Search

Background: Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances., Methods: We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis-Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups., Results: FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio., Conclusions: Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.

Early-onset psychosis (EOP) is a complex disorder characterized by a wide range of symptoms, including affective symptoms. Our aim was to (1) examine the dimensional structure of affective symptoms in EOP, (2) evaluate the predominance of the clinical dimensions and (3) assess the progression of the clinical dimensions over a 2-year period. STROBE-compliant prospective principal component factor analysis of Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale-21 (HDRS-21) at baseline, 6-months, 1-year and 2-year follow-up. We included 108 EOP individuals (mean age = 15.5 ± 1.8 years, 68.5% male). The factor analysis produced a four-factor model including the following dimensions: mania, depression/anxiety, sleep and psychosis. It explained 47.4% of the total variance at baseline, 60.6% of the total variance at 6-months follow-up, 54.5% of the total variance at 1-year follow-up and 49.5% of the total variance at 2-year follow-up. According to the variance explained, the mania factor was predominant at baseline (17.4%), 6-month follow-up (23.5%) and 2-year follow-up (26.1%), while the depression/anxiety factor was predominant at 1-year follow-up (23.1%). The mania factor was the most stable; 58.3% items that appeared in this factor (with a load > 0.4) at any time point appeared in the same factor at ≥ 3/4 time points. Affective symptoms are frequent and persistent in EOP. Mania seems to be the most predominant and stable affective dimension. However, depression and anxiety may gain predominance with time. A comprehensive evaluation of the dimensional structure and the progression of affective symptoms may offer clinical and therapeutic advantages., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Childhood trauma, particularly sexual abuse, has been associated with transition to psychosis in individuals at "ultra-high risk" (UHR). This study investigated whether the effects of various forms of childhood trauma on transition to psychosis are mediated by cortical thickness and surface area abnormalities., Methods: This prospective study used data from 62 UHR individuals from a previous (PACE 400) cohort study. At follow-up, 24 individuals had transitioned to psychosis (UHR-T) and 38 individuals had not transitioned (UHR-NT). Student-t/Mann-Whitney-U tests were performed to assess morphological differences in childhood trauma (low/high) and transition. Mediation analyses were conducted using regression and bootstrapping techniques., Results: UHR individuals with high sexual trauma histories presented with decreased cortical thickness in bilateral middle temporal gyri and the left superior frontal gyrus compared to those with low sexual trauma. Participants with high physical abuse had increased cortical thickness in the right middle frontal gyrus compared to those with low physical abuse. No differences were found for emotional abuse or physical/emotional neglect. Reduced cortical thickness in the right middle temporal gyrus and increased surface area in the right cingulate were found in UHR-T compared to UHR-NT individuals. Sexual abuse had an indirect effect on transition to psychosis, where decreased cortical thickness in the right middle temporal gyrus was a mediator., Conclusions: Results suggest that childhood sexual abuse negatively impacted on cortical development of the right temporal gyrus, and this heightened the risk of transition to psychosis in our sample. Further longitudinal studies are needed to precisely understand this link., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cognitive impairment is a major unmet need in the treatment of schizophrenia. Over the last decade, the MATRICS Consensus Cognitive Battery (MCCB) has been used to assess the effects of novel treatments for cognitive impairment in schizophrenia. However, other cognitive-neuroscience-based cognitive batteries, such as the Cambridge Neuropsychological Test Automated Battery (CANTAB) have been suggested as an alternative to the MCCB. Although both batteries purport to assess cognitive function in psychosis, no previous study has attempted to examine their validity longitudinally and the potential overlap between the two batteries over time. The aim of the current study was to assess the relationship between the MCCB and the CANTAB in the longitudinal assessment of cognitive impairment in schizophrenia. A sample of 39 stable schizophrenia outpatients and 18 controls completed the MCCB and the CANTAB battery at baseline, and at 2, 4 and 8-weeks follow-up. Correlation analyses and a mixed-model repeated measures approach were used. We found no significant effect of time in the MCCB. In contrast, for the CANTAB a significant effect of time consistent with practice effects for the attention domain in the control group and for the visual learning, reasoning and problem-solving, and social cognition domains in patients, with subjects performing better at follow-up. In particular, a significant time ∗ battery interaction was found for those cognitive domains. These findings suggest there are specific differences across cognitive tests to assess cognitive impairments in schizophrenia and that measures derived from the CANTAB appear to be more prone to practice effects in these patients., Competing Interests: Declaration of competing interest CA has been a consultant and/or received honoraria or grants from Acadia, Abbott, Angellini, Amgen, Janssen-Cilag, Lundbeck, Merck, Otsuka, Pfizer, Roche, Servier, Shire, Sunovion, Takeda, and Schering-Plough. SWL has received honoraria from Janssen and Otsuka Digital. All other authors declare no conflict of interest., (Copyright © 2019. Published by Elsevier B.V.)

