Human CRY1 variants associate with attention deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder (ADHD) is a common and heritable phenotype frequently accompanied by insomnia, anxiety, and depression. Here, using a reverse phenotyping approach, we report heterozygous coding variations in the core circadian clock gene cryptochrome 1 in 15 unrelated multigenerational families with combined ADHD and insomnia. The variants led to functional alterations in the circadian molecular rhythms, providing a mechanistic link to the behavioral symptoms. One variant, CRY1Δ11 c.1657+3A>C, is present in approximately 1% of Europeans, therefore standing out as a diagnostic and therapeutic marker. We showed by exome sequencing in an independent cohort of patients with combined ADHD and insomnia that 8 of 62 patients and 0 of 369 controls carried CRY1Δ11. Also, we identified a variant, CRY1Δ6 c.825+1G>A, that shows reduced affinity for BMAL1/CLOCK and causes an arrhythmic phenotype. Genotype-phenotype correlation analysis revealed that this variant segregated with ADHD and delayed sleep phase disorder (DSPD) in the affected family. Finally, we found in a phenome-wide association study involving 9438 unrelated adult Europeans that CRY1Δ11 was associated with major depressive disorder, insomnia, and anxiety. These results defined a distinctive group of circadian psychiatric phenotypes that we propose to designate as “circiatric” disorders.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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Abstract Sleep problems are common in school-age children and linked to numerous negative outcomes. Sleep disturbances are particularly common in children with mental health disorders, such as attention-deficit/hyperactivity disorder, depression, and anxiety. Despite frequent use of nonpharmacological pediatric sleep interventions to treat common sleep problems, there is a paucity of research on whether these interventions are effective. Further, it is unclear whether by targeting sleep, these interventions lead to broader improvements in the domains of functioning that are commonly affected by poor sleep. The pre...
Source: Behavior Therapy - Category: Psychiatry & Psychology Authors: Tags: Behav Ther Source Type: research
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Source: L Encephale - Category: Psychiatry Tags: Encephale Source Type: research
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Source: Dreaming - Category: Psychiatry & Psychology Source Type: research
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Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
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Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
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Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: Alternative and Nutritional Supplements Disorders General Research Treatment cannabidiol Cannabis cbd cbd oil Marijuana THC Source Type: blogs
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Source: Journal of Developmental and Behavioral Pediatrics - Category: Child Development Tags: Challenging Case Source Type: research
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Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Current Issue Review excessive daytime sleep fatigue head injury modafinil stroke TBI traumatic brain injury Source Type: research
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Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Current Issue Review anxiety disorder depression insomnia psychiatric disorder psychosis schizophrenia sleep disorder Source Type: research
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