Corticotropin-releasing factor 1 receptor haplotype and cognitive features of major depression. 2018

Elena Goetz Davis, and Jennifer Keller, and Joachim Hallmayer, and Heather Ryan Pankow, and Greer M Murphy, and Ian H Gotlib, and Alan F Schatzberg
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, USA. elena.davis@stanford.edu.

Corticotropin-releasing factor signaling through CRF receptor type 1 (CRF1) has been shown to contribute to learning and memory function. A haplotype of alleles T-A-T in a set of common polymorphisms in the gene encoding for CRF1 (CRHR1) has been associated with both depression vulnerability and alterations in cognitive functioning. The present study investigated the relations between the TAT haplotype and specific symptoms of depression, self-reported ruminative behaviors, and neuropsychological performance on a learning and memory task. Participants were adults with major depression with and without psychotic features (N = 406). Associations were examined between TAT haplotype and endorsement of depression symptoms from diagnostic interviews, scores on the rumination response scale (RRS), and verbal memory performance on the California Verbal Learning Test-II (CVLT-II). All analyses included depression subtype, age, and sex as covariates; CVLT-II analyses also included evening cortisol levels. Across the entire sample, carriers of more copies of the TAT haplotype reported greater endorsement of the symptom describing difficulty concentrating and making decisions. In separate subsamples, TAT homozygotes had higher rumination scores on the RRS, both brooding and reflection subscales, and more TAT copies were associated with poorer CVLT-II performance in both total learning and free recall trials. These data demonstrate that the CRHR1 TAT haplotype is associated with cognitive features of depression including difficulty with decision-making, higher rumination, and poorer learning and memory. It will be important in future research to identify the specific molecular mechanisms for CRF1 signaling that contribute to depression-related cognitive dysfunction.

UI MeSH Term Description Entries
D003071 Cognition Intellectual or mental process whereby an organism obtains knowledge. Cognitive Function,Cognitions,Cognitive Functions,Function, Cognitive,Functions, Cognitive
D003865 Depressive Disorder, Major Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5) Depression, Involutional,Major Depressive Disorder,Melancholia, Involutional,Paraphrenia, Involutional,Psychosis, Involutional,Depressive Disorders, Major,Involutional Depression,Involutional Melancholia,Involutional Paraphrenia,Involutional Paraphrenias,Involutional Psychoses,Involutional Psychosis,Major Depressive Disorders,Paraphrenias, Involutional,Psychoses, Involutional
D006239 Haplotypes The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX. Haplotype
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000073219 Memory and Learning Tests Tests designed to evaluate general and specific areas of behaviors and abilities associated with memory and/or learning. Memory And Learning Test,California Verbal Learning Test,Rey Auditory Verbal Learning Test,Rivermead Behavioural Memory Test,TOMAL,Test of Memory Malingering,Test of Memory and Learning
D018019 Receptors, Corticotropin-Releasing Hormone Cell surface proteins that bind corticotropin-releasing hormone with high affinity and trigger intracellular changes which influence the behavior of cells. The corticotropin releasing-hormone receptors on anterior pituitary cells mediate the stimulation of corticotropin release by hypothalamic corticotropin releasing factor. The physiological consequence of activating corticotropin-releasing hormone receptors on central neurons is not well understood. CRH Receptors,Corticotropin Releasing-Factor Receptor,Corticotropin Releasing-Hormone Receptors,Receptors, CRH,CRF Receptor,CRF Receptors,CRH Receptor,Corticotropin Releasing-Factor Receptors,Corticotropin Releasing-Hormone Receptor,Receptors, CRF,Corticotropin Releasing Factor Receptor,Corticotropin Releasing Factor Receptors,Corticotropin Releasing Hormone Receptor,Corticotropin Releasing Hormone Receptors,Corticotropin-Releasing Hormone Receptors,Hormone Receptors, Corticotropin-Releasing,Receptor, CRF,Receptor, CRH,Receptor, Corticotropin Releasing-Factor,Receptor, Corticotropin Releasing-Hormone,Receptors, Corticotropin Releasing Hormone,Receptors, Corticotropin Releasing-Factor,Receptors, Corticotropin Releasing-Hormone,Releasing-Factor Receptor, Corticotropin,Releasing-Factor Receptors, Corticotropin,Releasing-Hormone Receptor, Corticotropin,Releasing-Hormone Receptors, Corticotropin

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