Brodnik Z.,Psychiatry Service 116A |
Bongiovanni R.,Psychiatry Service 116A |
Double M.,Psychiatry Service 116A |
Jaskiw G.E.,Psychiatry Service 116A |
Jaskiw G.E.,Case Western Reserve University
Neurochemistry International | Year: 2012
Tyrosine hydroxylation is considered to be the rate-limiting step in catecholamine synthesis. It is also assumed that under usual conditions, tyrosine 3-monooxygenase (EC 18.104.22.168) (tyrosine hydroxylase - TH) is close to full saturation with its l-tyrosine substrate and hence that raising the availability of l-tyrosine does not substantially increase 3,4- dihydroxyphenylalanine (DOPA) synthesis. We evaluated this in vivo by reverse dialysis of the aromatic-l-amino-acid decarboxylase (EC 22.214.171.124) inhibitor NSD-1015 (20 μM) and selected concentrations of l- or d-tyrosine. In striatum, extracellular DOPA levels increased linearly (maximum 250% control) as l-tyrosine concentrations were raised from 0-1000 μM. In medial prefrontal cortex, DOPA levels reached a maximum (300% control) at l-tyrosine 62.5-125 μM but still remained significantly elevated (200% control) at higher l-tyrosine concentrations (250-500 μM). At the l-tyrosine concentrations tested, DOPA levels were never below those of controls. d-tyrosine (62.5 μM) did not affect DOPA levels. The degree to which the elevation of DOPA levels represents a net increase in tyrosine hydroxylation as opposed to heteroexchange of l-TYR for intracellular DOPA remains to be determined. However, one interpretation of the data is that under usual in vivo conditions brain TH may not be near full saturation with l-tyrosine and that mechanisms other than tyrosine hydroxylation may be more important in the acute regulation of brain catecholamine synthesis than previously appreciated. This would have implications for the pathophysiology and treatment of neuropsychiatric conditions in which dysregulation of DA transmission and l-tyrosine transport have been implicated. © 2012 Elsevier Ltd. All rights reserved.
PubMed | Psychiatry Service 116A
Type: Journal Article | Journal: Suicide & life-threatening behavior | Year: 2010
In order to examine risk factors for attempting suicide in heroin dependent patients, a group of 527 abstinent opiate dependent patients had a psychiatric interview and completed the Childhood Trauma Questionnaire. Patients who had or had never attempted suicide were compared on putative suicide risk factors. It was found that 207 of the 527 heroin abusers (39.3%) had attempted suicide. Attempters were younger; more were female, reported childhood trauma, a family history of suicidal behavior, a history of aggression, treatment with antidepressant medication, and alcohol and cocaine dependence. Logistic regression revealed that a family history of suicidal behavior, alcohol dependence, cocaine dependence, and treatment with antidepressant medication were significant predictors of attempting suicide. These results suggest that attempting suicide is common among opiate dependent patients and that both distal and proximal risk factors may play a role.
PubMed | Psychiatry Service 116A
Type: Journal Article | Journal: The Journal of clinical psychiatry | Year: 2011
To examine the relationship of childhood trauma to depressive symptoms in type 1 diabetes, a chronic disease in which the frequency of depression is increased.One hundred fifty African American patients with type 1 diabetes seen between August 1993 and January 1998 completed the Beck Depression Inventory and Childhood Trauma Questionnaire. They were also genotyped for a functional serotonin transporter promoter polymorphism (5-HTTLPR) that modulates resiliency. Patients who had Beck Depression Inventory scores above and below 14 were compared.Diabetic patients who had Beck Depression Inventory scores 14 had experienced significantly more different types of childhood trauma than those with Beck Depression Inventory scores < 14 (P < .001), independent of potential interaction with 5-HTTLPR genotype.Childhood trauma appears to be a determinant of depressive symptoms in type 1 diabetes, independently of genotype of a functional locus modulating resiliency.