Brain functions associated with verbal working memory tasks among young males with alcohol use disorders

This study aimed to investigate the differences in brain functions during verbal working memory between individuals with alcohol use disorders (AUD) and normal controls. fMRI was used to scan brain activations associated with verbal working memory while participants performed 2-back and 0-back tasks. A total of 21 young male college students participated in the study. Eleven of those who clinically met the criteria for AUD were assigned to the AUD group, whereas ten demographically similar subjects who were social drinkers but not AUD were assigned to the normal control group. The AUD group showed less activation in bilateral frontal and precentral, left superior temporal, left superior parietal, and left cerebellar cortex during the 2-back task relative to 0-back task compared to the normal control group. In contrast, the control group showed less activation only in the right uncus than the AUD group. These results suggest that subjects with AUD present abnormality in brain functioning during verbal working memory.     

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.     

Cognitive deficits in relation to personality type and hypothalamic-pituitary-adrenal (HPA) axis dysfunction in women with stress-related exhaustion

Exhaustion caused by long-term work-related stress may cause cognitive dysfunction. We explored factors that may link chronic stress and cognitive impairment. Personality, psychiatric screening, and behavior were assessed by self-reporting measures in 20 female patients (mean age 39.3 years; range 26-53) with a preliminary diagnosis of stress-related exhaustion and in 16 healthy matched controls. Cognitive performance was investigated with a detailed neuropsychological test battery. Cortisol axis function was assessed by urinary and saliva collections of cortisol, dexamethasone suppression, Synacthen response, and corticotropin-releasing hormone (CRH) tests. Proinflammatory cytokines were measured. Hippocampal volumes were estimated by magnetic resonance imaging. Multivariate and univariate statistical methods were used to explore putative differences between groups and factors linked to cognitive impairment. Cognitive function clearly differed between groups, with decreased attention and visuospatial memory in the patient group, suggesting frontal cortex/medial temporal cortex-network dysfunction. Increased harm avoidance and persistence was present among patients, with lowered self-directedness linked to lower quality of life, increased anxious and depressive tendencies, and experiences of psychosocial stress. Attention was decreased with concomitantly impaired visuospatial memory. The pituitary (adrenocorticotropic hormone, ACTH) response to CRH was decreased in patients, with an increased cortisol/ACTH response to CRH. However, cortisol production rates, diurnal or dexamethasone-suppressed saliva cortisol levels, and the cortisol response to Synacthen were unaltered. Hippocampal volumes did not differ between groups. These findings suggest that cognitive dysfunction in stress-related exhaustion is linked to distinct personality traits, low quality of life, and a decreased ACTH response to CRH.     

Brain activation and deactivation during location and color working memory tasks in 11-13-year-old children

Using functional magnetic resonance imaging (fMRI) and n-back tasks we investigated whether, in 11-13-year-old children, spatial (location) and nonspatial (color) information is differentially processed during visual attention (0-back) and working memory (WM) (2-back) tasks and whether such cognitive task performance, compared to a resting state, results in regional deactivation. The location 0-back task, compared to the color 0-back task, activated segregated areas in the frontal, parietal and occipital cortices whereas no differentially activated voxels were obtained when location and color 2-back tasks were directly contrasted. Several midline cortical areas were less active during 0- and 2-back task performance than resting state. The task-induced deactivation increased with task difficulty as demonstrated by larger deactivation during 2-back than 0-back tasks. The results suggest that, in 11-13-year-old children, the visual attentional network is differently recruited by spatial and nonspatial information processing, but the functional organization of cortical activation in WM in this age group is not based on the type of information processed. Furthermore, 11-13-year-old children exhibited a similar pattern of cortical deactivation that has been reported in adults during cognitive task performance compared to a resting state.     

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.     

