Biomedical subjects

John J Mann

Publications and source records attributed to John J Mann.

4 recordsLinked to original sources

PubMed2006

Sex differences in the familial transmission of mood disorders.

BACKGROUND: Mood disorders exhibit familial transmission due to both environmental and genetic risk factors. Mood disorders are more common in women, yet the role of gender in the familial transmission of mood disorders is unclear. This study examines rates of mood disorder transmission to offspring based on the sex of affected parent, sex of offspring and role of clinical factors, such as childhood abuse history, comorbid psychiatric disorders, and traits of aggression and impulsivity. METHODS: Risk of transmission of mood disorder to offspring from females and males was compared in a sample of 272 probands with a major mood disorder using generalized estimating equations (GEE). Demographic and clinical characteristics of all male and female probands were compared. Characteristics that differed in probands were entered into the model to obtain an unbiased test of gender differences in transmission rate. Multivariate GEE models, one for male probands and one for female probands, were used to test for risk factors in transmission of mood disorder. RESULTS: Familial transmission rate of mood disorders from female probands was almost double that of males. There was no difference in transmission to male or female offspring. For male probands, offspring mood disorder was independently associated with earlier age of proband mood disorder onset, greater number of proband years ill, and proband history of childhood abuse. For female probands, offspring mood disorder was associated with higher aggression scores in probands. LIMITATIONS: We did not directly interview offspring and also had limited data on psychopathology in co-parents. This is a cross-sectional study and cannot account for emergence of illness in offspring in the future. CONCLUSIONS: The two-fold higher rate of maternal transmission of mood disorder may reflect differences in regulation of maternal and paternal transmission of mood disorder. Future studies need to determine the relative contribution of genetic and non-genetic factors and identify the factors responsible for higher rates of transmission of mood disorders by females with a mood disorder.

Adult↗

PubMed2004

Immobilization stress elevates tryptophan hydroxylase mRNA and protein in the rat raphe nuclei.

BACKGROUND: Stress triggers adaptive and maladaptive changes in the central nervous system, including activation of the hypothalamic-pituitary-adrenal axis, and can trigger mood disorders and posttraumatic stress disorder. We examined the effect of immobilization stress (IMO) on gene expression of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, and the role of cortisol in that response. METHODS: Regular and adrenalectomized Sprague-Dawley rats were exposed to various repetitions of IMO. Tryptophan hydroxylase messenger ribonucleic acid (mRNA) was determined by competitive reverse transcriptase polymerase chain reaction, and TPH protein was examined by immunoblot and immunocytochemistry. RESULTS: Elevation of TPH mRNA by IMO was tissue-specific and dose-dependent. A single IMO elicited a threefold rise in TPH mRNA in median raphe nucleus (MRN), but repeated (3x) IMOs were needed for similar response in dorsal raphe nucleus (DRN). Repeated daily IMO, up to 7 days, triggered a robust induction (6-10-fold) in TPH mRNA, accompanied by corresponding rise in TPH protein levels in raphe nuclei but not in the pineal gland. The rise in TPH immunoreactivity was widespread throughout the DRN and MRN. Bilateral adrenalectomy did not prevent the IMO-triggered increase in TPH immunoreactive protein in the raphe nuclei. CONCLUSIONS: This study reveals adrenal glucocorticoid-independent induction of TPH gene expression in raphe nuclei in response to immobilization stress.

Animals↗

PubMed2004

Using the gene ontology for microarray data mining: a comparison of methods and application to age effects in human prefrontal cortex.

One of the challenges in the analysis of gene expression data is placing the results in the context of other data available about genes and their relationships to each other. Here, we approach this problem in the study of gene expression changes associated with age in two areas of the human prefrontal cortex, comparing two computational methods. The first method, "overrepresentation analysis" (ORA), is based on statistically evaluating the fraction of genes in a particular gene ontology class found among the set of genes showing age-related changes in expression. The second method, "functional class scoring" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step. We find that FCS yields more consistent results than ORA, and the results of ORA depended strongly on the gene selection threshold. Our findings highlight the utility of functional class scoring for the analysis of complex expression data sets and emphasize the advantage of considering all available genomic information rather than sets of genes that pass a predetermined "threshold of significance."

Adolescent↗

PubMed2002

A randomized comparison of high-charge right unilateral electroconvulsive therapy and bilateral electroconvulsive therapy in older depressed patients who failed to respond to 5 to 8 moderate-charge right unilateral treatments.

BACKGROUND: Electroconvulsive therapy (ECT) is the treatment of choice in some older patients with severe depression. When compared with younger depressed patients, older patients have been shown to be as likely to respond to ECT but more likely to develop cognitive impairment. This study addresses whether adults aged 50 years and over who have already failed to respond to at least 5 moderate-charge right unilateral (RUL) ECT treatments (150% above seizure threshold) are more likely to benefit from a switch to high-charge RUL ECT (450% above threshold) or to bilateral (BL) ECT. METHOD: Twenty-four patients who were treated with 5 to 8 moderate-charge RUL ECT treatments and who failed to improve sufficiently were randomly assigned to receive either BL ECT (N = 11) or high-charge RUL ECT (N = 13). Depressive (24-item Hamilton Rating Scale for Depression) and cognitive scores (Mini-Mental State Examination [MMSE]) were compared under double-blind conditions at 3 phases of treatment. RESULTS: Patients in the BL ECT group exhibited significantly greater cognitive impairment (mean MMSE score decrease of 1.13) than those receiving high-charge RUL ECT (mean MMSE increase of 1.71). There were no statistically significant differences in clinical response to BL or high-charge RUL ECT (63.6% and 61.5%, respectively) or in depressive symptom remission (18.1% and 46.2%). CONCLUSION: These results suggest that older patients who fail to respond to moderate-charge RUL ECT may benefit from a switch to high-charge RUL ECT rather than BL ECT. Larger future studies will be needed to compare clinical response in patients switched from moderate-dose RUL ECT to higher-dose RUL or to BL ECT.

Aged↗