Patients with depression show abnormalities in the neural circuitry supporting working memory. However, it is unclear if these abnormalities are present in unmedicated remitted depressed patients. To address this question, the current study employed functional magnetic resonance imaging (fMRI), in combination with a simple verbal n-back task, in a cohort of unmedicated remitted depressed patients.

We studied 15 healthy control subjects (HC) and 15 unmedicated remitted depressed patients (rMDD). Participants performed a verbal working memory task of varying cognitive load (n-back) while undergoing fMRI. We used multiple regression analyses to assess overall capacity (1-, 2-, 3-back versus 0-back) as well as quadratic modulation of cognitive demand.

Performance accuracy and response latency did not differ between groups, and overall capacity was similar. However, rMDD showed a positive quadratic load response in the bilateral hippocampus; the converse was true for HC.

Our data suggest that remitted depression was associated with a perturbed pattern of activation in the bilateral hippocampus during a verbal working memory task. We propose that a reduced ability to dampen task-irrelevant activity may reflect a neurobiological risk factor for recurrent depression.

Short-term antidepressant administration has been reported to decrease amygdala response to threat in healthy volunteers and depressed patients. Neuroticism (N) is a risk factor for depression but has also been associated with slow or incomplete remission with antidepressant drug treatment. Our aim was to investigate early selective serotonin reuptake inhibitor (SSRI) administration neural effects on implicit processing of fearful facial expressions in volunteers with high levels of N.

Highly neurotic subjects received 20 mg/day citalopram versus placebo for 7 days in a double-blind, between-groups design. On the last day haemoperfusion and functional magnetic resonance imaging (fMRI) data during a gender discrimination task with fearful and happy faces were acquired. A control group of non-neurotic volunteers was also tested.

High-N volunteers had reduced responses to threatening facial expressions across key neural circuits compared to low-N volunteers. SSRI treatment was found to elevate resting perfusion in the right amygdala, increase bilateral amygdalae activation to positive and negative facial expressions and increase activation to fearful versus happy facial expressions in occipital, parietal, temporal and prefrontal cortical areas.

These results suggest that 7 days of SSRI administration can increase neural markers of fear reactivity in subjects at the high end of the N dimension and may be related to early increases in anxiety and agitation seen early in treatment. Such processes may be involved in the later therapeutic effects through decreased avoidance and increased learning about social ‘threat’ cues.

Antidepressant drugs such as selective serotonin re-uptake inhibitors (SSRIs) remediate negative biases in emotional processing in depressed patients in both behavioural and neural outcome measures. However, it is not clear if these effects occur before, or as a consequence of, changes in clinical state.

In the present study, we investigated the effects of short-term SSRI treatment in depressed patients on the neural response to fearful faces prior to clinical improvement in mood. Altogether, 42 unmedicated depressed patients received SSRI treatment (10 mg escitalopram daily) or placebo in a randomised, parallel-group design. The neural response to fearful and happy faces was measured on day 7 of treatment using functional magnetic resonance imaging. A group of healthy controls was imaged in the same way.

Amygdala responses to fearful facial expressions were significantly greater in depressed patients compared to healthy controls. However, this response was normalised in patients receiving 7 days treatment with escitalopram. There was no significant difference in clinical depression ratings at 7 days between the escitalopram and placebo-treated patients.

Our results suggest that short-term SSRI treatment in depressed patients remediates amygdala hyperactivity in response to negative emotional stimuli prior to clinical improvement in depressed mood. This supports the hypothesis that the clinical effects of antidepressant treatment may be mediated in part through early changes in emotional processing. Further studies will be needed to show if these early effects of antidepressant medication predict eventual clinical outcome.

Processing emotional facial expressions is of interest in eating disorders (EDs) as impairments in recognizing and understanding social cues might underlie the interpersonal difficulties experienced by these patients. Disgust and anger are of particular theoretical and clinical interest. The current study investigated the neural response to facial expressions of anger and disgust in bulimia nervosa (BN).

Participants were 12 medication-free women with BN in an acute episode (mean age 24 years), and 16 age-, gender- and IQ-matched healthy volunteers (HVs). Functional magnetic resonance imaging (fMRI) was used to examine neural responses to angry and disgusted facial expressions.

Compared with HVs, patients with BN had a decreased neural response in the precuneus to facial expressions of both anger and disgust and a decreased neural response to angry facial expressions in the right amygdala.

The neural response to emotional facial expressions in BN differs from that found in HVs. The precuneus response may be consistent with the application of mentalization theory to EDs, and the amygdala response with relevant ED theory. The findings are preliminary, but novel, and require replication in a larger sample.

Previous imaging studies have revealed that acute major depression is characterized by altered neural responses to negative emotional stimuli. Typically, responses in limbic regions such as the amygdala are increased while activity in cortical regulatory regions such as the dorsolateral prefrontal cortex (DLPFC) is diminished. Whether these changes persist in unmedicated recovered patients is unclear.

We used functional magnetic resonance imaging to examine neural responses to emotional faces in a facial expression-matching task in 16 unmedicated recovered depressed patients and 21 healthy controls.

Compared with controls, recovered depressed patients had increased responses bilaterally to fearful faces in the DLPFC and right caudate. Responses in the amygdala did not distinguish the groups.

Our findings indicate that clinical recovery from depression is associated with increased activity in the DLPFC to negative emotional stimuli. We suggest that this increase may reflect a compensatory cortical control mechanism with the effect of limiting emotional dysregulation in limbic regions such as the amygdala.

Selective serotonin reuptake inhibitors (SSRIs) are typically thought to have a delay of several weeks in the onset of their clinical effects. However, recent reports suggest they may have a much earlier therapeutic onset. A reduction in amygdala responsivity has been implicated in the therapeutic action of SSRIs.

To investigate the effect of a single dose of an SSRI on the amygdala response to emotional faces.

Twenty-six healthy volunteers were randomised to receive a single oral dose of citalopram (20 mg) or placebo. Effects on the processing of facial expressions were assessed 3 h later using functional magnetic resonance imaging.

Volunteers treated with citalopram displayed a significantly reduced amygdala response to fearful facial expressions compared with placebo.

Such an immediate effect of an SSRI on amygdala responses to threat supports the idea that antidepressants have an earlier onset of therapeutically relevant effects than conventionally thought.

Depression is associated with neural abnormalities in emotional processing.

This study explored whether these abnormalities underlie risk for depression.

We compared the neural responses of volunteers who were at high and low-risk for the development of depression (by virtue of high and low neuroticism scores; high-N group and low-N group respectively) during the presentation of fearful and happy faces using functional magnetic resonance imaging (fMRI).

The high-N group demonstrated linear increases in response in the right fusiform gyrus and left middle temporal gyrus to expressions of increasing fear, whereas the low-N group demonstrated the opposite effect. The high-N group also displayed greater responses in the right amygdala, cerebellum, left middle frontal and bilateral parietal gyri to medium levels of fearful v. happy expressions.

Risk for depression is associated with enhanced neural responses to fearful facial expressions similar to those observed in acute depression.

We previously found that children of parents with depression showed impaired performance on a task of emotional categorisation.

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.

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.

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.

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.