Serotonergic candidate genes and puerperal psychosis: an association study.
BACKGROUND
Altered serotonergic function is implicated in the aetiology and pathogenesis of a host of psychiatric disorders, and structural variations/polymorphisms in genes encoding the serotonin transporter and various serotonin receptor subtypes are attractive candidates to investigate the biological component underlying these disorders. Specific phenotypic subtypes, that perhaps represent homogeneous forms of the disorder, may increase the power to detect genes in complex diseases.


OBJECTIVE
We investigated regulatory and functional polymorphic DNA markers of serotonergic candidate genes using a case-control approach in puerperal psychosis and bipolar affective disorder probands.


METHODS
We genotyped 320 female participants (104 puerperal psychosis probands, 102 bipolar disorder participants and 114 controls) at the serotonin transporter SERT (5-HTT) 5-HTTVNTR and 5-HTTLPR locus; serotonin receptor 2A (5-HT2A)-T102C and His452Tyr loci, the serotonin receptor 2C (5-HT2C)-Cys23Ser locus, and seven unrelated Alu polymorphic markers.


RESULTS
We observed an association of the puerperal psychosis phenotype with the allele 10 of 5-HTTVNTR of SERT (P=0.004) and a modest association with the genotypic frequencies of the 5-HTTLPR (P=0.036). A nominal P value of 0.006 was observed with the S-10 haplotype in the PP group as compared with bipolar affective disorder probands. Significant association was observed with bipolar affective disorder phenotype with Tyr allele of the 5-HT2A His452Tyr gene polymorphism (P=0.00043) even after a conservative multiple test correction. No association was observed, however, with the 5-HT2A T102C locus, and the distribution of the other seven Alu markers did not differ between the groups.


CONCLUSIONS
The association between polymorphisms in serotonergic genes (SERT and 5-HT2A, 5-HT2C) suggests that these genetic factors can modulate vulnerability to puerperal psychosis in female bipolar participants.
Kumar
H B Kiran
HB
Molecular Genetics Laboratory, [corrected] National Institute of Mental Health and Neurosciences, [corrected] Bangalore, Karnataka [corrected] India.
Purushottam
Meera
M
Kubendran
Shobana
S
Gayathri
Praveena
P
Mukherjee
Odity
O
Murthy
A Ram
AR
Ghosh
Saurabh
S
Chandra
Prabha
P
Reddy
Y C Janardhan
YC
Benegal
Vivek
V
Brahmachari
Samir Kumar
SK
Jain
Sanjeev
S
D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D011644:Puerperal Disorders / Q000235:genetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D012701:Serotonin / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin