Contextual recognition memory deficits in major depression are suppressed by cognitive support at encoding.

OBJECTIVES: To investigate the effect of cognitive support (an associative orienting instruction at encoding) on contextual memory in depressed patients. METHODS: Seventeen patients (age 20-40 years, 14 women) diagnosed with major depressive disorder (MDD) and 22 healthy controls matched for age, gender and education completed a recognition memory task for item (object) and context (location), with or without an incidental binding cue at encoding. In addition, participants completed the vocabulary subtest of the Wechsler Adult Intelligence Scale (WAIS III) and the Wisconsin Card Sorting Test (WCST). Salivary samples were collected at 7 AM, 4 PM and 10 PM on the day of testing for cortisol and DHEA level measurement. RESULTS: Depressed patients showed a deficit in contextual memory in the absence of a binding cue but did not differ from healthy controls in item memory or when a binding cue was present. Cortisol and cortisol/DHEA ratios were lower in depressed patients compared to healthy controls and correlated with memory deficits. CONCLUSIONS: Contextual memory deficits in MDD patients can be reduced by providing cognitive support at encoding.

Neuroimmunoendocrine interactions in patients with recurrent major depression, increased early life stress and long-standing posttraumatic stress disorder symptoms.

BACKGROUND: Traumatic events experienced in childhood may lead to psychiatric diseases in adult life, including major depressive disorder (MDD). It remains obscure to what extent early life stress (ELS) is associated with biologically relevant changes in MDD. OBJECTIVE: We investigated both neuroendocrine and immunological correlates in recurrent MDD with ELS and current posttraumatic stress disorder symptoms. METHODS: Thirty-eight female MDD patients with or without childhood trauma and 15 healthy controls took part in this study. Salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed by radioimmunoassays. Peripheral blood mononuclear cells (PBMCs) were isolated and T cell proliferation and cellular sensitivity to steroids and DHEAS were evaluated by colorimetric assays. Th1/Th2 cytokines were assessed by cytometric bead arrays. RESULTS: MDD patients with or without previous trauma had similarly lower salivary cortisol and DHEAS in parallel with blunted T cell proliferation. PBMCs of depressives were significantly less sensitive to dexamethasone or epinephrine than those of the controls. PBMCs of MDD patients produced significantly lower interleukin (IL)-2, IL-4 and tumor necrosis factor-α levels when compared to healthy controls. CONCLUSION: We found that a history of ELS did not modify the blunted neuroendocrine and immunological alterations presented by recurrent depressed patients.

Analysis of leukocytes in medication-overuse headache, chronic migraine, and episodic migraine.

OBJECTIVE: To evaluate the number of immune cells in the peripheral blood of medication-overuse headache (MOH), chronic migraine (CM), and migraine without aura (MWA) patients, as well as from controls. BACKGROUND: Migraine has been linked to immunologic disturbances, but the role of the immune system in chronic forms of headache that evolve from migraine has not been studied. Psychiatric co-morbidity has been related to both headache chronification and immunologic alterations. METHODS: This cross-sectional study comprised 68 subjects divided in 4 groups: MOH, CM, MWA, control. Subjects were gender-matched, had no physical co-morbidity, and were taking only acetaminophen. Clinical and psychological data were recorded in a standardized protocol. Samples of peripheral blood for hematological analysis were obtained in the morning during the ictal (MOH, CM, and MWA groups) and interictal periods (MWA group), as well from control group. RESULTS: A higher lymphocyte count was measured in MOH patients relative to the MWA patients (mean ± standard deviation: 2448.7/mm3 ± 775.8 vs. 1859.7/mm3 ± 564.7; P = .027). The numbers of blood lymphocytes for CM and control subjects were 2086.1/mm3 ± 540.5 and 1961.7/mm3 ± 385.6, respectively. Multiple linear regression analysis demonstrated that only MOH and MWA groups remained associated with lymphocyte count (B = 540.7; CI 95%: 55.2-1026.1; P = .03; R2 = 19.2%). Analysis for linearity of variables in the spectrum control/MWA/CM/MOH resulted positive for body mass index (from 23.5 ± 3.25 in controls to 26.5 ± 4.49 in MOH patients; P = .034), scores on Beck Depression Inventory (from 3.29 ± 3.05 to 14.65 ± 11.21; P < 0.001) and Hamilton Anxiety Scale (from 4.29 ± 3.93 to 23.24 ± 11.01; P < 0.001), hemoglobin (from 13.7 ± 0.79 to 14.6 ± 1.31; P = .022), and lymphocyte count (from 1961.7 ± 385.6 to 2448.7 ± 775.8; P = .01), but negative for CD8+ T lymphocytes (from 34.0 ± 8.82 to 30.0 ± 6.64; P = .046). CONCLUSIONS: A higher lymphocyte count in the MOH group relative to the MWA group may indicate a chronic inflammatory state. Several clinical and laboratorial characteristics have a range along a spectrum extending from healthy subjects to patients suffering from chronic forms of migraine.

Salivary cortisol and dehydroepiandrosterone (DHEA) levels, psychological factors in patients with oral lichen planus.

OBJECTIVE: The aim of this study was to determine the salivary levels of dehydroepiandrosterone (DHEA) and cortisol and scores of depression, anxiety and stress in patients with oral lichen planus (OLP). STUDY DESIGN: Thirty-one patients with a diagnosis of OLP were selected; they were matched by sex and age with 31 control patients. Symptoms of depression, anxiety and stress were investigated by the instruments Beck Depression Inventory, Beck Anxiety Inventory and Lipp's Inventory of Stress Symptoms for Adults, respectively. Saliva was collected in the morning and at night for the determination of DHEA and cortisol levels by radioimmunoassay. RESULTS: There was no significant difference between the groups with respect to depression (P=0.832), anxiety (P=0.061) or stress (P=0.611), or with respect to morning and night salivary levels of DHEA (P=0.888, P=0.297) and cortisol (P=0.443, P=0.983). CONCLUSIONS: The results suggest an association of OLP with anxiety. However, DHEA and cortisol levels did not differ between groups, which does not support any neuroendocrine aetiology for OLP.

Emotional memory deficit and its psychophysiological correlate in family caregivers of patients with dementia.

This study examined the cortisol secretion pattern and declarative memory performance of dementia caregivers. An illustrated story paradigm memory task was used to evaluate the effects of emotional arousal on memory and assess the caregivers' cognitive compensation capacity. Younger (n=19) and elderly (n=24) noncaregivers and elderly caregivers (n=14) took part in 2 experiments to elucidate the effects of aging (experiment 1) and chronic stress (experiment 2) on memory performance and cortisol levels. Each group was divided in 2 subgroups: one that was exposed to an emotionally neutral story, and one that was exposed to a similar, but emotionally arousing story. Participants completed a multiple-choice questionnaire in the test session. Salivary cortisol samples were collected at 8:00 AM, 4:00 PM, and 10:00 PM, 1 day after memory testing. Experiment 1 showed that, despite an age-related memory deficit, arousal manipulation produced a similar effect in both age groups. Experiment 2 showed that, in addition to the characteristic memory decline of aging, elderly caregivers did not benefit from emotionally arousing material as their noncaregiver counterparts did. This impairment correlated with elevated nighttime cortisol levels, indicating a potential worsening impact of caregiver burden on age-related cognitive decline.

Subjective mild depressive symptoms are associated with abnormal diurnal cycle of salivary cortisol in older adults.

BACKGROUND: Alterations in cortisol secretion pattern seem to be involved in the associations between aging, depression, and cognitive decline. OBJECTIVE: The aim of this study was to mainly assess cortisol circadian profile in older adults with subjective depressive symptoms. METHODS: Salivary cortisol samples from healthy young (n = 22) and old adults (n = 22), and from older adults who self-reported depressive symptoms in Geriatric Depression Scale (n = 22) were collected at 7 AM, 4 PM, and 10 PM and were analyzed by radioimmunoassay. RESULTS: Older adults with depressive symptoms presented the characteristic cortisol circadian pattern, but they showed higher cortisol levels at 10 PM than healthy young and elderly controls. CONCLUSIONS: Our data suggest that mild depressive symptoms could be associated with a cortisol secretion pattern previously described as being predictive of cognitive decline.