Aims: Memory impairment in psychosis may be mediated through detrimental effects of hypothalamic-pituitary-adrenal (HPA) axis function. This study prospectively investigated the relationship between cortisol, sulphate dehydroepiandrosterone (DHEA(S) and cortisol: DHEA(S) ratio and memory in 35 first-episode psychosis (FEP) patients during the first 12 weeks of treatment and 23 healthy controls (HC)., Methods: Morning blood sampling and tests of attention, working memory and verbal memory occurred at baseline and 12-week follow-up., Results: FEP and HC groups did not significantly differ in levels of cortisol, DHEA(S) or their ratio at baseline or over 12-weeks. The FEP group performed significantly below HC on all cognitive measures at baseline and over 12-weeks. Cortisol levels were unrelated to cognition in both groups. At baseline, DHEA(S) was positively associated with attention in HCs, but negatively associated with attention in FEP participants. Change in DHEA(S) was negatively associated with change in memory over 12-weeks in both groups. At 12-weeks, there was a negative correlation between the cortisol: DHEA(S) ratio and attention in both groups., Conclusions: These findings are mostly in contrast to findings in chronic schizophrenia. Investigation at different illness phases and over longer-follow-up periods is required to determine the complex relationship between HPA-axis and memory functioning in psychosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study aims to examine regional gray matter (GM) changes over a period of 2 years in patients diagnosed with early-onset first-episode psychosis (EO-FEP), and to identify baseline predictors of abnormalities at the follow-up. Fifty-nine patients with EO-FEP aged 11-17 years were assessed. Magnetic resonance imaging was carried out at admission and 2 years later. Changes over time were assessed with voxel-based morphometry. Fifty-nine patients (34 schizophrenia-SCZ, 15 bipolar disorder-BP, and 10 other psychotic disorders) and 70 healthy controls were assessed. At baseline no differences were found between the EO-FEP groups and control subjects. Over time, SCZ patients presented a larger GM decrease in the orbitofrontal cortex, anterior midline frontal cortex, cingulate, left caudate, and thalamus. BP patients also had a larger GM decrease in the right putamen, right orbitofrontal cortex, and anterior and midline region of the right superior frontal gyrus and left caudate, but with fewer areas showing significant differences than in the comparison between SCZ and controls. In the cross-sectional analysis, only SCZ patients showed differences with respect to controls in some GM areas. Significant baseline predictors of a 2-year reduction in GM were IQ and working memory. EO-FEP patients did not show differences in GM compared to controls at baseline. Both SCZ and BP patients showed a greater decrease in specific areas during the first 2 years. At follow-up, only SCZ patients differed significantly from controls in specific brain areas. The GM reduction was predicted by baseline cognitive variables.

