site study. Measures of stress included the Stressful Life Events Schedule (SLES) and the G4 item of the Scale for Prodromal Syndromes (SOPS) scale. Child and adolescent PRS subjects presented greater number of SLEs during the previous year, greater total accumulated stress, greater sensitivity to stress, and more impaired tolerance to normal stress than did HC subjects. Stress measures showed a relationship with positive and negative attenuated symptoms, clinical variables and functionality. Our results support the role of stress in the PRS status. It reinforces the suggested differences for clinical presentation of PRS in terms of age, highlighting the importance of gathering data on the under-18 population.

Abstract Background A dysregulation in one-carbon metabolism, involving folate, vitamin B12 and homocysteine (Hcys) could be implicated in the physiopathology of schizophrenia (for a review, Frankenburg, 2007). Higher Hcys levels have been associated with the disease compared to healthy controls in adults as well as in children and adolescents (Levere et al, 2014). Up to our knowledge, there are no studies in children and adolescents at risk for schizophrenia and other psychosis (Psychosis Risk Syndrome, PRS) testing the one-carbon metabolism parameters. Only a few groups have published results focused only in this population (for a review, Tor et al, 2018). This study aims to compare blood parameters associated with one-carbon metabolism, the clinical and demographic characteristics and stressful life events of a sample of children and adolescents with PRS and healthy controls (HC). Methods A prospective longitudinal study in which help-seeking subjects who met PRS criteria were recruited from the Child and Adolescent Psychiatry and Psychology departments of Hospital Clinic and Hospital Sant Joan de Déu (Barcelona, Spain). Inclusion criteria were: 1) Attenuated positive or negative symptoms in the previous 12 months; 2) Brief intermittent psychotic symptoms; 3)First or second degree relative with schizophrenia or schizotypical disorder plus impairment of functioning; age:10–17 years. Exclusion criteria: IQ<70 and a diagnosis of neurodevelopmental disorder. At baseline, the Semistructured Interview for Prodromal Syndromes and Scale of Prodromal Symptoms (SIPS/SOPS) were administered, as well as a clinical scale battery including measures of stress such as the Stressful Live Events Scale. Blood analysis measuring vitamin B12, folic acid and homocysteine were done. Types of treatment, and dosages were also registered. A sample of age and gender matched HCs were also included. Exclusion criteria: 1st or 2nd degree familiar with a psychotic disorder; a diagnosis of neurodevelopmental disorder and IQ<70.The same assessment was performed in the HC sample. Results 60 PRS subjects (14.9±1.8 years, range: 11–17 years; 74.1% females) and 40 HC (15.4±1.5 years, range: 11–17 years; 65% females) were included. In the PRS sample, 59.4% met criterion 1 for inclusion. 59.4% had familiar history of psychotic disorder. All the SOPS, GAF, LSP, Hamilton and Young scores were significantly higher in PRS than in HC. Number of stressful life events and their subjective affectation were also higher in PRS subjects than in HC (t=-4.939, p<<0.001; t=-5.380, p<0.001). There were no differences in Hcys and, folic acid levels between PRS subjects and HC. However, vitamin B12 levels were different between them, with lower levels in PRS vs HC (425.7±185.7 vs.526.4±159.1, t=2.755, p=0.007) without reaching deficit levels (<300 pg/mL). Higher Hcys levels was correlated with higher number of life events (R=0.245, p=0.037). Lower levels of vitamin B12 were correlated with higher number of stressful life events (R=-0.393, p=0.001) and higher subjective affectation (R=-0.381, p=0.001). Discussion In children and adolescents with PRS, lower vitamin B12 levels than HC have been found, which were associated with higher stressful life events and their subjective affectation. Vitamin B12 is key for brain development, and the possible dysregulation of one carbon metabolism and their association with stress in children and adolescents at risk for psychosis should be further explored as well as the diet of these subjects in a bigger sample to draw consistent conclusions.

AimDespite the interest in psychosis risk syndrome (PRS) in children and adolescents, information on the syndrome in this population is scarce.MethodsProspective naturalistic multi‐site study in which 10‐ to 17‐year‐old help‐seeking subjects who met PRS criteria (positive or negative attenuated symptoms; brief limited intermittent psychotic symptoms; genetic risk or schizotypal personality disorder plus impairment in functioning) were included, along with 45 age and sex‐matched healthy controls (HC). All subjects were clinically and functionally assessed.ResultsNinety‐one PRS subjects (PRSS) with a mean age of 15.5 ± 1.4 met inclusion criteria (IC). Compared with HC, PRSS presented worse global and academic functioning in the previous year, had experienced more psychiatric and psychological problems, and presented gestational ages outside the normal range. More than 80% of PRSS met ≥2 IC, with 65.9% having one Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision diagnosis, and 61.7% of those having ≥2 diagnoses. Some 49.5% of PRSS had a first‐ or second‐degree family history (FH) of psychosis. Patients with first‐ and second‐degree FH do not differ in their clinical expression.ConclusionsChildren and adolescents with PRS are a patient group with a pattern of neurodevelopmental impairment and clinical complexity similar to patients with schizophrenia spectrum disorders, highlighting the importance of assessing these variables in child and adolescent samples. PRSS with first‐ and second‐degree relatives with FH do not present differences in their clinical presentation, suggesting that including these two groups of patients in the genetic risk criteria would enrich knowledge of these criteria.

