Download Psychopathology in Primary Dystonia

Psychopathology in Primary Dystonia.
Introduction
The dystonias are a group of movement disorders that are characterised by
sustained, involuntary muscle contractions leading to repetitive twisting movements
and abnormal posturing1,2,3. The movements can resemble spasticity or rigidity, and
can be confused with other disorders of movement such as cerebral palsy1. It is
usually aggravated by stress and fatigue, and improves with rest 3, it can also be
aggravated by voluntary movement4. Pain is rarely a feature, except in cervical
dystonia (spasmodic torticollis)1, but tremor may be present2. Dystonia is classified
according to distribution, and may be generalised or focal, with the latter type usually
affecting the face arm or neck, but rarely the legs1. It is also useful to classify
dystonia according to age at onset. Early-onset dystonia usually begins before the age
of 25 years, and starts in an arm or leg, eventually progressing to involve the whole
body4. Adult-onset dystonia (onset after 25 years) usually remains focal 1,2, so this
classification gives useful prognostic information.
Dystonia is classified as primary where there are no other neurological
symptoms, and the cause is either unknown or genetic. The condition may also arise
secondary to an identified neurological condition, metabolic abnormality or drug4.
There are also dystonia-plus syndromes, in which dystonia is associated with another
movement disorder such as rapid-onset dystonia-parkinsonism1,4. Paroxysmal
dystonias begin in childhood, and here there are brief episodes of dystonia with
episodes of normality in between1,4.
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Many of the dystonia syndromes are genetic. The genes for the disorders have
been identified in a number of cases. Thirteen different types of dystonia have been
distinguished genetically, and these are designated dystonia types (DYT) 1-13.
Primary Generalised Torsion Dystonia, for example, is caused by a guanine-adenineguanine (GAG) deletion in the DYT 1 gene and is inherited in an autosomal dominant
fashion2.
There is disagreement within the literature as to the prevalence of dystonia.
One study finds a prevalence of 0.7-50 per million for early onset dystonia1, while
another study looking at prevalence among Ashkenazi Jews living in New York gave
a figure of 111 per million5. Late onset dystonia was found with a prevalence of 600
per million in the North of England and in the Italian population over 50 years old it
was found to be 300 per million5.
The pathophysiology of primary dystonia is not fully understood. It is
hypothesized that it arises from dysfunction of the basal ganglia1,3,6. Damage to the
basal ganglia has been shown to produce dystonia1,7, in particular lesions of the
putamen and thalamus3. It is thought that an over activity of these areas, in particular
the lateral globus pallidus, may be responsible for the symptoms of the primary
dystonias6,8. A study which used microelectrode recordings and EMG in patients with
primary and secondary dystonia who were undergoing surgery showed abnormalities
in the ventral thalamic nuclear group, the globus pallidus internus and the subthalamic
nuclei 9. The authors believe that these areas are likely to be directly involved in the
production of dystonic movements. Dopamine levels may also play a role, as seen in
Dopa-Responsive dystonia. Dopamine blocking agents have been used with some
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success to treat primary generalised dystonia3. The loss of function at the basal
ganglia leads to impaired inhibition of the cerebral cortex, which causes loss of the
normal inhibition at the brainstem and spinal level, which in turn leads to the dystonic
movements.
Studies have shown an increased rate of psychiatric comorbidity in patients
with primary dystonia8. This paper will examine the literature for evidence of this,
and explore a possible mechanism for this link.
Epidemiology of Psychiatric Illness in Dystonia
The prevalence of comorbid psychiatric illness with dystonia may be as high
as 65.9% (lifetime and current diagnoses) 8. Other sources state that the lifetime risk
of psychiatric comorbidity was increased 2.6 times in dystonia compared with the
general population11. The diagnoses that have been reported with dystonia include
panic disorder, major depressive disorder, social phobia and bipolar disorder 7,10.,11,12.
There is no clear consensus as to the cause of this increased prevalence. There may
be a common pathological background linking psychiatric illness and
dystonia13,14,15,16. Lesions to the basal ganglia causing dystonia have been shown to
cause concurrent psychiatric disorders such as bipolar disorder and obsessive
compulsive disorder 7,19. Other movement disorders involving the basal ganglia, for
example Parkinson’s Disease and Huntington’s Disease, have prominent psychiatric
features, disrupted functioning in this area in dystonia could have a similar effect 16.
However studies comparing dystonia patients with groups of patients with similarly
disabling and disfiguring conditions found no difference in terms of psychopathology
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between the two groups17,18. This suggests that the psychopathology is a result of
living with a disability.
Psychopathology in Primary Generalised Torsion Dystonia.
