Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity.

The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis-risk (>40-fold). Systematic research offers avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. We report the first in-depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). We also explore correlations between psychotic symptoms and posterior fossa abnormalities. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms; ratings demonstrated select sex differences but no domain-wise correlations with IQ. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in psychosis-risk.

Developmental perspectives on the origins of psychotic disorders: The need for a transdiagnostic approach.

Research on serious mental disorders, particularly psychosis, has revealed highly variable symptom profiles and developmental trajectories prior to illness-onset. As Dante Cicchetti pointed out decades before the term "transdiagnostic" was widely used, the pathways to psychopathology emerge in a system involving equifinality and multifinality. Like most other psychological disorders, psychosis is associated with multiple domains of risk factors, both genetic and environmental, and there are many transdiagnostic developmental pathways that can lead to psychotic syndromes. In this article, we discuss our current understanding of heterogeneity in the etiology of psychosis and its implications for approaches to conceptualizing etiology and research. We highlight the need for examining risk factors at multiple levels and to increase the emphasis on transdiagnostic developmental trajectories as a key variable associated with etiologic subtypes. This will be increasingly feasible now that large, longitudinal datasets are becoming available and researchers have access to more sophisticated analytic tools, such as machine learning, which can identify more homogenous subtypes with the ultimate goal of enhancing options for treatment and preventive intervention.

Borderline personality features among individuals at clinical high risk for psychosis (CHR-P): A brief report.

AIM: This exploratory study reports on borderline symptomatology within a sample of individuals at clinical high risk for psychosis (CHR-P) through a validated, self-report instrument, the short version of the Borderline Symptom List (BSL-23). METHODS: The sample consisted of 44 help-seeking CHR-P youth (ages 14-29 years) who completed an initial evaluation at a specialized clinic for psychosis-risk. RESULTS: The mean BSL-23 score was 1.5 (SD = 1.0, range 0.1-4.0). Higher scores were strongly associated with greater reported depressive symptoms (r = 0.84, p < 0.001). Additionally, borderline symptoms associated with attenuated positive symptoms (r = 0.32, p = 0.034) and social anxiety (r = 0.34, p = 0.027). Borderline symptomatology was not associated with role or social functioning. CONCLUSIONS: This study is one of the first examinations of borderline symptomatology within a CHR-P sample through a validated self-report measure. Future research replicating these results is required to determine their robustness.

Comorbid early psychosis and borderline personality disorder: Conceptualizing clinical overlap, etiology, and treatment.

Despite substantial efforts aimed at the detection and intervention for early symptoms of mental illness, there is relatively limited research on the clinical overlap between borderline personality disorder (BPD) and early psychosis, for example, clinical high risk (CHR) for psychosis, in young people. We present a narrative review of the clinical overlap between BPD and psychosis spectrum symptoms. Both conditions have unstable temporal course, and both are marked by functional impairment, increased suicide risk, and higher rates of psychiatric inpatient services. We then review evidence-based treatments for psychosis and BPD, emphasizing treatments for early presentations of these symptoms and initial research considering treatments for the overlap. Psychotherapies with the strongest empirical support include cognitive behavioral models, with BPD showing limited response to adjunctive pharmacotherapy. We end by discussing specific recommendations for future research, including longitudinal studies to determine the predictors of the course of illness and the development of treatments to target comorbid BPD and CHR symptoms.

Deep phenotyping in 3q29 deletion syndrome: recommendations for clinical care.

PURPOSE: To understand the consequences of the 3q29 deletion on medical, neurodevelopmental, psychiatric, brain structural, and neurological sequalae by systematic evaluation of affected individuals. To develop evidence-based recommendations using these data for effective clinical care. METHODS: Thirty-two individuals with the 3q29 deletion were evaluated using a defined phenotyping protocol and standardized data collection instruments. RESULTS: Medical manifestations were varied and reported across nearly every organ system. The most severe manifestations were congenital heart defects (25%) and the most common were gastrointestinal symptoms (81%). Physical examination revealed a high proportion of musculoskeletal findings (81%). Neurodevelopmental phenotypes represent a significant burden and include intellectual disability (34%), autism spectrum disorder (38%), executive function deficits (46%), and graphomotor weakness (78%). Psychiatric illness manifests across the lifespan with psychosis prodrome (15%), psychosis (20%), anxiety disorders (40%), and attention deficit-hyperactivity disorder (ADHD) (63%). Neuroimaging revealed structural anomalies of the posterior fossa, but on neurological exam study subjects displayed only mild or moderate motor vulnerabilities. CONCLUSION: By direct evaluation of 3q29 deletion study subjects, we document common features of the syndrome, including a high burden of neurodevelopmental and neuropsychiatric phenotypes. Evidence-based recommendations for evaluation, referral, and management are provided to help guide clinicians in the care of 3q29 deletion patients.