Relationship of psychopathology to the human serotonin(1B) genotype and receptor binding kinetics in postmortem brain tissue

Knockout of the 5-HT1B,, gene in mice results in increased aggression, as w ell as alcohol and cocaine consumption. Given the clinical association of a ggression, suicide, alcoholism, and substance abuse, toe studied relationsh ip of psychopathology to the human 5-HT1B receptor gene (N = 178) and postm ortem human 5-HT1B receptor binding (N = 96) in the brain. The sample compr ised: 71 suicide victims, 107 nonsuicides, 45 with a history of major depre ssion and 79 without, 64 with a history of a alcoholism or substance abuse and 60 without, as well as 36 with a history of pathological aggression and 42 without. Single-strand conformational polymorphism (SSCP) analysis and DNA sequencing techniques were used to screen the coding region of the huma n 5-HT1B receptor gene In genomic DNA isolated from postmortem human brain tissue. Two common polymorphisms were identified in the 5-HT1B receptor gen e, involving a silent C to T substitution at nucleotide 229 and a silent G to C substitution at nucleotine 861 of the coding region. These polymorphis ms were found with the same frequency in the suicide and the nonsuicide gr groups and in those with and without a history of major depression, alcohol ism, or pathological aggression. The binding indices (B-max and K-D of the 5-HT1B receptor in prefrontal cortex also did not differ in suicides and co ntrols, major depression, alcoholism, and cases with a history of pathologi cal aggression. The C129 or G861 allele had 20% fewer 5-HT1B,, receptor com pared to the 129T or 861C allele. We dim not identify a relationship betwee n suicide, major depression, alcoholism, or pathological aggression with 5- HT1B,, receptor binding indices or genotype. (C) 1999 American College of N europsychopharmacology. Published by Elsevier Science Inc.