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Leventhal AM, Gelernter J, Oslin D, Anton RF, Farrer LA, Kranzler HR. Agitated depression in substance dependence. Drug and Alcohol Dependence. 2011 Jul 1; 116(1-3):163-9.
BACKGROUND: Depression with psychomotor agitation (PMA; "agitated depression") is a putative psychiatric phenotype that appears to associate with some forms of substance dependence. However, it is unclear whether such relationships extend across different substances and independent (I-MDE) versus substance-induced (SI-MDE) subtypes of major depressive episodes. METHOD: We examined whether lifetime depression with (vs. without) PMA was associated with lifetime substance dependence across individuals with lifetime: (1) I-MDE only (n = 575); and (2) SI-MDE only (n = 1683). Data were pooled from several family and genetic studies of substance dependence in which participants received identical structured interviews to diagnose DSM-IV mental disorders. RESULTS: In I-MDE, PMA was significantly associated with alcohol, cocaine, opioid, other drug (hallucinogen, inhalant, speed-ball), and sedative dependence. After controlling for demographic and clinical co-factors, PMA''s relationship to dependence on opioids, other drugs, and sedatives remained significant, but not its relationship to alcohol or cocaine. In SI-MDE, PMA was significantly associated with alcohol, cocaine, opioid, and other drug dependence. After adjusting for co-factors, associations remained significant for dependence on cocaine and opioids, but not alcohol or other drugs. Relationships between PMA and opioid dependence were stronger in I-MDE than SI-MDE. Depression subtype (I-MDE vs. SI-MDE) did not moderate relations between PMA and non-opioid forms of substance dependence. CONCLUSIONS: Agitated depression associates with certain forms of substance dependence, particularly opioid dependence. MDE subtype did not alter most PMA-dependence associations, which suggests that the mechanisms underlying this comorbidity are complex and potentially bidirectional.