Onset of Regular Cannabis Use & Young Adult Insomnia: An Analysis of Shared Genetic Liability.

STUDY OBJECTIVES Estimate the genetic and environmental influences on the relationship between onset of regular cannabis use and young adult insomnia. METHODS In a population-based twin cohort of 1882 twins (56% female, mean age = 22.99, SD = 2.97) we explored the genetic/environmental etiology of the relationship between onset of regular cannabis use and insomnia-related outcomes via multivariate twin models. RESULTS Controlling for sex, current depression symptoms, and prior diagnosis of an anxiety or depression disorder, adult twins who reported early onset for regular cannabis use (age 17 or younger) were more likely to have insomnia (β = 0.07, p = 0.024) and insomnia with short sleep on weekdays (β = 0.08, p = 0.003) as young adults. We found significant genetic contributions for the onset of regular cannabis use (a2 = 76%, p < 0.001), insomnia (a2 = 44%, p < 0.001) and insomnia with short sleep on weekdays (a2 = 37%, p < 0.001). We found significant genetic correlations between onset of regular use and both insomnia (rA = 0.20, p = 0.047) and insomnia with short sleep on weekdays (rA = 0.25, p = 0.008) but no significant environmental associations between these traits. CONCLUSION We found common genetic liabilities for early onset of regular cannabis use and insomnia, implying pleiotropic influences of genes on both traits.

[1]  J. Hewitt,et al.  Onset of regular cannabis use and adult sleep duration: Genetic variation and the implications of a predictive relationship. , 2019, Drug and alcohol dependence.

[2]  N. Ashpole,et al.  Aging circadian rhythms and cannabinoids , 2019, Neurobiology of Aging.

[3]  M. Pearson,et al.  Insomnia symptoms, cannabis protective behavioral strategies, and hazardous cannabis use among U.S. college students. , 2019, Experimental and clinical psychopharmacology.

[4]  N. Allen,et al.  Early Adolescent Drinking and Cannabis Use Predicts Later Sleep-Quality Problems , 2019, Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors.

[5]  Max A. Little,et al.  Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates , 2019, Nature Communications.

[6]  A. Auton,et al.  Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways , 2019, Nature Genetics.

[7]  Samuel E. Jones,et al.  Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms , 2019, Nature Communications.

[8]  P. Innominato,et al.  Several clock genes polymorphisms are meaningful risk factors in the development and severity of cannabis addiction , 2018, Chronobiology international.

[9]  Gabriel J. Merrin,et al.  Patterns of marijuana use and physical health indicators among Canadian youth , 2018, International journal of psychology : Journal international de psychologie.

[10]  C. Lindgren,et al.  GWAS identifies 14 loci for device-measured physical activity and sleep duration , 2018, Nature Communications.

[11]  Zachary F. Gerring,et al.  GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability , 2018, Nature Neuroscience.

[12]  J. Edinger,et al.  Neurocognitive performance in insomnia disorder: The impact of hyperarousal and short sleep duration , 2018, Journal of sleep research.

[13]  Susan Redline,et al.  Insomnia with objective short sleep duration and risk of incident cardiovascular disease and all-cause mortality: Sleep Heart Health Study , 2018, Sleep.

[14]  Seong-Jin Cho,et al.  fMRI brain activation in patients with insomnia disorder during a working memory task , 2018, Sleep and Breathing.

[15]  I. Colrain,et al.  Effects of sleep on substance use in adolescents: a longitudinal perspective , 2018, Addiction biology.

[16]  K. Hong,et al.  Effects of genetic variants of ST8SIA2 and NCAM1 genes on seasonal mood changes and circadian preference in the general population , 2018, Chronobiology international.

[17]  A. Pfefferbaum,et al.  Eveningness and Later Sleep Timing Are Associated with Greater Risk for Alcohol and Marijuana Use in Adolescence: Initial Findings from the National Consortium on Alcohol and Neurodevelopment in Adolescence Study , 2017, Alcoholism, clinical and experimental research.

