To further explore the genetic components of MDD and utility of 5-HT(1A) imaging as a potential tool for biomarker or treatment response prediction, these findings should be replicated in a larger cohort using the [(11)C]CUMI-101 agonist tracer.
Twenty patients with DSM-IV PTSD (13 with comorbid major depressive disorder, [MDD]) and 49 healthy volunteers underwent PET imaging with 5-HT1A antagonist radioligand [C-11]WAY100635.
In self-identified white patients with major depressive disorder (N=126) treated with open-label duloxetine (60-120 mg/d), a significant association of (P=0.020) of a composite risk score (based on SLC6A2 rs5569 [G1287A] AA, HTR1Ars6295 [C(-1019)G] GG, and COMT rs174697 AA/AG) with 17-item Hamilton Depression Rating Scale total score change from baseline to 12 weeks was observed.
Targeted therapeutics to inhibit 5-HT(1A) autoreceptor expression and induce 5-HT(1A) heteroreceptor expression may ameliorate treatment of anxiety and major depression.
Over-expression of the 5-HT1A autoreceptor has been implicated in reducing serotonergic neurotransmission, and is associated with major depression and suicide.
In our study, the HTR1A C(-1019)G polymorphism was found to be associated to the frequent clinical presentation of comorbid MD and GAD, suggesting a common genetic background for mixed depression and anxiety states.
Despite the fact that the contribution of the "genome" remains elusive when it comes to major depression, intriguing evidence has recently emerged pointing to sexually dimorphic influences of certain polymorphisms in genes related to the pathophysiology of major depression and antidepressant response, such as the serotonin transporter (5-HTT), serotonin 1A (5HT1A) receptor, monoamine oxidase A (MAO-A) and others.
The combined effects of the 5-HTTLPR and 5-HTR1A genes modulates the relationship between negative life events and major depressive disorder in a Chinese population.
Concerning neuroreceptor PET imaging, decreased 5-HT(1A) binding potential in the raphe, medial temporal lobe, and medial prefrontal cortex (mPFC) has been strongly associated with MDD, and may be impacted by a functional single nucleotide polymorphism in the promoter region of the 5-HT(1A) gene (HTR1A: -1019 C/G; rs6295).
The sample comprised 426 patients suffering from unipolar MD as well as 643 healthy control subjects for the variants of the 5-HT(1A) receptor and the NET.
Future studies should evaluate the role of genetic and environmental factors in producing elevated 5-HT(1A) BP(F) and MDD, and should examine whether 5-HT(1A) BP(F) is a vulnerability factor to MDEs that could have a role in screening high-risk populations for MDD.
Polymorphisms of the serotonin transporter (5-HTTLPR) and 5-HT1a receptor are associated with increased amygdala activation investigated with functional MRI in patients with MD.
The present study adds to the clarification of the role of 5-HT1A variation in treatment response in major depression by providing preliminary support for poor treatment response mediated by the 5-HT1A-1019C allele repressing 5-HT1A activity specifically in the melancholic subtype of depression.
These results suggest that 5-HTR1A C (-1019) G polymorphism is probably associated with MDD and it is likely to be the susceptible gene locus for the female and late-onset MDD.
Several studies have linked 5-HT1AC1019G and BDNF G196A (Val66Met) gene polymorphisms to major depressive disorder (MDD) and the actions of antidepressants.
This study used an imaging genomics approach to investigate amygdala activity in major depression as a function of common functional polymorphisms in the serotonin transporter gene (5-HTTLPR) and the serotonin receptor 1A gene (5-HT(1A)-1019C/G).
Genotyped and determined 5-HT(1A) binding potential (BP) by positron emission tomography (PET) using [carbonyl-C-11]-WAY-100635 in 28 medication-free MDD subjects during a current major depressive episode and 43 controls.