Adolescent Psychotic Experiences and Adverse Mental Health Outcomes in Adulthood in a General Population Sample.

Purpose This study estimated risk of incident mental disorders in adulthood associated with both transient and persistent adolescent psychotic experiences (PEs). Methods A nested case-control design was used within the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort study which recruited expectant mothers from 1991-1992. Participants consisted of 8822 offspring of ALSPAC mothers who completed the Psychosis-like Symptoms Interview Questionnaire (PLIKSi-Q).

Generation of a human induced pluripotent stem cell line JHUi004-A with heterozygous mutation for spinocerebellar ataxia type 12 using genome editing.

Spinocerebellar ataxia type 12 (SCA12) is caused by a CAG expansion mutation in PPP2R2B, a gene encoding brain-specific regulatory units of protein phosphatase 2A (PP2A); while normal alleles carry 4 to 31 triplets, the disease alleles carry 43 to 78 triplets. Here, by CRISPR/Cas9n genome editing, we have generated a human heterozygous SCA12 iPSC line with 73 triplets for the mutant allele. The heterozygous SCA12 iPSCs have normal karyotype, express pluripotency markers and are able to differentiate into the three germ layers.

Tobacco smoking and nicotine vaping in persons with first episode psychosis.

Tobacco smoking is highly prevalent in persons with psychosis and is the leading cause of preventable mortality in this population. Less is known about tobacco smoking in persons with first episode psychosis (FEP) and there have been no estimates about the prevalence of nicotine vaping in FEP. This study reports rates of tobacco smoking and nicotine vaping in young people with FEP enrolled in Coordinated Specialty Care programs in Pennsylvania and Maryland.

Huntington disease-like 2: insight into neurodegeneration from an African disease.

Huntington disease (HD)-like 2 (HDL2) is a rare genetic disease caused by an expanded trinucleotide repeat in the JPH3 gene (encoding junctophilin 3) that shows remarkable clinical similarity to HD. To date, HDL2 has been reported only in patients with definite or probable African ancestry. A single haplotype background is shared by patients with HDL2 from different populations, supporting a common African origin for the expansion mutation.

Bidirectional Transcription at the PPP2R2B Gene Locus in Spinocerebellar Ataxia Type 12.

Background: Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by expansion of a CAG repeat in the PPP2R2B gene.

Objective: In this study, we tested the hypothesis that the PPP2R2B antisense (PPP2R2B-AS1) transcript containing a CUG repeat is expressed and contributes to SCA12 pathogenesis.

Methods: Expression of PPP2R2B-AS1 transcript was detected in SCA12 human induced pluripotent stem cells (iPSCs), iPSC-derived NGN2 neurons, and SCA12 knock-in mouse brains using strand-specific reverse transcription polymerase chain reaction.

Bidirectional transcription at the gene locus in spinocerebellar ataxia type 12.

Objective: Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by expansion of a CAG repeat in the . Here we tested the hypothesis that the ( ) transcript containing a CUG repeat is expressed and contributes to SCA12 pathogenesis.

Methods: Expression of transcript was detected in SCA12 human induced pluripotent stem cells (iPSCs), iPSC-derived NGN2 neurons, and SCA12 knock-in mouse brains using strand-specific RT-PCR (SS-RT-PCR).

Parental perceptions of second opinion consultations for recent onset schizophrenia.

Aim: Correct early diagnosis and intervention for schizophrenia is associated with improved outcomes. This study sought to determine the potential value of specialized consultations for individuals thought to have a recent-onset schizophrenia spectrum disorder who were not receiving specialized care.

Methods: 121 consecutive one-time consultations were performed in a clinic specializing in recent-onset schizophrenia.

Mutation of GPR143 Associated With Ocular Albinism Type 1, Intellectual Disability, and Schizophrenia: The Complex Biological and Social Interactions Between Genetic Syndromes and Mental Illness.

Copy number variations, which manifest primarily as deletions and duplications, contribute significantly to the genetic risk of schizophrenia. Specific syndromes associated with copy number variations, exemplified by the 22q11 deletion syndrome, confer both congenital abnormalities and an elevated risk of schizophrenia. We report the case of a patient with a deletion of exons 2 through 8 of GPR143.

Generation of a human induced pluripotent stem cell line JHUi003-A with homozygous mutation for spinocerebellar ataxia type 12 using genome editing.

Spinocerebellar ataxia type 12 (SCA12) is caused by a CAG expansion mutation in PPP2R2B, a gene encoding a brain-specific regulatory unit of protein phosphatase 2A (PP2A); while normal alleles carry 4 to 31 triplets, the disease alleles carry 43 to 78 triplets. Here, by CRISPR/Cas9 genome editing, we have generated a human homozygous SCA12 iPSC line with 69 and 72 triplets for each allele. The homozygous SCA12 iPSCs have normal karyotype, express pluripotency markers and are able to differentiate into the three germ layers.

Use of single guided Cas9 nickase to facilitate precise and efficient genome editing in human iPSCs.

Cas9 nucleases permit rapid and efficient generation of gene-edited cell lines. However, in typical protocols, mutations are intentionally introduced into the donor template to avoid the cleavage of donor template or re-cleavage of the successfully edited allele, compromising the fidelity of the isogenic lines generated. In addition, the double-stranded breaks (DSBs) used for editing can introduce undesirable "on-target" indels within the second allele of successfully modified cells via non-homologous end joining (NHEJ).

Hearing Voices and Seeing Things: Symptoms of Anxiety Misconstrued as Evidence of Schizophrenia in an Adolescent.

A patient's complaint of "hearing voices" or "seeing things" or of similar perceptual abnormalities leaves the clinician with 2 decisions: (1) Is the patient actually experiencing a hallucination, or does the complaint reflect a different mental experience, ranging from outright fabrication to the misinterpretation or mislabeling of vivid thoughts and emotions? (2) How should the experience reported by the patient, whether determined to be a hallucination or not, be understood in the context of the patient's entire history and mental state? We report the case of a 16-year-old whose cartoon-like hallucinations had led to the diagnosis of schizophrenia and had directed attention of the patient, her parents, and her clinicians away from critical issues of anxiety, depression, learning difficulties, and traumatic school experiences. This case illustrates how the diagnosis of schizophrenia can be driven by the prominence and vividness of psychotic-like symptoms reported by a patient, the expectation that patients' chief complaints must be directly and immediately addressed, insufficient attention to collateral information, and the distortions of a "checklist" approach to psychiatric diagnosis driven by the criteria in the Diagnostic and Statistical Manual of Mental Disorders, insurers, and the properties of electronic medical records. Given the consequences of either underdiagnosing or overdiagnosing schizophrenia, and the current lack of validated objective tests to assist with this diagnosis, clinicians are obligated to perform a thorough clinical assessment of such patients, including a probing exploration of the patient's mental state and a systematic collection of collateral information.

A high-throughput screening to identify small molecules that suppress huntingtin promoter activity or activate huntingtin-antisense promoter activity.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of huntingtin (HTT). While there are currently no disease-modifying treatments for HD, recent efforts have focused on the development of nucleotide-based therapeutics to lower HTT expression. As an alternative to siRNA or oligonucleotide methods, we hypothesized that suppression of HTT expression might be accomplished by small molecules that either (1) directly decrease HTT expression by suppressing HTT promoter activity or (2) indirectly decrease HTT expression by increasing the promoter activity of HTT-AS, the gene antisense to HTT that appears to inhibit expression of HTT.

Pharmacological rescue in patient iPSC and mouse models with a rare DISC1 mutation.

We previously identified a causal link between a rare patient mutation in DISC1 (disrupted-in-schizophrenia 1) and synaptic deficits in cortical neurons differentiated from isogenic patient-derived induced pluripotent stem cells (iPSCs). Here we find that transcripts related to phosphodiesterase 4 (PDE4) signaling are significantly elevated in human cortical neurons differentiated from iPSCs with the DISC1 mutation and that inhibition of PDE4 or activation of the cAMP signaling pathway functionally rescues synaptic deficits. We further generated a knock-in mouse line harboring the same patient mutation in the Disc1 gene.

Impaired response of cerebral oxygen metabolism to visual stimulation in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disease caused by a CAG triplet repeat expansion in the Huntingtin gene. Metabolic and microvascular abnormalities in the brain may contribute to early physiological changes that subserve the functional impairments in HD. This study is intended to investigate potential abnormality in dynamic changes in cerebral blood volume (CBV) and cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO) in the brain in response to functional stimulation in premanifest and early manifest HD patients.

Research Domain Criteria: Strengths, Weaknesses, and Potential Alternatives for Future Psychiatric Research.

The Research Domain Criteria (RDoC) paradigm was launched 10 years ago as a superior approach for investigation of mental illness. RDoC conceptualizes normal human behavior, emotion, and cognition as dimensional, with mental illnesses as dimensional extremes. We suggest that RDoC may have value for understanding normal human psychology and some conditions plausibly construed as extremes of normal variation.

Differential Changes in Functional Connectivity of Striatum-Prefrontal and Striatum-Motor Circuits in Premanifest Huntington's Disease.

Background: Huntington's disease (HD) is a progressive neurodegenerative disorder. The striatum is one of the first brain regions that show detectable atrophy in HD. Previous studies using functional magnetic resonance imaging (fMRI) at 3 tesla (3 T) revealed reduced functional connectivity between striatum and motor cortex in the prodromal period of HD.

Comparison of the Huntington's Disease like 2 and Huntington's Disease Clinical Phenotypes.

Background: Huntington's disease like 2 (HDL2) is the most common Huntington's disease (HD) phenocopy in many countries and described as the phenocopy with the greatest resemblance to HD. The current clinical description of HDL2 is based on retrospective data. It is unknown whether HDL2 has clinical features that distinguish it from HD.

Increased Protein Insolubility in Brains From a Subset of Patients With Schizophrenia.

Objective: The mechanisms leading to schizophrenia are likely to be diverse. However, there may be common pathophysiological pathways for subtypes of the disease. The authors tested the hypothesis that increased protein insolubility and ubiquitination underlie the pathophysiology for a subtype of schizophrenia.