This is a chronic, severely disabling disorder. It begins in childhood in an arm
or leg, and spreads to involve the whole body4. It is usually inherited as an autosomal
dominant trait and has a penetrance of 30-40%2. The mutation in the DYT 1 gene
which causes the disorder, leads to the abnormal production of a brain protein, torsin
A, found in the highest concentrations in the basal ganglia. A study examined a
possible link between the DYT 1 mutation and major depression13. Families with the
mutation were split into three groups; symptomatic carriers, non symptomatic carriers
and non carriers of the mutation and interviewed for evidence of major depression.
The risk of recurrent major depression was increased in both symptomatic and non
symptomatic carriers compared with non carriers, and the depression manifested at an
earlier age compared with the general population. There was no relationship between
depression and severity of disease. These findings suggest that early onset recurrent
depression is a clinical expression of the DYT 1 mutation. This has implications for
patients and their families; depression may add significantly to the patient’s suffering,
and affect their quality of life, and how they cope with their illness20,21. Non
symptomatic carriers are also at risk for major depression, and should be observed for
signs of mental health problems. They may be particularly at risk if they are carers
for a patient with a disability22,23. Only one other study was identified which
examined the prevalence of depression in DYT 1 gene carriers, compared with age
and sex matched healthy controls11. Here no significant differences were found
between the two groups in terms of episodes of major depression and anxiety.
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Psychopathology in Primary Focal Dystonia
More research has been done into the psychiatric comorbidities of focal
dystonia, perhaps because this form of the disease is more prevalent, but it may be
due to a stronger link between the two conditions. The focal dystonias most
commonly studied are idiopathic spasmodic torticollis (IST) and blepharospasm. The
former involves dystonic movements of the muscles in the cervical region, and the
latter involves the muscles around the eyes.
Obsessive Compulsive Disorder in Focal Dystonia
The strongest evidence in favour of similar pathological mechanism is for
obsessive compulsive disorder (OCD)10,14,17,25. Decreased volume and metabolic rates
have been found in the caudate nucleus of OCD patients, and OCD resembles
dystonia in it’s persistent, repetitive, preservative and involuntary symtoms 25. A high
incidence of OCD has been observed in patients and relatives of patients with with
Gilles de la Tourette’s syndrome, which is a neurological disorder characterised by
involuntary motor and vocal tics26. Studies of patients with blepharospasm and IST,
looked for obsessions and compulsions using DSM IV and symptom 90 checklist
criteria for diagnosis14,17,25. They found that dystonia patients had significantly higher
scores than controls. The risk of OCD in families of IST patients was found to be
increased at 13.8%, which may point to an early manifestation of basal ganglia
instability14. Increased rates of OCD have also been found in association with
myoclonus dystonia, one of the dystonia plus syndromes, which is further evidence
for a physiological link15. However when compared with another group with a similar
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disfiguring disorder (hemifacial spasm), no significant differences were found in the
prevalence of obsessions and compulsions, so the previous findings may indicate that
OCD is a reaction to a disfiguring disabling illness14. If there is a similar
physiological pathway for OCD and dystonia, it may be possible to improve the
dystonia using agents for the treatment of OCD, such as selective serotonin reuptake
inhibitors (SSRIs), but there is no evidence at present relating to this.
Mood Disorders in Focal Dystonia
Mood disorders have also been found with increased frequency in patients
with focal dystonia. Depression is a common finding, and several studies found some
level of depression in dystonia patients 11,16,18,20,21,25,27-30. Bipolar disorder (BD) was
found to have developed after the onset of dystonia in three out of five patients with
concurrent BD and focal dystonia3. The risk of mood disorders was reported as 2.4
times that of the general population in a group of patients with IST11. This preceeded
the onset of dystonia in some cases, suggesting it is not simply reactive to the chronic
illness29,31. The rate of major depression is increased in first degree relatives of IST,
so there may be genetic factors involved28. It would be expected that sufferers of a
disabling, disfiguring chronic condition would have higher rates of depression than
the general population, but when compared with patients suffering from similar sorts
of conditions, such as cervical spondylosis, dystonia patients still have higher rates of
depression16,18. Females may have higher rates of depression than males21.
Prominent features of depression in focal dystonia include self-blame, negative body
image, and self-deprecation16,18,29. Some of the evidence finds no difference in
depression rates in dystonia patients and controls24,27. The mechanism of the
depression is unclear. If there is no common pathological pathway for the two
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conditions, and no genetic link, it may be that patients with dystonia are more likely
to be depressed due to the effect of their condition on their life. A finding that neck
pain is the major determinant of depression in IST suggests that this may be the
case21. The condition may be more likely to make patients feel depressed than other
conditions, and more research should be done into why this is so, in order to better
support these patients. Studies have shown that depression has a negative impact on
quality of life and adjustment to focal dystonia20,29.
