Early-onset First-episode Psychosis Research Articles

Fronto-Parietal Gray Matter Volume Loss Is Associated with Decreased Working Memory Performance in Adolescents with a First Episode of Psychosis.

Cognitive maturation during adolescence is modulated by brain maturation. However, it is unknown how these processes intertwine in early onset psychosis (EOP). Studies examining longitudinal brain changes and cognitive performance in psychosis lend support for an altered development of high-order cognitive functions, which parallels progressive gray matter (GM) loss over time, particularly in fronto-parietal brain regions. We aimed to assess this relationship in a subsample of 33 adolescents with first-episode EOP and 47 matched controls over 2 years. Backwards stepwise regression analyses were conducted to determine the association and predictive value of longitudinal brain changes over cognitive performance within each group. Fronto-parietal GM volume loss was positively associated with decreased working memory in adolescents with psychosis (frontal left (B = 0.096, p = 0.008); right (B = 0.089, p = 0.015); parietal left (B = 0.119, p = 0.007), right (B = 0.125, p = 0.015)) as a function of age. A particular decrease in frontal left GM volume best predicted a significant amount (22.28%) of the variance of decreased working memory performance over time, accounting for variance in age (14.9%). No such association was found in controls. Our results suggest that during adolescence, EOP individuals seem to follow an abnormal neurodevelopmental trajectory, in which fronto-parietal GM volume reduction is associated with the differential age-related working memory dysfunction in this group.

Depressive symptoms and their relationship with negative and other psychotic symptoms in early onset psychosis.

The importance of depression in adult people with first-episode psychosis (FEP) has been demonstrated. However, it has hardly been studied in children and adolescents. There is a need to broaden knowledge of the relationship between psychotic symptoms and specific depression symptomatology. The aims of study were (a) to examine the frequency of presence and type of depressive symptoms in early onset FEP, and (b) to assess the relationship between depressive symptoms and psychotic symptomatology, and specifically negative symptoms. An observational cross-sectional study was performed in 62 FEP cases. Inclusion criteria were two or more psychotic symptoms, age 7-17years old, first mental health service consultation, and fewer than 6months from the first contact with the service. Participants were assessed with clinical and socio-demographic questionnaires: the Positive and Negative Syndrome Scale (PANSS) and the Children Depression Inventory (CDI). A Student t test was performed to compare psychotic symptoms in both groups: presence of depression and the absence of depression. A Pearson correlation was performed in order to relate subscales of the PANSS and each of the depression subscales and factors, as well the relation between negative and depressive symptoms. Our results show that a high percentage of people with an early onset of a FEP scored positively for depression. The most prevalent depressive symptoms were associated with schooling. The presence of depression was associated with negative, affective, and excited symptoms. Self-esteem, school problems, negative affect, and biological dysregulation were associated with psychotic symptoms. Finally, depressive items related to social functioning were more closely associated with negative symptoms of the PANSS. In conclusion, owing to the high incidence of depression in FEP in those suffering early onset of psychosis, there is a need for instruments to measure the depression more specifically in children and adolescent, and to uncover the clinical characteristics of depression in this population.

Early onset first-episode psychosis during treatment with thalidomide for refractory ulcerative colitis: a case report

BackgroundInflammatory bowel disease and schizophrenia spectrum disorders are complex and multifactorial conditions characterized by great variability of age at onset, clinical presentation, and longitudinal course. Several lines of evidence suggested different connections among immunological dysregulation, gastrointestinal inflammation, and psychosis, but to date many controversial issues still exist in this field.Case presentationWe present the case of a 14-year-old Caucasian boy with refractory ulcerative colitis, admitted to the Child Neuropsychiatry Unit of the Polyclinic Hospital of Bari in the course of his first-episode psychosis. He showed an acute onset of psychotic symptomatology during treatment with thalidomide, an immunomodulatory drug used in the experimental therapy of refractory inflammatory bowel disease. Thalidomide was discontinued and orally administered mesalazine was restarted. In addition, treatment with antipsychotics and mood stabilizers was introduced with gradual improvement of psychotic symptoms. According to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, a diagnosis of partial remission of a first episode of schizoaffective disorder was formulated after a 6-month follow-up. Throughout this period, both psychopharmacological and mesalazine-based gastrointestinal treatments were maintained with partial remission of psychiatric and gastrointestinal symptoms.ConclusionsWe propose that refractory ulcerative colitis and psychosis might represent different manifestations of a common pathological pathway. However, it is also conceivable that thalidomide may have played a role in promoting the manifestation of psychotic symptoms in an individual with a specific vulnerability to schizoaffective disorders. Further investigations are needed to improve our knowledge regarding the complexity of brain–gut interactions, thus improving the management of co-existing inflammatory bowel and schizophrenia spectrum disorders.

