Increased risk for recurrent depression in DYT1 dystonia mutation carriers

Department of Epidemiology of Joseph L. Mailman School of Public Health, Columbia University, New York 10032, USA.
Neurology (Impact Factor: 8.29). 09/2004; 63(4):631-7. DOI: 10.1212/WNL.64.10.1821-a
Source: PubMed


Prior studies suggest that dystonia is comorbid with affective disorders. This comorbidity could be a reaction to a chronic debilitating disorder or expression of a predisposing gene. The authors took advantage of the identification of a gene for dystonia, DYT1, to test these alternative explanations.
The authors administered a standardized psychiatric interview to members of families with an identified DYT1 mutation. The authors classified family members into three groups: mutation carriers with dystonia (manifesting carriers; n = 96), mutation carriers without dystonia (non-manifesting carriers; n = 60), and noncarriers (n = 65).
The risk for recurrent major depressive disorder was increased in both non-manifesting carriers (RR = 4.95, CI = 1.72 to 14.29) and manifesting carriers (RR = 3.62, CI = 1.00 to 10.53) compared with noncarriers. Mutation carriers also had earlier age at onset of recurrent major depressive disorder than noncarriers. The severity of motor signs was not associated with the likelihood of recurrent depression. Mutation carriers did not have an increased risk for other affective disorders, such as single major depression or bipolar disorder.
Early-onset recurrent major depression is associated with the DYT1 GAG mutation and this association is independent of motor manifestations of dystonia. These findings suggest that early-onset recurrent depression is a clinical expression of the DYT1 gene mutation.

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Available from: Rachel Saunders-Pullman, MD, MPH, Nov 13, 2014
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    • "Psychiatric symptoms in 96 motor affected mutation (GAG deletion) carriers (MC) were compared to 125 controls (60 NMC and 65 non-carriers (NC)) [2] [3]. The relative risk of recurrent major depressive disorder (MDD) was found to be increased in mutation carriers (MC 3.62, NMC 4.95) compared to NC. Mutation carriers also had an earlier age at onset of these symptoms, which were also independent of motor symptom severity. "
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    • "le , in electrophysiological responses ( Edwards et al . , 2003b ) , temporal processing of sensory stimuli ( Fiorio et al . , 2007 ) , motor sequence learning ( Carbon et al . , 2011 ; Ghilardi et al . , 2003 ) , and sensorimotor cortical activity ( Carbon et al . , 2010 ) , as well as an increase in susceptibility to recurrent major depression ( Heiman et al . , 2004 ) . Second , our results demonstrate that strong neuro - nal activity can alter the synaptic phenotype , and therefore may serve as a ' ' second hit ' ' in DE - torsinA neurons . The low penetrance and phenotypic variabil - ity of DYT1 dystonia imply that genetic polymor - phisms ( Kock et al . , 2006 ; Risch et al . , 2007 ) or envi - "
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    • "Nonpharmacological antidepressant treatment has ants exist than were genotyped. On the other hand, the previously claimed association may stem from overestimating the prevalence of recurrent major depression in ∆GAG deletion carriers [2], owing to the relatedness of subjects , a disproportionately small number of "
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