OBJECTIVE To analyze liver function tests (LFT), weight, metabolic syndrome (MetS) and at risk of meeting MetS criteria (AR-MetS) in children and adolescents on antipsychotics (AP) during a year-long follow-up. METHODS Two hundred sixteen patients, AP naïve or quasi-naïve (<30 days on AP), were included. Total bilirubin, the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), weight and other parameters of MetS were measured at baseline, and at 3, 6 and 12 months, while patients remained on the same AP. RESULTS At baseline, patients (mean age: 14.1 ± 3.1 years; 60.2% male) were on risperidone (N = 143), olanzapine (N = 37), or quetiapine (N = 36), although the sample decreased over time to 67 patients at 12 months (risperidone N = 46, olanzapine N = 10, and quetiapine N = 11). Around 3% of patients had ALT/AST levels that were at least twice the upper limit of normal (ULN) at 3 and 6 months; whereas roughly 19% of patients had ALP levels that were at least twice the ULN in at least one assessment after baseline, but had no clinical symptoms. From baseline to 6 months, significant increases were observed in ALT levels in the whole sample (p = 0.005), whereas ALP increased only in patients on risperidone. Patients showed significant weight gain, and more individuals met criteria for MetS and AR-MetS over time (from baseline: 2.8% and 8.3%, to 1 year: 10.5% and 23.9%, respectively). There was a trend-level group effect in global ALT across time (p = 0.076). Patients with MetS showed higher ALT concentrations (28.9 [18.4-39.4] U/L) than AR-MetS (20.4 [8.5-32.2] U/L), and no-AR-MetS (19.2 [8.4-29.9] U/L). CONCLUSIONS Less than 3% of children and adolescents on AP during 1-year follow-up showed an increase in ALT or AST levels in one or more of the assessments, and none of these increases was of clinical significance. Patients with MetS and AR-MetS increased during this period, and the possible role of ALT levels to monitor these patients deserves further study.

Background Visual mental imagery might be critical in the ability to discriminate imagined from perceived pictures. Our aim was to investigate the neural bases of this specific type of reality-monitoring process in individuals with high visual imagery abilities. Methods A reality-monitoring task was administered to twenty-six healthy participants using functional magnetic resonance imaging. During the encoding phase, 45 words designating common items, and 45 pictures of other common items, were presented in random order. During the recall phase, participants were required to remember whether a picture of the item had been presented, or only a word. Two subgroups of participants with a propensity for high vs. low visual imagery were contrasted. Results Activation of the amygdala, left inferior occipital gyrus, insula, and precuneus were observed when high visual imagers encoded words later remembered as pictures. At the recall phase, these same participants activated the middle frontal gyrus and inferior and superior parietal lobes when erroneously remembering pictures. Conclusions The formation of visual mental images might activate visual brain areas as well as structures involved in emotional processing. High visual imagers demonstrate increased activation of a fronto-parietal source-monitoring network that enables distinction between imagined and perceived pictures.

BACKGROUND Prescriptions of antipsychotic drugs (AP) in children and adolescents have significantly increased in Europe as well as in the United States. However, there is limited evidence of the cardiac safety of second-generation antipsychotics (SGA) in the pediatric population. OBJECTIVE The aim of the study is to evaluate the cardiac side effects of SGA in children and adolescents, and how they are influenced by clinical, demographic, and treatment factors. METHODS This article presents a naturalistic, longitudinal, multicenter study conducted in 216 treatment-naïve or quasi-naïve children and adolescents receiving AP treatment. It analyzed the possible influence of AP treatment on variables such as corrected QT (QTc) intervals and heart rate for a period of 12 months (baseline, 3 months, 6 months, and 12 months). Differences among the three main prescribed drugs used in the sample (risperidone, quetiapine, and olanzapine) were assessed. RESULTS A total of 211 received one of the three most prescribed AP (quetiapine, risperidone or olanzapine). There were no significant QTc variations in the sample during follow-up (p = 0.54). There were no differences in QTc rates between the different SGA (risperidone-olanzapine p = 0.43; risperidone-quetiapine p = 0.42; olanzapine-quetiapine p = 0.23). When demographic, clinical, or concomitant treatment variables were considered, only baseline overweight correlated with QTc prolongation (p = 0.003). The heart rate in the whole sample tended to decrease during follow-up (p = 0.054). However, patients on quetiapine showed increased heart rate compared with those on risperidone (p = 0.04). CONCLUSIONS In this sample, SGA seem to have a safe heart side effect profile in the child and adolescent population. There was no observed mean increase in QTc or in heart rate.