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HD CAG Repeats & Psychiatric symptoms
Eight studies on the psychiatric and cognitive symptoms and HD
These are older studies. Check the HD Lighthouse for
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A controlled psychiatric
study of individuals at risk for Huntington's disease
Br J Psychiatry 1994 Oct;165(4):500-5
Shiwach RS, Norbury CG-Deal Mental Health Centre, Kent.
BACKGROUND.
The study tested specific hypotheses that (a) there is an increased incidence of psychiatric disorders
in asymptomatic heterozygotes for Huntington's disease (HD) compared with the normal homozygotes, and (b) there is an increased
incidence of psychiatric disorders in the adult offspring of Huntington's disease patients compared with their partners.
METHOD.
A controlled study was made of 93 apparently healthy individuals (at 50% risk), who had given DNA
samples for the predictive test, and 70 of their partners. Current and past psychopathology was assessed and compared with
the DNA predictive test results based on linkage analyses. The results of psychiatric assessments of the two groups were compared.
RESULTS.
DNA test results were available for 53 subjects (of 93). Five subjects at risk for HD were omitted
from the study. The asymptomatic heterozygotes (n = 20) showed no significant increase in the incidence of any psychiatric
episode, depression, schizophrenia or behavioural disorder when compared with the normal homozygotes (n = 33). The whole tested
group showed a significantly greater number of psychiatric episodes than their partners (n = 43).
CONCLUSIONS.
Asymptomatic HD gene carriers do not have a greater incidence of psychiatric
disorders than the non-gene carriers born to a HD parent.
PMID: 7804665 |
Psychiatric symptoms and CAG expansion in Huntington's disease
Am J Med Genet 1996 Feb 16;67(1):53-7
Weigell-Weber M, Schmid W, Spiegel R.-Institute of Medical Genetics, University of Zurich, Switzerland.
The mutation responsible for Huntington's disease (HD) is an elongated
CAG repeat in the coding region of the IT15 gene. A PCR-based test with high sensitivity and accuracy is now available to
identify asymptomatic gene carriers and patients.
An inverse correlation between CAG copy number and age at disease onset has been found in a large
number of affected individuals. The influence of the CAG repeat expansion on other phenotypic manifestations, especially specific
psychiatric symptoms has not been studied intensively.
In order to elucidate this situation we investigated the relation between CAG
copy number and distinct psychiatric phenotypes found in 79 HD-patients. None of the four differentiated categories
(personality change, psychosis, depression, and nonspecific alterations) showed significant differences in respect to size
of the CAG expansion. In addition, no influence of individual sex on psychiatric presentation could be found.
On the other hand in patients with personality changes maternal transmission
was significantly more frequent compared with all other groups. Therefore we suggest that clinical severity
of psychiatric features in HD is not directly dependent on the size of the dynamic mutation involved.
The complex pathogenetic mechanisms leading to psychiatric alterations are still unknown and thus
genotyping does not provide information about expected psychiatric symptoms in HD gene carriers.
PMID: 8678115 |
Psychiatric symptoms do not correlate with cognitive decline, motor symptoms, or CAG repeat
length in Huntington's disease
Arch Neurol 1996 Jun;53(6):493-7
Zappacosta B, Monza D, Meoni C, Austoni L, Soliveri P, Gellera C, Alberti R, Mantero M, Penati G,
Caraceni T, Girotti F.-Istituto Nazionale Neurologico C. Besta, Milan, Italy.
OBJECTIVES:
To investigate the hypothesis that psychiatric disturbances in Huntington's disease are related to
degree of cognitive or motor compromise and to determine correlations between CAG repeat length within the gene for Huntington's
disease and disease severity.
DESIGN:
Consecutive series of patients with Huntington's disease.
SETTING:
Neurological specialty hospital.
PATIENTS:
Seventeen men and 12 women from 24 families.
