Neurobehavioral Signatures in Overgrowth Intellectual Disability Syndromes: Dissecting Genotype-Phenotype Relationships in the PI3K-AKT-MTOR Pathway.

Overgrowth intellectual disability syndromes (OGIDs) caused by mutations in the PI3K-AKT-MTOR pathway present significant neurobehavioral challenges. While PTEN Hamartoma Tumor Syndrome (PHTS) has been behaviorally characterized, Smith-Kingsmore Syndrome (SKS) has not, limiting our understanding of shared and unique features across OGIDs. We conducted comprehensive neurobehavioral assessments in 17 individuals with SKS and compared them to previously characterized cohorts with PHTS (n=74), macrocephaly-associated autism (n=33), and healthy controls (n=32).

Long Read Genome Sequencing Elucidates Diverse Functional Consequences of Structural and Repeat Variation in Autism.

Long-read whole genome sequencing (LR-WGS) technologies enhance the discovery of structural variants (SVs) and tandem repeats (TRs). Application of LR-WGS has potential to identify novel risk factors that contribute to autism spectrum disorder (ASD). We performed LR-WGS on 243 individuals from 63 ASD families and generated an integrated call set combining long- and short-read data.

Psychiatric Genetics in Clinical Practice: Essential Knowledge for Mental Health Professionals.

Objective: The authors provide recommendations on incorporating recent advances in psychiatric genetics into clinical practice for mental health clinicians.

Method: The International Society for Psychiatric Genetics Education Committee met monthly to come to a consensus on priority topics in psychiatric genetics. Topics were then assigned to small teams of subspecialty experts to summarize the current knowledge base and create an illustrative clinical case.

Diagnostic abnormalities, disease severity and immunotherapy responsiveness in individuals with Down syndrome regression disorder.

Introduction: Down Syndrome Regression Disorder (DSRD) is a neuropsychiatric condition causing insomnia, catatonia, encephalopathy, and obsessive-compulsive behavior in otherwise healthy individuals with Down syndrome (DS). Smaller cohorts have identified heterogenous diagnostic abnormalities which have predicted immunotherapy responsiveness although pattern analysis in a large cohort has never been performed.

Methods: A multi-center, retrospective study of individuals with DSRD was performed.

Genomics-informed neuropsychiatric care for neurodevelopmental disorders: Results from a multidisciplinary clinic.

Purpose: Patients with neurodevelopmental disorders (NDDs) have high rates of neuropsychiatric comorbidities. Genomic medicine may help guide care because pathogenic variants are identified in up to 50% of patients with NDDs. We evaluate the impact of a genomics-informed, multidisciplinary, neuropsychiatric specialty clinic on the diagnosis and management of patients with NDDs.

Monoallelic loss-of-function variants in GSK3B lead to autism and developmental delay.

De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of de novo potential splicing-disrupting variants (PSDVs) in 5048 probands compared to 4090 unaffected siblings. We identified 55 genes with recurrent de novo PSDVs that were highly intolerant to variation.

The Face and Features of RNU4-2: A New, Common, Recognizable, Yet Hidden Neurodevelopmental Disorder.

Background: RNU4-2 is a newly identified, noncoding gene responsible for a significant proportion of individuals with neurodevelopmental disorders (NDDs). Diagnosis is hampered by the inability of commonly employed clinical testing methods, including exome sequencing and currently formulated multigene panels, to detect variants in the noncoding region. The relatively high prevalence of this condition, predicted to affect thousands of undiagnosed children with NDDs, makes it even more relevant to have better tools to facilitate diagnosis.

A genetics-guided approach to the clinical management of schizophrenia.

Schizophrenia is a highly heritable, severe mental illness characterized by hallucinations, delusions, social withdrawal, and cognitive dysfunction present in ∼1% of populations across cultures. There have been recent major advancements in our understanding of the genetic architecture of schizophrenia. Both rare, highly penetrant genetic variants as well as common, low-penetrant genetic variants can predispose individuals to schizophrenia and can impact the way people metabolize psychoactive medications used to treat schizophrenia.

Catatonia in autism and other neurodevelopmental disabilities: a state-of-the-art review.