Objective: To investigate whether the beneficial effects of a structured, psychoeducational, parallel-group program for adolescents with early-onset psychosis and their families observed immediately after the intervention were maintained 2 years later., Method: The present study examines the longitudinal efficacy of a randomized controlled trial based on a psychoeducational, problem-solving, structured group intervention for adolescents with early-onset psychosis and their families (PE) and compares it with that of a nonstructured group intervention (NS) after a 2-year follow-up. We analyzed whether the differences between PE and NS found after the intervention persisted 2 years later. Intergroup differences in number and duration of hospitalizations, symptoms, and functioning were also assessed., Results: After 2 years of follow-up, we were able to reassess 89% of patients. In the PE group, 13% of patients had visited the emergency department, compared with 50% in the NS group (p = .019). However, no statistically significant differences were found between the groups for negative symptoms or number and duration of hospitalizations. A significant improvement in Positive and Negative Syndrome Scale (PANSS) general symptoms was observed in the PE group., Conclusion: Our psychoeducational group intervention showed sustained effects by diminishing the number of visits to emergency departments 2 years after the intervention. Our findings indicate that this psychoeducational intervention could provide patients with long-lasting resources to manage crises more effectively. Clinical trial registration information-Intervention Module AGES (AGES-CM); http://clinicaltrials.gov/; NCT02101372., (Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to study baseline clinical and biological predictors of 2-year outcome in a cohort of children and adolescents with a first episode of psychosis., Method: Standard instruments were used to evaluate symptoms and functioning in 110 children and adolescents (mean age = 15.47 years) with first episode of psychosis at admission (between 2003 and 2005) and after 2-year follow-up. Clinical assessments included diagnostic assessment to yield DSM-IV diagnosis, developmental, premorbid, and past-year data, together with structural neuroimaging and other biological parameters (genetics and oxidative stress). Eighty-three subjects had assessments at baseline (including the Strauss-Carpenter Outcome Scale [SCOS]) and at 2-year follow-up. Association and multistep regression analyses were conducted to show correlates and predictors of primary outcome measures: functional outcome (Children's Global Assessment Scale [CGAS]), improvement (CGAS change), and primary negative symptoms (Proxy for the Deficit Syndrome Scale)., Results: The SCOS predicted 27.46% (P < .001) of the variance in CGAS score at 2 years. Baseline severity (measured by CGAS) predicted 30.9% (P < .001) of CGAS improvement after 2 years, and SCOS total score predicted an added 24.1% (P < .001). A diagnosis of nonaffective psychosis, primary negative symptoms, and less white matter at baseline predicted more primary negative symptoms at follow-up. The prediction of functional outcome was not increased by genetic, oxidative stress, or neurostructural markers., Conclusions: Baseline clinical assessments have a better predictive value than biological assessments for 2-year follow-up functioning of children and adolescents with a first episode of psychosis. Patients with primary negative symptoms at baseline continue to have negative symptoms 2 years later, and neurostructural markers predict these. Clinicians must still rely on clinical variables to judge the functional prognosis of early-onset first psychotic episodes., (© Copyright 2015 Physicians Postgraduate Press, Inc.)

Progressive loss of cortical gray matter (GM) and increase of cerebrospinal fluid (CSF) have been reported in early-onset psychosis (EOP). EOP typically begins during adolescence, a time when developmental brain trajectories differ by gender. This study aimed to determine gender differences in progression of brain changes in this population. A sample of 61 (21 females) adolescents with a first psychotic episode and a matched sample of 70 (23 females) controls underwent both baseline and 2-year follow-up anatomical brain imaging assessments. Regional GM and CSF volumes were obtained using automated methods based on the Talairach's proportional grid system. At baseline, only male patients showed a clear pattern of alterations in the frontal lobe relative to controls (smaller GM and larger CSF volumes). However, parallel longitudinal changes for male and female patients relative to controls were observed, resulting in a common pattern of brain changes across both genders: rate of left frontal lobe GM volume loss was larger in male (-3.8%) and female patients (-4.2%) than in controls (-0.7% males; -0.4% females). The reverse was found for the CSF volume in the left frontal lobe. While the GM and CSF volumes of females with EOP appear to be within the normal range at initial illness onset, our results point to a similar trajectory of increased/accelerated brain changes in both male and female patients with EOP. The pattern of progression of brain changes in psychosis appears to be independent of gender or structural alterations on appearance of psychotic symptoms.

