Stella W. Y. Chan

Highly neurotic never-depressed students have negative biases in information processing

BACKGROUNDnCognitive theories associate depression with negative biases in information processing. Although negatively biased cognitions are well documented in depressed patients and to some extent in recovered patients, it remains unclear whether these abnormalities are present before the first depressive episode.nnnMETHODnHigh neuroticism (N) is a well-recognized risk factor for depression. The current study therefore compared different aspects of emotional processing in 33 high-N never-depressed and 32 low-N matched volunteers. Awakening salivary cortisol, which is often elevated in severely depressed patients, was measured to explore the neurobiological substrate of neuroticism.nnnRESULTSnHigh-N volunteers showed increased processing of negative and/or decreased processing of positive information in emotional categorization and memory, facial expression recognition and emotion-potentiated startle (EPS), in the absence of global memory or executive deficits. By contrast, there was no evidence for effects of neuroticism on attentional bias (as measured with the dot-probe task), over-general autobiographical memory, or awakening cortisol levels.nnnCONCLUSIONSnThese results suggest that certain negative processing biases precede depression rather than arising as a result of depressive experience per se and as such could in part mediate the vulnerability of high-N subjects to depression. Longitudinal studies are required to confirm that such cognitive vulnerabilities predict subsequent depression in individual subjects.

Risk for depression and neural responses to fearful facial expressions of emotion

BACKGROUNDnDepression is associated with neural abnormalities in emotional processing.nnnAIMSnThis study explored whether these abnormalities underlie risk for depression.nnnMETHODnWe 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).nnnRESULTSnThe 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.nnnCONCLUSIONSnRisk for depression is associated with enhanced neural responses to fearful facial expressions similar to those observed in acute depression.

Cognitive bias modification training in adolescents: effects on interpretation biases and mood

BACKGROUNDnNegative biases in the interpretation of ambiguous material have been linked to anxiety and mood problems. Accumulating data from adults show that positive and negative interpretation styles can be induced through cognitive bias modification (CBM) paradigms with accompanying changes in mood. Despite the therapeutic potential of positive training effects, training paradigms have not yet been explored in adolescents.nnnMETHODSnEighty-two healthy adolescents (aged 13-17 years) were randomly allocated to either positive or negative CBM training. To assess training effects on interpretation bias, participants read ambiguous situations followed by test sentences with positive or negative interpretations of the situation. Participants rated the similarity of these sentences to the previously viewed ambiguous situations. Training effects on negative and positive affect were assessed using visual analogue scales before and after training.nnnRESULTSnAfter training, adolescents in the negative condition drew more negative and fewer positive interpretations of new ambiguous situations than adolescents in the positive condition. Within the positive condition, adolescents endorsed more positive than negative interpretations. In terms of mood changes, positive training resulted in a significant decrease in negative affect across participants, while the negative condition led to a significant decrease in positive affect among male participants only.nnnCONCLUSIONnThis is the first study to demonstrate the plasticity of interpretation bias in adolescents. The immediate training effects on mood suggest that it may be possible to train a more positive interpretation style in youth, potentially helping to protect against anxiety and depressive symptoms.

Risk for depression is associated with neural biases in emotional categorisation.

Negative biases in emotional processing are a major characteristic of depression. Recent research has shown that such negative biases are evident in high risk individuals even in the absence of personal history of depression, suggesting that they may serve as key vulnerability markers of depression. However, the neural basis of these behavioural observations has not been fully explored. This study therefore aimed to (1) illustrate the neural processes involved in the categorisation of emotional personality-trait words; and (2) examine whether these neural mechanisms are biased towards negative information in high risk individuals. Risk for depression was defined by high neuroticism (N). We recruited a sample of high risk (high N) and low risk (low N) never-depressed young adults. Functional magnetic resonance imaging (fMRI) was acquired during the categorisation and memory for positive and negative self-referent personality-trait words (e.g. honest, rude). High risk volunteers showed greater responses in the right superior parietal cortex than low risk volunteers specifically during the categorisation of negative words. Moreover, neuroticism score was positively correlated with neural responses in the left anterior cingulate during the categorisation of negative words but negatively correlated within the same region during the retrieval of these words. These results highlight a role of the fronto-parietal circuitry in emotional processing and further suggest that negative biases in these neural processes may be involved in risk for depression.