MAIN OUTCOME MEASURES:
The Hamilton Psychiatric and Anxiety Rating Scales and Brief Psychiatric Rating Scale were used to
assess psychiatric disturbances; Folstein's Quantified Neurological Examination to evaluate motor status; and the Mini-Mental
State Examination, Raven Progressive Matrices), Phonemic Verbal Fluency Test, Short Tale Test, Visual Search Test, and Benton's
Visual Orientation Line Test to evaluate cognitive function. The length of the CAG repeat sequence in the Huntington's gene
was determined by quantitative polymerase chain reaction.
RESULTS:
Cognitive test scores correlated significantly with each other; of these, results of the Visual Search
and Short Tale tests correlated significantly with the Folstein's Quantified Neurological Examination score (P = .05 and P
= .03, respectively). Results of the Folstein's Quantified Neurological Examination also correlated with the illness duration
and the length of the CAG repeat. Although psychiatric scores correlated significantly among themselves (P < .01), neither
cognitive compromise, motor deterioration, nor CAG length were related to the extent of psychiatric compromise. Patients who
were depressed when they were examined tended to have a history of psychiatric disorders.
CONCLUSIONS:
The lack of correlation between disease severity and psychiatric disturbances
indicates that psychiatric disorders progress nonlinearly, possibly because of differential degeneration of
the striatal-cortical circuits; the possibility that psychiatric disorders are prevalent in certain families with a member
who has Huntington's disease is being further investigated. The lack of correlation between CAG length and cognitive and psychiatric
variables needs further investigation.
PMID: 8660149
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Neuropsychological stability over two years in asymptomatic carriers of the Huntington's disease
mutation
J Neurol Neurosurg Psychiatry 1996 Dec;61(6):621-4
Campodonico JR, Codori AM, Brandt J.-Department of Psychiatry and Behavioral Sciences, The Johns Hopkins
University School of Medicine, Baltimore, Maryland 21287-7218, USA.
This study examined whether neuro-psychological changes emerge over
time in asymptomatic adults who have the Huntington's disease mutation. We also evaluated whether scores on cognitive tests
or psychological symptom scales varied as a function of CAG repeat length or proximity to disease onset.
Twenty two healthy "mutation positive" and 37 "mutation negative" adults completed cognitive tests
and psychological rating scales before disclosure of their genetic test results and on an annual basis thereafter. Repeated
measures ANOVAs analysed differences between the two groups over three assessments.
Correlations of cognitive and psychological symptom test scores with estimated number of years to
disease onset and CAG repeat length were computed. The two groups did not differ at study entry; nor did they differ in the
rate of change over time. Tests of sustained attention and mental speed correlated with estimated years to disease onset,
but not with repeat length.
As a group, clinically asymptomatic adults with the Huntington's disease mutation do not display neuropsychological
deficits when studied over a two year interval. However, persons who are likely nearing clinical onset of Huntington's disease
may develop minor deficits in selected cognitive domains before they reach threshold for diagnosis.
PMID: 8971112
Psychiatric symptoms and CAG repeats in neurologically asymptomatic Huntington's disease gene
carriers.
Psychiatry Res 2001 Jul 24;102(3):217-25
Berrios GE, Wagle AC, Markova IS, Wagle SA, Ho LW, Rubinsztein DC, Whittaker J, Ffrench-Constant C,
Kershaw A, Rosser A, Bak T, Hodges JR-Department of Psychiatry, University of Cambridge, Addenbrookes Hospital (Box 189),
Hills Road, CB2-2QQ, Cambridge, UK.
The putative relationship between the psychiatric profile of a sample of neurologically asymptomatic
Huntington's disease gene carriers and CAG repeats was investigated. The psychiatric assessments (by consultant psychiatrist
and computerised battery) were undertaken before the genetic testing was carried out. In this way, the informational distortions
caused by neurological and cognitive deficits were avoided.
The hypothesis that there is a relationship between psychiatric and CAG repeats was tested by seeking
direct correlations between psychiatric systems and CAG repeats, and also by correcting the correlation by the number of years
above or below the estimated age of onset in Huntington's disease. Scores for irritability and cognitive failures were high
in the sample.
There was no correlation between any psychiatric variable and CAG repeats.
Possible explanations for this lack of correlations are discussed. |
Familial aggregation of psychotic symptoms in Huntington's disease.
Am J Psychiatry 2000 Dec;157(12):1955-9
Tsuang D, Almqvist EW, Lipe H, Strgar F, DiGiacomo L, Hoff D, Eugenio C, Hayden MR, Bird TD-Northwest
Mental Illness Research, Education, and Clinical Center, Department of Veteran's Affairs Puget Sound Health Care System, Seattle,
WA 98108-1597, USA. dwt1@u.washington.edu
OBJECTIVE:
The mutation responsible for Huntington's disease is an elongated and unstable trinucleotide (CAG)
repeat on the short arm of chromosome 4. Psychotic symptoms are more common in patients with Huntington's
disease than in the general population. This study explored the relationship of psychosis in Huntington's
disease patients with the number of CAG repeats and family history of psychosis.
METHOD:
Forty-four patients with Huntington's disease, 22 with and 22 without psychotic symptoms, were recruited
from two university-affiliated medical genetics clinics in Seattle and Vancouver, B.C. Psychiatric assessments of the subjects
were made through chart review, and diagnoses were validated by structured interviews in a subset of patients. The demographic
and clinical characteristics of the psychotic and nonpsychotic patients were compared.
RESULTS:
The two groups did not differ in demographic and clinical characteristics, except that subjects with
psychosis were significantly more likely than nonpsychotic subjects to have a first-degree relative with psychosis. In eight
of nine families in which Huntington's disease probands with psychosis had a first-degree relative with psychosis, the relative's
psychosis co-occurred with Huntington's disease. In the Huntington's disease probands with psychosis, the onset of psychosis
correlated with the onset of the neurological symptoms of Huntington's disease, and the age at onset of psychosis was lower
in probands with a higher number of CAG repeats.
CONCLUSIONS:
Patients with Huntington's disease and psychotic symptoms may have a familial predisposition to develop
psychosis. This finding suggests that other genetic factors may influence susceptibility to a particular phenotype precipitated
by CAG expansion in the Huntington's disease gene. |
Longitudinal personality changes among presymptomatic Huntington disease gene carriers.
Neuropsychiatry Neuropsychol Behav Neurol 2002 Sep;15(3):192-7
Kirkwood SC, Siemers E, Viken R, Hodes ME, Conneally PM, Christian JC, Foroud T.-Department of Medical
and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202, USA.
OBJECTIVE:
To determine whether longitudinal changes in personality as measured by the Minnesota Multiphasic
Personality Inventory (MMPI) can be detected among clinically presymptomatic individuals carrying the expanded Huntington
disease (HD) allele.
BACKGROUND:
Emotional symptoms are considered one of the cardinal features of HD. However, the literature is replete
with conflicting reports of psychiatric symptoms in presymptomatic HD gene carriers.
METHODS:
A longitudinal, case-control, double-blind study comparing presymptomatic gene carriers and nongene
carriers at risk for HD evaluated with an abbreviated MMPI and a quantified neurologic rating scale examined an average of
3.7 years apart.
RESULTS:
Presymptomatic gene carriers (PSGC) had a greater increase in abnormality over time for the MMPI scales,
cynical hostility (repeated-measures ANOVA, = 0.04) and irritability (repeated measures ANOVA, = 0.005), when compared with
the nongene carriers (NGC). Among both the PSGCs and NGCs, no significant correlation was found between the number of CAG
repeats and the change in MMPI score between visits.
CONCLUSIONS:
This study provides significant evidence for increasing irritability and cynical hostility in presymptomatic
gene carriers before the onset of overt clinical symptoms. |
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