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M M Robertson

Publications and source records attributed to M M Robertson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Sex of parent transmission effect in Tourette's syndrome: evidence for earlier age at onset in maternally transmitted cases suggests a genomic imprinting effect.

Parent of origin effects caused by genomic imprinting may influence the phenotypic expression of a number of heritable human disorders. To test this phenomenon in Tourette's syndrome (TS), we studied 437 first degree relatives systematically ascertained through 57 probands. We compared age at onset, age at diagnosis, and phenotypic expressions as observed in the diagnosis of TS, chronic motor tics, and obsessive compulsive behavior in the offspring of affected males with the offspring of affected females. Of the 437 subjects, 16.7% had matrilineal inheritance and 13.9% had patrilineal inheritance, as determined by family history methodology. Chi-square analysis of the different phenotypic expressions and sex of the transmitting parent failed to provide evidence of significant group differences. We found no significant differences in the age at diagnosis either. However, the maternally transmitted offspring showed a significantly earlier age at onset. This points to a parent of origin effect on the putative TS gene that could be explained by meiotic events or even intrauterine environmental influences. These findings may help explain the hitherto conflicting reports about the nature of genetic transmission in TS, and suggest a need to re-examine family data separately for maternally and paternally transmitted cases, taking into account the possible role of imprinting.

Age of Onset↗
PubMed1997

A volumetric MRI study of Gilles de la Tourette's syndrome.

The neuroanatomic or neuropathologic basis of Gilles de la Tourette's syndrome (GTS) remains unknown. Recent studies have suggested abnormalities of cerebral asymmetry and basal ganglia volumes. We studied 17 patients with GTS and eight normal controls using volumetric MRI techniques for measuring the caudate nucleus, amygdala, and corpus callosum. One subject with GTS was subsequently excluded because he was left handed. No absolute differences in caudate nucleus volumes between patient and control groups were evident. There was an increase in corpus callosum (CC) cross-sectional area and a loss of the normal asymmetry of the caudate nucleus in the patient group. A loss of the normal correlation between cross-sectional area of the CC and whole brain index (WBI) in the patient group also was found. The amygdala measurements had a poor interrater reliability.

Adolescent↗
PubMed1997

The Gilles de la Tourette syndrome.

The Gilles de la Tourette syndrome is a neuropsychiatric condition characterized by waxing and waning tics, both vocal and motor, over a lifelong course with an onset under the age of 21 years. Once considered a rare curiosity, its prevalence is now agreed to be around 5/10,000, and is seen worldwide. Many cases are mild and never require medical attention. It is now thought to have a genetic basis, but linkage has not yet been achieved, owing possibly to the inadequacy of a single-gene hypothesis. There is a strong association with obsessive compulsive disorder, and some postulate that many other psychiatric conditions may be determined as variations of the same phenotype. Attention deficit hyperactivity disorder is also common among sufferers. Management is with a combination of psychosocial measures and drugs; in particular dopamine antagonists, the efficacy of which has led to the theory that the syndrome is caused by an abnormality of the dopaminergic system. Studies using functional imaging techniques have both supported and rejected this hypothesis. Future research is expected to concentrate on the further application of genetic and brain imaging techniques in addition to clinical trials to identify optimal treatments. Studies relating to clinical, genetic, etiological, and historical aspects are reviewed.

Brain↗
PubMed1996

The use of fluoxetine in Gilles de la Tourette syndrome and obsessive compulsive behaviours: preliminary clinical experience.

1. Obsessive Compulsive Behaviours (OCB) occur in more than 50% of patients with the Gilles de la Tourette Syndrome (GTS) and in some cases these behaviours are more disabling than the tics themselves. 2. Fluoxetine, a specific serotonin reuptake inhibitor (SSRI) has been demonstrated to be effective in patients with Obsessive Compulsive Disorder. 3. The authors report on their clinical experience of fluoxetine in 30 GTS patients with OCB, in an open retrospective study. 4. There was an overall improvement in OCB as judged by the clinician in 76% of cases. Most patients received fluoxetine at a daily dose of 20 to 40mg for an average period of 6 months (24 +/- 4 weeks). In general, fluoxetine was well tolerated and further studies are indicated.

