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.

Differential Effects of Disruptive Mood Dysregulation Disorder Comorbidity in Attention Deficit Hyperactivity Disorder on Social Cognition and Empathy.

OBJECTIVE: This study aimed to investigate social cognition and empathy properties in children among Disruptive Mood Dysregulation Disorder (DMDD) + Attention and Hyperactivity Disorder(ADHD); ADHD and healthy controls from Türkiye. METHODS: Twenty-two children with DMDD were compared to matched 30 children with ADHD and 60 healthy controls. We administered Affective Reactivity Index (ARI), KaSi Empathy Scale, Kiddie-SADS, and Reading Mind in the Eyes Test (RMET) to evaluate Theory of Mind skills to all study participants. RESULTS: DMDD + ADHD group had lower performance in ToM skills and empathy than in two groups. The ARI scores were found to be statistically significantly higher in the DMDD group than in two groups. It was also found that ARI, empathy, and ToM scores were significantly related in children with DMDD + ADHD. CONCLUSION: These results might be important to understand the difficulties in social functioning and interpersonal relationship in children with DMDD and ADHD. Children with DMDD may attend specific therapeutic programs which include specific techniques in social cognition, emotion regulation, and irritability.

functional outcome in late adolescence/early adulthood of patients with autism spectrum disorder and its relationships with parental burnout and depression: A preliminary multi-center, cross-sectional study.

The aim of this study is to determine the functioning of adults with autism spectrum disorders (ASDs) diagnosed in childhood and depression and burnout levels among their parents. A total of 261 adults with ASDs and their parents were recruited for the study. Both parents completed the Beck Depression and Maslach Burnout Inventories and reported the functioning of their adult offspring with ASDs. Only 5.4 % of our sample reported "good" or "very good" outcomes. The most common psychiatric comorbidities were intellectual disabilities and attention-deficit/hyperactivity disorder. Maternal burnout and depression scores were significantly elevated compared to those of fathers. There is an undeniable urgent need for more research to identify the needs of adults and families suffering from ASD. Modifications for those with ASD may have to be made for support in workplaces, achieving driving licenses, using public transportation and attendance at tertiary education.

Reduced Cortical Thicknesses of Adolescents with Bipolar Disorder and Relationship with Brain-derived Neurotrophic Factor.

Background: Cortical thickness (CT) and brain-derived neurotrophic factor (BDNF) were widely investigated in bipolar disorder (BD). Previous studies focused on the association between the volume of subcortical regions and neurotrophic factor levels. Objective: In this study, we aimed to evaluate the association of the CT in youth with early-onset BD with BDNF levels as a potential peripheral marker of neuronal integrity. Method: Twenty-three euthymic patients having a clinical diagnosis of BD and 17 healthy subjects as an age-matched control group with neuroimaging and blood BDNF levels were found eligible for CT measurement. A structural magnetic resonance scan (MRI) and timely blood samples were drawn. Results: Youth with BD exhibited lower cortical thickness in caudal part of left (L) middle frontal gyrus, right (R) paracentral gyrus, triangular part of R inferior frontal gyrus, R pericalcarine region, R precentral gyrus, L precentral gyrus, R superior frontal gyrus and L superior frontal gyrus when compared to healthy controls. The effect sizes of these differences were moderate to large (d=0.67-0.98) There was a significant correlation between BDNF levels with caudal part of the R anterior cingulate gyrus (CPRACG) in adolescents with BD (r=0.49, p=0.023). Conclusion: As a special region for mood regulation, the CT of the caudal part of the R anterior cingulate gyrus had a positive correlation with BDNF. Regarding the key role of CPRACG for affective regulation skills, our results should be replicated in future follow-up studies, investigating a predictive neuroimaging biomarker for the early-onset BD.

Parent rated bedtime resistance and comorbidity may predict levels of attention among Turkish children diagnosed with ADHD in on-line education classes during the COVID-19 outbreak.

OBJECTIVE: This study aimed to compare the attention levels, of Turkish children and adolescents with Attention Deficit/ Hyperactivity Disorder (ADHD) in on-line education classes with healthy controls. METHODS: This study is a cross-sectional, internet-based, case-control study that recruited 6-18 years old patients diagnosed with ADHD and receving treatment and healthy controls from eight centers. The measurements used in the study were prepared in the google survey and delivered to the participants via Whatsapp application. RESULTS: Within the study period, 510 children with ADHD and 893 controls were enrolled. Parent- rated attention decreased significantly in both groups during on-line education classes due to COVID-19 outbreak (p<0.001; for each). Children and adolescents with ADHD had significantly elevated bedtime resistance, problems in family functioning difficulties than control children according to parental reports (p=0.003; p<0.001; p<0.001, respectively). Furthermore, bedtime resistance and comorbidity significantly predicted attention levels in on-line education. CONCLUSION: Our findings may underline the need to augment student engagement in on-line education both for children without attention problems and those with ADHD. Interventions shown to be effective in the management of sleep difficulties in children as well as parent management interventions should continue during on-line education.