[18]  Shishun Fu,et al.  Abnormal whole-brain functional connectivity in patients with primary insomnia , 2017, Neuropsychiatric disease and treatment.

[19]  K. Jackson,et al.  The Prospective Association Between Sleep and Initiation of Substance Use in Young Adolescents. , 2017, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[20]  M. Munafo,et al.  Assessing causality in associations between cannabis use and schizophrenia risk: a two-sample Mendelian randomization study , 2016, Psychological Medicine.

[21]  P. Gehrman,et al.  Genetic Pathways to Insomnia , 2016, Brain sciences.

[22]  C. Drake,et al.  DSM-5 Insomnia and Short Sleep: Comorbidity Landscape and Racial Disparities. , 2016, Sleep.

[23]  Y. Hurd,et al.  Cross-generational THC exposure alters the developmental sensitivity of ventral and dorsal striatal gene expression in male and female offspring. , 2016, Neurotoxicology and teratology.

[24]  D. Clark,et al.  Restless Sleep and Variable Sleep Timing During Late Childhood Accelerate the Onset of Alcohol and Other Drug Involvement. , 2016, Journal of studies on alcohol and drugs.

[25]  G. Coppola,et al.  Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells , 2016, Journal of Neuroinflammation.

[26]  Duanping Liao,et al.  Insomnia is Associated with Cortical Hyperarousal as Early as Adolescence. , 2016, Sleep.

[27]  E. Tagliazucchi,et al.  Wake High-Density Electroencephalographic Spatiospectral Signatures of Insomnia. , 2016, Sleep.

[28]  K. Lisdahl,et al.  Dose-dependent cannabis use, depressive symptoms, and FAAH genotype predict sleep quality in emerging adults: a pilot study , 2016, The American Journal of Drug and Alcohol Abuse.

[29]  E. Mihailov,et al.  Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium , 2016, Translational Psychiatry.

[30]  D. Strong,et al.  Marijuana use patterns and sleep among community-based young adults , 2016, Journal of addictive diseases.

[31]  Y. Shao,et al.  Functional connectivity of paired default mode network subregions in primary insomnia , 2015, Neuropsychiatric disease and treatment.

[32]  R. Murray,et al.  Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis. , 2015, Schizophrenia bulletin.

[33]  S. Rajaratnam,et al.  Risky drug use and effects on sleep quality and daytime sleepiness , 2015, Human psychopharmacology.

[34]  Daniel J Buysse,et al.  Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society. , 2015, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[35]  D. Clark,et al.  Sleep and circadian contributions to adolescent alcohol use disorder. , 2015, Alcohol.

[36]  E. D’Amico,et al.  Examining Racial/Ethnic Disparities in the Association between Adolescent Sleep and Alcohol or Marijuana Use. , 2015, Sleep health.

[37]  D. Poyares,et al.  Objective short sleep duration is associated with the activity of the hypothalamic-pituitary-adrenal axis in insomnia. , 2015, Arquivos de neuro-psiquiatria.

[38]  S. Gautam,et al.  Sleep characteristics as predictor variables of stress systems markers in insomnia disorder , 2015, Journal of sleep research.

[39]  Daniel J Buysse,et al.  Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society. , 2015, Sleep.

[40]  Joseph R. Scarpa,et al.  A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders. , 2015, Cell reports.

[41]  D. Cota,et al.  Cannabinoid type 1 (CB1) receptors on Sim1-expressing neurons regulate energy expenditure in male mice. , 2015, Endocrinology.

[42]  J. Perrier,et al.  Specific EEG Sleep Pattern in the Prefrontal Cortex in Primary Insomnia , 2015, PloS one.

[43]  C. Morin,et al.  Cognitive impairment in individuals with insomnia: clinical significance and correlates. , 2014, Sleep.

[44]  C. Drake,et al.  Stress and sleep reactivity: a prospective investigation of the stress-diathesis model of insomnia. , 2014, Sleep.

[45]  S. Øverland,et al.  Midlife insomnia and subsequent mortality: the Hordaland health study , 2014, BMC Public Health.