Cognitive functioning and cortisol profiles in first episode major depression

Major Depressive Disorder (MDD) is often associated with high levels of stress and disturbances in the Hypothalamic Pituitary Adrenal (HPA) system, yielding high levels of cortisol, in addition to cognitive dysfunction. Previous studies have shown a relationship between cortisol profile and cognitive functioning in recurrent MDD in general. More specifically, the association between hypercortisolism and cognitive functioning, such as memory and Executive Functioning (EF), and also more recently cortisol suppression has been explored. However, no studies have investigated these relationships in patients diagnosed with first episode MDD. The aim of the present study was to examine the relationship between cortisol levels before and after the Dexamethasone suppression test (DST) and cognitive function in first episode MDD patients. Twenty‐one patients meeting the DSM‐IV criteria for a first episode of MDD diagnosis were included in the study. The control group was matched for age, gender and education level. Cortisol was measured in saliva collected with Salivette sampling devices. Saliva samples were collected 4 times during a 24 hours period over two consecutive days: at awakening, after 45 minutes, after 7 hours and at 11 pm. Dexamethasone (1.0 mg) was given orally on Day 1 at 11 pm. The neuropsychological test battery consisted of standardized tests measuring executive functioning (EF) and memory functioning. Cortisol levels did not differ significantly between patients and controls on Day 1, except for the last sample before Dexamethasone administration, where the control group showed higher levels. Both groups showed suppression after Dexamethasone. On Day 2 there was a significant difference between groups at the third sample, showing a significantly lower level in the control group, suggesting that the controls have a more effective suppression profile than the patients. There were no significant correlations between cortisol levels before or after Dexamethasone and cognitive measures. The results indicate impairment on HPA‐axis functioning in first episode MDD patients, with less suppression functioning compared to healthy controls, but no relationship between cortisol profile and cognitive functioning in EF or Memory.     

Neural correlates of variable working memory load across adult age and skill: dissociative patterns within the fronto-parietal network

We examined neural changes related to variations in working memory load by using an n -back task with three levels and functional magnetic resonance imaging. Younger adults were divided into high- and low-performing groups (Young-High; Young-Low) and compared with older adults. Relative to Young-High, capacity-constraints in working memory were apparent between load 1–2 for the elderly and between load 2–3 for Young-Low. Capacity-constraints in neural activity followed this pattern by showing a monotonically increasing response in parietal cortex and thalamus for Young-High, whereas activity leveled off at 1-back for the elderly and at 2-back for Young-Low. The response in dorsal frontal cortex followed a similar pattern with the addition that the magnitude of activation differed within capacity limitations (Old > Young at 1-back; Young-Low > Young-High at 2-back). These findings indicate that an important determinant of WM capacity is the ability to keep the frontal cortex adequately engaged in relation to current task demands.     

皮质醇日常节律与儿童问题行为及心理社会因素的关系

HPA轴(下丘脑?垂体?肾上腺皮质轴, hypothalamic-pituitary-adrenal cortex axis)是人体应对压力的重要神经内分泌系统, 其终产物皮质醇常作为测量压力的生物学指标。目前的研究多通过皮质醇日常节律表示静息状态下HPA轴的活动, 而日常节律因其较高的稳定性和可靠性成为儿童生理健康评估的最佳指标。儿童期迅速发育的神经内分泌系统与儿童的行为相互作用, 并受到多种心理社会因素的影响。以往研究主要关注皮质醇日常节律与儿童问题行为及心理社会因素的关系, 未来研究应讨论逆境条件下影响儿童成长的危险性因素和保护性因素, 并探索环境对儿童行为影响可能存在的内分泌机制。     

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.     

Psychosocial stress and HPA functioning: no evidence for a reduced resilience in healthy elderly men