Hippocampal volume in vulnerability and resilience to depression

BACKGROUNDnReduced hippocampal volume has been associated with clinical depression. However, it remains unclear whether these changes are a biological vulnerability marker or a consequence of this disorder. METHODS AND RESULTS (STUDY 1): We first compared hippocampal volumes between (i) never-depressed individuals with elevated risk for depression by virtue of high neuroticism (ii) recovered depressed individuals with matched levels of neuroticism; and (iii) individuals with low neuroticism and no history of depression. We replicated the finding of reduced hippocampal volume in the recovered group; unexpectedly however, the never-depressed high-risk group showed an increase in volume. One hypothesis is that this group had a mean age above the typical onset age for depression; hence, these participants who have remained euthymic despite their personality risk might in fact possess some resilience. METHODS AND RESULTS (STUDY 2): A subsequent study was therefore carried out to compare hippocampal volume between high-neurotic vs. low-neurotic volunteers in a younger sample. No group difference was found.nnnLIMITATIONSnThe present findings are limited by a small sample size; the cross-sectional design precluded us from makineg definitive conclusions about causal effect.nnnCONCLUSIONnOur overall results suggest that reduced hippocampal volumes is a neural marker for the scar effect of depression, although this structural impairment could also be seen as a vulnerability marker for the development of future recurrent episodes. By contrast, larger hippocampal volumes could be a biological marker of resilience. These findings have clinical implications regarding treatment development for the prevention of illness onset and recurrent depressive episodes.

Is cognitive bias modification training truly beneficial for adolescents

BACKGROUNDnCognitive Bias Modification (CBM) has been shown to change interpretation biases commonly associated with anxiety and depression and may help ameliorate symptoms of these disorders. However, its evidence base for adolescents is scarce. Previous results have been hard to interpret because of methodological issues. In particular, many studies have used negative bias training as the control condition. This would tend to inflate any apparent benefits of CBM compared to a neutral control. Most studies also only examined the effects of a single training session and lacked follow-up assessment or ecologically valid outcome measures.nnnMETHODnSeventy-four adolescents, aged 16-18 years, were randomised to two sessions of CBM training or neutral control. Interpretation bias and mood were assessed three times: at baseline, immediately post-training and 1 week post-training. A controlled experimental stressor was also used, and responses to everyday stressors were recorded for 1 week after training to assess responses to psychological challenges. Feedback for the training programme was collected.nnnRESULTSnThe CBM group reported a greater reduction in negative affect than control participants. However, other hypothesised advantages of CBM were not demonstrated. Regardless of training group, participants reported increased positive interpretations, decreased negative interpretations, reduced depressive symptoms and no change in trait anxiety. The two groups did not differ in their stress reactivity. After controlling for group differences in training performance, all the mood effects disappeared.nnnCONCLUSIONSnWhen tested under stringent experimental conditions the effects of CBM in healthy adolescents appear to be minimal. Future studies should concentrate on participants with elevated cognitive biases and/or mood symptoms who may be more sensitive to CBM.

Prospective longitudinal voxel-based morphometry study of Major Depressive Disorder in young individuals at high familial risk

BACKGROUNDnPrevious neuroimaging studies indicate abnormalities in cortico-limbic circuitry in mood disorder. Here we employ prospective longitudinal voxel-based morphometry to examine the trajectory of these abnormalities during early stages of illness development.nnnMETHODnUnaffected individuals (16-25 years) at high and low familial risk of mood disorder underwent structural brain imaging on two occasions 2 years apart. Further clinical assessment was conducted 2 years after the second scan (time 3). Clinical outcome data at time 3 was used to categorize individuals: (i) healthy controls (low risk, n = 48); (ii) high-risk individuals who remained well (HR well, n = 53); and (iii) high-risk individuals who developed a major depressive disorder (HR MDD, n = 30). Groups were compared using longitudinal voxel-based morphometry. We also examined whether progress to illness was associated with changes in other potential risk markers (personality traits, symptoms scores and baseline measures of childhood trauma), and whether any changes in brain structure could be indexed using these measures.nnnRESULTSnSignificant decreases in right amygdala grey matter were found in HR MDD v. controls (p = 0.001) and v. HR well (p = 0.005). This structural change was not related to measures of childhood trauma, symptom severity or measures of sub-diagnostic anxiety, neuroticism or extraversion, although cross-sectionally these measures significantly differentiated the groups at baseline.nnnCONCLUSIONSnThese longitudinal findings implicate structural amygdala changes in the neurobiology of mood disorder. They also provide a potential biomarker for risk stratification capturing additional information beyond clinically ascertained measures.

