Search

Byline: Marcus R. Munafo (Department of Experimental Psychology, University of Bristol, Bristol, UK, marcus.munafo@bristol.ac.uk); Zola N. Mannie (Department of Psychiatry, University of Oxford, Oxford, UK); Philip J. Cowen (Department of [...]

Using proton magnetic resonance spectroscopy (MRS), we have demonstrated regional abnormalities in cortical γ-aminobutyric acid (GABA) and glutamate in medication-free recovered depressed patients. It is unclear whether these changes represent an underlying trait vulnerability to depression, or an after-effect of episodes of illness or its treatment. We sought to examine this question by examining a group of high-risk, never-depressed, individuals. We used MRS to measure GABA and glutamate in parieto-occipital cortex in young people (ages 16–21 yr) with a family history of parental depression (n=24) but no personal history of illness and a control group without a history of depression in any first-degree relative (n=28). Participants with a parental history of depression had significantly higher levels of glutamate than controls in parieto-occipital cortex (F1,47=5.5, p=0.02). These findings suggest that abnormalities in glutamate neurotransmission may reflect a trait marker of vulnerability to depression. [ABSTRACT FROM AUTHOR]

Background: Patients with depression show abnormalities in the neural circuitry supporting working memory. These abnormalities apparently persist into clinical remission, raising the possibility that they might be trait markers indicating vulnerability to depression. Methods: We studied 17 young people who had a depressed parent but no personal history of depressive illness (FH) and 15 healthy control subjects with no family history of depression. Participants performed a verbal working memory task of varying cognitive load (n-back) while undergoing functional magnetic resonance imaging scanning. We used multiple regression analyses to assess overall capacity (1-, 2-, 3-back vs. 0-back) as well as linear and quadratic modulation of cognitive demand. Results: Performance accuracy and response latency did not differ between groups, and overall capacity was similar. However, for both linear and quadratic load response activity, FH participants showed greater activation in lateral occipital cortex, superior temporal cortex, and superior parietal cortex. Conclusions: Our data suggest that, as in depressed patients, maintenance of task performance in FH participants is associated with a significant increase in the load-response activity of the cortical regions involved in working memory. This neural abnormality could form part of the predisposition to develop depressive disorders. [Copyright &y& Elsevier]

The role of dopamine (DA) pathways in the pathophysiology of depressive disorder is poorly understood. However, because DA plays a key role in motivational behavior, it is important to study in a disorder characterized by anhedonia, lack of energy and psychomotor retardation. A recently developed dietary manipulation (`tyrosine (TYR) depletion') offers a novel method to assess the role of DA in major depression. We studied 1.5 euthymic women with a past history of recurrent depression, who received a 74 g amino-acid drink lacking TYR and phenylalanine (PHE) (TYR-free) and a balanced (BAL) amino acid drink on two separate occasions in a double-blind, random-order, crossover design. Plasma prolactin levels rose following the TYR-free drink relative to the balanced mixture, while performance on a spatial recognition memory task was impaired. However, relative to the BAL drink, the TYR-free drink did not lower objective or subjective measures of mood. We conclude that as in healthy volunteers, TYR depletion in euthymic subjects, with a past history of major depression, attenuated DA function, as reflected in increased plasma prolactin levels and decreased spatial memory performance. However ratings of depression were unaffected, suggesting that disruption of dopaminergic function by this manipulation does not induce a lowering of mood in individuals vulnerable to depression. [ABSTRACT FROM AUTHOR]