Neuroanatomical deficits shared by youth with autism spectrum disorders and psychotic disorders.

Autism spectrum disorders (ASD) and early-onset psychosis (EOP) are neurodevelopmental disorders that share genetic, clinical and cognitive facets; it is unclear if these disorders also share spatially overlapping cortical thickness (CT) and surface area (SA) abnormalities. MRI scans of 30 ASD, 29 patients with early-onset first-episode psychosis (EO-FEP) and 26 typically developing controls (TD) (age range 10-18 years) were analyzed by the FreeSurfer suite to calculate vertex-wise estimates of CT, SA, and cortical volume. Two publicly available datasets of ASD and EOP (age range 7-18 years and 5-17 years, respectively) were used for replication analysis. ASD and EO-FEP had spatially overlapping areas of cortical thinning and reduced SA in the bilateral insula (all p's < .00002); 37% of all left insular vertices presenting with significant cortical thinning and 20% (left insula) and 61% (right insula) of insular vertices displaying decreased SA overlapped across both disorders. In both disorders, SA deficits contributed more to cortical volume decreases than reductions in CT did. This finding, as well as the novel finding of an absence of spatial overlap (for ASD) or marginal overlap (for EOP) of deficits in CT and SA, was replicated in the two nonoverlapping independent samples. The insula appears to be a region with transdiagnostic vulnerability for deficits in CT and SA. The finding of nonexistent or small spatial overlap between CT and SA deficits in young people with ASD and psychosis may point to the involvement of common aberrant early neurodevelopmental mechanisms in their pathophysiology.

Dilemmas in the treatment of early-onset first-episode psychosis.

Early-onset first-episode psychosis (EOP) is a severe mental disorder that can pose a number of challenges to clinicians, young people and their families. Its assessment and differentiation from other neurodevelopmental and mental health conditions may at times be difficult, its treatment may not always lead to optimal outcomes and can be associated with significant side effects, and its long-term course and prognosis seem to be less favourable compared with the adult-onset disorder. In this paper, we discuss some dilemmas associated with the evaluation and management of EOP and propose approaches that can be used in the clinical decision-making process. A detailed and well-informed assessment of psychotic symptoms and comorbidities, a systematic approach to treatment with minimum possible medication doses and close monitoring of its effectiveness and adverse effects, and multidimensional interventions taking into consideration risks and expectations associated with EOP, are paramount in the achievement of the most favourable outcomes for affected children and young people.

Persistent Negative Symptoms in First-Episode Psychosis: Early Cognitive and Social Functioning Correlates and Differences Between Early and Adult Onset.

To characterize the early cognitive and social functioning characteristics of a sample of first-episode psychosis patients with and without persistent negative symptoms (PNS) and to examine the prevalence and cognitive and functional correlates of PNS in patients with early-onset versus adult-onset first-episode psychosis. Participants were 235 patients with first-episode psychosis (51 early-onset, 184 adult-onset) and 240 healthy controls from a multicenter longitudinal study (recruited between 2009 and 2011). Standard instruments were used to evaluate symptoms, cognition, and social functioning. Diagnoses were determined according to DSM-IV criteria. PNS proxy was derived from clinical assessments (Positive and Negative Syndrome Scale and Montgomery-Asberg Depression Scale) at 2-, 6-, and 12-month follow-up. Association tests were used to compare the prevalence of PNS in the early-onset versus adult-onset groups. Multivariate analysis of variance was used to examine differences in early cognitive and social functioning (at the 2-month assessment) between patients with and without PNS and between early-onset and adult-onset patients with PNS. Thirty-eight patients (16.2%) met criteria for PNS during the first year. This PNS group showed a selective deficit in executive functions and in global, community, and occupational functioning (P < .05). Having PNS was associated with a diagnosis of a schizophrenia spectrum disorder at the 12-month follow-up. The prevalence of PNS was almost double for those patients with an early-onset (0.25 vs 0.14; OR = 2.18; 95% CI, 1.02-4.64), and this was associated with greater cognitive (P < .05) but not social deficits. There was an early, detectable, social and executive dysfunction associated with PNS in first-episode psychosis and a high risk of having PNS in early-onset first-episode psychosis, which in turn was associated with more widespread cognitive impairment. Specific therapeutic interventions for PNS in early-onset first-episode psychosis might be needed.

