Abstract
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. 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. 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. 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.
Highlights
Abnormalities in the function and structure of the hippocampus are often described in patients with major depression
It has been suggested that loss of hippocampal volume in depression might be associated with increased glutamate activity (MacQueen & Frodl, 2011) and in a previous study we found that young people at increased familial risk of depression showed increased cortical levels of glutamate relative to controls (Taylor et al 2011)
No group-related differences were observed for memory recognition performance or reaction times, both of which were recorded after functional magnetic resonance imaging (fMRI) task-related acquisition (Supplementary Table S1)
Summary
Abnormalities in the function and structure of the hippocampus are often described in patients with major depression. Consistent with this, meta-analyses have consistently shown small but significant reductions in hippocampal volume in depressed patients (Campbell et al 2004; Kempton et al 2011). How far these volume reductions are linked to severe and recurrent illness is controversial (Moylan et al 2013). Major depression is associated with abnormalities in the function and structure of the hippocampus It is unclear whether these abnormalities might be present in people ‘at risk’ of illness
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