title: Neurophysiological and genetic distinctions between pure and comorbid anxiety disorders.
abstract: Anxiety disorders are often comorbid with major depression (MD) and alcohol use disorders (AUD). Two common functional polymorphisms in catechol-O-methyltransferase (COMT Val158Met) and brain-derived neurotrophic factor (BDNF Val66Met) genes have been implicated in the neurobiology of anxiety and depression. We hypothesized that attentional response and working memory (auditory P300 event-related potential and Weschler Adult Intelligence Scale, Revised digit symbol scores) as well as genetic vulnerability would differ between pure anxiety disorders and comorbid anxiety. Our study sample comprised 249 community-ascertained men and women with lifetime DSM-III-R diagnoses. We analyzed groups of participants with pure anxiety disorders, pure MD, pure AUD, comorbid anxiety, and no psychiatric disorder. Participants were well at the time of testing; state anxiety and depressed mood measures were at most only mildly elevated. Individuals with pure anxiety disorders had elevated P300 amplitudes (P=0.0004) and higher digit symbol scores (P<0.0001) compared with all the other groups. Individuals with comorbid anxiety had the greatest proportion of COMT Met158 and BDNF Met66 alleles (P=0.009) as well as higher harm avoidance-neuroticism (P<0.0005) than all other groups. Our results suggest that there may be two vulnerability factors for anxiety disorders with differing genetic susceptibility: (a) heightened attention and better working memory with mildly elevated anxiety-neuroticism, a constellation that may be protective against other psychopathology; and (b) poorer attention and working memory with greater anxiety-neuroticism, a constellation that may also increase vulnerability to AUD and MD. This refinement of the anxiety phenotype may have implications for therapeutic interventions.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. maenoch@niaaa.nih.gov
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Enoch
authors.forename: Kenneth V
authors.initials: KV
authors.lastname: White
authors.forename: Juwaria
authors.initials: J
authors.lastname: Waheed
authors.forename: David
authors.initials: D
authors.lastname: Goldman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001008:Anxiety Disorders / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D001143:Arousal / Q000235:genetics / Q000502:physiology; D001288:Attention / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D004569:Electroencephalography; D018913:Event-Related Potentials, P300 / Q000235:genetics* / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics* / Q000523:psychology; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D010552:Personality Assessment; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D014888:Wechsler Scales
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002394:Catechol O-Methyltransferase