Neurology -- Correspondence for Heiman et al., 63 (4) 631-637

Correspondence published:

Reply to Duane: Gary A. Heiman, Ruth Ottman, Susan B. Bressman (21 January 2005)

Increased risk for recurrent major depression in DYT1 dystonia mutation carriers: Drake D. Duane (21 January 2005)

Reply to Duane 21 January 2005

Gary A. Heiman,
Columbia University
722 West 168th Street, 5th floor, Rm R-502, New York, NY 10032,
Ruth Ottman, Susan B. Bressman
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Re: Reply to Duane

gah13{at}columbia.edu Gary A. Heiman, et al.

We thank Dr. Duane for his interest in our article. The possible increased rate of depression in patients and families with focal dystonia is consistent with our finding of an increased rate of early-onset recurrent major depressive disorder (MDD) in DYT1 gene carriers and suggests shared pathophysiological mechanisms for dystonia and depression.
Our study design addressed many of the methodological weaknesses in the studies of cervical dystonia referenced by Duane. [3,4,5] For example, in previous studies, depression was directly assessed only in individuals exhibiting symptoms of dystonia, in whom it is impossible to tell whether depression results from a gene for focal dystonia or a response to having a chronic, debilitating disorder. In addition, retrospective recall of age at onset of depression relative to onset of dystonia is difficult and unreliable and hence has limited value in proving that depression is not reactive to dystonia. Some studies suggest that first-degree relatives of individuals with dystonia have increased rates of depression. [4,5] These studies did not assess the genetic status of the relatives so they could not distinguish an effect of a dystonia mutation from the psychosocial effects of having a close relative with a debilitating disorder.
Unlike cervical and other focal dystonias, in which understanding of genetic contributions is limited, we studied a population of DYT1 mutation carriers manifesting and not manifesting dystonia and used as controls their first-degree non-mutation carrying relatives. This design eliminated the need to determine whether depression or dystonia occurred first. Comparison of manifesting and non-manifesting mutation carriers to their family members without the DYT1 mutation allowed us to discriminate between genetic effects and the effects of either having or being related to someone with a chronic debilitating disorder. We also conducted a series of analyses to confirm that the result was not due to confounding or bias, including adjustment for the effect of knowledge of genetic status. In our study, all of the non-manifesting carriers who underwent genetic testing had an onset of recurrent MDD prior to testing.
Evidence for a relationship between dystonia and depression is accumulating. Additional studies of DYT1 families are needed to confirm our findings. As the genetic causes for the focal dystonias are identified, studies of genetic subtypes will be better able to characterize their range of expression including psychiatric symptoms.

Increased risk for recurrent major depression in DYT1 dystonia mutation carriers 21 January 2005

Drake D. Duane,
Arizona State University / Arizona Dystonia Institute
10210 North 92nd Street Suite 300 Scottsdale, AZ 85258
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Re: Increased risk for recurrent major depression in DYT1 dystonia mutation carriers

dduane{at}arizonaneurology.com Drake D. Duane

Heiman et al [1] reported a possible link between DYT1 gene carrier-state and major depression (MD). They conclude that there is a shared biologic mechanism for MD and a childhood onset generalized form of dystonia (GD).
Although the pathophysiologic basis of primary focal dystonia (FD) is unknown and uncommonly associated with the DYT1 gene, [2] most investigators assume that the dysfunction in both GD and FD lies within basal ganglion networks. An association between MD and FD raises the possibility that primary FD pathophysiology also places affected individuals at risk for MD as in DYT1 carriers. If there are causal genetic factors in FD patients, then their first-degree relatives may also be at risk for MD.
Depression and anxiety are unusually prevalent in FD. [3] A recent investigation of MMPI results in a referred population of 224 cervical dystonia (CD) patients (mean age 55-years, 67% female, 33% an additional dystonic site) demonstrated a rate of 53% for anxiety (ANX) and 72% for depression (DEP). [4] Symptoms of DEP in FD may antedate dystonic clinical onset suggesting that the affective symptoms are not a reaction to an often painful, potentially disabling disorder. [3] We found that, of 195 CD patients, 18% had a history of psychiatric diagnosis antecedent to onset of dystonic symptoms.
Utilizing DSM-IV criterion referencing the rate of DEP in first-degree CD relatives in the above study was 28%, 34% alcohol abuse and 10% ANX disorder. [4] Scheidt et al [5] reported 13% of CD patients had a first-degree relative with a history of �severe mental disorder.� Recalled family history data may be flawed. However, if valid, these observations suggest that non-DYT1 based FD gene sites may also place individuals at dual risk for MD and FD. Although the rate of dystonia in first-degree relatives of FD subjects is less than 10%, families of CD patients have high rates of essential head tremor and scoliosis suggesting perhaps a genetic component with heterogenous clinical expression. [4]
Neurologists should be aware of concomitant mood and cognitive manifestations of focal and generalized dystonia patients. These data reinforce the reunion of mind and brain.
References
1. Heiman GA, Ottman R, Saunders-Pullman RJ, Ozelius LJ, Risch MJ, Bressman SB. Increased risk for recurrent major depression in DYT1 dystonia mutation carriers. Neurology, 2004; 63: 631-637.
2. Bressman SB, De Leon D, Raymond D, et al. Clinical-genetic spectrum of primary dystonia. Adv Neurol, 1998; 78: 79-91.
3. Jahanshahi M, Marsden CD. Depression in torticollis: a controlled study. Psychological Medicine, 1988; 18: 925-933.
4. Duane DD, Vermilion KJ. Cognition and affect in patients with cervical dystonia with and without tremor. Adv Neurol, 2004; 94: 179-189.
5. Scheidt CE, Heinen F, Nickel T, et al. Spasmodic torticollis � a multicentre study on behavioral aspects IV: psychopathology. Behav Neurol, 1996; 9: 97-103.