Background: Substantial controversy has been generated since the proposal to include "Attenuated Psychosis Syndrome" in DSM-5, based on research criteria used to identify young people at "ultra high risk" (UHR) for psychosis. The syndrome was ultimately included in the section for further research. The criteria specified that the person experienced attenuated psychotic symptoms (APS) that were sufficiently distressing to warrant clinical attention. Although APS are the main means of determining whether a person meets UHR criteria, clinical experience suggests that such symptoms are often not the main source of clinical distress in this patient group. However, little is known about the sources of distress in the UHR group. We aimed to assess the main sources of clinical distress in UHR patients at the time of referral to a specialized UHR clinic., Method: Sources and intensity of distress in 73 UHR patients were gathered from treating clinicians. The association with transition to psychosis was explored., Results: Of the total sample, 89.04% fulfilled the APS UHR criteria. APS symptoms were reported to be distressing for 58.5% of this subsample, but social and functioning difficulties (78.1%) and depressive symptoms (58.9%) were the highest sources of distress leading UHR patients to seek help. Intensity of distress associated with APS, anxiety symptoms and substance use was associated with transition to psychosis., Conclusions: APS were reported to be distressing for approximately half of UHR patients. The intensity of distress associated to these symptoms may be associated with increased risk for subsequent transition to full threshold psychotic disorder., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Identifying early-onset schizophrenia spectrum disorders (SSD) at a very early stage remains challenging. To assess the diagnostic predictive value of multiple types of data at the emergence of early-onset first-episode psychosis (FEP), various support vector machine (SVM) classifiers were developed. The data were from a 2-year, prospective, longitudinal study of 81 patients (age 9-17 years) with early-onset FEP and a stable diagnosis during follow-up and 42 age- and sex-matched healthy controls (HC). The input was different combinations of baseline clinical, neuropsychological, magnetic resonance imaging brain volumetric and biochemical data, and the output was the diagnosis at follow-up (SSD vs. non-SSD, SSD vs. HC, and non-SSD vs. HC). Enhanced recursive feature elimination was performed for the SSD vs. non-SSD classifier to select and rank the input variables with the highest predictive value for a diagnostic outcome of SSD. After validation with a test set and considering all baseline variables together, the SSD vs. non-SSD, SSD vs. HC and non-SSD vs. HC classifiers achieved an accuracy of 0.81, 0.99 and 0.99, respectively. Regarding the SSD vs. non-SSD classifier, a combination of baseline clinical variables (severity of negative, disorganized symptoms and hallucinations or poor insight) and neuropsychological variables (impaired attention, motor coordination, and global cognition) showed the highest predictive value for a diagnostic outcome of SSD. Neuroimaging and biochemical variables at baseline did not add to the predictive value. Thus, comprehensive clinical/cognitive assessment remains the most reliable approach for differential diagnosis during early-onset FEP. SVMs may constitute promising multivariate tools in the search for predictors of diagnostic outcome in FEP.

Stress is implicated in the development and course of psychotic illness, but the factors that influence stress levels are not well understood. The aim of this study was to examine the impact of neuropsychological functioning and coping styles on perceived stress in people with first-episode psychosis (FEP) and healthy controls (HC). Thirty-four minimally treated FEP patients from the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, and 26 HC participants from a similar demographic area participated in the study. Participants completed a comprehensive neuropsychological test battery as well as the Coping Inventory for Stressful Situations (task-, emotion- and avoidance-focussed coping styles) and Perceived Stress Scale (PSS). Linear regressions were used to determine the contribution of neuropsychological functioning and coping style to perceived stress in the two groups. In the FEP group, higher levels of emotion-focussed and lower levels of task-focussed coping were associated with elevated stress. Higher premorbid IQ and working memory were also associated with higher subjective stress. In the HC group, higher levels of emotion-focussed coping, and contrary to the FEP group, lower premorbid IQ, working memory and executive functioning, were associated with increased stress. Lower intellectual functioning may provide some protection against perceived stress in FEP., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The relationship between duration of untreated psychosis (DUP) and