Neuroendocrine and immunological correlates of chronic stress in 'strictly healthy' populations.

BACKGROUND: Chronic stress has been associated with detrimental or maladaptive neuroendocrine and immunological changes. OBJECTIVES: We assessed the neuroendocrine and immunological correlates of a realistic chronic stress experienced by strictly healthy caregivers of Alzheimer's disease patients and age-matched controls. METHODS: We screened 330 caregivers and 206 non-caregivers according to the 'strictly healthy' conditions established by the SENIEUR protocol. Forty-one strictly healthy caregivers (60.56 +/- 16.56 years) and 33 non-stressed controls (60.27 +/- 14.11 years) were selected for this study. Salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at multiple points by radioimmunoassay. Peripheral T cell proliferation and cellular sensitivity to glucocorticoids (corticosterone and dexamethasone, DEX) were evaluated by colorimetric assays. We also examined the hypothalamic-pituitary-adrenal (HPA) axis response to the administration of a low-dose DEX in vivo. RESULTS: The caregivers were significantly more stressed, anxious and depressed than non-caregivers (all p < 0.0001), in contrast to similar cortisol levels. Caregivers had reduced DHEAS levels (-32%, p < 0.0001), an increased cortisol/DHEAS ratio (39.7%, p < 0.0001) and impaired HPA axis response to DEX intake. Caregivers had a higher T cell proliferation (p < 0.0001) and increased sensitivity to glucocorticoids in vitro (p < 0.01) as compared to non-stressed controls. CONCLUSIONS: Our results suggest that the maintenance of health in chronically stressed populations may be associated with both protective and detrimental neuroendocrine and immunological changes.

Salivary dehydroepiandrosterone (DHEA) levels in patients with the complaint of burning mouth: a case-control study.

OBJECTIVE: This study was conducted to evaluate salivary dehydroepiandrosterone (DHEA) levels, salivary flow rate (SFR), depression, and hopelessness in patients with the complaint of burning mouth (BM). STUDY DESIGN: Thirty female patients with BM and 30 age-matched control women without any complaint of burning mouth were enrolled. After anamnesis and oral examination, the salivary flow rate was determined. Depression and hopelessness were evaluated by the application of inventories. Two saliva samples were collected for DHEA analysis. RESULTS: Dysgeusia (P = .045) and xerostomia (P = .003) were significantly higher in the BM group. The BM patients showed significantly lower salivary flow rate, both under stimulation (P = .001) and at rest (P < .001). Significant differences between the groups were not found in the depression (P = .416) or hopelessness (P = .597) scores. The BM group revealed significantly lower salivary DHEA levels in the morning samples (P = .003). CONCLUSION: Patients with BM exhibit decreased morning salivary DHEA as well as dysgeusia and hyposalivation more frequently than control subjects. Additional investigations are needed to clarify this association.

Contextual memory and encoding strategies in young and older adults with and without depressive symptoms.

OBJECTIVES: This study examines the role of depressive symptoms associated with age on contextual memory and how this association could impair the use of strategic instructions during encoding. METHOD: Young and older controls and older adults with depressive symptoms performed memory recognition tests for item and context. RESULTS: Memory results indicated that mild depressive symptoms did not aggravate the age-related contextual memory pattern, but interfered with the magnitude of the memory enhancement provided by specific encoding instructions when compared with young adults. These between-group differences in the use of memory strategies were eliminated with the inclusion of the performance on Wisconsin Card Sorting Test as a covariate. CONCLUSION: Mild depressive symptoms were associated with an impaired ability to use incidental memory strategies at encoding, suggesting the need for further investigation on the effects of non-clinical depressive symptomatology on cognitive decline in aging.

