Background
The evaluation of child and adolescent offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) may help understand changes taking place in the brain in individuals at ...heightened risk for disease during a key developmental period.
Methods
One hundred twenty‐eight individuals (33 SzO and 46 BpO, considered jointly as ‘Familial High Risk’ (FHR), and 49 controls) aged 6–17 years underwent clinical, cognitive and neuroimaging assessment at baseline, 2‐ and 4‐year follow‐up. Twenty FHR participants (11 SzO and 9 BpO) developed psychotic spectrum symptoms during follow‐up, while 59 FHR participants did not. Magnetic resonance imaging was performed on a 3Tesla scanner; cortical surface reconstruction was applied to measure cortical thickness, surface area and grey matter volume.
Results
FHR participants who developed psychotic spectrum symptoms over time showed greater time‐related mean cortical thinning than those who did not and than controls. By subgroups, this effect was present in both BpO and SzO in the occipital cortex. At baseline, FHR participants who developed psychotic spectrum symptoms over time had smaller total surface area and grey matter volume than those who did not and than controls. Over time, all FHR participants showed less longitudinal decrease in surface area than controls. In those who developed psychotic spectrum symptoms over time, this effect was driven by BpO, while in those who did not, this was due to SzO, who also showed less grey matter volume reduction.
Conclusion
The emergence of psychotic spectrum symptoms in FHR was indexed by smaller cross‐sectional surface area and progressive cortical thinning. Relative preservation of surface area over time may signal different processes according to familial risk. These findings lay the foundation for future studies aimed at stratification of FHR youth.
Objective
The period immediately after the onset of first‐episode psychosis (FEP) may present with high risk for suicidal ideation (SI) and attempts, although this risk may differ among patients. ...Thus, we aimed to identify trajectories of SI in a 2‐years follow‐up FEP cohort and to assess baseline predictors and clinical/functional evolution for each trajectory of SI.
Methods
We included 334 FEP participants with data on SI. Growth mixture modeling was used to identify trajectories of SI. Putative sociodemographic, clinical, and cognitive predictors of the distinct trajectories were examined using multinomial logistic regression.
Results
We identified three distinct trajectories: Non‐SI trajectory (85.53% sample), Improving SI trajectory (9.58%), and Worsening SI trajectory (6.89%). Multinomial logistic regression model revealed that greater baseline pessimistic thoughts, anhedonia, and worse perceived family environment were associated with higher baseline SI followed by an Improving trajectory. Older age, longer duration of untreated psychosis, and reduced sleep predicted Worsening SI trajectory. Regarding clinical/functional evolution, individuals within the Improving SI trajectory displayed moderate depression at baseline which ameliorated during the study period, while the Worsening SI subgroup exhibited persistent mild depressive symptoms and greater functional impairment at follow‐up assessments.
Conclusion
Our findings delineated three distinct trajectories of SI among participants with FEP, one experiencing no SI, another in which SI might depend on acute depressive symptomatology, and a last subset where SI might be associated with mild but persistent clinical and functional impairments. These data provide insights for the early identification and tailored treatment of suicide in this at‐risk population.
Schizophrenia (SZ) and bipolar disorder (BD) share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in ...patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7-19 years, comprising offspring of patients with SZ (N = 27), offspring of patients with BD (N = 39) and offspring of community control parents (N = 40). We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence.
Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group.
Total antioxidant status ...(TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls.
A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients.
Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology.
Cognitive impairment is an enduring and functionally relevant feature of early-onset schizophrenia (EOS). Cognitive remediation therapy (CRT) improves cognition and functional outcome in adults with ...schizophrenia, although data in adolescents with EOS remain scarce. The purpose of this study is to examine the efficacy of CRT in improving cognition and functional outcomes in a sample of symptomatically stable but cognitively disabled adolescents with EOS.
We performed a randomized, controlled trial of individually delivered CRT plus treatment-as-usual compared with treatment-as-usual (TAU). Fifty adolescents with EOS were randomly assigned to receive CRT (n = 25) or TAU (n = 25) and were included in an intention-to-treat analysis. Clinical symptoms and cognitive and functional performance were assessed before and after treatment in both groups and after 3 months in the CRT group. Cognitive domains were defined according to the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus battery and averaged in a global cognitive composite score.
After CRT, significant improvements were found in verbal memory and executive functions, with medium-to-large effect sizes (ES). The derived cognitive composite score showed an improvement after the treatment, with a large ES. This change was reliable in more than two-thirds of the treated patients. Medium-sized ES were found for improvements after CRT in daily living and adaptive functioning, whereas large ES were observed for improvements in family burden. With the exception of functional gains, these changes were maintained after 3 months.
CRT appears to be a useful intervention strategy for adolescents with EOS. Cognitive improvements can be achieved through CRT, although further research is warranted to determine the durability of functional gains. Clinical trial registration information-Cognitive Remediation Therapy (CRT) in Adolescents With EOS; www.clinicaltrials.gov; NCT01701609.
Background: 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).
Aim: To describe diagnostic stability and the variables related to diagnostic changes.
Methods: 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.
Results: 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.
Conclusions: 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.
Background
The affective dimension has scarcely been studied in early‐onset psychosis. Our aims were to investigate the prevalence and type of affective symptoms in the prodromal and acute phases of ...early‐onset psychosis and to examine their relationship with suicide. We also sought to establish whether the presence of premorbid antecedents or the presence of affective symptoms during the prodromal and acute phase might predict a later diagnosis of bipolar disorder (BP) or schizophrenia (SZ).
