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Abstract Objective Widespread use of diagnostic tools like the Structured Interview for Prodromal Symptoms (SIPS) has highlighted that youth at Clinical High Risk for Psychosis (CHR-P) present with heterogeneous symptomatology. This pilot study aims to highlight the range of clinical characteristics of CHR-P youth, investigate the role of the non-positive (negative, disorganization, and general) symptoms in risk assessment, and determine if specific profiles are associated with severe symptomatology. Methods 38 participants aged 7–18 were administered the SIPS and designated as CHR-P. Descriptive statistics and mean difference t-tests were used to describe the range in prevalence and severity of SIPS symptoms and to identify symptoms associated with greater overall symptomatology. Results Participants who had a greater number of positive symptoms also had significantly more negative, disorganization, and general symptoms. A number of SIPS symptoms were associated with greater number of positive symptoms. Conclusion CHR-P youth represent a heterogeneous group, presenting with a wide range in clinical presentation as reflected in both the number of SIPS symptoms and their severity. Though the severity and duration of positive SIPS symptoms determines the CHR-P classification, high ratings on several of the other SIPS negative, disorganization, and general items may be useful indicators of elevated symptomatology.

Abstract Background TRRAP encodes a multidomain protein kinase that works as a genetic cofactor to influence DNA methylation patterns, DNA damage repair, and chromatin remodeling. TRRAP protein is vital to early neural developmental processes, and variants in this gene have been associated with schizophrenia and childhood disintegrative disorder. Case presentation Here, we report on a patient with a de novo nonsynonymous TRRAP single-nucleotide variant (EST00000355540.3:c.5957G > A, p.Arg1986Gln) and early onset major depression accompanied by a psychotic episode (before age 10) that occurred in the context of longer standing nonverbal learning disability and a past history of obsessions and compulsions. Conclusions The de novo variant and presentation of very early onset psychosis indicate a rare Mendelian disorder inheritance model. The genotype and behavioral abnormalities of this patient are reviewed.

Complex phenotypes may represent novel syndromes that are the composite interaction of several genetic and environmental factors. We describe an 9-year old male with high functioning autism spectrum disorder and Muckle-Wells syndrome who at age 5 years of age manifested perseverations that interfered with his functioning at home and at school. After age 6, he developed intermittent episodes of fatigue and somnolence lasting from hours to weeks that evolved over the course of months to more chronic hypersomnia. Whole exome sequencing showed three mutations in genes potentially involved in his clinical phenotype. The patient has a predicted pathogenic de novo heterozygous p.Ala681Thr mutation in the ATP1A3 gene (chr19:42480621C>T, GRCh37/hg19). Mutations in this gene are known to cause Alternating Hemiplegia of Childhood, Rapid Onset Dystonia Parkinsonism, and CAPOS syndrome, sometimes accompanied by autistic features. The patient also has compound heterozygosity for p.Arg490Lys/p.Val200Met mutations in the NLRP3 gene (chr1:247588214G>A and chr1:247587343G>A, respectively). NLRP3 mutations are associated in an autosomal dominant manner with clinically overlapping auto-inflammatory conditions including Muckle-Wells syndrome. The p.Arg490Lys is a known pathogenic mutation inherited from the patient's father. The p.Val200Met mutation, inherited from his mother, is a variant of unknown significance (VUS). Whether the de novoATP1A3mutation is responsible for or plays a role in the patient's episodes of fatigue and somnolence remains to be determined. The unprecedented combination of two NLRP3 mutations may be responsible for other aspects of his complex phenotype. Keywords: Autism spectrum disorder, Fatigue, Sleep disorder

This article has been withdrawn at the request of the authors(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.The full article title has been removed because it contains two rare conditions that may identify the patient.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease’s pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis n=22, at clinical high risk (CHR) for psychosis n=29, and healthy controls n=17 to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones − mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants

Background: Despite the existing research exploring caregiver burden in adult psychosis, few studies have examined the experience of providing care to children diagnosed with psychotic disorders (PDs) and those identified as having clinical high risk for psychosis (CHR-P)., Aim: This study measured the level of burden in caregivers of children with PD and CHR-P and examined associated risk factors, including social support, caregiver-child relationship, severity of illness, and frequency of psychiatric hospitalizations., Methods: A total of 56 caregivers completed validated measures and provided demographic information. Measures included the Zarit Burden Interview, the Multidimensional Scale of Perceived Social Support, the Behavior Assessment System for Children, Third Edition, Parenting Relationship Questionnaire-Child and Adolescent Form (BASC-3 PRQ-CA), and the Clinical Global Impression-Severity scale., Results: The majority of caregivers were women (86%), mothers (84%), White (63%), married (66%), working full-time (50%), college-educated (79%), and whose mean age was 45.7 years ( SD = 8.09). Nearly half of the caregivers (45%) reported a high level of caregiver burden, 39% rated their burden in the mild to moderate range, and 16% reported little to no burden. There was no significant difference in mean burden between PD and CHR-P groups. Higher caregiver burden was associated with lower levels of social support ( r = -.408, p = .002), lower levels of parenting confidence ( r = -.514, p < .001), higher levels of relational frustration ( r = .612, p < .001), and higher severity of illness ( r = .316 p = .025)., Conclusions: These findings underscore the critical unmet need for support for caregivers of children with PD and CHR-P. Applications to clinical practice are discussed., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JGH holds equity in and is founding head of the scientific advisory board for Mightier/Neuromotion Labs, a company making emotional regulation training video games, and has received consulting income from Alkermes, Sunovion, and Neurocrine pharmaceutical companies. The other authors have no known conflicts of interest to disclose.