[46]  D. Shi,et al.  Functional connectivity changes between parietal and prefrontal cortices in primary insomnia patients: evidence from resting-state fMRI , 2014, European Journal of Medical Research.

[47]  Johannes Kornhuber,et al.  Impaired sleep quality and sleep duration in smokers—results from the German Multicenter Study on Nicotine Dependence , 2014, Addiction biology.

[48]  S. Tapert,et al.  Effects of cannabis on the adolescent brain. , 2014, Current pharmaceutical design.

[49]  O. Prospero-Garcia,et al.  Endocannabinoids and sleep , 2013, Neuroscience & Biobehavioral Reviews.

[50]  R. Maldonado,et al.  Cannabinoid-hypocretin cross-talk in the central nervous system: what we know so far , 2013, Front. Neurosci..

[51]  J. Kaprio,et al.  Genetic factors in evolution of sleep length – a longitudinal twin study in Finnish adults , 2013, Journal of sleep research.

[52]  W. Kremen,et al.  Genetic and environmental influences on sleep quality in middle‐aged men: a twin study , 2013, Journal of sleep research.

[53]  Kenji F. Tanaka,et al.  Influence of inhibitory serotonergic inputs to orexin/hypocretin neurons on the diurnal rhythm of sleep and wakefulness. , 2013, Sleep.

[54]  A. Vgontzas,et al.  Insomnia with Short Sleep Duration: Nosological, Diagnostic, and Treatment Implications. , 2013, Sleep medicine clinics.

[55]  M. Walker,et al.  Neural correlates of working memory performance in primary insomnia. , 2013, Sleep.

[56]  Duanping Liao,et al.  Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. , 2013, Sleep medicine reviews.

[57]  S. Hong,et al.  Brain Gray Matter Deficits in Patients with Chronic Primary Insomnia. , 2013, Sleep.

[58]  T. Lallukka,et al.  Bidirectional associations between insomnia symptoms and unhealthy behaviours , 2013, Journal of sleep research.

[59]  B. Feige,et al.  How smoking affects sleep: a polysomnographical analysis. , 2012, Sleep medicine.

[60]  R. Corley,et al.  Colorado Twin Registry: An Update , 2012, Twin Research and Human Genetics.

[61]  J. Brook,et al.  Trajectories of cigarette smoking in adulthood predict insomnia among women in late mid-life. , 2012, Sleep medicine.

[62]  Leslie A Lytle,et al.  Longitudinal Bi-directional Relationships Between Sleep and Youth Substance Use , 2012, Journal of Youth and Adolescence.

[63]  R. Bootzin,et al.  Circadian rhythms, sleep, and substance abuse. , 2012, Sleep medicine reviews.

[64]  F. Paccaud,et al.  Association between substance use and psychosocial characteristics among adolescents of the Seychelles , 2011, BMC pediatrics.

[65]  J. Croft,et al.  Relationships between hours of sleep and health-risk behaviors in US adolescent students. , 2011, Preventive medicine.

[66]  C. Drake,et al.  Sleep reactivity and insomnia: genetic and environmental influences. , 2011, Sleep.

[67]  O. Arias-Carrión,et al.  The emerging role of the endocannabinoid system in the sleep-wake cycle modulation. , 2011, Central nervous system agents in medicinal chemistry.

[68]  N. Fakier,et al.  Associations among sleep problems, learning difficulties and substance use in adolescence. , 2011, Journal of adolescence.

[69]  D. Léger,et al.  Societal costs of insomnia. , 2010, Sleep medicine reviews.

[70]  T. Brugha,et al.  Persecutory ideation and insomnia: Findings from the second British National Survey Of Psychiatric Morbidity , 2010, Journal of psychiatric research.

[71]  I. Hickie,et al.  Short sleep duration in prevalent and persistent psychological distress in young adults: the DRIVE study. , 2010, Sleep.

[72]  H. de Wit,et al.  Endocannabinoid signalling: has it got rhythm? , 2010, British journal of pharmacology.

[73]  E. Bixler,et al.  Cognitive-Emotional Hyperarousal as a Premorbid Characteristic of Individuals Vulnerable to Insomnia , 2010, Psychosomatic medicine.

