Decision making in young people at familial risk of depression.

BACKGROUND: Major depression is associated with abnormalities in reward processing at neural and behavioural levels. Neural abnormalities in reward have been described in young people at familial risk of depression but behavioural changes in reward-based decision making have been less studied in this group. METHOD: We studied 63 young people (mean age 18.9 years) with a parent with a diagnosis of major depression but who had never been depressed themselves, that is with a positive family history of depression (the FH+ group). Participants performed the Cambridge Gambling Task (CGT), which provides several measures of decision making including deliberation time, quality of decision making, risk taking, risk adjustment and delay aversion. A control group of 49 age- and gender-matched young people with no history of mood disorder in a first-degree relative undertook the same task. RESULTS: Both FH+ participants and controls had low and equivalent scores on anxiety and depression self-rating scales. Compared to controls, the FH+ participants showed overall lower risk taking, although like controls they made more risky choices as the odds of a favourable outcome increased. No other measures of decision making differed between the two groups. CONCLUSIONS: Young people at increased familial risk of depression have altered risk taking that is not accounted for by current affective symptomatology. Lowered risk taking might represent an impairment in reward seeking, which is one of several changes in reward-based behaviours seen in acutely depressed patients; however, our findings suggest that decreased reward seeking could be part of a risk endophenotype for depression.

Structural and functional imaging of the hippocampus in young people at familial risk of depression.

BACKGROUND: Major depression is associated with abnormalities in the function and structure of the hippocampus. However, it is unclear whether these abnormalities might also be present in people 'at risk' of illness. METHOD: We studied 62 young people (mean age 18.8 years) at familial risk of depression (FH+) but who had never been depressed themselves. Participants underwent magnetic resonance imaging to assess hippocampal structure and neural responses to a task designed to activate hippocampal memory networks. Magnetic resonance spectroscopy was used to measure levels of a combination of glutamine and glutamate (Glx) in the right hippocampus. A total of 59 matched controls with no history of mood disorder in a first-degree relative underwent the same investigations. RESULTS: Hippocampal volume did not differ between FH+ participants and controls; however, relative to controls, during the memory task, FH+ participants showed increased activation in brain regions encompassing the insular cortices, putamen and pallidum as well as the dorsal anterior cingulate cortex (ACC). FH+ participants also had increased hippocampal levels of Glx. CONCLUSIONS: Euthymic individuals with a parental history of depression demonstrate increased activation of hippocampal-related neural networks during a memory task, particularly in brain regions involved in processing the salience of stimuli. Changes in the activity of the ACC replicate previous findings in FH+ participants using different psychological tasks; this suggests that task-related abnormalities in the ACC may be a marker of vulnerability to depression. Increased levels of Glx in the hippocampus might also represent a risk biomarker but follow-up studies will be required to test these various possibilities.

The effect of the serotonin transporter polymorphism (5-HTTLPR) on amygdala function: a meta-analysis.

The 5-HTTLPR polymorphism has been widely regarded as a potential genetic risk factor for affective disorders. Consistent with this, this polymorphism has been associated with altered amygdala responses at rest and in response to aversive stimuli. However, the strength of this association remains uncertain. We sought to synthesize existing data on the association between the 5-HTTLPR polymorphism and amygdala activation and ascertain the strength of evidence for this association. Meta-analytic techniques were applied to data from relevant published studies and unpublished data sets to obtain an estimate of the likely magnitude of effect of any association. The large number of studies allowed us to apply a formal test of publication bias, as well as explore the impact of various study-level characteristics on the magnitude of the observed effect size. Our meta-analysis indicated that there is a statistically significant but small effect of 5-HTTLPR on left and right amygdala activity. However, there was considerable between-study heterogeneity, which could not be fully accounted for by the study design and sample characteristics that we investigated. In addition, there was evidence of excess statistical significance among published studies. These findings indicate that the association between the 5-HTTLPR and amygdala activation is smaller than originally thought, and that the majority of previous studies have been considerably under powered to reliably demonstrate an effect of this size.

Memory impairment in young women at increased risk of depression: influence of cortisol and 5-HTT genotype.

BACKGROUND: Memory deficits are common in depressed patients and may persist after recovery. The aim of the present study was to determine whether memory impairments were present in young women at increased familial risk of depression and whether memory performance was related either to cortisol secretion or to allelic variation in the promoter region of the serotonin transporter gene (5-HTT). METHOD: Young women (n=35, age range 16-21 years) with no personal history of depression but with a depressed parent (FH+) carried out the Rey Auditory Verbal Learning Test (RAVLT). They also provided samples for the measurement of waking salivary cortisol and for 5-HTT genotyping. An age-matched control group of women (n=31) with no family history of depression were similarly studied. RESULTS: The FH+ participants had decreased immediate recall and recognition memory compared to controls. The impairment in recall, but not recognition, correlated negatively with increased cortisol secretion in FH+ subjects. There was no significant effect of 5-HTT allelic status on either memory or waking cortisol secretion. CONCLUSIONS: Impairments in declarative memory are present in young women at increased genetic risk of depression and may be partly related to increased cortisol secretion. Further studies are needed to explore the neural mechanisms underlying the memory impairments and whether they predict the development of clinical illness.