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Cognitive Control as a 5-HT1A-Based Domain That Is Disrupted in Major Depressive Disorder.
Langenecker, Scott A; Mickey, Brian J; Eichhammer, Peter; Sen, Srijan; Elverman, Kathleen H; Kennedy, Susan E; Heitzeg, Mary M; Ribeiro, Saulo M; Love, Tiffany M; Hsu, David T; Koeppe, Robert A; Watson, Stanley J; Akil, Huda; Goldman, David; Burmeister, Margit; Zubieta, Jon-Kar.
Afiliação
  • Langenecker SA; The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States.
  • Mickey BJ; Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
  • Eichhammer P; The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States.
  • Sen S; Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
  • Elverman KH; Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
  • Kennedy SE; The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States.
  • Heitzeg MM; Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
  • Ribeiro SM; Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
  • Love TM; The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States.
  • Hsu DT; The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States.
  • Koeppe RA; Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
  • Watson SJ; The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States.
  • Akil H; The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States.
  • Goldman D; The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States.
  • Burmeister M; Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
  • Zubieta JK; The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States.
Front Psychol ; 10: 691, 2019.
Article em En | MEDLINE | ID: mdl-30984083
ABSTRACT
Heterogeneity within Major Depressive Disorder (MDD) has hampered identification of biological markers (e.g., intermediate phenotypes, IPs) that might increase risk for the disorder or reflect closer links to the genes underlying the disease process. The newer characterizations of dimensions of MDD within Research Domain Criteria (RDoC) domains may align well with the goal of defining IPs. We compare a sample of 25 individuals with MDD compared to 29 age and education matched controls in multimodal assessment. The multimodal RDoC assessment included the primary IP biomarker, positron emission tomography (PET) with a selective radiotracer for 5-HT1A [(11C)WAY-100635], as well as event-related functional MRI with a Go/No-go task targeting the Cognitive Control network, neuropsychological assessment of affective perception, negative memory bias and Cognitive Control domains. There was also an exploratory genetic analysis with the serotonin transporter (5-HTTLPR) and monamine oxidase A (MAO-A) genes. In regression analyses, lower 5-HT1A binding potential (BP) in the MDD group was related to diminished engagement of the Cognitive Control network, slowed resolution of interfering cognitive stimuli, one element of Cognitive Control. In contrast, higher/normative levels of 5-HT1A BP in MDD (only) was related to a substantial memory bias toward negative information, but intact resolution of interfering cognitive stimuli and greater engagement of Cognitive Control circuitry. The serotonin transporter risk allele was associated with lower 1a BP and the corresponding imaging and cognitive IPs in MDD. Lowered 5HT 1a BP was present in half of the MDD group relative to the control group. Lowered 5HT 1a BP may represent a subtype including decreased engagement of Cognitive Control network and impaired resolution of interfering cognitive stimuli. Future investigations might link lowered 1a BP to neurobiological pathways and markers, as well as probing subtype-specific treatment targets.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 1_ASSA2030 Problema de saúde: 1_doencas_nao_transmissiveis Tipo de estudo: Prognostic_studies Idioma: En Revista: Front Psychol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 1_ASSA2030 Problema de saúde: 1_doencas_nao_transmissiveis Tipo de estudo: Prognostic_studies Idioma: En Revista: Front Psychol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
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