The role of stress factors during aging of the immune system.

This manuscript reviews current evidence suggesting that aging of the immune system (immunosenescence) may be closely related to chronic stress and stress factors. Healthy aging has been associated with emotional distress in parallel to increased cortisol to dehydroepiandrosterone (DHEA) ratio. The impaired DHEA secretion together with the increase of cortisol results in an enhanced exposure of lymphoid cells to deleterious glucocorticoid actions. The lack of appropriated growth hormone signaling during immunosenescence is also discussed. It follows that altered neuroendocrine functions could be underlying several immunosenescence features. Indeed, changes in both innate and adaptive immune responses during aging are also similarly reported during chronic glucocorticoid exposure. In addition, chronically stressed elderly subjects may be particularly at risk of stress-related pathology because of further alterations in both neuroendocrine and immune systems. The accelerated senescent features induced by chronic stress include higher oxidative stress, reduced telomere length, chronic glucocorticoid exposure, thymic involution, changes in cellular trafficking, reduced cell-mediated immunity, steroid resistance, and chronic low-grade inflammation. These senescent features are related to increased morbidity and mortality among chronically stressed elderly people. Overall, these data suggest that chronic stress leads to premature aging of key allostatic systems involved in the adaptation of the organisms to environmental changes. Stress management and psychosocial support may thus promote a better quality of life for elderly people and at the same time reduce hospitalization costs.

Relaxation and guided imagery program in patients with breast cancer undergoing radiotherapy is not associated with neuroimmunomodulatory effects.

OBJECTIVE: Treatment of breast cancer is usually associated with significant psychological stress. In this study, we examined the effects of relaxation and visualization therapy (RVT) on psychological distress, cortisol levels, and immunological parameters of breast cancer patients undergoing radiotherapy. METHODS: Participants were randomly assigned to either the experimental (n=20) who underwent group RVT for 24 consecutive days or control group (n=14) who were on radiotherapy only. Psychological scores (stress, anxiety, and depression) were measured by structured clinical interviews. Salivary cortisol was assessed along the day. Lymphocytes were isolated and cultured to measure T-cell proliferation and sensitivity to glucocorticoids (GCs). RESULTS: RVT was effective to reduce stress, anxiety, and depression scores (all P<.05). However, cortisol levels as well as proliferation remained unchanged following RVT. Although T cells of experimental group were more sensitive to GCs than cells of controls at baseline, no changes were noted following RVT. Cortisol levels were positively correlated to anxiety and depression scores and inversely correlated to T-cell proliferation and sensitivity to GCs. CONCLUSION: We conclude that the psychological intervention was capable to attenuate the emotional distress presented during radiotherapy treatment. A longer RVT or worse psychological morbidity at baseline may be necessary to translate psychological into biological changes.

Hematological and nutritional parameters in apparently healthy elderly individuals

A non-probabilistic study in an elderly free living community was performed. The first analysis was cross-sectional in design and the additional analysis, a case-control design. In the first analysis, 745 subjects were enrolled. Additional analyses, made in 46 apparently healthy elderly subjects (AHE) and 33 young adults (YA) included: clinical, hematological and biochemical analyses, 24-hours nutritional recall and diet frequency questionnaire. The AHE were selected using the Senieur test protocol. To avoid selection bias in the AHE sample, additional analysis comparing cultural, socioeconomic, and health variables were compared between AHE and non-selected elderly with same dysfunction or morbidity (DE). The prevalence of AHE was 6.17 percent (n=46) among whom 4.3 percent were anemic. There were no statistically differences in hematocrit, hemoglobin, leukocytes and vitamin B12 levels between AHE and YA groups. Mean values of MCV, RDW, eosinophils, folate and ferritin were higher in the AHE than the YA group. On the other hand, platelets were higher in the YA group. No statistically significant difference occurred between the AHE and DE groups when nutritional indicators were compared. The comparison between nutritional indicators of anemic and non-anemic apparently healthy elderly people showed statistically significant differences in vitamin B12 and protein intake, which were lower in the anemic elderly. The results suggest independent biological differences between hematological parameters of elderly and young individuals.

