Etiology
Comparison of the concordance rates for Tourette’s
disorder in monozygotic and dizygotic twins identifies Tourette’s disorder as an
inherited condition. The twin studies, however, are unable to identify a
particular mode of genetic transmission or to identify the breadth of the
clinical phenotype. To answer these questions, other research methods are
required. Segregation analyses of family study data have been used to identify
the pattern of ge-netic transmission and alternative phenotypes of the
Tourette’s disorder genetic diathesis. Linkage studies of Tourette’s disorder
based on the assumption of Tourette’s disorder as an autosomal dominant
condition have been undertaken but to date have not been successful. Candidate
gene studies based on the neurotrans-mitter hypotheses of the etiology of
Tourette’s disorder have also not been successful in identifying the Tourette’s
disorder gene(s). Recently, a large federally funded sibpairs study of
Tourette’s disorder has published encouraging results.
Evidence from twin studies suggests an important
role for both ge-netic and nongenetic factors in the development of Tourette’s
dis-order. Two large twin studies have shown high concordance rates in
monozygotic twins for Tourette’s disorder (both twins have Tourette’s disorder)
and for tic disorders (one twin has Tourette’s disorder, the other has tics but
not Tourette’s disorder). In both of the studies, the concordance rate for
Tourette’s disorder in monozy-gotic twins was more than 50%. When the
concordance rates were calculated for the presence of any tic disorder, they
approached 100%. By comparing the concordance rates of monozygotic twins with
dizygotic twins, one can separate the role of genetic factors from other
environmental factors. In the one study in which such a comparison was done,
the concordance rate for Tourette’s disorder in monozygotic twins was
significantly higher than the concord-ance rate in dizygotic twins (Price et al., 1985), further suggesting a
powerful role for genetics in Tourette’s disorder.
In Tourette’s disorder, the complex clinical
presentation suggests several neuroanatomical sites of disease as well as
neurochemical substrates including the basal ganglia and their interconnections
with the frontal cortex and limbic system. Abnormalities in these structures
could readily cause the wide variety of motor, sensory– motor, cognitive and
affective symptoms seen in patients with Tourette’s disorder. The complex
phenotypic presentation seen in Tourette’s disorder could also be produced by a
neurochemical abnormality at various locations within this circuitry. Reports
of group A beta-hemolytic streptococcus-related antineuronal an-tibodies being
associated with the development or exacerbation of tics and OCD suggest a role
for infectious agents and autoim-mune processes in the etiology of these
complex disorders.
Increasingly sophisticated imaging methods, such as
volumetric magnetic resonance imaging (MRI) and functional neuroimag-ing, have
identified subtle abnormalities in the basal ganglia and its interconnections
with cortical and limbic regions of the brain.
Two volumetric magnetic resonance studies
identified the absence of the usual left–right asymmetry in the basal ganglia,
leading to speculation of hypoplasia or atrophy of the left basal ganglia in
Tourette’s disorder. Areas associated with tic suppres-sion may reflect brain
areas involved in central nervous system dis-inhibition and ultimately tic
symptoms. Functional neuroimaging studies, such as single-photon emission
computed tomogra-phy, have identified decreased blood flow to the basal
ganglia, specifically the left lenticular region. Positron emission tomog-raphy
identified similar decrements of glucose use in the basal ganglia. Areas
associated with increased functioning in Tourette’s disorder include the
midbrain, lateral premotor and supplemental motor cortexes and areas associated
with sensorimotor, executive and paralimbic functioning. Areas associated with
decreased func-tioning include the circuitry involving the caudate and
thalamus, and their interconnections with the cortical and limbic areas.
A number of neurochemical abnormalities have been
proposed in Tourette’s disorder, in large part on the basis of responsiveness of
symptoms to specific pharmacological agents. Tic suppression with dopamine
blockers such as haloperidol and beta-adrenergic agonists such as clonidine
have implicated the dopamine–acetyl-choline and adrenergic systems,
respectively. The serotonin sys-tem has been implicated because of the
association of Tourette’s disorder with OCD and the positive therapeutic effect
of serot-onin reuptake inhibitors in OCD.
