Genetic factors in bipolar depression

Families with multiple cases of bipolar depression have been described that are compatible with both autosomal dominant and X-linked modes of genetic transmission.

Hypothesised pathways
Because antidepressant and stimulant drugs that help to ameliorate depression and mania are thought to act by affecting catecholamine neurotransmitter systems such as adrenaline, noradrenaline and dopamine,etc workers have sought to link genetic control mechanisms to the condition.

Genetic linkage studies have been carried out investigating mutations affecting the tyrosine hydroxylase (TH) gene which encodes the rate-limiting enzyme for the synthesis of these three neurotransmitters, tyrosine hydroxylase, the variable portion of the Harvey-ras-1 (HRAS1)10 locus and the variable region of the insulin gene (INS)11. All three markers are closely linked on chromosome 11 and might therefore be responsible for causing the manic depressive phenotype.

Gerhard et al .found linkage between manic depression and HRAS1 in a single large Amish kindred.

Hodgkinson et al (2002) studied three Icelandic families where there were 44 cases amongst 73 individuals at risk. They uses all three markers to observe the segregation of restriction fragment length polymorphisms (RFLPs) in the three affected kindreds but they found no evidence for linkage to these markers in any of the three families.

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Books

 * Perris, C.(ed.)(1979). Genetic Aspects of Affective Illness  9−19 SP Medical and Scientific, New York,

Papers

 * Gerhard, D. S. et al.(1984). Am. J. hum. Genet. 36, S35
 * Gerhard, D. S. et al.(1986). Symp. Genet. Res. Psychiat. Berlin
 * Nurnberger, J. I. & Gershon, E. S.(1982). In Handbook of Affective Disorders (ed. Paykel, E. S.) 126−145 Churchill Livingstone, London,
 * Boyd, J. H. & Weissman, M. W. Archs gen. Psychiat. 38, 1039−1046 (1981).
 * Mendelwicz, J.(1985). IVth World Congress. Biol. Psychiat. Philadelphia
 * Winokur, G. & Clayton, P.(1967) In Recent Adv. biol. Psychiat. 9, 35−50
 * Winokur, G., Clayton, P. & Reich, T.(1969). In Manic Depressive Illness (eds Winokur, G., Clayton, P. & Reich, T.) 1−150 (Mosley, St Louis,

Papers

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