Foi realizado um estudo não probabilístico em idosos que vivem na comunidade. A primeira análise teve um delineamento transversal e análises adicionais um delineamento caso-controle. Na primeira análise foram incluídos 745 indivíduos. Análises adicionais foram feitas em 46 idosos saudáveis (HE) e em 33 adultos jovens (YA) incluindo: análises clínicas, hematológicas e bioquímicas, recordatório nutricional de 24 horas e questionário de freqüência dietética. Os idosos saudáveis foram selecionados através do uso do protocolo Seniour. Para evitar viés de seleção na amostra HE, uma análise adicional comparando variáveis culturais, socioeconômicas e saúde com a dos idosos não selecionados (DE). A prevalência de HE foi de 17 por cento (n=46) sendo que, entre estes, 4,3 por cento estavam anêmicos. Não ocorreram diferenças estatísticas de hematócrito, hemoglobina, leucócitos, neutrófilos e vitamina B12 entre os grupos AHEe YA. Níveis médios de MCV, RDW, eosinofilos folato and ferritina foram mais altos no grupo AHE do que no YA. Ao contrário, as plaquetas foram mais altas no grupo YA. Não ocorreram diferenças significativas entre os grupos AHE e DE quando os indicadores nutricionais foram comparados. A comparação entre indicadore nutricionais de idosos anêmicos e não-anêmicos em idosos aparentemente saudáveis mostrou diferenças significativas na ingestão de vitamina B12 e de proteína, que foi mais baixa nos idosos anêmicos. Os resultados sugerem diferenças biológicas independentes entre os parâmetros hematológicos de idosos e jovens.

Healthy aging is associated with unaltered production of immunoreactive growth hormone but impaired neuroimmunomodulation.

BACKGROUND: Both endocrine and immune systems are continuously remodeled during aging. OBJECTIVE: Here, we investigated to what extent adrenal and somatosenescence are associated reciprocal changes in the immune system during strictly healthy aging. METHODS: Forty-six elderly subjects and 33 young adults were recruited according to the health criteria of the SENIEUR protocol. Peripheral blood mononuclear cells were isolated and stimulated in vitro with lipopolysaccharide or phytohemagglutinin to assess the production of immunoreactive growth hormone (GH). Peripheral sensitivity to steroids was assessed in vitro by dexamethasone-, cortisol- or dehydroepiandrosterone (DHEA)-induced inhibition of T-cell proliferation. DHEA and GH levels were measured by radioimmunoassays. RESULTS: Healthy elderly had lower salivary DHEA and serum GH levels (somatosenescence). They presented reduced T-cell sensitivity to dexamethasone but similar cellular sensitivities to cortisol and DHEA. Their cells produced similar levels of immunoreactive GH compared to the cells of young adults. CONCLUSIONS: These data indicate that healthy aging is associated with adrenal and somatosenescence as well as impaired neuroendocrine immunoregulation at the level of the lymphocyte. In addition, somatosenescence may not be associated with a reciprocal decline in immunoreactive GH.

Psychoneurodendocrine correlates of lymphocyte subsets during healthy ageing.

Ageing has been associated with increased cortisol levels and absolute counts of T lymphocytes with memory phenotype. Although the mechanisms underlying these changes are still unknown, it has been speculated that this could be related to a dysfunction in FAS/CD95 expression in naive or memory cells. In this study, we investigated the role of psychoneuroendocrine variables in regulating CD95 expression on lymphocyte subsets. Forty-six elderly subjects (65-91 years) and 33 young adults (20-40 years) were recruited accordingly the SENIEUR protocol. The psychological status was measured by structured clinical interviews, salivary cortisol was assessed along the day (9, 12 and 22h) and peripheral blood lymphocytes were immunophenotyped. The elderly were more stressed, depressed and anxious than the young subjects. Cortisol levels were increased in the elderly, indicating an activation of the hypothalamic-pituitary-adrenal (HPA) axis. We observed reduced counts of CD45RA+CD95+ cells in the elderly compared to young adults. The elderly subjects also showed a reduced expression of CD3 and CD62L in contrast to increased CD95 expression in CD45RA+ cells. The emotional state was positively correlated with the lymphocyte markers. Our data suggest the healthy ageing is associated with psychoneuroendocrine alterations that may be implicated in the regulation of CD95 expression on peripheral T cells.

