Information processing in patients with first episode major depression

Hammar, Å., Kildal, A. B. & Schmid, M. (2012). Information processing in patients with first episode major depression. Scandinavian Journal of Psychology 53, 445–449. Few studies have investigated cognitive functioning in a group of patients experiencing a first episode of depression. The aim of this study was to investigate how patients diagnosed with a first episode of depression perform in effortful and non‐effortful information processing compared to healthy controls. An experimental paradigm based on a visual search test was applied. Thirty‐one patients and thirty‐one healthy controls were included in the study. All patients experienced a severe level of symptom load at the time of testing. Results showed no significant differences between groups under any of the conditions. Findings in the present study indicate that patients with a first episode of depression perform equally to healthy controls in tasks requiring visual attention in both effortful and non‐effortful information processing.     

Adolescent Personality: Associations With Basal,Awakening, and Stress‐Induced Cortisol Responses

The purpose of the present study was to investigate the associations between personality facets and hypothalamic‐pituitary‐adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress‐induced HPA‐axis activation. We hypothesized that other characteristics of HPA‐axis functioning would have a stronger association with personality based on the neuroendocrine literature. Data (n = 343) were used from the TRacking Adolescents' Individual Lives Survey (TRAILS), a large prospective cohort study of Dutch adolescents. We studied the association between facets of Neuroticism, Extraversion, and Conscientiousness and basal cortisol, the cortisol awakening response (CAR), and four measures of stress‐induced HPA‐axis activity. Basal cortisol levels were related to facets of all three personality traits. The CAR and stress‐induced cortisol were not related to personality. Possibly due to its more trait‐like nature, basal cortisol seems more informative than stress‐induced cortisol when investigating trait‐like characteristics such as personality facets.     

PTSD,comorbid depression,and the cortisol waking response in victims of intimate partner violence: preliminary evidence

Posttraumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) are two highly comorbid and debilitating disorders experienced by more than half of intimate partner violence victims (IPV). Hypothalamic–pituitary–adrenal (HPA) abnormalities are common in both disorders, though the direction of abnormalities often differs. The present study examined the relationship between comorbid PTSD and MDD, and the (salivary) cortisol waking response in 104 recently abused IPV victims. Waking cortisol levels, area under the waking curve with respect to ground (AUCg), and AUC with respect to increase (AUCi) were examined to determine the relation of HPA dynamics to comorbidity for basal versus more dynamic measures. Prior to accounting for comorbidity, women with PTSD or MDD showed significantly greater AUCi than women without the respective disorder. Accounting for comorbidity, PTSD only did not differ from other groups, while MDD only and PTSD + MDD showed greater AUCi than women with neither disorder. Results were nonsignificant for waking cortisol levels or AUCg. Results suggest that MDD drives elevated waking cortisol response, but not basal cortisol activity in recently abused IPV victims. Results demonstrate the importance of examining comorbid diagnoses and HPA activity from a dynamic perspective. Therapeutic implications are discussed.     

Brain activation patterns in major depressive disorder and work stress-related long-term sick leave among Swedish females

Deficits in executive functioning and working memory associated with frontal lobe dysfunction are prominent in depression and work-related long-term sick leave (LTSL). This study used functional magnetic resonance imaging (fMRI) to investigate potential differences in brain activation patterns in these conditions. In addition, the function of the hypothalamic-pituitary-adrenal (HPA) axis was examined and compared between groups. Since there is a clear overrepresentation of women in these diagnostic groups, and to ensure a more homogenous sample population, only women were included. To examine the neural correlates of relevant cognitive processes in patients on sick leave >90 days due to work-related LTSL, recently diagnosed patients with major depression Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV criteria, untreated), and healthy controls (n?=?10, each group), a 2-back working memory task and a visual long-term memory task were administered during fMRI scanning. HPA axis functioning was investigated using a diurnal curve of saliva cortisol and a dexamethasone suppression test. Task performance was comparable among the three groups. Multivariate image analysis revealed that both memory tasks engaged a similar brain network in all three groups, including the prefrontal and parietal cortex. During the 2-back task, LTSL patients had significant frontal hypoactivation compared to controls and patients with depression. Saliva cortisol measurements showed a flattening of the diurnal rythmicity in LTSL patients compared to patients with depression and healthy contols. Taken together, these findings indicate that work stress-related LTSL and major depression are dissociable in terms of frontal activation and diurnal cortisol rhythmicity.     

Cognitive performance in patients with burnout, in relation to diurnal salivary cortisol

This study investigated cognitive performance in patients with burnout, in relation to the flexibility of the hypothalamic-pituitary-adrenal (HPA) axis. Clinical cases with work stress-induced burnout (n = 65), and demographically matched, healthy reference subjects (n = 65), were given six neuropsychological tests and a self-rating scale for cognitive problems. Diurnal salivary cortisol was measured among burnout cases and an external reference group (n = 174), including a dexamethasone suppression test (DST) among burnout cases. Compared with referents, the burnout group under-performed in a cognitive speed test (Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol), but not in any other test of sustained attention, episodic memory, or vocabulary. Burnout cases had considerably more subjective cognitive problems, but ratings were unrelated to test performance. Compared with referents, burnout cases had similar morning salivary cortisol levels and similar awakening response, but lower evening cortisol. Among burnout cases, lower diurnal cortisol variability was related to slower performance in several tests. The DST response showed no consistent relationship with any cognitive parameter. Hence, despite considerable subjective cognitive problems, the burnout group showed only a partial, mild deviation in cognitive performance. A flatter diurnal cortisol profile was related to lower cognitive processing speed, but diurnal cortisol pattern and DST response were normal, suggesting a maintained HPA axis flexibility.     

创伤后应激障碍患者的HPA轴功能变化的时间序列特征

已知创伤后应激障碍(posttraumatic stress disorder, PTSD)患者表现出HPA轴(hypothalamic-pituitary- adrenocortical axis)功能异常, 而皮质醇是反映PTSD患者HPA轴功能的重要生物标记。近期的研究结果提示, PTSD患者的皮质醇水平变化可能有明显的时间序列特征, 即应激事件发生后先升高, 后下降至正常水平之下。这一特征受到生物标记的时间特性, 患者病程, 应激源类型和强度, 伴生疾病等因素的干扰和掩蔽。未来研究应进一步采用长期追踪设计, 控制干扰因素的影响, 结合急性应激和慢性应激生物标记来综合验证PTSD患者皮质醇水平变化的时间序列特征|并利用该特征预测PTSD的发生、发展, 以便及时进行干预|考虑皮质醇的代谢、拮抗等机制, 结合多种生物标记综合评估、诊断PTSD患者的HPA轴功能活性。     

Loneliness,HPA stress reactivity and social threat sensitivity: Analyzing naturalistic social challenges

Loneliness has been linked to poor health through an increased activation of threat surveillance mechanisms, such as the hypothalamic‐pituitary‐adrenal axis (HPA ). The socio‐cognitive model (Cacioppo & Hawley) proposes that lonely people have an increased social threat sensitivity which activates the HPA axis. The current study examined the impact of loneliness on HPA stress reactivity and social threat sensitivity in response to naturally occurring social challenges. Participants (N = 45) were prospective undergraduates attending a 3‐day university preparation programme over the summer, prior to commencing their university studies. Cortisol levels and perceived stress were measured before and after an ice breaker session on Day 1 and a lecture session on Day 3. Social threat sensitivity was also measured on the first and third day. When meeting unfamiliar peers in the ice breaker session, HPA stress reactivity was evident, but it was not markedly different in those who reported high levels of loneliness than those with low levels. The high loneliness group had higher levels of perceived stress and increased social threat sensitivity than the low loneliness group on both testing days. The findings show partial support for the socio‐cognitive model of loneliness because increased threat sensitivity was demonstrated in the high loneliness group. The findings indicate that lonely people do not respond in a physiologically different way to specific social challenges, but they typically report higher social threat sensitivity and higher perceived stress than their non‐lonely peers.     

Attachment status and salivary cortisol in a normal day and during simulated interpersonal stress in young men

Attachment insecurity, as assessed via the adult attachment interview (AAI), may be expected to relate to basal hypothalamic-pituitary-adrenal (HPA) activity because it is retrodictive of stressful early experiences, which may influence HPA development. In addition, because AAI insecurity may reflect limitations on concurrent cognitive, emotional, and behavioral strategies for managing interpersonal distress, insecurity may also relate to cortisol reactivity specifically during inter-personal challenges. Nevertheless, only two studies have examined associations between AAI insecurity and cortisol, and in total only eight non-clinical men were included. To expand upon past research, the current study focused on college aged men and examined relations between attachment status (via categories and continuous scores) and cortisol levels during daily life and during interpersonal laboratory challenges, wherein subjects were asked to visualize and respond to hypothetical situations concerning loss, separation, and abandonment. Unlike prior research, salivary cortisol was measured during cognitive challenges (e.g. non-autobiographical memory tests), so as to inform questions concerning the specificity of effects. Contrary to expectations, only limited evidence suggested a relation between insecurity and basal HPA functioning. However, in keeping with expectations, associations between insecurity, and in particular dismissing idealization, and comparatively higher cortisol values following interpersonal challenges were observed.     

Examining HPA-axis functioning as a mediator of the relationship between depression and cognition across the adult lifespan

Altered HPA-axis functioning is a hypothesized mechanism for worsened cognition in depression. The current study examines the indirect effects of depression on processing speed, executive functioning, and memory as a function of the HPA-axis. 38 individuals with a depression diagnosis and 50 healthy controls (HCs) aged 18–86 underwent neuropsychological testing and at-home diurnal salivary cortisol collection. Depression was assessed via structured clinical interviews and rating scales. Cognitive composite scores were derived from factor analysis. Daytime cortisol exposure was estimated using area under the curve (AUC). Depression was associated with higher cortisol levels and slower processing speed . A significant suppression effect of AUC was present on the relationship between depression and processing speed. Limitations include the cross-sectional design and limited sample heterogeneity. Though poorly modulated HPA-axis is one proposed mechanism of cognitive alterations in depression, our results did not support this conclusion for processing speed. Alternative mechanisms should be considered to inform interventions to target cognitive alterations in depression.     

A follow-up of cognitive performance and diurnal salivary cortisol changes in former burnout patients

The purpose of this study was to determine whether recovery from burnout is associated with improved cognitive functioning, and whether such improvement is associated with changes in hypothalamic-pituitary-adrenal axis activity and return to work. Forty-five former burnout patients were followed up after 1.5 years with a neuropsychological examination, diurnal salivary cortisol measurements, dexamethasone suppression test (DST), and self-ratings of cognitive problems. At follow-up, improved cognitive performance was observed on several tests of short-term memory and attention. Self-rated cognitive problems decreased considerably, but this decrease was unrelated to the improvement on neuropsychological tests. Diurnal salivary cortisol concentrations at awakening, 30?min after awakening, and in the evening, did not change from baseline to follow-up, nor did the cortisol awakening response. However, slightly, but significantly, stronger suppression of cortisol in response to the DST was observed at follow-up. Improvements in subjective or objective cognitive functioning and changes in diurnal cortisol concentration were unrelated to the extent of work resumption. However, a decreased DST response at follow-up was partially related to improved cognitive performance and work resumption. The clinical implications are that burnout seems to be associated with slight and significantly reversible cognitive impairment, and that self-rated cognitive change during recovery poorly reflects objective cognitive change.     

Cortisol in mood disorders

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has been well-described in mood disorders. Hypercortisolaemia, which has been attributed to a breakdown in glucocorticoid-receptor-mediated negative feedback mechanisms within the HPA axis, may be central to the pathogenesis of both the depressive symptoms and the cognitive deficits, which characterise severe mood disorders. Strategies to normalise glucocorticoid receptor (GR) function, and thus restore HPA functional integrity, have been the focus of recent research. Preliminary preclinical and clinical studies report encouraging results which suggest that lowering circulating cortisol levels, by up-regulating GRs, may have therapeutic efficacy in terms of improvements in depressive symptoms and cognitive functioning.     

Dexamethasone and stressor-magnitude regulation of stress-induced transcription of HPA axis secretagogues in the rat

Regulation of the production of hypothalamic-pituitary-adrenal (HPA) axis secretagogues, corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), may be differentially sensitive to the negative feedback effects of glucocorticoids. We chose to study this phenomenon by examining the ability of dexamethasone to influence CRH and AVP heteronuclear RNA (hnRNA) levels in an escapable/inescapable (ES/IS) foot-shock stress paradigm. On Day 1, adult male rats were subjected to either ES or IS foot-shock; on Day 2, saline or dexamethasone (100 microg/kg) was administered 2 h prior to the stressor. We found that ES/IS foot-shock stimulated similar robust increases in plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations, and medial parvocellular division of the paraventricular nucleus (mpPVN) AVP and CRH hnRNA and c-fos mRNA levels in saline-treated ES/IS rats. Dexamethasone pretreatment suppressed ACTH and corticosterone levels similarly in IS and ES animals. Dexamethasone pretreatment also suppressed mpPVN CRH and AVP hnRNA levels at 30 min. However, by 120 min, the mpPVN AVP hnRNA levels in dexamethasone-treated rats were similar to those measured in the saline group. We also found that rats that received the most shocks on Day 1 had greater HPA axis activation on Day 2. We conclude that the magnitude of the foot-shock stressor, determined by learned and immediate cues, is important in determining the magnitude of the HPA response.     