In order to investigate if HPA functioning is altered with age, the present study was conducted. Fifteen healthy elderly men (60-76 years; mean age 66.5 +/- 1.48 yrs.) and 12 younger adults (20-29 years; mean age 25.6 +/- 0.77 yrs.) collected salivary free cortisol profiles after awakening for basal HPA activity. Then, all subjects were exposed to the "Trier Social Stress Test" (TSST). This psychosocial stress protocol consists of a free speech and a mental arithmetic task of 13 minutes duration performed in front of an audience. Beside the assessment of endocrine and cardiovascular responses to the stressful task ratings of depression, mood and perceived stressfulness were obtained. Results show that younger and elderly men had similar morning cortisol profiles after awakening with both groups showing the expected rise after awakening (P=0.004). The TSST induced significant increases in ACTH, total plasma cortisol, saliva free cortisol, and heart rates (all P<0.0001). Regardless of age, both age groups showed comparable endocrine response patterns when confronted with the stressor. However, cardiovascular responses were significantly higher in younger men compared to elderly men (P=0.03). Catecholamine data revealed significant norepinephrine and epinephrine increases due to the stressor (both P<0.0001) with a trend toward elevated norepinephrine levels in elderly men (P=0.058). In sum, the investigated basal and response parameters of HPA functioning neither support the idea of a reduced resilience in healthy aged humans nor do they appear to strengthen assumptions derived from the so called "glucocorticoid cascade hypothesis".     

Adaptive influence of long term high altitude residence on spatial working memory: An fMRI study

With an increasing population living at a high altitude (HA), the impact of HA residence on human cognitive function has raised concerns. We recruited two groups of college students with one group born and grew up at HA until early adulthood and the control group born and grew up at near sea level (SL); the two groups were matched at age, gender ratio, educational level, the ancestral lines, and peripheral physiology (especially the hemoglobin concentration). A 2-back spatial working memory task was performed by each subject in the scanner while fMRI data were acquired. Compared to the SL control group, the HA group showed equal response accuracy, with more variance in reaction time and a larger average value. fMRI data indicated that both groups showed common activation patterns in the neural pathway typically associated with working memory. The HA group had greater activation at the left pyramis, the left superior temporal gyrus and less activation at the left middle occipital gyrus. Significant correlations were found within each group between the reaction times and BOLD signal change amplitudes at the frontal cortex and the precentral cortex.     

Does HPA‐Axis Dysregulation Account for the Effects of Income on Effortful Control and Adjustment in Preschool Children?

The effects of low income on children's adjustment might be accounted for by disruptions to hypothalamic–pituitary–adrenal (HPA)‐axis activity and to the development of effortful control. Using longitudinal data and a community sample of preschool‐age children (N = 306, 36–39 months) and their mothers, recruited to over‐represent low‐income families, we explored the associations among diurnal cortisol levels and effortful control, and we tested a model in which diurnal cortisol and effortful control account for the effects of family income on child adjustment. Continuous indicators of morning cortisol level and diurnal slope, as well as dichotomous indicators reflecting low morning levels and flat diurnal slope, were examined as predictors of rank‐order changes in two dimensions of effortful control, executive control and delay ability. Low income was related to a flat diurnal cortisol slope, and above the effects of family income, a flat diurnal cortisol slope predicted lower social competence. Low morning cortisol level predicted smaller gains in executive control and higher total adjustment problems. Further, delay ability predicted lower adjustment problems above the effects of income and diurnal cortisol levels. The results suggest that HPA‐axis dysregulation and effortful control contribute additively to children's adjustment. Copyright © 2013 John Wiley & Sons, Ltd.     

In Search of HPA Axis Dysregulation in Child and Adolescent Depression

Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative perspective on research investigating the various components of HPA axis functioning among depressed young people. The present narrative review synthesizes evidence from the following five categories of studies conducted with children and adolescents: (1) those examining the HPA system’s response to the dexamethasone suppression test (DST); (2) those assessing basal HPA axis functioning; (3) those administering corticotropin-releasing hormone (CRH) challenge; (4) those incorporating psychological probes of the HPA axis; and (5) those examining HPA axis functioning in children of depressed mothers. Evidence is generally consistent with models of developmental psychopathology that hypothesize that atypical HPA axis functioning precedes the emergence of clinical levels of depression and that the HPA axis becomes increasingly dysregulated from child to adult manifestations of depression. Multidisciplinary approaches and longitudinal research designs that extend across development are needed to more clearly and usefully elucidate the role of the HPA axis in depression.     

