Showing papers by "Fatemeh Haghighi published in 2008"

Genetic architecture of the human tryptophan hydroxylase 2 Gene: existence of neural isoforms and relevance for major depression.

Abstract: Impaired brain serotonin neurotransmission is a potential component of the diathesis of major depression. Tryptophan hydroxylase-2 (TPH2), is the rate limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and a cause of impaired serotonin transmission. Here, we identify a novel TPH2 short isoform with truncated catalytic domain expressed in human brainstem, prefrontal cortex, hippocampus and amygdala. An exploratory study of 166 Caucasian subjects revealed association with major depression or suicide of a novel single nucleotide polymorphism (SNP) g.22879A>G located in exon 6 of this short isoform. This SNP and additional SNPs were discovered through a systematic characterization of the genetic architecture of the TPH2 gene for further genetic and functional investigations of its relationship to major depression and other psychopathology.

No Association of COMT Val158Met Polymorphism with Suicidal Behavior or CSF Monoamine Metabolites in Mood Disorders

Abstract: The Met allele of the Catechol-O-Methyltransferase (COMT) gene functional polymorphism (COMT-V158M) is associated with lower enzymatic activity than the Val allele and is reported to be associated with aggression, depression, and suicidal behavior. Since depression and impulsive-aggressive behavior may mediate risk for suicidal behavior, we assessed the association of this polymorphism with suicidal behavior. Clinical (impulsive aggression) and biological (CSF monoamine metabolites) endophenotypes were tested as potential mediators of the effect of genotype on suicide risk. Subjects with mood disorders (N = 486) and healthy volunteers (N = 119), all European Caucasian, were genotyped for COMT-V158M and assessed for DSM IV diagnoses, lifetime suicidal behavior, lifetime impulsivity, hostility, and aggression. CSF monoamine metabolites were assayed in a sub-sample of mood disorder patients (N = 111). We found no association between genotype and mood disorder diagnosis or with reported history of suicide attempt in mood disorder subjects. There was no association between genotype and lethality or method of suicide attempt, or with aggressive/impulsive traits. Further, there was no difference in monoamine metabolites by genotype. The COMT-V158M polymorphism was not associated with suicidal behavior in a Caucasian sample of mood disorder subjects, or with possible clinical or biological endophenotypes.