Adolescent↗
PubMed1996

Linkage analysis and exclusion of regions of chromosomes 3 and 8 in Gilles de la Tourette syndrome following the identification of a balanced reciprocal translocation 46 XY, t(3:8)(p21.3 q24.1) in a case of Tourette syndrome.

Gilles de la Tourette syndrome (GTS) and related disorders such as chronic multiple tics and obsessive compulsive behaviour are likely to be genetically transmitted with a Mendelian autosomal dominant mode of transmission. Following our discovery of a patient with GTS who also carried a balanced translocation 46 XY, t(3:8) (p21.3 q24.1), a linkage study of several families was performed covering the areas on chromosomes 3 and 8 implicated by the cytogenetic abnormality in this unique GTS patient. A positive multipoint lod score of 2.9 was obtained on chromosome 3 with markers at the loci RAF1, THRB and D3S11. Subsequently, the genetic map of this region was improved and new polymorphic markers close to our original three markers were identified. With the new map the maximum two-point lod with any marker was reduced to 1.77 at RAF1, and the FASTMAP approximate multipoint lod excluded the likely region of the breakpoint. After constructing a somatic cell hybrid, the original three markers were mapped relative to the break point of the translocation and to other new markers. It was confirmed that the original markers were at least 20 cM away from the position of the break point. In addition, we traced further family members of our translocation GTS proband, and identified affected individuals who did not possess the translocation. We concluded that the translocation was not responsible for the GTS symptoms in our affected proband.

Chromosome Mapping↗
PubMed1996

Non-obscene complex socially inappropriate behavior in Tourette's syndrome.

The authors surveyed 87 adolescent or adult patients with Tourette's syndrome (TS) regarding the presence, characteristics, and functional impact of non-obscene socially inappropriate (SI) behavior. Reported behaviors included insulting others (22%), other SI comments (5%), and SI actions (14%). More often, subjects described having an urge to carry out these behaviors (30%, 26%, 22%, respectively), which they often attempted to suppress. Non-obscene SI behavior was usually directed at a family member or familiar person, at home or in a familiar setting. Social difficulties commonly resulted. Non-obscene SI behavior is a common and potentially disabling feature of TS. It is closely associated with conduct disorder and attention deficit disorder and may represent part of a more general dysfunction of impulse control in TS.

Adolescent↗
PubMed1996

Tourette's syndrome in the year 2000.

OBJECTIVE: To examine the current status of knowledge of Tourette's syndrome (TS) and to highlight those areas of research that are most likely to have the most significant advances in the next few years into the 21st century. METHOD: Index Medicus was consulted from its beginning in 1885 until 1964 (inclusive), looking initially under the title 'tics' and subsequently under 'Tourette's Disorder'. From 1965 and the advent of MEDLINE, a search was performed looking for 'Tourette's'. A chronological examination of TS in the medical literature is presented. Some issues surrounding Huntington's Disease (HD) research are pertinent to TS and may serve as a guide in the future direction of TS research; these issues have been identified and illustrated in the context of TS. Where relevant, other medical disorders are also commented on. RESULTS: There has been a steady increase in the volume of TS literature since 1885, with a marked increase since 1980, changing in focus from a psychological to a neurobiological viewpoint. Current areas of interest include genetics, comorbid psychopathologies, neuroimaging, treatments, epidemiology and educational considerations. Issues raised by HD and other movement disorders such as Parkinson's Disease (PD) are predictive testing, gene therapy and neural transplants. CONCLUSIONS: The year 2000 is likely to herald a significant increase in our knowledge of the genetics and neuroimaging of TS, with new developments in therapy. A broadening of awareness of TS among health workers and teachers in particular is likely to increase the number of diagnosed patients and, hence, new challenges will be posed to existing resources for health and educational provision.

Brain↗
PubMed1996

Dysthymia in neurological disorders.

Dysthymia is characterized by long-lasting periods of lowered mood. Epidemiological studies in the USA and Europe have demonstrated that the prevalence of dysthymia is at least 3% of the general population. Its pervasive occurrence makes dysthymia a public health problem worldwide. One feature of this disorder is its co-occurrence with medical and neurological disorders. A World Health Organization meeting on dysthymia in neurological disorders was held in Geneva, 1-3 July 1996 to address this topic. Some of the major goals of this meeting were to clarify the definition of dysthymia in the presence of neurological disorders and to evaluate current research in the field, to point out new areas for investigation, and to discuss current psychological and pharmacological treatments for dysthymia in neurological disorders. The potential roles of neuroendocrine and molecular mechanisms in dysthymia were identified through specific problems related to dysthymia occurring in disorders such as Parkinson's disease, Alzheimer's disease, stroke, multiple sclerosis and epilepsy. This meeting provided direction and opportunity for future studies in the under-recognized and under-investigated relationship between dysthymia and neurological disorders.

Dysthymic Disorder↗
PubMed1995

Predictors of response to amine-specific antidepressants.

Discriminant function analysis of data from a double-blind comparative trial of lofepramine (a noradrenaline-specific reuptake inhibitor) and fluoxetine (a serotonin-specific reuptake inhibitor), involving 183 patients was used to identify predictors of response. Psychic anxiety significantly predicted a positive response to antidepressant medication, whereas psychomotor retardation, observed sadness, subjective lassitude and somatic complaints were significant predictors of nonresponse. Age, gender, endogenicity, duration of illness and number of previous episodes were not predictive of response. Significant differences were found between predictors of response to fluoxetine and lofepramine (P < 0.001 all groups). Predictors of response to lofepramine were similar to overall predictors, i.e., psychic anxiety predicted responders whilst observed sadness, psychomotor retardation, lassitude, inability to feel and somatic complaints predicted nonresponders. In contrast, baseline weight loss predicted response to fluoxetine, whereas anxiety, reduced insight and a tendency to blame others significantly predicted nonresponse. Such findings have practical implications for the management of depressive illness.

Adult↗
PubMed1995

The genetic susceptibility to Gilles de la Tourette syndrome in a large multiple affected British kindred: linkage analysis excludes a role for the genes coding for dopamine D1, D2, D3, D4, D5 receptors, dopamine beta hydroxylase, tyrosinase, and tyrosine hydroxylase.

Segregation analyses have shown that Gilles de la Tourette Syndrome (GTS) is transmitted as an autosomal dominant gene disorder indicating that classical linkage analysis should be able to identify susceptibility loci. Previous studies of GTS have included investigations of neuroreceptor function, neurotransmitters, and their metabolites as well as neurotransmitter-related enzymes in an attempt to determine the pathophysiology of GTS. The neurotransmitter systems most often thought to be involved in GTS include those involving adrenaline, noradrenaline, and dopamine. We have carried out research to test the hypothesis that genes encoding proteins in the catecholamine pathways may contribute to the genetic etiology of GTS. Polymorphic markers at or near the D1, D2, D3, D4, D5 neuroreceptor gene loci as well as at the genes encoding dopamine beta hydroxylase (DBH), tyrosinase (TY) and tyrosine hydroxylase (TH) were studied in one large multiple affected pedigree. The linkage results of this investigation exclude a major role of these candidate genes in the etiology of GTS in the pedigree.

Chromosome Aberrations↗
PubMed1995

Exclusion of the 5-HT1A serotonin neuroreceptor and tryptophan oxygenase genes in a large British kindred multiply affected with Tourette's syndrome, chronic motor tics, and obsessive-compulsive behavior.

OBJECTIVE: Previous studies have demonstrated a relationship between obsessive-compulsive disorder or behavior and Gilles de la Tourette syndrome. It has been hypothesized that the serotonergic system is implicated in the etiology of obsessive-compulsive disorder. Therefore, the authors investigated whether genetic variation in a serotonergic receptor and a modifying enzyme were associated with Tourette's syndrome. METHOD: A linkage analysis using DNA and blood group markers was carried out in a large British kindred multiply affected with Tourette's syndrome, chronic motor tics, and obsessive-compulsive behavior. RESULTS: There was no evidence to support the hypothesis that genetic variation in the serotonin 5-HT1A receptor and tryptophan oxygenase genes causes susceptibility to Tourette's syndrome and chronic multiple tics. CONCLUSIONS: The results eliminate two possible candidate genes from having a role in the pathophysiology of Tourette's syndrome.

Female↗
PubMed1995

Placebo-controlled trial of lithium augmentation of fluoxetine and lofepramine.

BACKGROUND: This study was designed to establish whether (as suggested in a number of open and relatively small controlled trials) lithium augmentation is more effective than continued antidepressant alone, where response to a standard course of antidepressant treatment has been absent or partial. METHOD: Lithium or placebo was added on a double-blind basis for six weeks to the drug regime of 62 patients with major depressive illness (in both hospital and primary care settings) who had failed to respond to a controlled trial of fluoxetine or lofepramine. Response was defined as a final Hamilton Depression Rating Scale (HDRS) score of < 10. RESULTS: Response was seen more frequently in patients taking lithium (15/29) than in those remaining on antidepressant alone (8/32; P < 0.05). Rapid response to lithium augmentation (LA) was not consistently observed in this cohort. Mean HDRS scores after six weeks were significantly lower (P < 0.01) in the lithium group after excluding those who had not achieved significant exposure to lithium (arbitrarily defined as two or more lithium levels > or = 0.4 mmol/l). No differences in the efficacy of LA were apparent between fluoxetine and lofepramine. CONCLUSIONS: Our results confirm that LA is a useful strategy in the treatment of antidepressant-resistant depression. Partial response was, however, frequently observed with continued antidepressant treatment alone, and the superiority of LA appears to depend on achieving adequate serum lithium levels.

Adolescent↗
PubMed1995

Brain perfusion abnormalities in Gilles de la Tourette's syndrome.

BACKGROUND: Functional brain imaging with technetium-99m d,l-hexamethyl propyleneamine oxime (HMPAO) Single Photon Emission Tomography (SPET) allows us to explore the cerebral pathophysiology of Gilles de la Tourette's Syndrome (GTS). METHOD: Fifty patients and 20 controls were examined. Patients were rated for tic severity and mood. Scans were analysed quantitatively using internal ratios to the occipital cortex. RESULTS: Patients different from controls on measures of relative blood flow to the left caudate, anterior cingulate cortex and the left dorsolateral prefrontal cortex. Severity of tics was related to hypoperfusion of the left caudate and cingulate and a left medial temporal region. Hypoperfusion in the left dorsolateral prefrontal region was related to mood. CONCLUSIONS: The areas found to be hypoperfused in this study are consistent with known functions of fronto-striatal circuits. A wide range of perfusion patterns is seen, however, and no characteristic patterns for behavioural subgroups has been documented with this technique.

Adolescent↗
PubMed1994

Platelet 5-HT uptake sites, labelled with [3H] paroxetine, in controls and depressed patients before and after treatment with fluoxetine or lofepramine.

Platelet [3H] paroxetine binding was measured in 73 depressed patients and in 64 healthy volunteers. No differences were found in Bmax or Kd either overall, or when the 61 depressed subjects who had never received psychotropic drugs were analysed separately. Within the depressed group, no differences in Bmax or Kd were found between subgroups divided on the basis of endogenicity, suicidal thoughts or severity of depression. None of the subgroups differed significantly from controls. Forty of the depressed subjects were retested after 6 weeks' treatment with fluoxetine (n = 22) or lofepramine (n = 18). Treatment was not associated with any change in Bmax but a similar and significant increase in Kd was noted following treatment with either antidepressant. Neither pre- nor post-treatment platelet binding parameters appeared to relate to clinical response to treatment.

Adolescent↗
PubMed1994

Dopamine receptor availability in Tourette's syndrome.

A large body of evidence suggests that abnormal dopaminergic activity is present in Gilles de la Tourette Syndrome (GTS). To investigate whether dopamine dysregulation involving the D2/D3 receptor occurs in GTS, we performed single slice dynamic single photon emission computed tomography (SPECT) with 123iodo-6-methoxybenzamide (123I-IBZM) in 15 GTS patients (eight unmedicated) and six healthy volunteers. After intravenous administration of 5 mCi (185 MBq) of 123I-IBZM, dynamic SPECT (5 minutes per slice) studies were performed at the level of the basal ganglia for 55 minutes. The mean activity per pixel in the basal ganglia was compared with the mean activity per pixel in the visual cortex. Unmediated GTS patients showed no differences from control subjects. However, GTS patients taking D2 blocking medications had significantly decreased 123I-IBZM binding compared with control subjects in both the right and left basal ganglia. Thus, D2/D3 receptor availability, as measured by 123I-IBZM SPECT, is not abnormal in GTS.

Adolescent↗