A preliminary association study between serotonin transporter (5-HTTLPR), receptor polymorphisms (5-HTR1A, 5-HTR2A) and depression symptom-clusters in a north Indian population suffering from Major Depressive Disorder (MDD)

Introduction: Major Depressive Disorder (MDD) is a broad heterogeneous diagnostic construct. Previous studies have shown that it can be resolved into several symptom-clusters which are proposed to be associated with single nucleotide polymorphisms (SNPs) of the serotonergic pathway (5-HTTLPR, 5HTR1A, 5-HTR2A).

Methods and material: In a cross-sectional study conducted at a tertiary level mental health care set-up in north India, 80 out-patients with MDD were evaluated with Montgomery Asberg Depression Rating Scale (MADRS) and then genotyping was done. The different clinical and genetic variables were compared across the factor structures of MADRS. Also, the comparison of the genetic data of cases was done with the pre-existing database of the non-blood related healthy ethnically-matched controls.

Results: There was no significant association between age, gender, other clinical variables, SNPs like 5-HTTLPR SS/SL, rs6295 CC/CG/GG, rs6311GG/GA/AA, rs6313 CC/CT/TT and different factor-structures like 'detachment' consisting of items like concentration difficulty, lassitude, inability to feel; 'psychic anxiety' consisting of suicidal thoughts and inner tension; 'mood-pessimism' consisting of symptoms like apparent sadness, reported sadness, pessimistic thoughts and 'vegetative symptoms' like decreased sleep, poor appetite. Neither there was any association between genotype of the cases compared with the controls.

Conclusions: No significant association was obtained between the four-factor structures of depression in MADRS and serotonin transporter and receptor SNPs in a study with a small sample size. This study evaluates whether depression symptom-clusters have distinct genotypic determinants and necessitates more comprehensive studies for unravelling the genetic determinants of depression.