Linkage of mood disorders with D2, D3 and TH genes: a multicenter study.
BACKGROUND
It has been suggested that the dopaminergic system is involved in the pathophysiology of mood disorders. We conducted a multicenter study of families with mood disorders, to investigate a possible linkage with genes coding for dopamine receptor D2, dopamine receptor D3 and tyrosine hydroxylase (TH).


METHODS
Twenty three mood disorder pedigrees collected within the framework of the European Collaborative Project on Affective Disorders were analyzed with parametric and non-parametric linkage methods. Various potential phenotypes were considered, from a narrow (only bipolar as affected) to a broad (bipolar+major depressive+schizoaffective disorders) definition of affection status.


RESULTS
Parametric analyses excluded linkage for all the candidate genes, even though small positive LOD (Limit of Detection) scores were observed for TH in three families. Non-parametric analyses yielded negative results for all markers.


CONCLUSIONS
The D2 and D3 dopamine receptors were, therefore, not a major liability factor for mood disorders in our sample, whereas TH may play a role in a subgroup of patients.
Serretti
A
A
Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, University of Milan School of Medicine, Via Luigi Prinetti 29, 20127, Milan, Italy. serretti.alessandro@hsr.it
Macciardi
F
F
Cusin
C
C
Lattuada
E
E
Souery
D
D
Lipp
O
O
Mahieu
B
B
Van Broeckhoven
C
C
Blackwood
D
D
Muir
W
W
Aschauer
H N
HN
Heiden
A M
AM
Ackenheil
M
M
Fuchshuber
S
S
Raeymaekers
P
P
Verheyen
G
G
Kaneva
R
R
Jablensky
A
A
Papadimitriou
G N
GN
Dikeos
D G
DG
Stefanis
C N
CN
Smeraldi
E
E
Mendlewicz
J
J
D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D005060:Europe; D015870:Gene Expression / Q000502:physiology; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D010641:Phenotype; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
C493593:DRD3 protein, human; D005819:Genetic Markers; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D014446:Tyrosine 3-Monooxygenase