Serotonin transporter gene (5-HTTLPR) is not associated with depressive symptomatology in mood disorders

Abstract

Disturbances of the serotoninergic neutrotransmitter system have been implicated in the pathogenesis of mood disorders. A functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has been recently reported to be associated with both unipolar and bipolar disorder. In this study, we investigated the possibility that the 5-HTTLPR might be associated with depressive symptomatology in a sample of mood disorder subjects. One hundred and thirty-two psychiatric inpatients affected by major depressive (n = 67) and bipolar (n = 65) disorder (DSM-IV) were assessed at admission by the Hamilton Depression Rating Scale (HAMD-21, divided into Core, Sleep, Activity, Psychic anxiety, Somatic anxiety and Delusion clusters) and were typed using PCR techniques. The only prior treatment permitted was low dose benzodiazepines (Ͻ5 mg diazepam or equivalent); no prior (Ͻ2 weeks) antidepressant or neuroleptic treatment was allowed. 5-HTTLPR variants were not associated with total depressive symptomatology as measured by HAMD. The short 5-HTTLPR variant was marginally associated with higher psychic anxiety scores (F = 7.11, d.f. = 1,262, P = 0.008). The association was stronger among bipolars and early onset subjects. 5-HTTLPR variants were not associated with the remaining symptom clusters. The upstream regulatory region of the serotonin transporter gene has not, therefore, a major influence on the depressive symptomatology in mood disorder subjects.

Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis

“…36,45,55 Six papers studied a specific clinical feature of BPD rather than the illness itself. 11,[28][29][30]72,73 Finally, two did not provide enough data to be included in the meta-analyses. 48,59 The 31 papers finally selected reported 43 studies related to the review objective in total since each paper frequently reported several separate studies.…”

Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders

“…To evaluate specific cluster depressive symptoms, the HAM-D items were grouped according to the following factors: core (Items 1, 2, 7, 8, 10, 13), sleep (Items 4, 5, 6), activity (Items 7, 8), psychic anxiety (Items 9, 10), somatic anxiety (Items 11, 12, 13), and delusion (Items 2, 15, 20), as described by Serretti et al 17 Both the total and subcategory HAM-D scores were subjected to statistical analysis. Therapeutic response was evaluated by the percentage score reduction in total and subcategory HAM-D scores ((baseline score − 4-week score) × 100/baseline score).…”

Evaluation of Antidepressant-related Behavioral Responses in Mice Lacking the Serotonin Transporter

“…The 5-HTT has been directly implicated in depression by the finding that brain 5-HTT binding density is reduced in brains and platelets of depressed patients (e.g., Nemeroff et al 1994;Malison et al 1998;Mann et al 2000). Moreover, a number of studies have found an association between genetic variation in the regulatory region of the 5-HTT gene and depression (e.g., Battersby et al 1996;Collier et al 1996a,b;Furlong et al 1998;Rees et al 1997;Menza et al 1999; but see Seretti et al 1999). The 5-HTT is also a major target for many antidepressant drug treatments (Blakely et al 1991;Ramamoorthy et al 1993).…”