[74]  Duanping Liao,et al.  Insomnia with objective short sleep duration is associated with deficits in neuropsychological performance: a general population study. , 2010, Sleep.

[75]  Nicholas A. Christakis,et al.  The Spread of Sleep Loss Influences Drug Use in Adolescent Social Networks , 2010, PloS one.

[76]  Sarah E Medland,et al.  Genetic and environmental influences on cannabis use initiation and problematic use: a meta-analysis of twin studies. , 2010, Addiction.

[77]  B. Schwaller,et al.  LACK OF CALBINDIN-D28K ALTERS RESPONSE OF THE MURINE CIRCADIAN CLOCK TO LIGHT , 2010, Chronobiology international.

[78]  H. Vrenken,et al.  Reduced Orbitofrontal and Parietal Gray Matter in Chronic Insomnia: A Voxel-Based Morphometric Study , 2010, Biological Psychiatry.

[79]  R. Zucker,et al.  Childhood sleep problems, early onset of substance use and behavioral problems in adolescence. , 2009, Sleep medicine.

[80]  R. Bartesaghi,et al.  Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood , 2009, Hippocampus.

[81]  Duanping Liao,et al.  Insomnia with objective short sleep duration is associated with a high risk for hypertension. , 2009, Sleep.

[82]  Yuting Liu,et al.  Analysis of Gene Regulatory Networks in the Mammalian Circadian Rhythm , 2008, PLoS Comput. Biol..

[83]  Brandy M. Roane,et al.  Adolescent insomnia as a risk factor for early adult depression and substance abuse. , 2008, Sleep.

[84]  S. Rombouts,et al.  Prefrontal hypoactivation and recovery in insomnia. , 2008, Sleep.

[85]  Karen I Bolla,et al.  Sleep disturbance in heavy marijuana users. , 2008, Sleep.

[86]  R. Malcolm,et al.  Adolescents with Insomnia and Substance Abuse: Consequences and Comorbidities , 2008, Journal of psychiatric practice.

[87]  T. Roth,et al.  Insomnia: definition, prevalence, etiology, and consequences. , 2007, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[88]  A. Madan,et al.  Transcriptional profiling of subjects from the Iowa adoption studies , 2007, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[89]  Vidya Krishnan,et al.  Gender differences in sleep disorders , 2006, Current opinion in pulmonary medicine.

[90]  D. Boomsma,et al.  Phenotypic Factor Analysis of Family Data: Correction of the Bias Due to Dependency , 2006, Twin Research and Human Genetics.

[91]  D. Cota,et al.  The emerging role of the endocannabinoid system in endocrine regulation and energy balance. , 2006, Endocrine reviews.

[92]  David Murray,et al.  Actigraphy validation with insomnia. , 2006, Sleep.

[93]  Eman Hassan,et al.  Recall Bias can be a Threat to Retrospective and Prospective Research Designs , 2005 .

[94]  Daniel J. Taylor,et al.  Epidemiology of insomnia, depression, and anxiety. , 2005, Sleep.

[95]  B. Vandermeer,et al.  Manifestations and management of chronic insomnia in adults. , 2005, Evidence report/technology assessment.

[96]  H. Fitzgerald,et al.  Sleep problems in early childhood and early onset of alcohol and other drug use in adolescence. , 2004, Alcoholism, clinical and experimental research.

[97]  S. Ebrahim,et al.  Mendelian randomization: prospects, potentials, and limitations. , 2004, International journal of epidemiology.

[98]  J. Hewitt,et al.  Genetic and environmental influences on substance initiation, use, and problem use in adolescents. , 2003, Archives of general psychiatry.

[99]  C. Morin,et al.  Actigraphy in the assessment of insomnia. , 2003, Sleep.

[100]  C. Pollak,et al.  The role of actigraphy in the study of sleep and circadian rhythms. , 2003, Sleep.

[101]  C. Guilleminault,et al.  Medical and socio-professional impact of insomnia. , 2002, Sleep.

[102]  N. Martin,et al.  Estimating Two-Stage Models for Genetic Influences on Alcohol, Tobacco or Drug Use Initiation and Dependence Vulnerability in Twin and Family Data , 2002, Twin Research.

[103]  N. Breslau,et al.  Sleep problems and substance use in adolescence. , 2001, Drug and alcohol dependence.

[104]  C. Guilleminault,et al.  Comparison of actigraphic, polysomnographic, and subjective assessment of sleep parameters in sleep-disordered patients. , 2001, Sleep medicine.

[105]  T. Roth,et al.  Sleep, sleepiness, sleep disorders and alcohol use and abuse. , 2001, Sleep medicine reviews.

[106]  C. Bell Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR Quick Reference to the Diagnostic Criteria from DSM-IV-TR , 2001 .

[107]  Christian Guilleminault,et al.  SF-36: Evaluation of Quality of Life in Severe and Mild Insomniacs Compared With Good Sleepers , 2001, Psychosomatic medicine.

[108]  S. Kunte Statistical computing , 2000 .

[109]  L. Cardon,et al.  Methodology for Genetic Studies of Twins and Families , 1992 .

[110]  L. Robins,et al.  The reliability of the CIDI-SAM: a comprehensive substance abuse interview. , 1989, British journal of addiction.

[111]  L. Radloff The CES-D Scale , 1977 .

[112]  I. Feinberg,et al.  Effeets of marijuana extract and tetrahydrocannabinol on electroencephalographic sleep patterns , 1976, Clinical pharmacology and therapeutics.

[113]  R. T. Pivik,et al.  Delta‐9‐tetrahydrocannabinol and synhexl: Effects on human sleep patterns , 1972, Clinical pharmacology and therapeutics.

[114]  J. Fernandez-Mendoza The insomnia with short sleep duration phenotype: an update on it's importance for health and prevention , 2017, Current opinion in psychiatry.

[115]  A. Krystal,et al.  Insomnia Patients With Objective Short Sleep Duration Have a Blunted Response to Cognitive Behavioral Therapy for Insomnia , 2017, Sleep.

[116]  C. Drake,et al.  Chapter 75 – Shift Work, Shift-Work Disorder, and Jet Lag , 2017 .

[117]  T. Dang-Vu,et al.  Cortical Thinning and Altered Cortico-Cortical Structural Covariance of the Default Mode Network in Patients with Persistent Insomnia Symptoms. , 2016, Sleep.

[118]  A. Krystal,et al.  Insomnia Patients with Objective Short Sleep Duration have a Blunted Response to Cognitive Behavioral Therapy for Insomnia. , 2016, Sleep.

[119]  L. Epstein,et al.  Neurobehavioral performance impairment in insomnia: relationships with self-reported sleep and daytime functioning. , 2014, Sleep.

[120]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[121]  Bengt Muthén,et al.  Weighted Least Squares Estimation with Missing Data , 2010 .

[122]  Don P. Buesching,et al.  Sleep problems and their correlates in a working population , 2007, Journal of General Internal Medicine.

[123]  J. Angst,et al.  The Zurich study , 2005, European archives of psychiatry and neurological sciences.

[124]  National Institutes of Health State of the Science Conference statement on Manifestations and Management of Chronic Insomnia in Adults, June 13-15, 2005. , 2005, Sleep.

[125]  C. Sneed,et al.  Acculturation and interrelationships between problem and health-promoting behaviors among Latino adolescents. , 2001, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[126]  P. Bentler,et al.  Fit indices in covariance structure modeling : Sensitivity to underparameterized model misspecification , 1998 .

[127]  H. Klonoff,et al.  Drug patterns in the chronic marijuana user. , 1976, The International journal of the addictions.

[128]  D. Kripke,et al.  Faculty Publications Physical Activity and Public Health Criterion Validity of the Pittsburgh Sleep Quality Index: Investigation in a Non-clinical Sample Publication Info Criterion Validity of the Pittsburgh Sleep Quality Index: Investigation in a Non-clinical Sample , 2022 .