Biomedical subjects

David Bakish

Publications and source records attributed to David Bakish.

5 recordsLinked to original sources

PubMed2002

High activity-related allele of MAO-A gene associated with depressed suicide in males.

Abnormalities in brain monoamine oxidase A activity have been implicated in the pathogenesis of depressive illness and suicidal behavior. The present investigation was to determine whether there is an association between MAO-A gene polymorphism and depressed suicide. The EcoRV polymorphism in MAO-A gene with alleles associated with enzyme activity was studied in postmortem brain samples from 44 depressed suicide victims and 92 control subjects of the same ethnic background. We have found significant differences in genotype/allele distribution between depressed suicide victims and controls in males (p = 0.012) but not in females or the total sample. The odds ratio (OR) for the high activity-related allele of the MAO-A gene associated with depressed suicide in males was 3.1. Our finding suggests that MAO-A may be a susceptibility gene in depressed male suicide victims. The results thus provide further evidence that genetic factors can modulate risk for depression, suicide or both by influencing monoaminergic activity in sexually dimorphic manner.

Adult↗

PubMed2002

Does fluoxetine influence major depression by modifying five-factor personality traits?

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of depression, though response to them is difficult to predict. The aims of this study were two-fold: (1) to determine the differences in personality profile between patients with major depression and healthy control subjects and (2) to assess the effect of treatment with fluoxetine on personality domain scores and determine whether any of the personality traits can predict the outcome of antidepressant treatment. METHODS: The study included 53 patients with major depression and 53 healthy controls. The NEO-Five-Factor Inventory (NEO-FFI) was administered to all subjects before and after 24 weeks of treatment with fluoxetine. RESULTS: The patients in an episode of major depression had a significantly different personality profile compared to healthy controls at baseline and the severity of their illness correlated with higher scores in the Neuroticism domain. Treatment with fluoxetine was associated with a reversal of high Neuroticism scores and low Extraversion scores in the whole sample and in a subgroup of responders but not in non-responders. Among the FFI personality domains, Agreeableness was a better predictor of treatment outcome than baseline HAMD-17 scores. LIMITATIONS: There was no placebo group, which would have permitted the evaluation of the effect of non-drug factors in treatment outcome and changes in personality domain scores. The sample size was only moderate. CONCLUSIONS: The results suggest that (a) significant differences exist between the personality profiles of depressed patients and healthy control subjects and (b) responders to treatment with fluoxetine show significant changes in personality profile. These changes may be attributed to improvement of depressive symptoms.

Adult↗

PubMed2002

Assessing full remission.

The 17-item Hamilton Rating Scale for Depression (HAM-D17) has been used for 4 decades as the "gold standard" instrument to assess the severity of depression and response to therapy in clinical research. The clinical utility of the HAM-D17 is hampered, in part, by the length of time required to administer the interview and by concern about a lack of inter-rater reliability. Several groups have developed shorter versions of the HAM-D17 for use in clinical practice. However, despite extensive research highlighting the importance of achieving full remission in minimizing the risk of relapse and recurrence, these shortened questionnaires have not been validated for the task of distinguishing between remission and response. A shortened form of the HAM-D17 with cut-off scores for full remission would offer a useful tool that physicians could readily employ in clinical practice. On the basis of the responses of a sample of 292 patients with major depression who received standard clinical treatment at a tertiary university affiliated hospital (Depression Clinic, Centre for Addiction and Mental Health, Toronto Ont.) we derived a shortened version of the HAM-D. Seven items with the greatest frequency of occurrence and sensitivity to change with treatment were identified and designated as the Toronto HAM-D7. A score of 3 or less on the Toronto HAM-D7 was found to correlate with the 17-item HAM-D definition of full remission (i.e., score of 7 or less).

Adult↗

PubMed2002

The neurobiology of treatment response to antidepressants and mood stabilizing medications.

As the neurobiology of mood disorders and the mechanisms of action of antidepressant drugs continue to be elucidated, there has been a shift in emphasis from changes in neurotransmitter release and metabolism to regulation of gene expression and neuroprotection. Evidence from animal studies suggests that drug therapy may act on specific transcription factors and target genes that regulate processes such as neuroprotection and neuronal survival. Clinical studies consistently identify changes in prefrontal cortex, hippocampus and amygdala that may be related to the course of illness and may be prevented with successful treatment. Together, these findings suggest that clinically relevant neurobiological correlations may ultimately be identified in patients who respond and remit to treatment. With these and future advances in the neuroscience of psychiatry, it may be possible to identify biological markers that will help in decisions about specific treatments for an individual patient.

Adenylyl Cyclases↗

PubMed2000

Tryptophan hydroxylase gene 218A/C polymorphism is not associated with depressed suicide.

Abnormalities in functioning of the central serotonergic system are believed to be involved in the pathogenesis of depressive illness and suicidal behaviour. Recently, polymorphism in the tryptophan hydroxylase (TPH) gene has been studied for association with aggression, anger-related traits and suicidal behaviour, but the results are inconclusive. The present investigation was to determine whether there are differences in genotype and allele distribution of the TPH gene 218A/C polymorphism in post-mortem brain samples from 35 depressed suicide victims and 84 control subjects of the same ethnic background. A functional polymorphism in the promoter region of 5-HT transporter gene was also re-examined in this increased sample size. No significant difference in TPH gene 218A/C polymorphism between controls and depressed suicide victims was detected. This may suggest that the TPH gene has no significant effect on suicidality in depressed subjects. In a previous study on a smaller sample we found the frequency of the long allele of 5-HT transporter gene to be higher in depressed suicide victims. In this increased sample size, both the genotype and alleles of the 5-HT transporter gene were significantly associated with completed suicide. The frequency of the L/L genotype in depressed suicide victims was almost double of that found in control group (48.6 vs. 26.2%). The odds ratio for the L allele associated with depressed suicide was 2.1 (95% CI, 1.2-3.7). The relatively small sample size does not exclude the possibility of false-positive results and the finding needs replication.

Journal Article↗