title: Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive-compulsive disorder as an example of overlapping clinical and genetic heterogeneity.
abstract: Individuals with obsessive-compulsive disorder (OCD) have also been shown to have comorbid lifetime diagnoses of major depressive disorder (MDD; rates greater than 70%), bipolar disorder (rates greater than 10%) and other anxiety disorders (e.g. panic disorder, post-traumatic stress disorder (PTSD)). In addition, overlap exists in some common genetic variants (e.g. the serotonin transporter gene (SLC6A4), the brain-derived neurotrophic factor (BDNF) gene), and rare variants in genes/chromosomal abnormalities (e.g. the 22q11 microdeletion syndrome) found across the affective/anxiety disorder spectrums. OCD has been proposed as a possible independent entity for DSM-5, but by others thought best retained as an anxiety disorder subtype (its current designation in DSM-IV), and yet by others considered best in the affective disorder spectrum. This review focuses on OCD, a well-studied but still puzzling heterogeneous disorder, regarding alterations in serotonergic, dopaminergic and glutamatergic neurotransmission in addition to other systems involved, and how related genes may be involved in the comorbidity of anxiety and affective disorders. OCD resembles disorders such as depression, in which gene × gene interactions, gene × environment interactions and stress elements coalesce to yield OC symptoms and, in some individuals, full-blown OCD with multiple comorbid disorders.
authors: Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Dennis L
authors: DL
authors: Murphy
authors: Pablo R
authors: PR
authors: Moya
authors: Meredith A
authors: MA
authors: Fox
authors: Liza M
authors: LM
authors: Rubenstein
authors: Jens R
authors: JR
authors: Wendland
authors: Kiara R
authors: KR
authors: Timpano
mesh_terms: D000818:Animals; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics / Q000378:metabolism; D015897:Comorbidity; D039721:Diagnostic and Statistical Manual of Mental Disorders; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics / Q000378:metabolism; D059647:Gene-Environment Interaction; D018740:Genetic Heterogeneity; D006801:Humans; D019964:Mood Disorders / Q000453:epidemiology / Q000235:genetics*; D009771:Obsessive-Compulsive Disorder / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D050580:Excitatory Amino Acid Transporter 3; D044263:Receptors, Serotonin, 5-HT1; C493400:SLC1A1 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins