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Biomedical subjects

D Dowlatshahi

Publications and source records attributed to D Dowlatshahi.

8 recordsLinked to original sources

Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication.

BACKGROUND: The cAMP signaling pathway, and its downstream neurotrophic factor BDNF, are major targets of antidepressant medications. Abnormalities in this pathway have previously been reported in postmortem brain of subjects with mood disorders. This study was designed to test whether the diagnosis of a mood disorder, or treatment with an antidepressant or mood stabilizer was associated with changes in hippocampal BDNF in postmortem brain. METHODS: Frozen postmortem anterior hippocampus sections were obtained from the Stanley Foundation Neuropathology Consortium. Tissue from subjects with major depression, bipolar disorder, schizophrenia and nonpsychiatric control subjects were stained for BDNF using immunohistochemistry. RESULTS: Increased BDNF expression was found in dentate gyrus, hilus and supragranular regions in subjects treated with antidepressant medications at the time of death, compared with antidepressant-untreated subjects. Furthermore, there was a trend toward increased BDNF expression in hilar and supragranular regions in depressed subjects treated with antidepressants, compared with the subjects not on these medications at the time of death. CONCLUSIONS: These findings are consistent with recent studies measuring CREB levels in this same subject sample, and support current animal and cellular models of antidepressant function.

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Abnormalities in the cAMP signaling pathway in post-mortem brain tissue from the Stanley Neuropathology Consortium.

There is an established relationship between the monoaminergic neurotransmitter system and mood disorders. In an attempt to define further the pathophysiology of mood disorders, research is focussing on intracellular second messenger systems, including cyclic adenosine 3',5'-monophosphate (cAMP) and the polyphosphoinositol generated second messengers. The availability of tissue from the Stanley Foundation Neuropathology Consortium has offered us the opportunity to make a number of observations with respect to these second messenger systems in tissue from patients with major depressive disorder and bipolar affective disorder. There is evidence that antidepressants stimulate components of the cAMP pathway in patients with depression while mood stabilizers blunt the same pathway in patients with bipolar disorder. Furthermore, downstream targets of this pathway appear to be altered in patients with mood disorders. The relations between changes in second messenger systems, gene transcription, and clinical effects of current therapeutic regimens has implications for development of novel treatments of mood disorders.

Adenylyl Cyclases↗

Increased hippocampal supragranular Timm staining in subjects with bipolar disorder.

Biochemical and structural abnormalities have been reported in hippocampus of subjects with mood disorders. This study examined the organization of mossy fibers in anterior hippocampus of subjects obtained from the Stanley Neuropathology Consortium. Frozen postmortem hippocampal sections from subjects with major depression, bipolar disorder, schizophrenia and non-psychiatric controls were stained using the Neo-Timm procedure, which selectively stains mossy fibers. Increased Timm staining in the supragranular layer was found in subjects with bipolar disorder relative to control subjects. These results are suggestive of neuronal sprouting in hippocampus of subjects with bipolar disorder. There were no significant associations between supragranular Timm staining and suicide, length illness or drug treatment at the time of death.

Adult↗

G Protein-coupled cyclic AMP signaling in postmortem brain of subjects with mood disorders: effects of diagnosis, suicide, and treatment at the time of death.

Components of cyclic AMP (cAMP) signaling were examined in postmortem cerebral cortex of a well characterized group of patients with mood disorders and nonpsychiatric control subjects. We measured G protein levels, adenylyl cyclase (AC) activity, and CREB levels in cerebral cortex of the subjects with respect to diagnosis, treatment, and suicide. There was no effect of diagnosis on any measure, except for a trend toward decreased stimulated AC activity in subjects with mood disorders relative to control subjects. We also detected a significant effect of suicide on temporal cortex CREB levels in subjects that died as a result of suicide relative to those that did not, which was more evident in patients with major depressive disorder. Bipolar disorder (BD) subjects treated with anticonvulsants at the time of death had decreased temporal cortex CREB levels relative to those not receiving anticonvulsants. Furthermore, we found a trend toward decreased occipital cortex G alpha(s) (short) levels in BD subjects treated with lithium. These results support the hypothesis of altered cAMP signaling in mood disorders and raise the possibility that factors other than diagnosis, such as treatment and suicide, may be relevant to cell-signaling abnormalities reported in the literature.

Adenylyl Cyclases↗

Life events and social stress in puerperal psychoses: absence of effect.

Thirty-three patients admitted to hospital with severe early onset puerperal psychiatric disorders were compared with matched normal puerperal controls. Interviews, which were administered after recovery, covered life events in the previous thirteen months and detailed assessment of previous and personal history, pregnancy and labour, other aspects of stress, social support, and marital relationships. No differences, except for previous history of psychiatric disorder, were found between patients and controls or between patients with depressive and with other diagnoses. These findings of absence of social stress contrast with previous studies of milder post-partum depression and of disorders with onset during pregnancy, and suggest that the aetiology of severe post-partum disorders is predominantly biological.

Adult↗

Computer based learning and assessment for diabetic patients.

A comparatively inexpensive microcomputer-based system of programmed diabetic instruction is described, matched to an interactive knowledge assessment questionnaire with or without prescriptive feedback. This provides an educational and assessment package for newly diagnosed and established diabetics, with additional analytical potential. The system is well accepted, demonstrates major areas of defective knowledge and allows cost-effective handling of large numbers of patients.

Computer-Assisted Instruction↗

Knowledge profile and control in diabetic patients.

Knowledge about diabetes was assessed using a previously described interactive computer-based questionnaire in 79 patients with insulin-dependent (IDDM) and 72 with non-insulin-dependent (NIDDM) diabetes mellitus routinely attending a single diabetic clinic. Simple linear correlation of total knowledge score with glycosylated haemoglobin (HbA1c) showed no significant relationship for either IDDM (r = 0.12: p = 0.18) or NIDDM (r = 0.15: p = 0.1). However, quintile grouping of knowledge scores showed the mean HbA1c to be significantly higher in the lowest scoring NIDDM quintile (10.6 +/- 0.5: +/- SE) with respect to the pooled mean of all the higher scoring quintiles (9.0 +/- 0.3) (p = 0.027). Mean HbA1c (9.6 +/- 0.5) was also higher in the least knowledgeable IDDM quintile than any other quintile group (range 8.8-9.0) but this was not significant with respect to the pooled mean of higher scoring patients (p greater than 0.1). The mean age of the lowest scoring IDDM quintile group (60.5 +/- 13.9 years) was significantly higher (p less than 0.01) than higher scoring IDDM groups (mean age range 36.5-43.3 years) but age was not significantly related to HbA1c in IDDM subjects. IDDM showed greater knowledge of diabetes than NIDDM but ignorance in key areas was unacceptably high in both diabetic subtypes, indicating that regular knowledge assessment and educational reinforcement may be essential for good diabetic control as well as patient safety, particularly in older IDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

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