Gray matter changes and cognitive predictors of 2-year follow-up abnormalities in early-onset first-episode psychosis.

This study aims to examine regional gray matter (GM) changes over a period of 2years 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 11-17years were assessed. Magnetic resonance imaging was carried out at admission and 2years 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 2years. At follow-up, only SCZ patients differed significantly from controls in specific brain areas. The GM reduction was predicted by baseline cognitive variables.

Glutathione S-Transferase Deletion Polymorphisms in Early-Onset Psychotic and Bipolar Disorders: A Case-Control Study.

To examine glutathione S-transferase (GST) deletion polymorphisms in development of early-onset severe mental disorders, with the hypothesis that patients with GSTM1-null and GSTT1-null genotypes will develop psychotic disorders at a younger age. We identified GSTM1 and GSTT1 deletion polymorphisms by multiplex polymerase chain reaction (PCR) in 93 patients with early onset severe mental disorders and 278 control individuals. The diagnoses were confirmed by Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and Schedule for Affective Disorders and Schizophrenia-Life-Time Version (K-SADS-PL) interviews. Individuals with the GSTM1-null genotype were at 3.36-fold higher risk of developing early-onset severe mental disorders than carriers of a corresponding active genotype. The risk of those disorders was increased by 6.59-fold in patients with GSTM1-null/GSTT1-active genotype. Patients with the GSTM1-null genotype were at approximately 2-fold increased risk for developing early-onset schizophrenia-spectrum disorder (EOS), early-onset bipolar disorder (EOBD) with psychotic symptoms, or early-onset first-episode psychosis (EOFEP), compared with patients with the GSTM1-active genotype. The GSTM1-null genotype might be associated with higher risk for early onset severe mental disorders.

Predictors of functional and clinical outcome in early-onset first-episode psychosis: the child and adolescent first episode of psychosis (CAFEPS) study.

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. 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). 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. 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.

Predictors of schizophrenia spectrum disorders in early-onset first episodes of psychosis: a support vector machine model.

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.

Cortical morphology of adolescents with bipolar disorder and with schizophrenia

IntroductionRecent evidence points to overlapping decreases in cortical thickness and gyrification in the frontal lobe of patients with adult-onset schizophrenia and bipolar disorder with psychotic symptoms, but it is not clear if these findings generalize to patients with a disease onset during adolescence and what may be the mechanisms underlying a decrease in gyrification. MethodThis study analyzed cortical morphology using surface-based morphometry in 92 subjects (age range 11–18years, 52 healthy controls and 40 adolescents with early-onset first-episode psychosis diagnosed with schizophrenia (n=20) or bipolar disorder with psychotic symptoms (n=20) based on a two year clinical follow up). Average lobar cortical thickness, surface area, gyrification index (GI) and sulcal width were compared between groups, and the relationship between the GI and sulcal width was assessed in the patient group. ResultsBoth patients groups showed decreased cortical thickness and increased sulcal width in the frontal cortex when compared to healthy controls. The schizophrenia subgroup also had increased sulcal width in all other lobes. In the frontal cortex of the combined patient group sulcal width was negatively correlated (r=−0.58, p<0.001) with the GI. ConclusionsIn adolescents with schizophrenia and bipolar disorder with psychotic symptoms there is cortical thinning, decreased GI and increased sulcal width of the frontal cortex present at the time of the first psychotic episode. Decreased frontal GI is associated with the widening of the frontal sulci which may reduce sulcal surface area. These results suggest that abnormal growth (or more pronounced shrinkage during adolescence) of the frontal cortex represents a shared endophenotype for psychosis.