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.

Psychomotor agitation and irritability in adolescents with manic episode: Clinical data from three inpatient units.

OBJECTIVES: We aimed to investigate the characteristics of adolescents with Bipolar disorder-I with irritability and agitation (Mania+IA) compared to those without irritability and agitation (Mania-IA) in a multi-center representative sample. METHODS: Data of 145 patients from three tertiary-care inpatient units between 2016 and 2021 were obtained. Psychomotor agitation was defined as a score of ≥3 on the YMRS "Increased Motor Activity--Energy" item, irritability as a score of ≥4 on the YMRS 'irritability' item, and severity anchors of speech and thought disturbance on the YMRS '6 and 7' items. RESULTS: Previous manic episodes (p = 0.013), involuntary hospitalization (p = 0.006), psychotic features (p = 0.001), formal thought disorder (p = 0.010) and aggressive/disruptive behavior (p = 0.021) were more frequent in the Mania+IA group. Conversely, depressive episodes (p = 0.006) and family history of depression (p = 0.024) were more frequent in the Mania-IA group. The Mania+IA had poorer functioning at the time of discharge. CONCLUSIONS: Irritability and agitation were closely related to complications, psychotic symptoms and thought disorder. Assessment and monitoring of psychomotor agitation and irritability may help child and adolescent psychiatrists to predict clinical difficulties and appropriate interventions.

Psychometric Properties of The Clinician Affective Reactivity Index for Assessment of Irritability in a Clinical Sample of Turkish Children and Adolescents.

Background: No clinician-oriented scale exists to assess irritability in Turkey. This pilot study aimed to evaluate the psychometric properties of the Turkish version of The Clinician Affective Reactivity Index (CL-ARI). Method: A total of 116 children and adolescents aged between 10 to 17 years (14.1 ± 2.1 years) were recruited from the psychiatric outpatient clinics. The participants completed a set of scales (Strengths and Difficulties Questionnaire [SDQ], Affective Reactivity Index [ARI], Revised Child Anxiety and Depression Scale, Swanson, Nolan, and Pelham, Version IV Scale). Diagnostic interviews were administered to confirm psychiatric diagnoses. Cronbach's alpha was calculated to assess internal consistency. Discriminant validity was further tested using independent sample t-test and Receiver Operating Characteristic curves. Interrater reliability was tested using intraclass correlation coefficients (ICC). Convergent validity was also tested using Pearson's correlation. Results: Cronbach's alpha values of CL-ARI were 0.919 total score, 0.842 for the temper outbursts score, 0.861 for the irritable mood score, and 0.840 for the impairment score. ICC values for interrater reliability were high for the temper outbursts (r = 0.993), the irritable mood (r = 0.993), the impairment (r = 0.917), and the total score (r = 0.991). In the sample, there was a high level of correlation between the self-report ARI-child/parent form and the CL-ARI total and subscale scores. Likewise, moderate-high level of correlations were found between the behavioral SDQ child/parent forms and the CL-ARI total and subscale scores. Conclusions: This is the Turkish validation of the CL-ARI, a dedicated interview and rating scale to assess irritability in the clinical sample. The results of this study suggest that the Turkish version of CL-ARI has adequate internal consistency and interrater reliability, and sufficient convergent and discriminant validity to be used in research settings.

Association between thyroid autoimmunity and antidepressant treatment-emergent mania in pediatric mood disorders.

Risk factors associated with antidepressant treatment-emergent mania(ATEM) are poorly characterized in child and adolescent populations. To identify better biomarkers, we aimed to explore whether thyroid autoimmunity is associated with ATEM in pediatric mood disorders. We enrolled two groups of pediatric mood disorders, those with ATEM+ (n = 29) and those with ATEM- controls (n = 31). All diagnoses were made according to structured interviews by the clinicians. Autoimmune thyroiditis (anti-thyroid peroxidase antibodies [TPO-abs] and thyroid function (thyroid-stimulating hormone [TSH] and free thyroxin [FT4]) were assessed. Logistic regression was used to explore the relationship between TPO-abs seroprevalence and ATEM+ while controlling for covariates. Group comparisons showed that the patient with ATEM+ had significantly higher seroprevalence and titer of TPO-abs compared to ATEM- controls. In logistic regression analysis adjusting for age, gender, Tanner stage, body mass index, antipsychotic treatments, smoking status and family history of thyroid disorder, the seroprevalence of TPO-abs (>60 U/mL) was significantly associated with ATEM+ (OR = 3.67, 95% confidence interval [CI] = 1.2-11.1, p = 0.022). Our findings demonstrated that seroprevalence and titer of TPO-abs in pediatric mood disorders are associated with ATEM+ status. TPO-abs could potentially serve as a biomarker when assessing the risk of ATEM in the child and adolescent population.

