Biomedical subjects

J P MacMurray

Publications and source records attributed to J P MacMurray.

18 recordsLinked to original sources

PubMed1998

Association between the gamma-aminobutyric acid A3 receptor gene and multiple sclerosis.

BACKGROUND: In a prior study we observed an association between the dopamine D2 receptor gene (DRD2) and the age of onset and/or diagnosis of multiple sclerosis (MS). We hypothesized that this effect was mediated through the dopaminergic control of the release of prolactin, a modulator of immune response. Since gamma-aminobutyric acid also modulates the release of prolactin, we examined the possible association between alleles of the GABRA3 (gamma-aminobutyric acid A3 receptor) gene and MS. DESIGN: We examined the GABRA3 alleles of 189 subjects with MS who died of their disease. They were divided into test group 1 (n=64) and retest group 2 (n=56). Each group had a separate set of controls (group 1, n=109; group 2, n=430). All subjects were white. All were tested at a dinucleotide cytosine-adenosine repeat polymorphism with 6 alleles representing 11 to 16 repeats. RESULTS: In the first group there was a significant difference in the frequency of the GABRA3 alleles (P<.002), with the most notable difference being an increase in the frequency of the 16-repeat allele in subjects with MS and a relative decrease in the other alleles. In the replication group there was again a significant difference in the distribution of the GABRA3 alleles (P<.001), and again the greatest difference was an increase in the frequency of the 16-repeat allele in subjects with MS. For both groups combined, a significant difference in the frequency of the 16-repeat allele was noted (chi2=46.30; P<.001). CONCLUSIONS: These results suggest the GABRA3 gene may be a risk factor for MS. As with the DRD2 gene, the effect may be mediated through its regulation of prolactin release.

Alleles↗

PubMed1996

Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: the additive and subtractive effect of the three dopaminergic genes--DRD2, D beta H, and DAT1.

Polymorphisms of three different dopaminergic genes, dopamine D2 receptor (DRD2), dopamine beta-hydroxylase (D beta H), and dopamine transporter (DAT1), were examined in Tourette syndrome (TS) probands, their relatives, and controls. Each gene individually showed a significant correlation with various behavioral variables in these subjects. The additive and substractive effects of the three genes were examined by genotyping all three genes in the same set of subjects. For 9 of 20 TS associated comorbid behaviors there was a significant linear association between the degree of loading for markers of three genes and the mean behavior scores. The behavior variables showing the significant associations were, in order attention deficit hyperactivity disorder (ADHD), stuttering oppositional defiant, tics, conduct, obsessive-compulsive, mania, alcohol abuse and general anxiety-behaviors that constitute the most overt clinical aspects of TS. For 16 of the 20 behavior scores there was a linear progressive decrease in the mean score with progressively lesser loading for the three gene markers. These results suggest that TS, ADHD, stuttering oppositional defiant and conduct disorder, and other behaviors associated with TS, are polygenic, due in part to these three dopaminergic genes, and that the genetics of other polygenic psychiatric disorders may be deciphered using this technique.

Adolescent↗

PubMed1996

Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential association with Tourette syndrome, substance abuse and other disorders.

Defects in serotonin metabolism, and abnormalities in both blood serotonin and tryptophan levels, have been reported in many psychiatric disorders. Tryptophan 2,3-dioxygenase (TDO2) is the rate limiting enzyme for the breakdown of tryptophan to N-formyl kenurenine. Functional variants of this gene could account for the observed simultaneous increases or decreases of both serotonin and tryptophan in various disorders. We have identified four different polymorphisms of the human TDO2 gene. Association studies show a significant association of one or more of these polymorphisms and Tourette syndrome (TS), attention deficit hyperactivity disorder (ADHD) and drug dependence. The intron 6G-->T variant was significantly associated with platelet serotonin levels. Only the association with TS was significant with a Bonferroni correction (p = 0.005). Our purpose here is not to claim these associations are proven, but rather to report preliminary results and show that easily testable polymorphisms are available. We hope to encourage additional research into the potential role the TDO2 gene in these and other psychiatric disorders.

Electrophoresis, Polyacrylamide Gel↗

PubMed1996

Genetic variants of the human obesity (OB) gene: association with body mass index in young women, psychiatric symptoms, and interaction with the dopamine D2 receptor (DRD2) gene.

To examine the possible role of genetic variants of the OB gene in obesity we examined alleles of a dinucleotide repeat polymorphism, D7S1875, close to the gene, in a group of adult, non-Hispanic Caucasians. There was a significant correlation with body mass index (BMI) at age 26-30 years for males and females combined (P = 0.04) and females only (P = 0.028). Because of the frequent association between obesity and psychiatric symptoms all subjects were screened with the Symptom List 90 (SCL-90). There was a significant increase in scores for anxiety (P = 0.0005), depression (P = 0.003), and other behaviors for subjects homozygous for the OB1875 < 208-bp alleles. Analysis of covariance indicated that this was directly related to the OB alleles and not secondary to the presence of obesity. There was a significant association between the BMI at ages 16 to 40 and homozygosity for the OB1875 < 208-bp alleles and/or the presence of the DRD2 Taq A1 allele for males and females combined (P = 0.002 to 0.005), and for females alone (P = 0.0017 to 0.0005). For females alone these two genes accounted for up to 22.8% of the variance of the BMI. These results are consistent with the polygenic inheritance of obesity, the greater involvement of genetic factors in women and younger individuals, and suggest that variants of the OB gene are causally involved not only in human obesity but its associated behavioral disorders.

Adult↗

PubMed1992

Effects of the interaction between ferric iron and L-dopa melanin on T1 and T2 relaxation times determined by magnetic resonance imaging.

T1 and T2 relaxation times of agar phantoms containing L-dopa melanin and Fe3+ were measured under MRI conditions. Fe3+ shortened T1 and T2 relaxation times. Melanin influenced relaxation times only in the presence of Fe3+; thus, contrast in MR images of the basal ganglia may depend upon levels of both paramagnetic iron and neuromelanin.

Basal Ganglia↗

PubMed1992

Thyroid stimulating hormone and prolactin responses to thyrotropin releasing hormone in nondepressed alcoholic inpatients.

Thyroid stimulating hormone (TSH) and prolactin (PRL) responses to thyrotropin releasing hormone (TRH) stimulation are sometimes blunted in alcoholic subjects; however, the mechanisms involved in these phenomena have not been established. We hypothesized that elevations in free thyroid concentrations might be related to these abnormal responses and then tested that hypothesis in a sample of nondepressed alcoholic inpatients (n = 21). Four alcoholic patients had delta max TSH responses that were < 7 mIU/l; three had PRL responses at or below 8 micrograms/l. Baseline TSH was the only significant predictor of peak TSH; however, free thyroxine (FT4) and baseline TSH both were significant predictors of peak PRL. The average baseline FT4 concentration in alcoholic patients was significantly higher than that in healthy control subjects (n = 10). Our data, thus, suggest that small elevations of FT4 play a role in the inhibition of TSH and PRL responses to TRH among nondepressed, abstinent alcoholic patients.

Adult↗

PubMed1991

Multidimensionality and state dependency of alexithymia in recently sober alcoholics.

In this study, we a) examined the appropriateness of using a single global score to represent alexithymia and b) constructed a model to examine the relationship between alexithymia and depression in recently sober alcoholics applying for inpatient care. To measure alexithymia, we used the Toronto Alexithymia Scale (TAS); to measure depression, we used the revised Beck Depression Inventory (BDI). Factor analyses identified three alexithymia factors (Feelings, Daydreaming, and External Thinking) and two depression factors (Somatic-Performance and Cognitive-Affective). The three TAS factors were not positively related to each other; the two BDI factors were. We used LISREL software to examine the relationships between the TAS factors and the BDI factors. The only two significant unidirectional coefficients were between the TAS-Feelings factor and the two BDI factors. Our results suggest that in recently sober alcoholics, alexithymia, as measured by the TAS, consists of three independent, unrelated dimensions. Moreover, only the dimension associated with an inability to identify feelings and to distinguish them from bodily sensations is related to depressive symptoms. To determine whether this alexithymia feelings dimension actually is dependent on situational depression and/or anxiety will require confirmation in additional samples, such as primary alexithymics and patients with major depressive disorders.

Adult↗

PubMed1990

ABO blood group differences in bone mineral density of recovering alcoholic males.

Since ABO blood group differences are associated with varying responses to many diseases, ABO blood type and bone density were studied in 39 recovering male alcoholics, comparing those with blood type O and non-O. The type O subjects had significantly higher bone densities as measured by quantitative computed tomography of the vertebrae than the non-O subjects (175.4 +/- 8.5 and 140.7 +/- 7.6, respectively, p = 0.004). There were no differences in age and indices of their alcoholism. Using multiple stepwise regression analysis, neither race nor maximal amount of alcohol consumed appeared to contribute to the differences in bone density. Only age, number of years of regular alcohol use and ABO blood type were determinants of the bone density differences. The ABO blood type contributed 20.3% to the differences in bone density (p = 0.001). The patients with non-O blood type lost a significant amount of bone with advancing age (r = -0.76, p = 0.0001) while those with blood type O did not (r = -0.37, p = 0.11). We conclude that, although alcoholism is a factor in the development of osteopenia, in males the ABO blood group status plays a significant role in the maximal mineralization of the skeleton and the amount of bone resorption during ageing, independent of alcohol abuse.

ABO Blood-Group System↗

PubMed1988

The relationship between alexithymia and depressive symptoms in a sample of newly abstinent alcoholic inpatients.

The purpose of this investigation was to measure alexithymia in 90 newly abstinent alcoholism treatment candidates and to examine the relationship between alexithymia and depressive symptoms. Subjects completed the Schalling-Sifneos Personality Scale (SSPS) and the Beck Depression Inventory (BDI) at the time of application for care. The correlation between subjects' SSPS scores and their BDI scores was statistically significant (r = -0.398; p less than 0.001). Study participants with high BDI scores tended to be 'more alexithymic' than were those with low BDI scores. The authors conclude that alexithymia may serve as a defensive operation for alcoholic patients denying painful affect.

Adult↗

PubMed1988

Validation of the Toronto Alexithymia Scale with substance abusers.

The purposes of this paper were to complete factor and item analyses of the Toronto Alexithymia Scale (TAS) in a sample of mixed substance abusers and to examine the correlations between patients' TAS scores and other variables. Results indicate that the TAS is a reliable, valid measure of alexithymia for substance abusers. The factor structure we found is congruent with the theoretical construct and is similar to those published in the normative studies; coefficient alpha reliability was 0.68. Additionally, a high percentage of the subjects (50.4%) scored in the alexithymic range while 24% had scores in the nonalexithymic range. Patients' TAS scores were positively associated with Beck Depression Inventory scores, with a reported paternal history of alcoholism, and with attempted suicide; TAS scores were negatively associated with being Black.

Adult↗

PubMed1988

Alexithymia: subscales and relationship to depression.

The purpose of this study was to determine the extent to which Toronto Alexithymia Scale (TAS) scores and derived subscale scores changed in a sample of newly abstinent alcoholic inpatients. Subjects completed the TAS and the Beck Depression Inventory (BDI) on the date of their application for care (Time 1) and at the end of their 3rd week in treatment (Time 2). Patients' mean BDI scores dropped significantly from Time 1 to Time 2; however, the expected concomitant drop in mean TAS scores did not occur. TAS subscales analysis suggests that the subscale associated with the ability to identify one's feelings and to distinguish them from bodily sensations may capture the alexithymia construct better by itself than when combined with the second 2 subscales, daydreaming and external thinking, to create the total TAS score.

Adult↗

PubMed1987

Prostaglandin synthesis among alcoholic suicide attempters and nonattempters.

Serum PGF2 alpha titers were examined in 8 sober alcoholic males who had attempted suicide and 19 nonattempting alcoholic males. Two of the 8 attempters had used violent means and the remaining 6 had used nonviolent means. The suicide attempters had significantly lower PGF2 alpha titers, relative to the nonattempters (p less than 0.005), with the violent attempters expressing maximally reduced titers. There were no significant differences between the groups with respect to age, alcohol consumption patterns, or admission scores on the Beck Depression Inventory.

Adult↗

PubMed1987

Depressive symptoms and persistence in treatment for alcohol dependence.

The relationship between alcoholics' depressive symptoms during their preadmission evaluations and persistence in treatment for alcohol dependence is evaluated. Hierarchical multiple regression was used to determine the contribution of Beck Depression Inventory (BDI) scores to the prediction of the criterion: number of continuous days in treatment (up to 120). After several sources of variance were removed (age, race, age X race interaction, number of previous treatments and referral source), BDI score explained 10.8% of the criterion's variance. The full model explained 28.2%. Early withdrawal occurred in association with freedom from measurable affective distress during preadmission evaluation. A model for the prediction of number of continuous days in treatment is presented.

Adult↗

PubMed1987

Prostaglandin synthesis and response to alcoholism treatment.

Serum prostaglandin F2 (PGF2) was assayed in 27 alcoholic patients and in 18 control subjects. No significant difference was observed in mean basal PGF2 titers of patients and controls. However, patients who completed four months of alcoholism treatment had a mean titer that was significantly higher than that of treatment dropouts. Patients who maintained continuous abstinence for 2 years following treatment had a mean titer that was significantly higher than that of patients who returned to pre-treatment drinking levels.

Adult↗

PubMed1983

Circannual changes in immune function.

Adrenocortical activity varies on a circannual basis with increased secretion in the winter and decreased secretion in the summer. One consequence of this variation is a circannual pattern in immune function. Adrenal corticosteroids, especially glucocorticoids, depress cellular immune function and seem to be more effective against T-suppressor cells. Thus, when adrenocortical activity is elevated, T-cell activity is depressed and B-cell activity is elevated. To the extent that T-cell "surveillance" is depressed in winter, there should be increased lymphoproliferative cancer risk during winter and in regions characterized by cold climates. This article presents data which suggest: (1) a winter, adrenal-corticoid induced, depression of T-cell function which is accompanied by elevated B-cell function; (2) elevated serum immunoglobulin levels in the winter; and (3) an inverse relationship between ambient temperature and serum immunoglobulin levels. The circannual pattern in immune function could help explain increased lymphoproliferative cancer risk, as a side effect of immunosuppression therapy during organ transplants, and as a function of latitude.

Adrenal Cortex Hormones↗

PubMed1983

Schizophrenia in Palau: a descriptive study.

The authors systematically studies 35 Palauan schizophrenic patients. Although these Western Pacific people demonstrated many of the usual features of schizophrenia, the sample showed an unusual 4:1 male predominance, a proclivity toward violence and substantial affective symptomatology. Male patients extensively abused alcohol and cannabis. The authors postulate that toxic, social change and cultural factors interact in Palau to place men at increased risk for schizophrenia.

Adult↗

PubMed1982

Male predominance among Palauan schizophrenics.

Data gathered in a three-month field study of known schizophrenics in the Palau Islands reveal a 4:1 ratio of males versus females. It si postulated that relatively rapid sociocultural changes over the last two decades have loosened traditional external restraints on behaviour, destabilised male role and gender identities, and created an environment which has been particularly schizophrenogenic for males. Statistical analysis of the age distribution of the schizophrenics is used to support the hypothesis. Evidence is also presented indicating that the gender distribution is not artifactual.

Acculturation↗

PubMedDate not supplied

Shared neuroendocrine patterns of post-traumatic stress disorder and alexithymia.

High norepinephrine/cortisol ratios have been shown to be useful indicators of post-traumatic stress disorder (PTSD). Alexithymia can result from overwhelming stress; thus, we hypothesized that sympathetic-adrenal medullary/hypothalamic-pituitary adrenal ratios would be positively associated with alexithymia severity. In the present study, we correlated 3-methoxy-4-hydroxyphenylethylene glycol (MHPG)/adrenocorticotropic hormone (ACTH) and MHPG/cortisol ratios with self-report Toronto Alexithymia Scale (TAS) scores in a group (n = 17) of nondepressed, formerly alcohol-dependent men. The correlations between the respective ratios and TAS scores were 0.515 (p = 0.034) and 0.561 (p = 0.019). We suggest that increasing degrees of alexithymia are accompanied by an increasing separation of these two endocrine systems and then speculate that this dissociation has an anatomical basis in the lateralization of emotions.

Adrenocorticotropic Hormone↗