- SLC6A4 (solute carrier family 6 (neurotransmitter transporter, serotonin), member 4)
Other Symbols:
5-HTT, 5-HTTLPR, 5HTT, HTT, OCD1, SERT, hSERT
1) Disease relevance:
Bipolar disorder (BD) has been related to abnormal functions of the ventral anterior cingulate cortex (vACC) and the amygdale. Amygdale is involved in emotional regulation. Reduced functional connectivity from the vACC to the amygdala may be associated with the long ‘l’ allele of the serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4) in BD patients (Shah et al., 2009).
The short ‘s’ allele of SLC6A4 may also affect the normal function in the vACC-amygdala neural system in BD. A total of 30 euthymic individuals with BD (20 s carriers, 10 ll) and 48 healthy comparison (HC) subjects (34 s, 14 ll) were examined when processing fearful, happy, or neutral faces (Shah et al., 2009). During fear and happy face processing, vACC activation was lower in the BD group. BD s carriers showed the largest magnitude of vACC dysfunction. The 5-HTTLPR s allele may also be linked to a neurobiological subgroup of BD with vACC dysfunction.
Sample size:
30 euthymic individuals with BD (20 s carriers, 10 ll) and 48 healthy comparison (HC) participants (34 s, 14 ll)
Polymorphisms/variants:
5-HTTLPR
Population group:
BD patients
References:
Shah MP, Wang F, Kalmar JH, Chepenik LG, Tie K, Pittman B, Jones MM, Constable RT, Gelernter J, Blumberg HP. Role of variation in the serotonin transporter protein gene (SLC6A4) in trait disturbances in the ventral anterior cingulate in bipolar disorder. Neuropsychopharmacology. 2009 Apr;34(5):1301-10. PMID: 19037205
2) Disease relevance:
A comparison was done about serotonin transporter (5-HTT) binding between unipolar-depressives (MDD), bipolar-depressives (BD) and healthy-controls (HC) among 18 MDD, 18 BD, and 34 healthy-control subjects (Cannon et al., 2007). Higher 5-HTT BP in the thalamus, insula and striatum were observed in the MDD and BD groups. The unipolar-depressives showed higher 5-HTT BP in the vicinity of the periaqueductal gray (PAG) compared with both BD and HC groups. The bipolar-depressives showed lower 5-HTT binding-potential (BP) in the vicinity of the pontine raphe nuclei compared with HC and MDD groups.
The study showed that depression-severity was associated with 5-HTT BP in the thalamus negatively in MDD-subjects. The depressed phases of MDD and BD have been linked to higher 5-HTT binding in the insula, thalamus and striatum, with abnormal functions in the brainstem.
Sample size:
18 unipolar-depressives (MDD), 18 bipolar-depressives (BD), and 34 healthy-controls (HC)
References:
Cannon DM, Ichise M, Rollis D, Klaver JM, Gandhi SK, Charney DS, Manji HK, Drevets WC. Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder. Biol Psychiatry. 2007 Oct 15;62(8):870-7. PMID: 17678634
3) Disease relevance:
Serotonin transporter (SLC6A4) is involved in the regulation of brain serotonergic neurotransmission. SLC6A4 polymorphisms may be related to psychiatric traits including bipolar affective disorder (BPD). Ten markers including 2 variable number tandem repeat and 8 single nucleotide polymorphisms (SNPs) on SLC6A4 were examined in 90 unrelated BPD, type I patients and 103 controls (Sun et al., 2004). The fifth commonest haplotype may be associated with a protection from BPD. A particular SLC6A4 haplotype with functional sequence variant may be related to BPD etiology.
Sample size:
90 unrelated BPD, type I patients and 103 controls
Polymorphisms/variants:
2 variable number tandem repeat and 8 single nucleotide polymorphisms (SNPs) on the SLC6A4
Population group:
Taiwanese population
References:
Sun HS, Wang HC, Lai TJ, Wang TJ, Li CM. Sequence variants and haplotype analysis of serotonin transporter gene and association with bipolar affective disorder in Taiwan. Pharmacogenetics. 2004 Mar;14(3):173-9. PMID: 15167705
