RESUMO
Objectives: Psychotic-spectrum disorders emerge during adolescence and early adulthood, which corresponds with the peak period for substance use initiation. Clinical and epidemiological data provide support that substance use is associated with psychotic symptom onset and severity. Experience-sampling methodology (ESM) data may provide additional insight into dynamic associations between substance use and psychotic symptoms. This is one of the first efforts to characterize substance use frequency and dynamic associations with psychotic symptoms and negative affect from ESM data in both clinical high risk (CHR) and early psychosis (EP) individuals. Methods: Using ESM, 33 individuals, including 17 with CHR and 16 EP (age range: 15-24), provided information on substance use, negative affect, and psychotic symptoms 6 times a day across a 21-day data collection window. Psychotic symptoms and negative affect included multi-item variables rated on a seven-point Likert Scale. Participants reported recent substance use for 4 drug classes (nicotine, cannabis, depressants, stimulants) via a yes/no item. Descriptive information included data on substance use frequency, and momentary negative affect and psychotic symptoms. Exploratory analyses included multi-level and person-level dynamic structural equation models, which assessed contemporaneous and lagged associations between substance use and symptoms. Results: Twenty-seven individuals (82%) reported recurrent substance use including stimulants (n = 12, 46%), nicotine (n = 9, 27%), cannabis (n = 6, 18%), and depressants (n = 4, 12%). Individuals with any recurrent substance use indicated usage at 47.7% of answered prompts; stimulants at 23.6%; nicotine at 74.2%; cannabis at 39.1%; and depressants at 20.1%. A multi-level dynamic structural equation model reflected that substance use (any class) was associated with lagged negative affect (ß = -0.02, CI: -0.06, < -0.00) but no significant contemporaneous or lagged associations between substance use and psychotic symptoms. Person-level models suggest potentially meaningful inter-individual variability. Conclusions: CHR and EP individuals use a range of substances that may both reflect and influence other experiences in daily life experiences. Data reflected moderate to high rates of recurrent substance use with more consistent use within nicotine and cannabis classes. ESM data have the potential to increase our understanding of the dynamic relationships between substance use and symptoms and to inform treatment for individuals in early course psychosis.
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The flaviviruses dengue virus (DENV) and Zika virus (ZIKV) are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of DENV and ZIKV, we completed orthologous functional genomic screens using RNAi and CRISPR/Cas9 approaches. The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF), heparin sulfation (NDST1 and EXT1), and transmembrane protein processing and maturation, including the endoplasmic reticulum membrane complex (EMC). We find that both flaviviruses require the EMC for their early stages of infection. Together, these studies generate a high-confidence, systems-wide view of human-flavivirus interactions and provide insights into the role of the EMC in flavivirus replication.
Assuntos
Vírus da Dengue/genética , Genômica/métodos , Zika virus/genética , Sistemas CRISPR-Cas , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Testes Genéticos , Células HeLa , Interações Hospedeiro-Patógeno/genética , Humanos , Membranas Intracelulares/metabolismo , Ligação Proteica , Mapas de Interação de Proteínas , Interferência de RNA , Replicação ViralRESUMO
Diabetes mellitus is a common childhood illness, and its management is often complicated by mental health challenges. Psychiatric comorbidities are common, including anxiety, depression, and eating disorders. The illness can profoundly affect the developing brain and family functioning and have lifelong consequences. The child mental health provider can provide valuable assistance to support the child and family and assessment and treatment of comorbid mental health problems and to promote positive family functioning and normal developmental progress.
RESUMO
Diabetes mellitus is a common childhood illness, and its management is often complicated by mental health challenges. Psychiatric comorbidities are common, including anxiety, depression, and eating disorders. The illness can profoundly affect the developing brain and family functioning and have lifelong consequences. The child mental health provider can provide valuable assistance to support the child and family and assessment and treatment of comorbid mental health problems and to promote positive family functioning and normal developmental progress.
RESUMO
Diabetes mellitus is a common childhood illness, and its management is often complicated by mental health challenges. Psychiatric comorbidities are common, including anxiety, depression, and eating disorders. The illness can profoundly affect the developing brain and family functioning and have lifelong consequences. The child mental health provider can provide valuable assistance to support the child and family and assessment and treatment of comorbid mental health problems and to promote positive family functioning and normal developmental progress.