A short form of the ambiguous scenarios test for depression in adolescents: development and validation

The Ambiguous Scenarios Test for Depression in Adolescents (AST-DA) is a 20-item measure of depressive interpretation bias. It has good face and construct validity and discriminates between clinical and non-clinical samples. However, a shorter measure would reduce burden on young people and make the instrument more useful in clinical settings. The aim of this study was to develop a valid and reliable short-form of the AST-DA. Adolescents recruited from the community (N = 206) completed the 20 item measure. Based on theoretical considerations and statistical analyses we selected 9 items to create a short form of the AST. This 9-item version was tested on a clinical sample of 69 young people referred for depression to a child and adolescent mental health service in the UK. The validity and internal reliability of the Short-AST-DA were confirmed. These data suggest that the Short-AST-DA is a robust measure of depressive interpretation bias in young people. Future work should investigate the measure’s test-retest reliability, sensitivity to change and convergent validity.

Intelligence and neuroticism in relation to depression and psychological distress: evidence of interaction using data from Generation Scotland: Scottish Family Health Study and UK Biobank

Background Neuroticism is a risk factor for selected mental and physical illnesses and is inversely associated with intelligence. Intelligence appears to interact with neuroticism and mitigate its detrimental effects on physical health and mortality. However, the inter-ralationships of neuroticism and intelligence for major depressive disorder (MDD) and psychological distress has not been well examined. Methods Associations and interactions between neuroticism and general intelligence (g) on MDD and psychological distress were examined in two population-based cohorts: Generation Scotland: Scottish Family Health Study (GS:SFHS, N=19,200) and UK Biobank (N=90,529). The Eysenck Personality Scale Short Form-Revised measured neuroticism and g was extracted from multiple cognitive ability tests in each cohort. Family structure was adjusted for in GS:SFHS. Results Neuroticism was associated with MDD and psychological distress in both samples. A significant interaction between neuroticism and g in predicting MDD status was found in UK Biobank (OR = 0.96, p < .01), suggesting that higher g ameliorated the adverse effects of neuroticism on the likelihood of having MDD. This interaction was not found in GS:SFHS. In both samples, higher neuroticism and lower intelligence were associated with increased psychological distress. A significant interaction was also found in both cohorts (GS:SFHS: ß = -0.05, p < .01; UK Biobank: ß = -0.02, p < .01), such that intelligence protected against the deleterious effect of neuroticism on psychological distress. Conclusions From two large cohort studies, our findings suggest intelligence acts a protective factor in mitigating the effects of neuroticism on risk for depressive illness and psychological distress.

Cognitive bias modification training in adolescents

BACKGROUNDnNegative biases in the interpretation of ambiguous material have been linked to anxiety and mood problems. Accumulating data from adults show that positive and negative interpretation styles can be induced through cognitive bias modification (CBM) paradigms with accompanying changes in mood. Despite the therapeutic potential of positive training effects, training paradigms have not yet been explored in adolescents.nnnMETHODSnEighty-two healthy adolescents (aged 13-17 years) were randomly allocated to either positive or negative CBM training. To assess training effects on interpretation bias, participants read ambiguous situations followed by test sentences with positive or negative interpretations of the situation. Participants rated the similarity of these sentences to the previously viewed ambiguous situations. Training effects on negative and positive affect were assessed using visual analogue scales before and after training.nnnRESULTSnAfter training, adolescents in the negative condition drew more negative and fewer positive interpretations of new ambiguous situations than adolescents in the positive condition. Within the positive condition, adolescents endorsed more positive than negative interpretations. In terms of mood changes, positive training resulted in a significant decrease in negative affect across participants, while the negative condition led to a significant decrease in positive affect among male participants only.nnnCONCLUSIONnThis is the first study to demonstrate the plasticity of interpretation bias in adolescents. The immediate training effects on mood suggest that it may be possible to train a more positive interpretation style in youth, potentially helping to protect against anxiety and depressive symptoms.