Family demographic profiles and their relationship with the quality of executive functioning subcomponents in kindergarten

Executive functioning (EF), needed for goal‐oriented behaviour, thoughts, and emotions, is important for various life domains. This study examined the relationship between family demographics and EF subcomponents. A kindergarten sample was tested on subcomponents of working memory, inhibition, and cognitive flexibility. Parents provided information on demographic variables. For 78 children both EF and demographic data were available. First, demographic profiles were identified within the sample. Two profiles were found: A low‐risk profile of mainly two‐biological‐parent, high‐income families with a highly educated mother who did not smoke during pregnancy and a high‐risk profile of low‐income families with a young, low‐educated mother who more often smoked during pregnancy. Second, children with different demographic profiles were compared on EF subcomponents. Results indicate differential relations between family demographics and EF subcomponents: Whereas for most EF subcomponents no association with family demographics was found, high‐risk children performed better on response shifting and tended to perform worse on verbal memory than low‐risk children. Parenting stress decreased performance only for high‐risk children. Although this study found limited impact of family demographics for EF, further longitudinal research can provide nuanced insights about which factors influence specific EF subcomponents during which developmental periods and guide targeted prevention of EF difficulties.     

The effects of exposure to an acute naturalistic stressor on working memory, state anxiety and salivary cortisol concentrations

Exposure to an acute naturalistic stressor induces both psychological and physiological changes in humans. The two studies reported here explored the impact of exposure to an acute naturalistic stressor on state anxiety, working memory and HPA axis activation (salivary cortisol). In both experiments, ten healthy male participants were exposed to an acute naturalistic stressor, helicopter underwater evacuation training (HUET), and their physiological and behavioural responses before (first study) and after (second study) the stressor were compared to ten non-stressed controls. The results of both experiments showed that working memory performance was preserved during anticipation of an acute stressor, but impairments were observed immediately after stress exposure. Participants reported significantly higher state anxiety levels during anticipation and following stress exposure, whereas significant elevations in cortisol levels were only observed 25 min post exposure to stress, but not before or immediately after stress exposure. The results of both experiments demonstrated a dissociation between behavioural and biochemical measures and provided evidence for a dissociation of the effects of stress on cognitive and physiological measures depending on the time of testing, with cognitive impairments most evident following stress exposure.     

Working memory and attention are still impaired after three years in patients with stress‐related exhaustion

Cognitive impairment is one of the most pronounced symptoms reported by patients with stress‐related mental health problems. Impairments related to executive function and to some extent speed and attention are therefore common in patients with stress‐related burnout/exhaustion. In this paper we present a follow‐up of cognitive performance in patients with stress‐related exhaustion several years after they initially sought medical care. Thirty patients and 27 healthy controls, mean age 49 years (SD 6.5) and 55 years (SD 6.7) respectively, were included, all of whom had undergone baseline measurements of neuropsychological functioning. The mean follow‐up time was three years. Half of the patients still reported mental health problems at follow‐up and over time no major changes in cognitive performance were noted. The patients still performed significantly poorer than controls with regard to cognitive functions, mainly related to speed, attention and memory function. Long‐lasting impairment of cognitive functions related to speed, attention and memory function noted in patients with stress‐related exhaustion should be acknowledged and taken into consideration during treatment and when discussing a return to work. Follow‐up periods longer than three years are needed to explore the persistence of the cognitive impairment.     

Circadian activity of the hypothalamic-pituitary-adrenal axis is differentially affected in the rat chronic mild stress model of depression

The altered activity of the hypothalamic-pituitary-adrenal (HPA) axis is often observed in stress-related disorders. According to the literature, about 60% of patients with major depressive disorder elicit high levels of cortisol. It is still unclear why high cortisol levels are not observed in all patients. In this study, we used the chronic mild stress (CMS) rat model of depression, which is based on continuous exposure to unpredictable stressors, to track longitudinal changes in HPA function using fecal corticosterone metabolites (FCM) as a read out. The dexamethasone suppression test was used to assess negative feedback inhibition of the HPA axis. Our results show (1) a disturbance in diurnal corticosterone rhythm measured as fluctuations of the diurnal FCM peak, (2) differences in corticosterone levels between stress-susceptible and stress-resilient animals, (3) recovery of diurnal corticosterone rhythm after 8 weeks of CMS, and (4) alterations in sensitivity to dexamethasone in negative feedback regulation of corticosterone secretion during the time course of CMS. Thus, a disruption of HPA axis circadian rhythmicity coincides with the initial state in the development of depression-like behavior. This chronobiological abnormality, as well as the hypersecretion of corticosterone, is state, rather than trait, dependent.     