A longitudinal study on the relationship between duration of untreated psychosis and executive function in early-onset first-episode psychosis

BackgroundThe 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 6months of positive symptoms. MethodsA total of 66 subjects were included in the study (19 females [28.8%], mean age 16.2±1.6years). 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. ResultsMean DUP was 65.0±6.9days (95% confidence interval [CI], 51.2, 78.8). Median DUP was 47.5days (range 2–180days). 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. ConclusionsIn early-onset FEP, shorter DUP was associated with greater improvement in EF over a 2-year follow-up period.

Basal low antioxidant capacity correlates with cognitive deficits in early onset psychosis. A 2-year follow-up study

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.

Duration of untreated psychosis predicts functional and clinical outcome in children and adolescents with first-episode psychosis: A 2-year longitudinal study

Longer duration of untreated psychosis (DUP) in adult patients with first-episode psychosis (FEP) has been associated with poor clinical and social outcomes. We aimed to estimate the influence of DUP on outcome at 2-year follow-up in subjects with an early-onset (less than 18years of age) FEP of less than 6months' duration. A total of 80 subjects (31.3% females, mean age 16.0±1.8years) were enrolled in the study. The influence of DUP on outcome was estimated using multiple regression models (two linear models for influence of DUP on the C-GAF at 2years and C-GAF change through the follow-up period, and a logistic model for influence of DUP on 41 PANSS remission at 2 years in schizophrenia patients (n=47)). Mean DUP was 65.3±54.7days. Median DUP was 49.5days. For the whole sample (n=80), DUP was the only variable significantly related to C-GAF score at 2-year follow-up (Beta=−0.13, p<0.01), while DUP and premorbid adjustment (Beta=−0.01, p<0.01; and Beta=−0.09, p=0.04, respectively) were the only variables significantly related to C-GAF change. In schizophrenia patients, DUP predicted both C-GAF score at 2years and C-GAF change, while in patients with affective psychosis (n=22), DUP was unrelated to outcome. Lower baseline C-GAF score (OR=0.91, p<0.01) and shorter DUP (OR=0.98, p=<0.01) were the only variables that significantly predicted clinical remission in schizophrenia patients. In conclusion, longer DUP was associated with lower C-GAF at 2years, less increase in C-GAF, and lower rates of clinical remission in early-onset FEP. Our findings support the importance of early detection programs, which help shorten DUP.

Predictors of Suicide Attempt in Early-Onset, First-Episode Psychoses

To study the prevalence of suicide attempts and factors associated with risk for suicide during the first episode of psychosis, and to identify early predictors of suicide attempts over a 24-month follow-up period in an early-onset, first-episode psychosis cohort. 110 subjects in their first episode of psychosis aged between 9 and 17 years were assessed by using the DSM-IV diagnostic interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and a battery of clinical instruments at baseline and at 12 and 24 months. Patients were enrolled in the study from March 2003 through November 2005. Suicide attempts and level of suicidality at each assessment were evaluated by using the Clinical Global Impression for Severity of Suicidality and the Hamilton Depression Rating Scale. Subjects were classified as being at high, low, or no risk of suicide, depending on their scores on certain items of these scales. Clinical associations between the outcome measures high risk for suicide during acute episode and suicide attempts during follow-up were investigated by 2 sets of logistic regression analyses. The 24-month prevalence of suicide attempters was 12.4%. History of suicide attempts prior to psychotic episode (OR = 20.13; 95% CI, 1.83-220.55; P = .01), severe depressive symptoms (OR = 8.78; 95% CI, 1.15-67.11; P = .003), and antidepressant treatment (OR = 15.56; 95% CI, 2.66-90.86; P = .002) were associated with being classified as high suicide risk at baseline. The categorization of high suicide risk at baseline predicted suicide attempts during follow-up (OR = 81.66; 95% CI, 11.61-574.35; P = .000). Suicide is a major concern in early-onset first-episode psychosis. Suicidal behavior and depressive symptoms at psychosis onset are important signs to be aware of to prevent suicide attempts during the early period after first-episode psychosis.

Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses

The longitudinal neuropsychological study of first-episode early-onset psychosis (EOP) patients, whose brain maturation is still in progress at the time of illness onset, provides a unique opportunity to compare their cognitive development with that of healthy subjects, in search of specific patterns resulting from the interaction between neurodevelopmental processes and the presence of psychotic disorders. Method Seventy-five first-episode EOP patients (schizophrenia n = 35; bipolar disorder n = 17; other forms of psychosis n = 23) with a mean age of 15.53 years were assessed with a neuropsychological battery that included measures of attention, working memory, memory and executive functions within 6 months following the onset of the first psychotic symptom (baseline) and 2 years later. Psychotic symptoms were assessed at both times with the Positive and Negative Symptom Scale (PANSS). Seventy-nine healthy subjects matched for age and education served as controls. EOP patients showed significant cognitive impairment at both baseline and the 2-year follow-up, with no significant differences between diagnostic groups at either time. Both healthy controls and EOP patients improved in all cognitive measures, except for patient working memory. Improvement in patient attention lost significance after controlling for psychotic symptom reduction. No significant time/diagnosis interaction was found among patients (p > 0.405). Cognitive impairment in EOP is already present at the first episode, and cognitive development seems to be arrested early in EOP patients compared to their healthy peers, at least for some cognitive functions. These and previous similar results support the neurodevelopmental hypothesis of psychosis.

Decreased glutathione levels predict loss of brain volume in children and adolescents with first-episode psychosis in a two-year longitudinal study

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±1.5years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2years 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.

Progressive Brain Changes in Children and Adolescents With First-Episode Psychosis

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. 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. Prospective, multicenter, naturalistic, 2-year follow-up study. Six child and adolescent psychiatric units in Spain. 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). The GM and cerebrospinal fluid (CSF) volumes in the total brain and frontal, parietal, and temporal lobes. 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. 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.

Cognitive Efficacy of Quetiapine in Early-Onset First-Episode Psychosis: A 12-Week Open Label Trial

Twenty-three adolescents with psychotic disorders, aged from 13 to 18years, participated in a 12-week open label trial (17 adolescents completed the study) in order to examine the impact of quetiapine on clinical status and cognitive functions (encompassing processing speed, attention, short-term memory, long-term memory and executive function). An improvement in Clinical Global Impression and Positive and Negative Symptom Scale (P's≤0.001) was observed. In addition, after controlling for amelioration of symptoms, a significant improvement was observed on one executive function (P=0.044; Trail Making Part B). The remaining cognitive abilities showed stability. In addition, we observed an interaction between quetiapine doses (>300mg/day or <300mg/day) and time, where lower doses showed more improvement in verbal short-term memory (P=0.048), inhibition abilities (P=0.038) and positive symptoms (P=0.020). The neuropsychological functioning of adolescents with psychotic disorders remained mainly stable after 12weeks of treatment with quetiapine. However, lower doses seemed to have a better impact on two components of cognition (inhibition abilities and verbal short-term memory) and on positive symptoms.

Two-year diagnostic stability in early-onset first-episode psychosis

Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP). To describe diagnostic stability and the variables related to diagnostic changes. Participants were 83 patients (aged 9-17 years) with an EO-FEP consecutively attended. They were assessed with a structured interview (Kiddie-Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version) and clinical scales at baseline and after 2 years. The global consistency for all diagnoses was 63.9%. The small group of bipolar disorder had high stability (92.31%) as did the group with schizophrenia spectrum disorders (90.00%). Depressive disorder had lower stability (37.50%) and the lowest values were for psychotic disorder not otherwise specified (11.76%) and brief psychotic disorder (0%).The most frequent diagnostic shift was to schizophrenia spectrum and bipolar disorders. One group of patients did not meet the criteria for any diagnosis at follow-up. Independent predictors of change to schizophrenia spectrum disorders were lower scores on the Children's Global Assessment Scale (CGAS) and the Hamilton Depression Rating Scale. Predictors of not having a diagnosis at follow-up were the CGAS and the Strauss-Carpenter Outcome Scale. Global diagnostic stability was 63.9%. Bipolar and schizophrenia spectrum disorders were the most stable diagnoses, while depressive disorder and other psychosis the least stable. Psychosocial functioning at baseline was a good predictor of diagnosis at follow-up. These data show the need for longitudinal follow-up in EO-FEP before a stable diagnosis is reached.