executive function (EF) in patients with first-episode psychosis (FEP) is controversial. We aim to assess the influence of DUP on changes in EF over a 2-year period in subjects with early-onset FEP (first psychotic symptom before age 18) and less than 6 months of positive symptoms., Methods: A total of 66 subjects were included in the study (19 females [28.8%], mean age 16.2 ± 1.6 years). The influence of DUP on changes in EF over the 2-year follow-up (expressed as a composite score of 5 cognitive abilities: attention, working memory, cognitive flexibility, response inhibition, and problem solving) was estimated using a multivariate linear regression model after removing the effect of intelligence quotient and controlling for age, gender, diagnosis, premorbid adjustment, severity of positive and negative symptoms at baseline, global functioning at baseline, and mean daily antipsychotic dosage during follow-up., Results: Mean DUP was 65.0 ± 6.9 days (95% confidence interval [CI], 51.2, 78.8). Median DUP was 47.5 days (range 2-180 days). Negative symptoms at baseline was the only variable significantly associated with EF at baseline (10.9% of explained variance [e.v. 10.9%], p=0.007). Only shorter DUP (e.v. 8.7%, p=0.013) and greater severity of baseline negative symptoms (e.v. 10.0%, p=0.008) were significantly associated with greater improvement in EF., Conclusions: In early-onset FEP, shorter DUP was associated with greater improvement in EF over a 2-year follow-up period., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: The present study aims to assess the efficacy of a structured psychoeducational group intervention for adolescents with early-onset psychosis and their families. The intervention was implemented in parallel in 2 separate groups by focusing specifically on problem-solving strategies and structured psychosis-related information to manage daily life difficulties associated with the disease, to mitigate crises, and to prevent relapses., Method: We performed a 9-month, randomized, rater-blinded clinical trial involving 55 adolescent patients with early-onset psychosis and either or both of their parents. A psychoeducational problem-solving group intervention (n = 27) was compared with a nonstructured group intervention (n = 28). The primary outcomes were number of hospitalizations, days of hospitalization, and visits to the emergency department. The secondary outcome measures were clinical variables and family environment., Results: Assessments were performed before and after the intervention. At the end of the group intervention, 15% of patients in the psychoeducational group and 39% patients in the nonstructured group had visited the emergency department (χ² = 3.62, df = 1, p = .039). The improvement in negative symptoms was more pronounced in the psychoeducational group (12.84 [7.87]) than in the nonstructured group (15.81 [6.37]) (p = .039)., Conclusion: A parallel psychoeducational group intervention providing written instructions in a structured manner could help adolescents with early-onset psychosis and their parents to manage crises by implementing problem-solving strategies within the family, thus reducing the number of visits to the emergency department. Negative symptoms improved in adolescents in the psychoeducational group. Clinical trial registration information--Intervention Module AGES (AGES-CM); http://clinicaltrials.gov/; NCT02101372. [corrected]., (Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

The objective of the study is to examine the association of baseline total antioxidant status (TAS) and glutathione (GSH) levels with short- and long-term cognitive functioning in patients with early onset first-episode psychosis, comparing affective and non-affective psychoses. We analysed 105 patients with an early onset-first episode psychosis (age 9-17 years) and 97 healthy controls. Blood samples were taken at admission for measurement of TAS and GSH, and cognitive performance was assessed at baseline and at 2years of follow-up. Regression analysis was used to assess the relationship between TAS/GSH levels at baseline and cognitive performance at both time points, controlling for confounders. Baseline TAS and GSH levels were significantly lower in patients than healthy controls. In patients, baseline TAS was positively associated with the global cognition score at baseline (p=0.048) and two years later (p=0.005), while TAS was not associated with cognitive functioning in healthy controls. Further, baseline TAS in patients was specifically associated with the memory domain at baseline and with the memory and attention domains two years later. Stratifying by affective and non-affective psychoses, significant associations were only found between TAS and cognition in the non-affective psychosis group. Baseline GSH levels were not associated with cognitive functioning at either time point in either group. The antioxidant defence capacity in early onset first-episode psychotic patients is directly correlated with global cognition at baseline and at 2years of follow-up, especially in non-affective psychosis., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Despite the large body of research on premorbid impairments in schizophrenia, studies comparing different early-onset psychoses are scarce., Aims: To examine premorbid impairments in first episodes of early-onset bipolar and schizophrenia disorders., Method: We compared premorbid adjustment and other premorbid variables such as IQ and developmental abnormalities in a cohort of children and adolescents (N=69) with bipolar disorder (BP) or schizophrenia (SZ) experiencing their first psychotic episode and in a healthy control group (N=91)., Results: Schizophrenia patients showed more social impairment in childhood than bipolar patients (p<0.05) and healthy controls (p<0.001) and had higher rates of developmental abnormalities (p<0.05) than healthy controls. Between childhood and early adolescence, schizophrenia and bipolar patients showed a greater decline in academic adjustment than healthy controls, more specifically in adaptation to school (p<0.01)., Conclusions: Early-onset schizophrenia patients show more early social impairment than early-onset bipolar patients. Intellectual premorbid abnormalities are less specific and probably more linked to early-onset psychosis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Progressive loss of cortical gray matter (GM), as measured by magnetic resonance imaging, has been described early in the course of first-episode psychosis. This study aims to assess the relationship between oxidative balance and progression of cortical GM changes in a multicenter sample of first-episode early-onset psychosis (EOP) patients from baseline to two-year follow-up. A total of 48 patients (13 females, mean age 15.9±1.5 years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5 years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2 years later were used for volumetric measurements of left and right gray matter regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline. In patients, after controlling for possible confounding variables, lower baseline GSH levels were significantly associated with greater volume decrease in left frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620, p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI: 0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total CSF (B=-0.560, 95% CI: -0.270 to -0.850, r=-0.722, p=0.001). Controls did not show significant associations between brain volume changes and GSH levels. GSH deficit during the first psychotic episode was related to greater loss of cortical GM two years later in patients with first-episode EOP, suggesting that oxidative damage may contribute to the progressive loss of cortical GM found in patients with first-episode psychosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Context: Progressive loss of brain gray matter (GM) has been reported in childhood-onset schizophrenia; however, it is uncertain whether these changes are shared by pediatric patients with different psychoses., Objective: To examine the progression of brain changes in first-episode early-onset psychosis and their relationship to diagnosis and prognosis at 2-year follow-up., Design: Prospective, multicenter, naturalistic, 2-year follow-up study., Setting: Six child and adolescent psychiatric units in Spain., Participants: A total of 110 patients and 98 healthy controls were recruited between March 1, 2003, and November 31, 2005. Magnetic resonance imaging of the brain was performed for 61 patients with schizophrenia (n = 25), bipolar disorder (n = 16), or other psychoses (n = 20) and 70 controls (both at baseline and after 2 years of follow-up). Mean age at baseline was 15.5 years (patients) and 15.3 years (controls)., Main Outcome Measures: The GM and cerebrospinal fluid (CSF) volumes in the total brain and frontal, parietal, and temporal lobes., Results: Compared with controls, patients with schizophrenia showed greater GM volume loss in the frontal lobe during the 2-year follow-up (left: -3.3 vs -0.6 cm(3), P = .004; right: -3.7 vs -0.8 cm(3), P = .005) and left frontal CSF volume increase (left: 6.7 vs 2.4 cm(3), P = .006). In addition to frontal volume, changes for total GM (-37.1 vs -14.5 cm(3), P = .001) and left parietal GM (-4.3 vs -2.2 cm(3), P = .04) were significantly different in schizophrenic patients compared with controls. No significant differences emerged for patients with bipolar disease. Greater left frontal GM volume loss was related to more weeks of hospitalization, whereas severity of negative symptoms correlated with CSF increase in patients with schizophrenia., Conclusions: Patients with schizophrenia or other psychoses showed greater loss of GM volume and increase of CSF in the frontal lobe relative to controls. Progressive changes were more evident in patients with schizophrenia than those with bipolar disorder. These changes in specific brain volumes after onset of psychotic symptoms may be related to markers of poorer prognosis.

