Psychological, endocrine, and neural correlates of attentional bias in subclinical depression.

BACKGROUND: Our knowledge with respect to psychological, endocrine, and neural correlates of attentional bias in individuals with high vulnerability to developing depression - the subclinically depressed, still remains limited. DESIGN: The study used a 2 × 2 mixed design. METHODS: Attentional bias toward happy and sad faces in healthy (N = 26) and subclinically depressed individuals (N = 22) was assessed via a neuroimaging dot-probe attention task. Participants also completed trait and state psychological measures and provided saliva samples for cortisol analysis. RESULTS: The subclinical group showed attentional bias toward happy faces; past use of problem-focused coping strategies when dealing with a personally relevant stressor as well as state levels of anxiety, together, contributed to this bias. In the control group, the happy attentional bias was positively correlated with activity in the right caudate. In the subclinical group, the bias was negatively associated with the left fusiform gyrus and positively with the left inferior parietal lobule and bilateral putamen. We observed group differences in association between cortisol levels during the task and neural activity during happy attentional bias processing within the key regions involved in attention. CONCLUSIONS: The attentional bias toward happy faces may reflect an active coping attempt by the subclinical participants.

n-back task performance and corresponding brain-activation patterns in women with restrictive and bulimic eating-disorder variants: preliminary findings.

Eating disorder (ED) variants characterized by "binge-eating/purging" symptoms differ from "restricting-only" variants along diverse clinical dimensions, but few studies have compared people with these different eating-disorder phenotypes on measures of neurocognitive function and brain activation. We tested the performances of 19 women with "restricting-only" eating syndromes and 27 with "binge-eating/purging" variants on a modified n-back task, and used functional magnetic resonance imaging (fMRI) to examine task-induced brain activations in frontal regions of interest. When compared with "binge-eating/purging" participants, "restricting-only" participants showed superior performance. Furthermore, in an intermediate-demand condition, "binge-eating/purging" participants showed significantly less event-related activation than did "restricting-only" participants in a right posterior prefrontal region spanning Brodmann areas 6-8-a region that has been linked to planning of motor responses, working memory for sequential information, and management of uncertainty. Our findings suggest that working memory is poorer in eating-disordered individuals with binge-eating/purging behaviors than in those who solely restrict food intake, and that observed performance differences coincide with interpretable group-based activation differences in a frontal region thought to subserve planning and decision making.

Psychological, endocrine and neural responses to social evaluation in subclinical depression.

This study aimed to identify vulnerability patterns in psychological, physiological and neural responses to mild psychosocial challenge in a population that is at a direct risk of developing depression, but who has not as yet succumbed to the full clinical syndrome. A group of healthy and a group of subclinically depressed participants underwent a modified Montreal Imaging Stress task (MIST), a mild neuroimaging psychosocial task and completed state self-esteem and mood measures. Cortisol levels were assessed throughout the session. All participants showed a decrease in performance self-esteem levels following the MIST. Yet, the decline in performance self-esteem levels was associated with increased levels of anxiety and confusion in the healthy group, but increased levels of depression in the subclinical group, following the MIST. The subclinical group showed overall lower cortisol levels compared with the healthy group. The degree of change in activity in the subgenual anterior cingulate cortex in response to negative evaluation was associated with increased levels of depression in the whole sample. Findings suggest that even in response to a mild psychosocial challenge, those individuals vulnerable to depression already show important maladaptive response patterns at psychological and neural levels. The findings point to important targets for future interventions.

Differentiating anticipatory from reactive cortisol responses to psychosocial stress.

Most psychosocial stress studies assess the overall cortisol response without further identifying the temporal dynamics within hormone levels. It has been shown, however, that the amplitude of anticipatory cortisol stress levels has a unique predictive value for psychological health. So far, no "best practice" in how to investigate the anticipatory cortisol stress response has emerged. The goal of the current research was to develop a protocol that would allow for a sensitive and easy-to-implement laboratory-based investigation into anticipatory cortisol stress levels. We initially tested 26 healthy men in either an anticipation- or stress-only condition of the Trier Social Stress Test (TSST) to map the distinct timelines of anticipatory and reactive cortisol release profiles (study 1). Subsequently, we administered the TSST to 50 healthy men such that the cortisol responses to anticipatory and reactive stress components could be dissociated (study 2). In both studies we sampled saliva cortisol at high frequency (at baseline, during 10min of anticipation and during and after 10min of acute stress) and the current mood state pre- and post-stress. We found anticipatory responder rates of 20% and 40%, with peak anticipatory cortisol levels between 14 and 20min after onset of anticipation. Visible changes in reactive cortisol levels occurred only after the termination of the acute stressor. We conclude that the best practice to detect a maximum number of anticipatory responders in the TSST would be to extend the anticipation phase to 15min. In doing so, the anticipatory cortisol peak could be captured at a time-point of the actual stressor that is uninfluenced by reactive cortisol levels. Overall, we could reveal several features of anticipatory responders. Most importantly, there was a positive correlation between anticipatory and reactive stress responses. There was no association between anticipatory cortisol and alpha-amylase as well as subjective-psychological stress responses. Future studies will have to determine whether the anticipatory responders differ with respect to various stress-sensitive parameters like sex, personality, psychological wellbeing or chronic stress.

