title: Shared dimensions of performance and activation dysfunction in cognitive control in females with mood disorders.
abstract: Major depressive disorder and bipolar disorder share symptoms that may reflect core mood disorder features. This has led to the pursuit of intermediate phenotypes and a dimensional approach to understand neurobiological disruptions in mood disorders. Executive dysfunction, including cognitive control, may represent a promising intermediate phenotype across major depressive disorder and bipolar disorder. This study examined dimensions of cognitive control in women with major depressive disorder or bipolar disorder in comparison to healthy control subjects using two separate, consecutive experiments. For Experiment 1, participants completed a behavioural cognitive control task (healthy controls = 150, major depressive disorder = 260, bipolar disorder = 202; age range 17-84 years). A sample of those participants (healthy controls = 17, major depressive disorder = 19, and bipolar disorder = 16) completed a similar cognitive control task in an event-related design functional magnetic resonance imaging protocol for Experiment 2. Results for Experiment 1 showed greater impairments on the cognitive control task in patients with mood disorders relative to healthy controls (P < 0.001), with more of those in the mood disorder group falling into the 'impaired' range when using clinical cut-offs (<5th percentile). Experiment 2 revealed only a few areas of shared activation differences in mood disorder greater than healthy controls. Activation analyses using performance as a regressor, irrespective of diagnosis, revealed within and extra-network areas that were more active in poor performers. In summary, performance and activation during cognitive control tasks may represent an intermediate phenotype for mood disorders. However, cognitive control dysfunction is not uniform across women with mood disorders, and activation is linked to performance more so than disease. These findings support subtype and dimensional approaches to understanding risk and expression of mood disorders and are a promising area of inquiry, in line with the Research Domain Criteria initiative of NIMH.
authors.affiliation: University of Michigan Medical School, Department of Psychiatry, 2101 Commonwealth Blvd, Suite C, Ann Arbor, MI 48105, USA‡ Present address: Ohio State University, Department of Psychiatry, Columbus, OH, USAδ Present address: Now in private practice in Portland, OR, USA† Present address: University of Illinois at Chicago, Department of Psychiatry, Chicago, IL, USA karyan@umich.edu.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Ryan
authors.affiliation: ‡ Present address: Ohio State University, Department of Psychiatry, Columbus, OH, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Dawson
authors.affiliation: University of Michigan Medical School, Department of Psychiatry, 2101 Commonwealth Blvd, Suite C, Ann Arbor, MI 48105, USA‡ Present address: Ohio State University, Department of Psychiatry, Columbus, OH, USAδ Present address: Now in private practice in Portland, OR, USA† Present address: University of Illinois at Chicago, Department of Psychiatry, Chicago, IL, USA.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Kassel
authors.affiliation: University of Michigan Medical School, Department of Psychiatry, 2101 Commonwealth Blvd, Suite C, Ann Arbor, MI 48105, USA‡ Present address: Ohio State University, Department of Psychiatry, Columbus, OH, USAδ Present address: Now in private practice in Portland, OR, USA† Present address: University of Illinois at Chicago, Department of Psychiatry, Chicago, IL, USA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Weldon
authors.affiliation: University of Michigan Medical School, Department of Psychiatry, 2101 Commonwealth Blvd, Suite C, Ann Arbor, MI 48105, USA‡ Present address: Ohio State University, Department of Psychiatry, Columbus, OH, USAδ Present address: Now in private practice in Portland, OR, USA† Present address: University of Illinois at Chicago, Department of Psychiatry, Chicago, IL, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Marshall
authors.affiliation: University of Michigan Medical School, Department of Psychiatry, 2101 Commonwealth Blvd, Suite C, Ann Arbor, MI 48105, USA‡ Present address: Ohio State University, Department of Psychiatry, Columbus, OH, USAδ Present address: Now in private practice in Portland, OR, USA† Present address: University of Illinois at Chicago, Department of Psychiatry, Chicago, IL, USA.
authors.forename: Kortni K
authors.initials: KK
authors.lastname: Meyers
authors.affiliation: University of Michigan Medical School, Department of Psychiatry, 2101 Commonwealth Blvd, Suite C, Ann Arbor, MI 48105, USA‡ Present address: Ohio State University, Department of Psychiatry, Columbus, OH, USAδ Present address: Now in private practice in Portland, OR, USA† Present address: University of Illinois at Chicago, Department of Psychiatry, Chicago, IL, USA.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Gabriel
authors.affiliation: δ Present address: Now in private practice in Portland, OR, USA.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Vederman
authors.affiliation: † Present address: University of Illinois at Chicago, Department of Psychiatry, Chicago, IL, USA.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Weisenbach
authors.affiliation: University of Michigan Medical School, Department of Psychiatry, 2101 Commonwealth Blvd, Suite C, Ann Arbor, MI 48105, USA‡ Present address: Ohio State University, Department of Psychiatry, Columbus, OH, USAδ Present address: Now in private practice in Portland, OR, USA† Present address: University of Illinois at Chicago, Department of Psychiatry, Chicago, IL, USA.
authors.forename: Melvin G
authors.initials: MG
authors.lastname: McInnis
authors.affiliation: University of Michigan Medical School, Department of Psychiatry, 2101 Commonwealth Blvd, Suite C, Ann Arbor, MI 48105, USA‡ Present address: Ohio State University, Department of Psychiatry, Columbus, OH, USAδ Present address: Now in private practice in Portland, OR, USA† Present address: University of Illinois at Chicago, Department of Psychiatry, Chicago, IL, USA.
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
authors.affiliation: ‡ Present address: Ohio State University, Department of Psychiatry, Columbus, OH, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Langenecker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000175:diagnosis / Q000503:physiopathology*; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000503:physiopathology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D008875:Middle Aged; D009483:Neuropsychological Tests; D055815:Young Adult
keywords: bipolar disorder; cognitive control; dimensional; major depression; mood disorders
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