Decision-making under risk conditions is susceptible to interference by a secondary executive task

Recent research suggests two ways of making decisions: an intuitive and an analytical one. The current study examines whether a secondary executive task interferes with advantageous decision-making in the Game of Dice Task (GDT), a decision-making task with explicit and stable rules that taps executive functioning. One group of participants performed the original GDT solely, two groups performed either the GDT and a 1-back or a 2-back working memory task as a secondary task simultaneously. Results show that the group which performed the GDT and the secondary task with high executive load (2-back) decided less advantageously than the group which did not perform a secondary executive task. These findings give further evidence for the view that decision-making under risky conditions taps into the rational-analytical system which acts in a serial and not parallel way as performance on the GDT is disturbed by a parallel task that also requires executive resources.     

挫折情境下自我肯定对执行功能的影响

为探讨挫折情境下自我肯定对执行功能的影响,创设挫折和非挫折情境,采用价值观自我肯定干预,通过Stroop范式和2-back范式分别测量抑制控制和工作记忆的刷新能力。结果发现,挫折情境下的Stroop任务和2-back任务反应时均高于非挫折情境;挫折情境下自我肯定组在Stroop任务和2-back任务上的反应时均显著低于非自我肯定组,而非挫折情境下两组的反应时没有显著性差异;Stroop效应量在情境与肯定条件上的交互作用不显著。结果表明挫折降低了执行功能的任务表现,自我肯定干预能够改善挫折情境下执行功能相关的任务成绩,促进了个体对工作记忆任务的刷新能力和Stroop任务的认知表现,但对抑制控制能力的改善没有明显作用。     

Diurnal patterns of salivary cortisol and DHEA in adolescent anorexia nervosa

Although there is well-documented evidence for hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis function in anorexia nervosa (AN), there has been little research into secretory patterns of salivary cortisol and dehydroepiandrosterone (DHEA) in this condition. The cortisol awakening response (CAR), a prominent and discrete feature of the cortisol cycle, has not been extensively explored in adolescent AN. Saliva samples were collected at awakening, 30?min and 12 h post-awakening on two consecutive weekdays from eight female adolescents with clinically diagnosed AN and 41 healthy control (HC) age-matched females. Adolescent AN patients had greater salivary cortisol and DHEA concentrations than HC girls at all points. Increased hormone secretion was unrelated to body mass index. However, despite hypersecretion of both hormones, the circadian pattern including the CAR paralleled that of the HC group. Findings from this preliminary study confirm dysregulation of HPA axis function in adolescent AN as evidenced by hypersecretion of both cortisol and DHEA, which share the common secretagogue adrenocorticotropic hormone. However, the parallel diurnal profiles for AN and HC participants, including the CAR, may indicate hypersecretion per se rather than differential regulation of the diurnal pattern of these two adrenal steroids in AN.     

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.     

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。     

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.     

Incidental retrieval of emotional contexts in post-traumatic stress disorder and depression: an fMRI study

In the present study, we used fMRI to assess patients suffering from post-traumatic stress disorder (PTSD) or depression, and trauma-exposed controls, during an episodic memory retrieval task that included non-trauma-related emotional information. In the study phase of the task neutral pictures were presented in emotional or neutral contexts. Participants were scanned during the test phase, when they were presented with old and new neutral images in a yes/no recognition memory task. fMRI results for the contrast between old and new items revealed activation in a predominantly left-sided network of cortical regions including the left middle temporal, bilateral posterior cingulate, and left prefrontal cortices. Activity common to all three groups when correctly judging pictures encoded in emotional contexts was much more limited. Relative to the control and depressed groups the PTSD group exhibited greater sensitivity to correctly recognised stimuli in the left amygdala/ventral striatum and right occipital cortex, and more specific sensitivity to items encoded in emotional contexts in the right precuneus, left superior frontal gyrus, and bilateral insula. These results are consistent with a substantially intact neural system supporting episodic retrieval in patients suffering from PTSD. Moreover, there was little indication that PTSD is associated with a marked change in the way negatively valenced information, not of personal significance, is processed.