Attention and executive functioning in infancy: Links to childhood executive function and reading achievement

This study provides the first analyses connecting individual differences in infant attention to reading achievement through the development of executive functioning (EF) in infancy and early childhood. Five‐month‐old infants observed a video, and peak look duration and shift rate were video coded and assessed. At 10 months, as well as 3, 4, and 6 years, children completed age‐appropriate EF tasks (A‐not‐B task, hand game, forward digit span, backwards digit span, and number Stroop). Children also completed a standardized reading assessment and a measure of verbal intelligence (IQ) at age 6. Path analyses on 157 participants showed that infant attention had a direct statistical predictive effect on EF at 10 months, with EF showing a continuous pattern of development from 10 months to 6 years. EF and verbal IQ at 6 years had a direct effect on reading achievement. Furthermore, EF at all time points mediated the relation between 5‐month attention and reading achievement. These findings may inform reading interventions by suggesting earlier intervention time points and specific cognitive processes (i.e. 5‐month attention).     

Wives' and Husbands' Cortisol Reactivity to Proximal and Distal Dimensions of Couple Conflict

Poor marital quality has been linked repeatedly to spouses' health problems, with alterations to physiological stress response systems, such as the hypothalamic‐pituitary‐adrenocortical (HPA) axis, as one putative mechanism. This study assessed wives' and husbands' HPA axis (i.e., cortisol) reactivity to marital criticism during laboratory‐based conflict discussions, in the context of marital aggression experienced during the previous year. Ninety‐five couples provided one saliva sample prior to—and three samples following—a triadic family conflict discussion involving their teenage child. Marital criticism during the conflict discussion was related to heightened HPA reactivity for husbands only. For wives, an interaction emerged between criticism during the conflict and previous‐year marital aggression: only those wives who had experienced high levels of marital aggression demonstrated a positive association between criticism and cortisol output. Husbands thus appeared to be more physiologically reactive to the in‐the‐moment critical behaviors, whereas wives' responses to proximal conflict were related to previous and perhaps more chronic experiences of marital aggression. These findings shed light on ways in which within‐couple processes during family conflicts involving children contribute to individual physiological functioning, enhancing our understanding of the role of family relationships in physical health outcomes.     

Executive Functioning in Children and Adolescents with Major Depressive Disorder

The present investigation examined neurocognitive functioning, focusing on executive functioning (EF), in 39 children and adolescents with Major Depressive Disorder (MDD) and 24 healthy control subjects all ages 8 to 17 years. The Wechsler Intelligence Scale for Children-Third Edition along with several measures of executive functioning including the Wisconsin Card Sorting Task, Trail Making Test, Controlled Oral Word Association Test, and the Stroop Color Word Test were administered. The neurocognitive profiles for the group of depressed children and adolescents were grossly intact as most scores on intellectual and EF measures fell within the average range and did not differ from the comparison group. Mental processing speed was decreased in the MDD versus normal control group and 27% of the depressed group performed below average on the Trail Making Test. This investigation provided a good base from which to compare future literature on EF in outpatients with early-onset MDD.     

Cognitive Reappraisal and Depression in Children with a Parent History of Depression

Although decades of research have documented that children whose parents have a history of Major Depressive Disorder (MDD) are at a higher risk of developing depression themselves, not all of these children go on to develop depression themselves, thus highlighting the need to understand potential moderators of risk. The current study examined whether child emotion regulation, specifically, the use of cognitive reappraisal and suppression, moderated the link between parent and child depression. We recruited 458 parents and their children between the ages of 7–11 from the community. The majority of children were Caucasian (74.2%) and approximately half were girls (46.1%). Among children with a parent history of MDD, those who reported using cognitive reappraisal more frequently were less likely to have a history of depressive diagnoses themselves and had higher current levels of positive affect. Although children’s use of suppression was not associated with their levels of depressive symptoms among children with a parent history of MDD, higher levels of suppression were related to higher levels of depressive symptoms among children with no parent history of MDD. These findings suggest that, among children with a history of parent depression, children’s use of cognitive reappraisal may influence their own risk for developing depression and highlights the potential utility of early interventions that focus on improving the use of emotion regulation strategies like cognitive reappraisal among children of depressed parents.