As participants with short-allele 5-HTTLPR genotypes may exhibit enhanced 5- HT vulnerability, this study examines the effects of tryptophan challenge on stress reactivity and performance in healthy participants with S’/S’ vs L’/L’ genotypes. Sixteen healthy subjects with homozygotic short alleles (S’/S’ = S/L(G), L(G)/L(G)) and 14 subjects with homozygotic long alleles (L’/L’ = L(A)/L(A)) of the 5-HTTLPR were tested
in a double-blind placebo-controlled design under acute stress exposure following tryptophan challenge or placebo. Although there were no 5-HTTLPR-related differences in stress responses, significant beneficial effects of tryptophan challenge on mood and stress performance were exclusively found in participants with S’/S’ genotypes. These findings suggest greater MK-1775 molecular weight brain 5- HT vulnerability to tryptophan manipulations
in participants with S’/S’ as compared with L’/L’ 5-HTTLPR genotypes. This apparent genetic 5- HT vulnerability may become a meaningful risk factor for depression when brain 5- HT falls below functional need in the face of real severe stressful life events. Neuropsychopharmacology (2009) 34, 2667-2674; doi:10.1038/npp.2009.92; published online 12 August 2009″
“The regional neuronal changes taking place in the early and late stages of antipsychotic treatment are still not well characterized in humans. In addition, it is not known whether these regional changes are predictive of or are correlated with treatment response. Using PET with (15)O, we evaluated the time course of regional cerebral blood flow (rCBF) patterns generated selleck kinase inhibitor by a first (haloperidol) and a second (olanzapine) generation antipsychotic drug in patients with schizophrenia during a 6-week treatment trial. Patients were initially scanned after withdrawal of all psychotropic medication (2 weeks), and then blindly randomized to treatment with haloperidol (n = 12) or olanzapine (n = 17) for a period of 6 weeks. Patients were scanned again after 1 and 6 weeks of
treatment. All assessments, including scanning sessions, were obtained in a double-blind manner. As hypothesized, we observed rCBF changes that were common to both the drugs, implicating cortico-subcortical and limbic neuronal networks in antipsychotic action. In addition, in these regions, some Mannose-binding protein-associated serine protease patterns seen at weeks 1 and 6 were distinctive, indexing neuronal changes related to an early (ventral striatum, hippocampus) and consolidated (anterior cingulate/medial frontal cortex) stage of drug response. Finally, both after 1 and 6 weeks of treatment, we observed differential patterns of rCBF activation between good and poor responders. After 1 week of treatment, greater rCBF increase in the ventral striatum and greater decrease in the hippocampus were associated with good response. Neuropsychopharmacology (2009) 34, 2675-2690; doi:10.1038/npp.2009.