title: Anxiety in major depression and cerebrospinal fluid free gamma-aminobutyric acid.
abstract: BACKGROUND
  Low gamma-aminobutyric acid (GABA) is implicated in both anxiety and depression pathophysiology. They are often comorbid, but most clinical studies have not examined these relationships separately. We investigated the relationship of cerebrospinal fluid (CSF) free GABA to the anxiety and depression components of a major depressive episode (MDE) and to monoamine systems.
  
  
  METHODS
  Patients with a DSM-IV major depressive episode (N = 167: 130 major depressive disorder; 37 bipolar disorder) and healthy volunteers (N = 38) had CSF free GABA measured by gas chromatography mass spectroscopy. Monoamine metabolites were assayed by high performance liquid chromatography. Symptomatology was assessed by Hamilton depression rating scale.
  
  
  RESULTS
  Psychic anxiety severity increased with age and correlated with lower CSF free GABA, controlling for age. CSF free GABA declined with age but was not related to depression severity. Other monoamine metabolites correlated positively with CSF GABA but not with psychic anxiety or depression severity. CSF free GABA was lower in MDD compared with bipolar disorder and healthy volunteers. GABA levels did not differ based on a suicide attempt history in mood disorders. Recent exposure to benzodiazepines, but not alcohol or past alcoholism, was associated with a statistical trend for more severe anxiety and lower CSF GABA.
  
  
  CONCLUSIONS
  Lower CSF GABA may explain increasing severity of psychic anxiety in major depression with increasing age. This relationship is not seen with monoamine metabolites, suggesting treatments targeting the GABAergic system should be evaluated in treatment-resistant anxious major depression and in older patients.
authors.affiliation: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University, 1051 Riverside Drive, New York, New York; Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, New York; Department of Radiology, Columbia University, 1051 Riverside Drive, New York, New York.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.forename: Kalycia Trishana
authors.initials: KT
authors.lastname: Watson
authors.forename: Maura
authors.initials: M
authors.lastname: Boldrini
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Malone
authors.forename: Steven P
authors.initials: SP
authors.lastname: Ellis
authors.forename: Gregory
authors.initials: G
authors.lastname: Sullivan
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Cooper
authors.forename: Shan
authors.initials: S
authors.lastname: Xie
authors.forename: Dianne
authors.initials: D
authors.lastname: Currier
mesh_terms: D000328:Adult; D000367:Age Factors; D001007:Anxiety / Q000134:cerebrospinal fluid* / Q000523:psychology; D001714:Bipolar Disorder / Q000134:cerebrospinal fluid* / Q000523:psychology; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003865:Major Depressive Disorder / Q000134:cerebrospinal fluid* / Q000523:psychology; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D012720:Severity of Illness Index; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000134:cerebrospinal fluid*
chemical_list: D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D006719:Homovanillic Acid
keywords: anxiety; cerebrospinal fluid; gamma-aminobutyric acid; major depression