Reliability and Validity of the Bipolar Prodrome Symptom Interview and Scale-Full Prospective in Its Turkish Translation.

Editors' Note: The Editors would like to address issues related to the acceptance of this manuscript. The original manuscript referenced the study tool as the Bipolar Prodrome Symptom Interview Scale-Prospective (BPSS-P). After the manuscript's initial acceptance, the authors requested a revision of the tool name to Bipolar Prodrome Symptom Interview Scale-Full Perspective (BPSS-FP). When this request was made, the original acceptance was rescinded, and the authors were asked to formally revise and resubmit the manuscript with an explanation for the change. This revision and subsequent review led to the final acceptance of the manuscript. The authors have assured us that the tool used in the manuscript was the BPSS-FP (version 5) as opposed to abbreviated forms of this tool that are also used in research (e.g., Bipolar Prodrome Symptom Scale-Abbreviated Screen for Patients (BPSS-AS-P). Background: No scale exists to assess patients at-risk for bipolar disorder (BD) in Turkey. We aimed to assess the psychometric properties of the Turkish version of the Bipolar Prodrome Symptom Interview and Scale-Full Prospective (BPSS-FP). Method: Psychiatric service users aged 11-18 years old were interviewed using the BPSS-FP translated into Turkish and the Kiddie Schedule for Affective Disorders and Schizophrenia. Youth with major depressive disorder (MDD, n = 63), bipolar-spectrum disorder (n = 47), and healthy controls (n = 122) were included. Cronbach's alpha was calculated to assess internal consistency. The Young Mania Rating Scale (YMRS) and Children's Depression Rating Scale-Revised (CDRS-R) were administered to test convergent/discriminant validity. Discriminant validity was further tested using one-way ANOVA and "receiver operating characteristic" (ROC) curves. Inter-rater reliability was tested using correlation coefficients. Findings: Across 232 youth, Cronbach's alpha values were 0.932 for the BPSS-FP total score, 0.878 for the Mania Symptom Index, 0.887 for the Depression Symptom Index, and 0.797 for the General Symptom Index. Correlation coefficients for inter-rater reliability were high for the Mania Symptom Index (r = 0.989), Depression Symptom Index (r = 0.973), and General Symptom Index (r = 0.981). There were high correlations between the BPSS-FP Mania Symptom Index subscore and YMRS (r = 0.732), and the BPSS-FP Depression Symptom Index subscore and CDRS-R (r = 0.754), whereas cross-polarity correlations were non-significant. ROC analysis cut-off value was ≥21 for the BPSS-FP Mania Symptom Index between patients with BD and MDD (specificity = 85.7%, sensitivity = 78.7%). Conclusion: The Turkish version of the BPSS-FP has good psychometric properties and can be used in research. Longitudinal studies are needed to confirm the predictive value of the BPSS-FP.

Index depressive episode and antidepressant exposure were associated with illness characteristics of pediatric bipolar disorder.

OBJECTIVE: Pediatric bipolar disorder (PBD) is a serious, recurrent disorder leading to severe functional impairment. As a first mood episode, index episode could affect the long-term course of the illness. This study aimed to investigate the clinical characteristics of youth with PBD from our multicenter, nationwide, naturalistic follow-up samples and to identify (i) the effects of index mood episode and (ii) the effect of previous antidepressant treatments on the age at mania onset of PBD. METHOD: The study sample consisted of 271 youth with BD-I followed by the child and adolescent psychiatry clinics of seven different university hospitals and three research state hospitals, representing six geographic regions across Turkey. All diagnoses were made according to structured interviews, and all data were retrospectively obtained from clinical records by the clinicians. RESULTS: When patients with index depressive/mixed episodes (IDE, n=129) and patients with index (hypo)manic episodes (IME, n=142) were compared, the total number of mood episodes and rapid cycling feature were significantly higher in the IDE group than in the IME group. The Cox regression analysis adjusted for sociodemographic and illness characteristics revealed female adolescents in the IDE group treated with antidepressants were more likely to have an earlier onset of mania (hazard ratio=2.03, 95% confidence interval=1.31-3.12, p=0.001). CONCLUSION: This is the first large-scale nationwide follow-up study in Turkey that indicated prior antidepressant treatments were associated with an earlier onset of mania in youth, particularly in adolescent females. Larger prospective studies are needed to identify neurodevelopmental processes underlying PBD and initiate prevention approaches.

Structural dysconnectivity in offspring of individuals with bipolar disorder: The effect of co-existing clinical-high-risk for bipolar disorder.

BACKGROUND: Bipolar disorder (BD) might be associated in disturbances in brain networks. However, little is known about the abnormalities in structural brain connectivity which might be related to vulnerability to BD and predictive of the emergence of manic symptoms. No previous study has investigated the effect of subthreshold syndromes on structural dysconnectivity in offspring of parents with BD (BDoff). METHODS: We investigated diffusion weighted images of 70 BDoff and 48 healthy controls (HC). Nineteen of the 70 BDoff had presented with subthreshold syndromes indicating a clinical high-risk (BDoff-CHR) and other 51 BDoff had no such history (BDoff-non-CHR). Global and regional network properties, rich club organization and inter-regional connectivity in BDoff and healthy controls were investigated using graph analytical methods and network-based-statistics (NBS). RESULTS: Global properties of WM networks appeared to be intact in BDoff-CHR and BDoff-non-CHR. However, decreased regional connectivity in right occipito-parietal areas and cerebellum was a common feature of both BDoff groups. Importantly, decreased interregional connectivity between nodes in right and left prefrontal regions, nodes in right prefrontal lobe and right temporal lobe and nodes in left occipital area and left cerebellum were evident in BDoff-CHR but not BDoff-non-CHR. LIMITATIONS: The cross-sectional nature of the study was the main consideration. CONCLUSION: Decreased regional connectivity in right posterior brain regions might be related to vulnerability to BD. On the other hand, interregional dysconnectivity in anterior frontal and limbic regions and left posterior brain regions might be evident in individuals genetically at risk for developing BD who had experienced subthreshold mood symptoms.

Neurocognition in young offspring of individuals with bipolar disorder: The role of co-existing familial and clinical high-risk for bipolar disorder.

Bipolar disorder (BD) is associated with cognitive dysfunction which has also been reported in offspring of individuals with BD (BDoff). However, it remains unclear whether cognitive underperformance in BDoff is associated with the presence of history of subclinical syndromes associated with risk for BD. To address this knowledge gap we assessed executive function, visual and verbal memory, working memory, processing speed and verbal fluency in 21 offspring with clinical high risk (CHR; BDoff+CHR), 54 offspring without CHR (BDoff-non-CHR), and 50 healthy individuals without familial risk of BD. BDoff underperformed compared to controls in most cognitive tasks. There was no significant neurocognitive difference between BDoff+CHR and BDoff-non-CHR except in the fluency/central executive domain (Cohen's d = 0.60, p = 0.03). Our results suggest that cognitive dysfunction in multiple domains is associated with familial predisposition to BD regardless of CHR status. On the other hand, abnormalities in central executive processes might be more pronounced in BDoff+CHR than BDoff-non-CHR. Further longitudinal studies investigating cognitive trajectory of BDoff and its interaction with the emergence of subclinical syndromes are needed to fully characterize the relationship between cognition and mood dysregulation in BD.

Neurocognitive heterogeneity in young offspring of patients with bipolar disorder: The effect of putative clinical stages.

BACKGROUND: Bipolar disorder (BD) is associated with significant cognitive heterogeneity. In recent years, a number of studies have investigated cognitive subgroups in BD using data-driven methods and found that BD includes several subgroups including a severely impaired and a neurocognitively intact cluster. Studies in offspring of BD (BDoff) are particularly important to establish the timing of emergence of cognitive subgroups but studies investigating cognitive heterogeneity in BDoff are lacking. Our aim was to investigate cognitive heterogeneity in BDoff and the relationship between cognitive heterogeneity and putative clinical stages of BD. METHODS: Seventy-one euthymic BDoff and 50 healthy controls were assessed using clinical measures and a battery of neuropsychological tests. Neurocognitive subgroups were investigated using latent class analysis. RESULTS: Three neurocognitive subgroups, including a severe impairment group, a good performance cluster, and a subgroup characterized by intermediate/selective impairment was found. Both severe and intermediate level impairment subgroups underperformed healthy controls in processing speed, verbal fluency, visual memory and working memory. Deficits in verbal memory and executive functions were only evident in severe impairment subgroup. The putative stage of the illness had no significant effect on cognitive clustering of BDoff. Trait impulsivity scores were significantly increased in severe and intermediate impairment clusters but not in the cognitively good functioning subgroup of BDoff. LIMITATIONS: The cross-sectional nature of the study was the main consideration. CONCLUSION: These results suggest that cognitive heterogeneity is premorbid characteristic of BD and cognitive subgroups of BDoff emerge prior to the onset of illness and prodromal symptoms.