The effect of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on hippocampal and lateral ventricular volume in psychosis.
BACKGROUND
Morphometric endophenotypes which have been proposed for psychotic disorders include lateral ventricular enlargement and hippocampal volume reductions. Genetic epidemiological studies support an overlap between schizophrenia and bipolar disorder, and COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes have been implicated in the aetiology of both these disorders. This study examined associations between these candidate genes and morphometric endophenotypes for psychosis.


METHODS
A total of 383 subjects (128 patients with psychosis, 194 of their unaffected relatives and 61 healthy controls) from the Maudsley Family Psychosis Study underwent structural magnetic resonance imaging and genotyping. The effect of candidate genes on brain morphometry was examined using linear regression models adjusting for clinical group, age, sex and correlations between members of the same family.


RESULTS
The results showed no evidence of association between variation in COMT genotype and lateral ventricular, and left or right hippocampal volumes. Neither was there any effect of the BDNF, 5-HTTLPR, NRG1 and DTNBP1 genotypes on these regional brain volumes.


CONCLUSIONS
Abnormal hippocampal and lateral ventricular volumes are among the most replicated endophenotypes for psychosis; however, the influences of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on these key brain regions must be very subtle if at all present.
Dutt
A
A
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK. Anirban.Dutt@kcl.ac.uk
McDonald
C
C
Dempster
E
E
Prata
D
D
Shaikh
M
M
Williams
I
I
Schulze
K
K
Marshall
N
N
Walshe
M
M
Allin
M
M
Collier
D
D
Murray
R
R
Bramon
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000235:genetics* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004292:Dominance, Cerebral / Q000235:genetics; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020890:Neuregulin-1 / Q000235:genetics*; D009929:Organ Size / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000235:genetics* / Q000473:pathology; D012016:Reference Values; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; C094131:NRG1 protein, human; D020890:Neuregulin-1; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase