Neurocognitive and social cognitive impairments in remission and symptomatic states of early-onset schizophrenia spectrum disorders.

Previous studies demonstrated neurocognitive impairments in early-onset schizophrenia (EOS) and other psychotic spectrum disorders (PSD). This study aimed to compare remitted and symptomatic cases in terms of neurocognition and theory of mind (ToM). 50 healthy controls (HC) and 106 patients diagnosed schizophrenia in remission (EOS-R, n = 38), symptomatic schizophrenia (EOS-S, n = 34), and other PSD (n = 34) were included in our study. The Positive and Negative Symptom Scale, Columbia-Suicide Severity Rating Scale, Reactive and Proactive Aggression Questionnaire were used to evaluate psychopathology. A cognitive battery was conducted to measure verbal learning/memory, visual learning/memory, executive functions (EF), inhibition, processing speed (PS), verbal fluency skills. Reading Mind in Eyes Test (RMET) and Faux-Pas tests were implemented to assess ToM. Principal Component Analysis was used to identify cognitive domain scores. Patient groups had poorer performance in cognitive domains than the HC group. The cognitive impairment and psychopathology levels of EOS-R and the PSD groups were comparable for all cognitive domains. The EOS-S group also had poorer scores in Rey verbal learning score (d = 0.87), RMET (d = 0.72), verbal fluency (d = 0.66), PS/EF (d = 0.82) and visual learning/memory (d = 0.83) test scores than the PSD group. Only RMET (d = 0.72) and executive function/processing speed domain (d = 0.63) were significantly impaired in the EOS-S group than the EOS-R group Cognitive impairments seen in remitted psychotic disorders were on the same continuum. Impaired EF/PS and ToM skills could be a cognitive marker for symptomatic illness in youth.

Electroconvulsive therapy or clozapine for adolescents with treatment-resistant schizophrenia: an explorative analysis on symptom dimensions.

OBJECTIVE: This study sought to compare pre-intervention patient characteristics and post-intervention outcomes in a naturalistic sample of adolescent inpatients with treatment-resistant psychotic symptoms who received either electroconvulsive therapy (ECT) or clozapine. METHODS: Data of adolescents with schizophrenia/schizoaffective disorder receiving ECT or clozapine were retrospectively collected from two tertiary-care psychiatry-teaching university hospitals. Subscale scores of the Positive and Negative Symptom Scale (PANSS) factors were calculated according to the five-factor solution. Baseline demographics, illness characteristics, and post-intervention outcomes were compared. RESULTS: There was no significant difference between patients receiving ECT (n = 13) and clozapine (n = 66) in terms of age, sex, and the duration of hospital stay. The ECT group more commonly had higher overall illness and aggression severity. Smoking was less frequent in the clozapine group. Baseline resistance/excitement symptom severity was significantly higher in the ECT group, while positive, negative, affect, disorganisation, and total symptom scores were not. Both interventions provided a significant reduction in PANSS scores with large effect sizes. CONCLUSION: Both ECT and clozapine yielded high effectiveness rates in adolescents with treatment-resistant schizophrenia/schizoaffective disorder. Youth receiving ECT were generally more activated than those who received clozapine.

When to Use Amisulpride in Adolescents: A Retrospective Chart Examination of Inpatients.

PURPOSE/BACKGROUND: Despite increasing interest in amisulpride, current knowledge about its use in the pediatric population is scarce. This chart review aimed to investigate the use of amisulpride in a naturalistic adolescent population. METHODS/PROCEDURES: Electronic medical records of a tertiary care adolescent inpatient unit were screened between January 2015 and April 2021. Sociodemographic data and all clinical information were collected via data collection forms, and targeted symptoms were obtained from patients' files. Patients with early-onset psychotic disorders (n = 58), bipolar I disorder (n = 29), major depressive disorder (n = 14), and other psychiatric diagnoses (n = 9) were included. Treatment response was defined as a Clinical Global Impression-Improvement of at least much improvement after treatment. FINDINGS/RESULTS: Median titration rate of amisulpride was 400 mg/wk, and the maximum administered daily dose ranged between 100 and 1200 mg/d. The maximum daily dose and number of previous antipsychotics were higher in the early-onset psychotic disorder group. Persistent positive symptoms and resistance to previous treatments were leading causes for amisulpride treatment. Other indications were also impulsive/disruptive behaviors, antipsychotic adverse effects, depressive symptoms, somatic complaints, and abnormalities in liver function tests. Finally, patients with lower daily treatment doses and more previous antipsychotic trials are less likely to benefit from the treatment. IMPLICATIONS/CONCLUSIONS: Persistent psychotic/mood symptoms, impulsive/disruptive behaviors, and abnormalities in liver function tests were reasons for the amisulpride treatment in adolescents. Randomized placebo-controlled trials are needed to evaluate the efficacy and safety of the treatment in adolescents.

The association between plasma thyroxine levels and neurocognitive impairment in early-onset schizophrenia and other psychosis spectrum disorders.

BACKGROUND/AIM: Limited studies have delved into the association between thyroid hormones and neurocognition in schizophrenia. We aimed to evaluate the relationship between thyroid hormone levels and neurocognitive functions in patients with schizophrenia and other psychosis spectrum disorders (SSD). METHOD: A total of 135 patients with early-onset SSD were included in the study. The participants underwent a cognitive assessment. Blood samples were collected to measure serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3). Subgroup analyses were conducted based on the severity of the psychosis. FINDINGS: The results revealed a significant association between fT4 levels and various cognitive domains, including processing speed, verbal fluency, working memory, verbal learning, verbal memory, and visual memory. However, serum TSH and fT3 levels exhibited no significant association with neurocognitive impairment in adjusted linear regression models. Specifically, the correlation between fT4 levels and global cognition was more pronounced in patients with higher scores. CONCLUSIONS: Serum fT4 levels were associated with the performance across various cognitive domains in cases of early-onset psychotic disorders. This correlation was accentuated among patients with higher illness severity. Future studies could focus on the effects of specific pathways that can affect the course and progression of psychosis.

The Contribution of Explainable Machine Learning Algorithms Using ROI-based Brain Surface Morphology Parameters in Distinguishing Early-onset Schizophrenia From Bipolar Disorder.

RATIONALE AND OBJECTIVES: To differentiate early-onset schizophrenia (EOS) from early-onset bipolar disorder (EBD) using surface-based morphometry measurements and brain volumes using machine learning (ML) algorithms. METHOD: High-resolution T1-weighted images were obtained to measure cortical thickness (CT), gyrification, gyrification index (GI), sulcal depth (SD), fractal dimension (FD), and brain volumes. After the feature selection step, ML classifiers were applied for each feature set and the combination of them. The SHapley Additive exPlanations (SHAP) technique was implemented to interpret the contribution of each feature. FINDINGS: 144 adolescents (16.2 ± 1.4 years, female=39%) with EOS (n = 81) and EBD (n = 63) were included. The Adaptive Boosting (AdaBoost) algorithm had the highest accuracy (82.75%) in the whole dataset that includes all variables from Destrieux atlas. The best-performing algorithms were K-nearest neighbors (KNN) for FD subset, support vector machine (SVM) for SD subset, and AdaBoost for GI subset. The KNN algorithm had the highest accuracy (accuracy=79.31%) in the whole dataset from the Desikan-Killiany-Tourville atlas. CONCLUSION: This study demonstrates the use of ML in the differential diagnosis of EOS and EBD using surface-based morphometry measurements. Future studies could focus on multicenter data for the validation of these results.

Illness-related outcomes of illicit substance use disorder in adolescents with early onset schizophrenia: a multicenter study.

OBJECTIVES: Lifetime co-occurring substance use disorders are common at the time of presentation for the treatment of primary psychosis. Our aim was to investigate the clinical characteristics of adolescents with early-onset schizophrenia/schizoaffective disorder (EOS), categorized as either with (EOS + SUD) or without SUD (non-SUD/EOS), in a multi-center sample. METHODS: Between 2016 and 2022, 255 patients were evaluated across three tertiary-care inpatient units. Diagnoses were confirmed by the treating physician according to the DSM-5 during the hospital stay. The severity of symptoms was measured using the Positive and Negative Syndrome Scale (PANSS). RESULTS: The EOS + SUD group exhibited a higher illness onset, fewer years of education, longer duration of untreated psychosis (DUP), a higher frequency of male gender, more frequent hospitalizations, increased use of clozapine and zuclopenthixol LAI, along with higher rates of post-traumatic stress disorder and conduct disorder. Notably, differences in DUP, clozapine use, and the number of hospitalizations did not persist in the multivariate logistic regression model. CONCLUSIONS: Our findings support the notion of SUD playing a role in modifying the course of illness in EOS. Future studies should emphasize exploring treatment responses to medications and interventions among youth with dual diagnoses.

Can diffusion tensor imaging have a diagnostic utility to differentiate early-onset forms of bipolar disorder and schizophrenia: A neuroimaging study with explainable machine learning algorithms.

BACKGROUND/AIM: Accurate diagnosis of early-onset psychotic disorders is crucial to improve clinical outcomes. This study aimed to differentiate patients with early-onset schizophrenia (EOS) from early-onset bipolar disorder (EBD) with machine learning (ML) algorithms using white matter tracts (WMT). METHOD: Diffusion tensor imaging was obtained from adolescents with either EOS (n = 43) or EBD (n = 32). Global probabilistic tractography using an automated tract-based TRACULA software was performed to analyze the fractional anisotropy (FA) of forty-two WMT. The nested cross-validation was performed in feature selection and model construction. EXtreme Gradient Boosting (XGBoost) was applied to select the features that can give the best performance in the ML model. The interpretability of the model was explored with the SHApley Additive exPlanations (SHAP). FINDINGS: The XGBoost algorithm identified nine out of the 42 major WMTs with significant predictive power. Among ML models, Support Vector Machine-Linear showed the best performance. Higher SHAP values of left acoustic radiation, bilateral anterior thalamic radiation, and the corpus callosum were associated with a higher likelihood of EOS. CONCLUSIONS: Our findings suggested that ML models based on the FA values of major WMT reconstructed by global probabilistic tractography can unveil hidden microstructural aberrations to distinguish EOS from EBD.

Body image among Turkish women during the first year postpartum.

In this study, we investigated the body image of Turkish women in their first year postpartum. We recruited 440 postpartum women who had applied to the outpatient clinics of the Maternity and Children's Hospital in the city of Ordu, Turkey. The mean of the women's body image scores was over the "middle level." The women's body image scale (BIS) score showed a significant negative relation with age, number of births, weight before pregnancy, weight gain, during pregnancy, weight soon after childbirth, present weight, postpartum weight gain, and postpartum body mass index (BMI).

Identifying clinical and psychological correlates of persistent negative symptoms in early-onset psychotic disorders.

Persistent negative symptoms (PNS) contribute to impairment in psychosis. The characteristics of PNS seen in youth remained under-investigated. We aimed to demonstrate clinical, treatment-related, and psychosocial characteristics of PNS in early-onset schizophrenia-spectrum disorders (EOSD). 132 patients with EOSD were assessed with Positive and Negative Symptom Scale, Brief Negative Symptom Scale, Calgary Depression Scale for Schizophrenia, and Simpson-Angus Scale. Parenting skills and resilience were evaluated using Parental Attitude Research Instrument and Child and Youth Resilience Measure-12. Longer duration of untreated psychosis (DUP) and prodromal phase were found in primary and secondary PNS groups, compared to the non-PNS group. The primary PNS group was characterized by earlier age-onset, lower smoking rates, and more common clozapine use. Resilience and egalitarian/democratic parenting were negatively correlated with symptoms related to motivation/pleasure and blunted expression. More blunted expression-related symptoms and longer DUP in the first episode significantly predicted primary/secondary PNS at follow-up. Using the data from total negative symptom scores and DUP, Receiver Operating Characteristic analyses significantly differentiated primary/secondary PNS groups from the non-PNS counterparts. PNS associated with blunted expression and low motivation/pleasure in the first episode could persist into clinical follow-up. Effective pharmacological treatment and psychosocial interventions are needed in youth.

Investigating Predictors of Clozapine Response in Adolescents with Schizophrenia and Schizoaffective Disorder.

Objectives: We aimed to determine the clinical predictors of clozapine response in patients with early-onset schizophrenia (EOS)/schizoaffective disorder and the effect of substance use disorder (SUD) on treatment outcomes. Methods: Medical records of patients with treatment-resistant EOS receiving clozapine were identified for data analysis dated between January 2015 and April 2020. Patients on clozapine were followed in an inpatient unit of a tertiary care mental health hospital. Using the Positive and Negative Symptom Scale (PANSS), ≥30% reduction was defined as the response criteria after clozapine treatment. Results: Of 50 subjects (age: 16.3 ± 1.3 years, 36.0% female), 22 subjects (44.0%) met the defined response criteria. Clozapine responder (CLZ-R) and clozapine nonresponder (CLZ-NR) groups were similar regarding age at illness onset, sex, and duration of untreated psychosis. The CLZ-R group had higher baseline positive PANSS scores (24.8 ± 8.1 vs. 17.1 ± 6.6, p = 0.001, d = 1.0) and total PANSS scores (94.8 ± 17.2 vs. 80.1 ± 19.8, p = 0.008, d = 0.8) compared with the CLZ-NR counterparts. The duration of hospital stay was longer in the CLZ-NR group (122.3 ± 48.2 vs. 87.3 ± 36.2 days, p = 0.007). Among 32 male patients, the presence of SUD (n = 9, 28.1%) was associated with a less reduction in total PANSS scores (F = 7.5, p = 0.010) and higher levels of positive symptoms at the end of the treatment (12.8 ± 4.1 vs. 18.8 ± 7.4, p = 0.006, d = 1.0). Synthetic cannabinoids were the most common substance type used among males with treatment-refractory EOS (25.0%). Conclusions: Our results did not support the role of sociodemographic variables in clozapine response. Positive symptoms and SUD yielded a prognostic value in patients receiving clozapine.