Investigation into the cross-correlation of salivary cortisol and alpha-amylase responses to psychological stress.

Stress is a multidimensional construct. To accurately represent stress physiology, multiple stress measures across multiple stress-related systems should be assessed. However, associations may be masked given that different systems underlie different time courses. Salivary cortisol and alpha-amylase (sAA) are reliable biological stress markers of the sympathetic nervous system (SNS) and the hypothalamus pituitary adrenal (HPA) axis, respectively. Studies examining the link between sAA and cortisol levels in response to stress have produced inconsistent results. Here, we investigated whether the covariance of stress-induced sAA and cortisol release is dependent on the distinct temporal dynamics of the two stress markers. A total of 50 male participants were exposed to a psychological laboratory stressor with high frequency (2-min interval) saliva sampling in two independent studies. Synchronized time series of sAA and cortisol measures before, during and after stress induction were obtained. Cross-correlation analysis was applied to test for the association of sAA and cortisol levels at various stages relative to the onset of the stressor. Positive and negative cross-correlations between lagged pairs of sAA and cortisol measures were found in both studies. The strongest correlation was found for sAA preceding cortisol release by 13.5 min (r = .27, p < .001). With a smaller effect size cortisol also significantly preceded sAA by 13.5 min (r = -.16, p < .001). We suggest that sAA and cortisol stress responses are reliably associated at various time lags throughout a stressful situation. As a possible connection site between HPA axis and SNS that may underlie sAA-cortisol associations, we discuss CRF neurons of the hypothalamus involved in sympathetic regulation.

Increased cortisol awakening response and afternoon/evening cortisol output in healthy young adults with low early life parental care.

RATIONALE: Growing evidence from animal and human studies suggests a profound and long-lasting influence of early life experiences--ranging from variations in parenting behavior to severe adversity--on hypothalamic-pituitary-adrenal axis function. OBJECTIVES: The aim of the current investigation was to examine the association between naturally occurring variations in early life parental care and the cortisol awakening response (CAR), afternoon/evening cortisol output and key psychological variables in a sample of healthy young adults. METHODS: Fifty-eight (19 male and 39 female) participants between 18 and 30 years of age completed psychological questionnaires and collected saliva at awakening, 30 min thereafter and at 3 p.m., 6 p.m., and 9 p.m. on three non-consecutive weekdays. RESULTS: Participants with low (compared to high) parental care experiences exhibited an increased CAR, increased afternoon/evening cortisol output, decreased self-esteem, and increased depressive symptomatology and anxiety. CONCLUSIONS: We suggest that the elevated CAR and afternoon/evening cortisol levels might reflect a biological correlate of adversity-induced vulnerability for psychopathology. This study is first to show an association between the retrospective perception of early life parental care and cortisol circadian rhythms in healthy young adults.

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress.

BACKGROUND: In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. METHODS: In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. RESULTS: Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. LIMITATIONS: Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. CONCLUSION: We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group.

Cortisol awakening response and hippocampal volume: vulnerability for major depressive disorder?

BACKGROUND: Major depressive disorder is associated with dysregulated basal cortisol levels and small hippocampal (HC) volume. However, it is still debated whether these phenomena are a consequence of the illness or whether they may represent a vulnerability marker existing before the illness onset. Here, we aimed to examine this notion of vulnerability by assessing whether abnormalities in basal cortisol secretion and HC volumes are already present in a sample of healthy young adults who showed varying levels of depressive tendencies, but at subclinical levels. METHODS: We recruited healthy young men and women from the local university. On the basis of depression scores derived from standard questionnaires, three groups were formed: a control group (n = 27), a subclinical group (n = 23), and a high-risk subclinical group (n = 9). The participants underwent a magnetic resonance imaging scan and collected saliva samples for the assessment of diurnal cortisol levels. RESULTS: Both the subclinical and the high-risk subclinical group failed to show a significant increase in cortisol levels after awakening. The high-risk subclinical group also showed a lower area-under-the-curve increase of cortisol levels after awakening compared with control subjects. In addition, this group also had smaller total HC volume compared with control subjects. CONCLUSIONS: The findings from this subclinical sample suggest that dysregulated cortisol awakening response and small HC volume may constitute vulnerability factors for major depressive disorder. Further investigations are needed to discern the mechanisms that may underlie these phenomena.