In several reports the development of tics as well
as obsessive– compulsive symptoms in children and adolescents has been
as-sociated in time with group A beta-hemolytic streptococcal in-fection. The
underlying mechanism is proposed to be similar to that involved in the
development of Sydenham’s chorea, in which antibodies developed in the course
of infection cross-react with basal ganglia tissues, resulting in the
characteristic choreiform movement disorder of Sydenham’s. Case reports have
described subjects with the abrupt onset or exacerbation in symptoms occur-ring
in parallel with antibody increases and with MRI changes in caudate size. These
cases have been given the acronym PANDAS for Pediatric Autoimmune
Neuropsychiatric Disorders Associated with Streptococcal Infection. These
preliminary findings link the development of a movement disorder and
psychiatric symptoms to an infectious agent and autoimmune processes, and
suggest new and alternative treatments including the potential for vaccines for
Tourette’s disorder and OCD, though the possibility of chance as-sociation is
high given that tics, obsessive–compulsive symptoms and streptococcal
infections are common events in childhood.
To date, studies have not identified any specific
factors that cause Tourette’s disorder, yet it is increasingly clear that
environmental factors have an impact on tic severity and, perhaps, even on the
types of symptoms expressed. Clinical wisdom suggests that tic severity
increases in response to stressful (e.g., examinations) or exciting life
experiences (e.g., amusement parks). It is also not uncommon for persons with
Tourette’s disorder to be able to identify a particular environmental stimulus
that initiated either a bout of symptoms or a new tic symptom.
Environmental factors associated with increases in
symp-tom severity can occur early in development, including prena-tal
(intrauterine) development. In a study comparing groups of Tourette’s disorder
subjects with severe versus mild tics, pro-tracted vomiting by a subject’s
mother during her pregnancy with the subject was a risk factor for increased
tic severity (Leckman et al., 1990).
Because of the male preponderance of Tourette’s dis-order, it has been
postulated that intrauterine exposure to andro-genic hormones may be a factor
in the development of tics and in tic severity. An open-label study of
flutamide, an antiandrogenic hormone, identified significant but transient tic
reduction in adult men, suggesting at least a partial role for sex hormones in
tic severity (Peterson et al., 1994).
Family-genetic and twin studies have also been useful for identifying factors
associated with tic severity and have found an association between birth weight
and tic severity suggesting that differences in intrauterine environ-ment may
be associated with tic severity.
Although psychosocial issues do not play a large
etiological role in the development of tic disorders they do play a major role
in adaptation and impairment and are often the focus of treatment and
rehabilitative efforts. Clinical work that involves the family, friends, school
and workplace is often the bedrock of treatment in a patient with Tourette’s disorder.
For children with Tourette’s disorder, the onset of
symptoms oc-curs early in development and directly affects family life and
re-lationships with peers and schoolmates. The diagnostic label of Tourette’s
disorder can be helpful for understanding the nature of a youngster’s problems
and can communicate the need to protect the youngster from excessive adversity.
The diagnostic label can, however, be a problem. There is a tension between
protecting a child with Tourette’s disorder from adversity while ensuring that
the child encounters and masters life’s challenges. With too much protection, a
child may run the risk of not developing a strong and complex identity adequate
for the rigors of adult life. Support from parents for mastering the challenges
of development is key to long-term functioning of children with Tourette’s
disorder.
The transition to adulthood is difficult enough for
most young peo-ple, but young adults with Tourette’s disorder have a particular
chal-lenge. The transition to adulthood often occurs when an important
component of their early experience and identity (i.e., Tourette’s disorder)
begins to show some improvement. Young adults most vulnerable during this
transition are those who, as a result of their Tourette’s disorder, did not
develop the foundations of an adult iden-tity as a child. These adults often
face the rigors of adult life without the necessary skills to manage, but also
without the presence of tic symptoms of sufficient severity to explain their
impairment.
Today’s adult with Tourette’s disorder belongs to a
different co-hort than today’s child with Tourette’s disorder. Most adults with
Tourette’s disorder were not diagnosed in childhood. They did not have the
“protection” of the diagnosis and often experienced significant confusion,
isolation and discrimination. Some adults with Tourette’s disorder have
significant anger, resentment and distrust related to their early life
experiences including ineffec-tive treatments, which can have an impact on
current function-ing. Many adults who appear to function well in spite of their
Tourette’s disorder may be doing so at an emotional cost.
Related Topics
Privacy Policy, Terms and Conditions, DMCA Policy and Compliant
Copyright © 2018-2023 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.