Anxiety in Focal Dystonia
Anxiety is also a prominent finding in patients with focal dystonia
10,11,18,24,27,30
. Panic disorder was found in 29.5% of IST patients, including diagnoses
made prior to the onset of dystonia10. Social phobia was ten times more common in a
group of patients with IST than in the general population, again this included predystonia diagnoses11. One would expect to find that patients with a disfigurement felt
more self conscious, and it may be that this translates into a social phobia. More
research is needed to find out how often the anxiety disorder precedes the dystonia to
find out if the anxiety is the result of a genetic predisposition or a similar pathological
mechanism19. Compared with patients with alopecia areata (a similarly disfiguring
condition in the same body area), the incidence of all psychiatric co morbidity was
increased, including that of anxiety16.
Psychosocial Factors in Primary Dystonia
Dystonia causes significant morbidity and disability, and would be expected to
have a negative impact on quality of life. This effect has been studied in patients with
IST and blepharospasm20,21,29. Patients reported lower quality of life scores than
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would be expected in the general population, both on physical and mental health
questionnaires. Compared with multiple sclerosis, rheumatoid arthritis, Parkinson’s
disease and epilepsy patients, similar psychosocial variables predicted the quality of
life in dystonia. The patients showed poor adjustment to their illness, and had few
sources of social support, but the length of their illness was associated with a better
quality of life, which may be due to the development of a successful coping
strategy20,21. Intrinsic personality features and educational status modified the
patients’ ability to cope. One area of possible research would be to investigate what
strategies dystonia patients are using to help them cope with their condition, as this
would be useful to help others who are not coping so well. Psychological therapies
and increased social support may have a positive impact on quality of life.
Implications for Treatment
Psychiatric comorbidity has been shown to have a significant effect on quality
of life, and treating the dystonia symptoms only does not improve this21. It is
important to treat any co-existing psychiatric problem, and current practice is to use
the same treatment regimes as in patients without dystonia. OCD is treated using a
form of behaviour therapy called exposure therapy and selective serotonin reuptake
inhibitors. There has been no trial of exposure therapy in dystonia patients with OCD,
however the treatment is safe and, if successful would significantly improve the
patients’ quality of life. Anxiety is usually treated using cognitive behavioural
therapy (CBT), and this is safe to use in dystonia. A study of CBT in dystonia found
that the disease was perpetuated by catastrophic thoughts and abnormal illness beliefs,
and that the dystonia itself was improved following therapy31. SSRIs may also be
useful in the treatment of anxiety. For treatment of depression and SSRI is used,
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followed by a tricyclic antidepressant or a monoamine oxidase inhibitor (MAOI) if
the patient does not respond. Care must be taken with these agents as they have been
shown to cause reversible dystonia as a rare side effect, in particular in patients who
have pre-existing neurological disorders, or who are using neuroleptics (a class of
drug that can be used to treat dystonia)32-34. SSRIs seem to cause this side effect more
frequently than the other types of antidepressant, so it may be prudent to use a
tricyclic or MAOI as a first line treatment for depression in dystonia, and to watch the
patient carefully for any deterioration33. If a reaction does occur, switching to another
class of drug, or adding a benzodiazepine, beta blocker or anticholinergic agent may
relieve symptoms and allow continued treatment of the depression32.
Conclusions
From the evidence in this paper, it seems that the prevalence of psychiatric
illness is higher in primary dystonia patients than in the general population. The
mechanism of this remains unclear. It seems likely that some common pathology
involving the basal ganglia, possibly caused by genetic factors may account for this in
some instances13,14, however the nature of the illness predisposes patients to an
increased risk of depression and anxiety and this may account for the high prevalence
of these. A multi-factoral view of the situation is needed in this case, and it may be
that people with a genetic predisposition to psychiatric illness, suffer considerable life
stresses due to having a chronic disabling illness, and so their risk of depression and
anxiety is increased beyond that of the general population and that of other chronic
illness. Personality factors may lead to some of this group having better coping
strategies and social factors may give them extra support, which prevent them from
developing psychiatric problems. More research is needed, with larger patient
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samples from a wide range of experiences in order to say for certain that there is any
link. The issues outlined here further emphasize the need for a integrated approach to
neurological disease in general, and dystonia specifically, so that we can better
understand the link with psychiatric illness. This also applies in practice, where a
holistic approach to dystonia patients will help to ensure that all their needs are met,
and that treatable conditions which are common in dystonia, and which have a
considerable detrimental effect on quality of life and response to their illness are not
overlooked.
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