Individuals with neurodevelopmental disabilities (NDDs) may be at increased risk for catatonia, which can be an especially challenging condition to diagnose and treat. There may be symptom overlap between catatonia and NDD-associated behaviors, such as stereotypies. The diagnosis of catatonia should perhaps be adjusted to address symptom overlap and to include extreme behaviors observed in patients with NDDs, such as severe self-injury.

Neurodevelopmental and neuropsychiatric disorders in cobalamin C disease: a case report and review of the literature.

Cobalamin C disease is the most common complementation class of cobalamin disorders. Here, we present a case of a 14-yr-old male with early-onset cblC disease and autism spectrum disorder (ASD) admitted to our inpatient medical service for behavioral decompensation. We use this case to highlight key aspects of the neurodevelopmental and neuropsychiatric disorders associated with cblC disease.

Development and Implementation of a Chief Resident for Research Role in a Psychiatry Residency Training Program.

Psychiatry residency programs with robust research training can prepare physician-scientists to make contributions that advance the mental health field. Our psychiatry residency developed a chief resident for research position to help provide mentorship, community building, and advising around scholarly activities for residents. We present the process of implementing this new position in our residency to offer a model for engaging psychiatry residents in research.

Dual orexin receptor antagonists for insomnia in youth with neurodevelopmental disorders: a case series and review.

Insomnia is a common, impairing, and difficult-to-treat comorbidity in children with neurodevelopmental disorders (NDDs). Behavioral interventions can be challenging because of developmental and behavioral features that interfere with treatment. Medication management also can be difficult due to a high burden of side effects, a high rate of paradoxical responses, and frequent treatment resistance.

Functional and structural analyses of novel Smith-Kingsmore Syndrome-Associated MTOR variants reveal potential new mechanisms and predictors of pathogenicity.

Smith-Kingsmore syndrome (SKS) is a rare neurodevelopmental disorder characterized by macrocephaly/megalencephaly, developmental delay, intellectual disability, hypotonia, and seizures. It is caused by dominant missense mutations in MTOR. The pathogenicity of novel variants in MTOR in patients with neurodevelopmental disorders can be difficult to determine and the mechanism by which variants cause disease remains poorly understood.

The Feasibility and Outcomes of Genetic Testing for Autism and Neurodevelopmental Disorders on an Inpatient Child and Adolescent Psychiatry Service.

Diagnostic genetic testing is recommended for children with autism spectrum disorder and other neurodevelopmental disorders. One approach to improve access to genetic testing is to offer it on the inpatient child and adolescent psychiatry (CAP) service. We provided medical genetics education to CAP fellows and retrospectively compared the genetic testing rates and diagnostic yield pre- and post-education.

What Should a Psychiatrist Know About Genetics? Review and Recommendations From the Residency Education Committee of the International Society of Psychiatric Genetics.

The International Society of Psychiatric Genetics (ISPG) created a Residency Education Committee with the purpose of identifying key genetic knowledge that should be taught in psychiatric training programs. Thirteen committee members were appointed by the ISPG Board of Directors, based on varied training, expertise, gender, and national origin. The Committee has met quarterly for the past 2 years, with periodic reports to the Board and to the members of the Society.

The Role of Regional Conferences in Research Resident Career Development: The California Psychiatry Research Resident Retreat.

Objective: For psychiatry research resident career development, there is a recognized need for improved cross-institutional mentoring and networking opportunities. One method to address this need is via regional conferences, open to current and recently graduated research residents and their mentors. With this in mind, we developed the biennial California Psychiatry Research Resident Retreat (CPRRR) and collected feedback from participants to 1) Assess resident satisfaction, 2) Determine the utility of the retreat as a networking and mentorship tool, and 3) Identify areas for improvement.

Towards an Understanding of Neuropsychiatric Manifestations in Fragile X Premutation Carriers.

Fragile X-associated disorders (FXD) are a group of disorders caused by expansion of non-coding CGG repeat elements in the fragile X () gene. One of these disorders, fragile X syndrome (FXS), is the most common heritable cause of intellectual disability, and is caused by large CGG repeat expansions (>200) resulting in silencing of the gene. An increasingly recognized number of neuropsychiatric FXD have recently been identified that are caused by 'premutation' range expansions (55-200).