Impact of psychological and endocrine factors on cytokine production of healthy elderly people.

Human ageing has been associated with immunological changes including blunted T-cell responses and increased production of pro-inflammatory cytokines. Here, we investigated the role of psychological and endocrine factors in the production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin (IL)-6) as well as soluble IL-2Ralpha, associated with T-cell activation. Forty-six elderly subjects (60-91 yrs) and 33 young adults (20-40 yrs) were recruited accordingly the SENIEUR protocol. The emotional status was measured by structured clinical interviews. Salivary cortisol levels (9, 12 and 22 h) and serum dehydroepiandrosterone (DHEA) were assessed by radioimmunoassays. The elderly were more stressed, depressed and anxious than the young subjects. Cortisol levels were increased whereas DHEA levels were significantly reduced in the elderly. Both groups showed equivalent production of pro-inflammatory cytokines as well as soluble IL-2Ralpha. Psychological scores were positively correlated to evening cortisol levels and negatively correlated to morning DHEA levels. No relationships were noted between psychological factors and cytokines studied. However, evening cortisol levels were found positively correlated to TNF-alpha and sIL-2Ralpha levels. These data indicate that healthy ageing is associated with significant distress and activation of the hypothalamic-pituitary-adrenal axis. Our data also suggest that there are complex psychoneuroendocrine relationships involved with cytokine production during ageing.

A resposta adrenocortical em crianças submetidas a uma situação de estresse (relacionada à observação do comportamento e da interação com os cuidadores, considerando as variáveis "temperamento e apego") / Adrenocortical responses in children to a stress-situation (relation with observation of behavior and interaction with caregivers, considering variables

Medir a variação dos níveis de cortisol salivar em crianças antes e depois de serem submetidas a uma situação de estresse, comparando-a, através de filmagem, com a observação do apego aos cuidadores e com o temperamento da criança, conforme avaliado pelos pais, através de respostas a questionário aplicado pelos pesquisadores. Para avaliar o temperamento, utilizou-se uma escala auto-aplicada para pais, sendo cada criança enquadrada, de acordo com a soma das respostas, como apresentando temperamento difícil, intermediário e fácil. A situação de estresse, com a criança em companhia da mãe, compóstarês segmentos, ou três situações que se sucedem, denominadas "palhaço", "robô" e "fantoches", foi filmada por uma camêra de vídeo fixa. O apego foi avaliado por dois avaliadores independentes, através da observação dos vídeos realizados. O apego foi classificado em 4 níveis: seguro, suficientemente seguro, predominantemente inseguro, inseguro. Para o cortisol salivar, coletou-se a saliva das crianças em 3 momentos: cortisol salivar básico, coleta em um dia neutro; coleta 3 minutos antes da situação de estresse; coleta 30 minutos a pós o início da situação. Para a medida do cortisol salivar, utilizou-se o kit Coat-A-Count Cortisol da DPL com a técnica de radioimunoensaio. Os resultados não foram estatisticamente significativos. Evidencia-se uma variação de resultados, entrelaçando as variáveis estudadas, com destaque para algumas respostas adenocorticais individuais, que confirmam as questões apontadas pela literatura revisada. É recomendável que essa complexa pesquisa prossiga, com populações diversas e/ou maiores, cruzando outras variáveis, a fim de se tentar evidenciar padrôes individuais bioquímicos que a observação clínico-fenomenológica parece não distinguir.