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Abstract: Background: The processing of aversive stimuli in patients with major depression is associated with increased neural activity in limbic areas while the activity in cortical regulatory regions is diminished. The aim of the present study was to examine whether related neural abnormalities might be present in young people at increased familial risk of depression but with no personal history of illness. Methods: We used a block designed functional magnetic resonance imaging to measure the neural responses to a task involving the matching of emotional facial expressions in 29 young people (age16–21years) who had a biological parent with a history of major depression, and 30 age- and gender-matched controls. Results: Relative to the controls, the participants with increased familial risk of depression (FH) had diminished responses in left dorsolateral prefrontal cortex (DLPFC) to the presentation of fearful faces while the activity in the amygdala did not distinguish the groups. Limitations: FH participants had more depressive symptomatology than the controls. Their FH status was based on self-report. Conclusions: Young people at increased familial risk of depression show evidence of decreased cortical regulation of aversive stimuli. Further studies will be needed to ascertain if this abnormality might predispose to the eventual development of clinical depression. [Copyright &y& Elsevier]

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: We previously found that children of parents with depression showed impaired performance on a task of emotional categorisation.Aims: To test the hypothesis that children of parents with depression would show abnormal neural responses in the anterior cingulate cortex, a brain region involved in the integration of emotional and cognitive information.Method: Eighteen young people (mean age 19.8 years) with no personal history of depression but with a biological parent with a history of major depression (FH+ participants) and 16 controls (mean age 19.9 years) underwent functional magnetic resonance imaging while completing an emotional counting Stroop task.Results: Controls showed significant activation in the pregenual anterior cingulate cortex to both positive and negative words during the emotional Stroop task. This activation was absent in FH+ participants.Conclusions: Our findings show that people at increased familial risk of depression demonstrate impaired modulation of the anterior cingulate cortex in response to emotionally valenced stimuli. [ABSTRACT FROM AUTHOR]

Objective: Cortisol hypersecretion is one of the most reliable biological abnormalities in major depression, but it is uncertain if it represents an illness marker or a trait vulnerability to mood disorder. The present study sought to answer this question by measuring waking salivary cortisol levels in young people at familial risk of depression but with no personal history of mood disorder. Method: The authors studied 49 young people who had not been depressed themselves but who had a parent with a history of major depression (FH+) and a comparison group of 55 participants who had no personal history of depression and no reported depression in a first-degree relative. The authors measured the amount of cortisol secreted in saliva during the first 30 minutes after awakening on a workday and on a nonworkday. Results: The amount of cortisol secreted by the FH+ subjects was greater than that of the comparison subjects n both work- days (mean=698 nmolxminutes/liter, SD= 243, versus mean=550, SD=225) and non-workdays (mean=633 nmolxminutes/liter, SD=216, versus mean=492, SD=166). The increase in cortisol secretion was not accounted for by differences in parental attachment, life events, personality, or current mental state. Conclusions: Hypersecretion of cortisol can be detected in asymptomatic individuals at genetic risk of depression and may represent an illness endophenotype. Further studies will be needed to find out if increased waking salivary cortisol levels can predict individual risk of illness and whether the increased cortisol secretion has implications for general health and cognitive function. [ABSTRACT FROM AUTHOR]

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]