Objective: To review data on efficacy and safety of second-generation antipsychotics (SGAs) in children and adolescents with psychotic and bipolar spectrum disorders., Methods: Medline/PubMed/Google Scholar search for studies comparing efficacy and/or tolerability: (i) between two or more SGAs; (ii) between SGAs and placebo; and (iii) between at least one SGA and one first-generation antipsychotic (FGA). The review focused on three major side-effect clusters: 1. body weight, body mass index, and cardiometabolic parameters, 2. prolactin levels, and 3. neuromotor side effects., Results: In total, 34 studies with 2719 children and adolescents were included. Studies lasted between 3 weeks and 12 months, with most studies (79.4%) lasting 3 months or less. Nine studies (n=788) were conducted in patients with schizophrenia, 6 (n=719) in subjects with bipolar disorder, and 19 (n=1212) in a mixed population. Data on efficacy showed that, except for clozapine being superior for refractory schizophrenia, there were no significant differences between SGAs. By contrast, safety assessments showed relevant differences between SGAs. Mean weight gain ranged from 3.8 kg to 16.2 kg in patients treated with olanzapine (n=353), from 0.9 kg to 9.5 kg in subjects receiving clozapine (n=97), from 1.9 kg to 7.2 kg in those on risperidone (n=571), from 2.3 kg to 6.1 kg among patients taking quetiapine (n=133), and from 0 kg to 4.4 kg in those treated with aripiprazole (n=451). Prolactin levels increased the most in subjects on risperidone (mean change ranging from 8.3 ng/mL to 49.6 ng/mL), followed by olanzapine (-1.5 ng/mL to +13.7 ng/mL). Treatment with aripiprazole was associated with decreased prolactin levels, while clozapine and quetiapine were found to be mostly neutral. With respect to neuromotor side effects, SGAs were associated with less parkinsonism and akathisia than FGAs. Most of the studies comparing neuromotor side effects between SGAs found no significant differences., Conclusions: SGAs do not behave as a homogeneous group in children and adolescents with psychotic and mood disorders. Except for clozapine, the heterogeneity within the SGA group is mainly due to differences in the rates and severity of adverse events, especially regarding weight gain as a proxy for the risk of cardiometabolic disturbances., (Published by Elsevier B.V.)

Background: Increasing evidence supports the important role of illness state and individual characteristics in insight., Methods: Insight, as measured with the Scale to Assess Unawareness of Mental Disorder, over the first 2 years of early-onset first-episode psychosis and its correlations with clinical, socio-demographic, cognitive, and structural brain variables are studied., Results: (1) insight at 2 years is poorer in schizophrenia spectrum disorders (SSDs) than in subjects with other psychoses; (2) the more severe the psychosis, the worse the insight. In SSD, depressive symptoms, poorer baseline executive functioning, lower IQ, longer duration of untreated psychosis (DUP), and poorer premorbid infancy adjustment are associated with poorer insight; frontal and parietal gray matter (GM) reductions at baseline correlate with worse insight into having psychotic symptoms at 2 years; (3) insight into having a mental disorder (Scale to Assess Unawareness of Mental Disorder [SUMD]1) at 1 year, DUP, and baseline IQ are the most consistent variables explaining different aspects of insight at 2 years in SSD patients. IQ and SUMD1 at 1 year, together with left frontal and parietal GM volumes, explain 80% of the variance of insight into having specific psychotic symptoms in SSD patients (adjusted R(2) = 0.795, F = 15.576, P < .001)., Conclusion: Insight is a complex phenomenon that depends both on severity of psychopathology and also on disease and subject characteristics, such as past adjustment, IQ, DUP, cognitive functioning, frontal and parietal GM volumes, and age, gender, and ethnicity.

Background: Early-onset psychosis is a symptomatically nonspecific and heterogeneous entity composed of several diagnoses. This study examined the dimensional structure of symptoms and the temporal stability of this structure during a 6-month follow-up., Method: A principal component factor analysis of the Positive and Negative Syndrome Scale was conducted at baseline, 4 weeks, and 6 months in a sample of 99 first-episode psychotic patients (mean age = 15.5 years)., Results: The factor analysis produced a 5-dimension solution (Positive, Negative, Depression, Cognitive, Hostility) that explained 62.4% of the variance at baseline, 63.4% at 4 weeks, and 65.1% at 6 months. Negative dimension was the most consistent and stable over time and was predominant at baseline (23.9%) and at 4 weeks (25.7%). Depression was predominant at 6 months (31.1%)., Conclusions: There is a stable 5-dimension structure of symptoms in early-onset psychosis with varying predominance of symptoms over time. Negative symptoms are a core feature of psychosis and are thus important diagnostic criteria., ((c) 2010 Physicians Postgraduate Press, Inc.)