Method
Participants were 95 youths, aged 9–17 years, experiencing a first episode of a psychotic disorder (FEP) according to DSM‐IV criteria. Prodromal affective symptoms in the year prior to the onset of full‐blown psychosis were assessed by means of the K‐SADS. Affective symptoms during the acute episode were evaluated using the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Suicidality was assessed during the acute episode and at 6 and 12 months.
Results
Half of the patients experienced affective symptoms during the prodrome, with depressive symptoms being the most frequently reported. During the acute episode, 23.2% presented depressive, 41.4% mixed and 18.9% manic symptoms. After logistic regression analysis, only the presence of depressive symptoms was significantly associated with suicidality during the 12 months following the FEP. Neither early premorbid antecedents nor the prevalence or type of affective symptoms during the FEP predicted a diagnosis of BP or SZ at 12 months. However, both depressive and manic prodromal symptoms were associated with a later diagnosis of BP.
Conclusions
The FEP of both SZ and BP is preceded by an identifiable prodromal phase. Early detection programs should target young people at clinical risk for the extended psychosis phenotype. The high prevalence of affective symptoms during the early phases of psychosis may encourage clinicians to identify and treat them in order to prevent suicide behaviour.
To report the neuropsychiatric features and frequency of NMDA receptor (NMDAR) and other neuronal immunoglobulin G antibodies in patients with first episode psychosis (FEP) and to assess the ...performance of reported warning signs and criteria for autoimmune psychosis (AP).
This was a prospective observational study of patients with FEP assessed for neuropsychiatric symptoms, serum and CSF neuronal antibodies (brain immunohistochemistry, cell-based assays, live neurons), and warning signs and criteria of AP. Previous autoimmune FEP series were reviewed.
One hundred five patients were included; their median age was 30 (range 14-75) years, and 44 (42%) were female. None had neuronal antibodies. Two of 105 (2%) had CSF pleocytosis, 4 of 100 (4%) had brain MRI abnormalities, and 3 of 73 (4%) EEG alterations. Thirty-four (32%) and 39 (37%) patients fulfilled 2 sets of warning signs of AP, and 21 (20%) fulfilled criteria of possible or probable AP, yet none developed AP. The cause of FEP was psychiatric in 101 (96%) and nonpsychiatric in 4 (4%). During this study, 3 patients with psychosis caused by anti-NMDAR encephalitis were transferred to our center; 2 did not meet criteria for possible AP. Of 1,159 reported patients with FEP, only 7 (1%) had CSF studies; 36 (3%) had serum NMDAR antibodies (without definite diagnosis of AP), and 4 had CSF NMDAR antibodies (3 classic anti-NMDAR encephalitis and 1 with isolated psychiatric features).
NMDAR antibodies were not found in patients with FEP unless they had anti-NMDAR encephalitis. Warning signs and criteria for AP have limited utility when neurologic symptoms are absent or paraclinical tests are normal. A diagnostic algorithm for autoimmune FEP is provided.
Oxidative stress is a pathophysiological mechanism potentially involved in psychiatric disorders. The objective of this study was to assess the relationship between total antioxidant status (TAS) and ...the functional status of patients with a first episode of psychosis at the onset of the disease. For this purpose, a sample of 70 patients aged between 9 and 17 years with a first episode of psychosis were followed up for a period of two years. Blood samples were drawn to measure TAS levels at three time points: at baseline, at one year, and at two years. Clinical symptoms and functioning were also assessed at the same time points using various scales. Linear regression analysis was performed to investigate the relationship between TAS and clinical status at each assessment, adjusting for potential confounding factors. The distribution of clinical variables was grouped in different percentiles to assess the dose-response in the relation between clinical variables and TAS. At baseline, patient's score on Children's Global Assessment Scale (CGAS) was directly and significantly associated with TAS with a monotonic increase in percentiles, and surprising this association was reversed after one and two years of follow-up with a monotonic decrease. In summary at the onset of the illness, TAS is positively related to clinical status, whereas as the illness progresses this correlation is reversed and becomes negative. This may be the result of an adaptive response.
Background
Obstetric complications (OCs) are key contributors to psychosis risk. However, it is unclear whether they increase psychosis vulnerability independently of genetic risk, in interaction ...with it, or are a manifestation of psychosis proneness. We examined the role of distinct types of OCs in terms of psychosis risk and tested whether they interact differently with genetic vulnerability, whilst accounting for other known environmental risk factors.
Study Design
405 participants (219 first episode psychosis patients and 186 healthy volunteers) underwent a comprehensive assessment of OCs, measured using the Lewis‐Murray scale and divided into complications of pregnancy, abnormalities of foetal growth and development, and complications of delivery. Participants were compared in terms of history of OCs, polygenic risk score for schizophrenia (PRS‐SZ) and interactions between these.
Results
Both complications of pregnancy and abnormalities of foetal growth were significantly associated with case–control status (p = 0.02 and 0.03, respectively), whereas complications of delivery were not. PRS‐SZ showed a significant association with psychosis (p = 0.04), but there were no significant interactions between genetic risk for schizophrenia and OCs, either when these were considered globally or separated based on their timeframe.
Conclusions
We observed no significant interaction between genetic and obstetric vulnerability, yet distinct types of OCs may have a different impact on psychosis risk, based on their nature and timeframe. Examining their differential role might clarify their relative contributions to this risk.
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