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A sex-specific role of type VII adenylyl cyclase in depression.

Major depression represents a complex mental disorder. The identification of biological markers that define subtypes of major depressive disorder would greatly facilitate appropriate medical treatments, as well as provide insight into etiology. Reduced activity of the cAMP signaling system has been implicated in the etiology of major depression. Previous work has shown low adenylyl cyclase activity in platelets and postmortem brain tissue of depressed individuals. Here, we investigate the role of the brain type VII isoform of adenylyl cyclase (AC7) in the manifestation of depressive symptoms in genetically modified animals, using a combination of in vivo behavioral experiments, gene expression profiling, and bioinformatics. We also completed studies with humans on the association of polymorphisms in the AC7 gene with major depressive illness (unipolar depression) based on Diagnostic and Statistical Manual of Mental Disorders IV criteria. Collectively, our results demonstrate a sex-specific influence of the AC7 gene on a heritable form of depressive illness.

Pubmed ID: 17135423

Authors

  • Hines LM
  • Hoffman PL
  • Bhave S
  • Saba L
  • Kaiser A
  • Snell L
  • Goncharov I
  • LeGault L
  • Dongier M
  • Grant B
  • Pronko S
  • Martinez L
  • Yoshimura M
  • Tabakoff B
  • World Health Organization/International Society for Biomedical Research on Alcoholism Study on State and Trait Markers of Alcohol Use and Dependence Investigators

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

November 29, 2006

Associated Grants

  • Agency: NIAAA NIH HHS, Id: K01 AA000240
  • Agency: NIAAA NIH HHS, Id: K01 AA000240-05
  • Agency: NIAAA NIH HHS, Id: R01 AA 13162
  • Agency: NIAAA NIH HHS, Id: R01 AA013148
  • Agency: NIAAA NIH HHS, Id: R01 AA013148-06
  • Agency: NIAAA NIH HHS, Id: U01 AA 13489

Mesh Terms

  • Adenylate Cyclase
  • Adult
  • Amino Acid Sequence
  • Animals
  • Depressive Disorder, Major
  • Female
  • Genetic Linkage
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Middle Aged
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide
  • Sex Characteristics