Diurnal Cortisol Levels Research Articles

Perinatal hypothalamic-pituitary-adrenal axis regulation among women with eating disorders and their infants

BackgroundPsychiatric illness is associated with heightened hypothalamic-pituitary-adrenal (HPA) axis activity during pregnancy which may have long term effects on infant stress regulation. HPA axis regulation has not previously been investigated in women with eating disorders (ED) or their infants during the perinatal period. MethodsWomen were recruited to a prospective longitudinal study in three groups: 1) current or active ED (C-ED=31), 2) past ED (P-ED=29) and healthy control (HC=57). Maternal psychopathology, diurnal cortisol levels, corticotropin-releasing hormone (CRH) and CRH binding protein (CRH-BP) were measured during the third trimester of pregnancy. At eight weeks postpartum infant cortisol was obtained before and after routine immunisations to determine infant hormonal response to a stressful situation. ResultsWomen with current ED had a significantly lower cortisol decline throughout the day compared to HC, in both adjusted and unadjusted analyses. Lower cortisol decline among women with a current ED were associated with higher levels of psychopathology during pregnancy. Women’s cortisol awakening response, CRH and CRH-BP levels did not differ across the three groups. Infants’ stress response was also significantly higher among those in the C-ED group, although this effect was attenuated after controlling for confounders. ConclusionsDuring pregnancy women with ED have lower cortisol declines, suggestive of blunted diurnal cortisol rhythms. Postnatally, their infants also have a heightened response to stress. This is the first study to identify HPA axis dysfunction in pregnancy in women with ED, and to show an intergenerational effect. Since dysfunctions in HPA activity during childhood may represent a risk factor for psychological and physical health problems later in life, further investigation of the potential long-term implications of these findings is crucial.

Development and validation of an enzyme-linked immunosorbent assay for detection of cortisol in human saliva

ABSTRACTNon-invasive measurement of cortisol in saliva is of prime importance as it represents a bioavailable neuroendocrine marker for stress. Therefore, in this study, we developed an enzyme immune assay that was suitable for salivary cortisol measurements. For that purpose, rabbit polyclonal antibody was raised against cortisol-3-CMO:BSA conjugate. The test was based on competition of liquid phase cortisol with conjugated cortisol on the solid phase. Primary antibody was used to bind available sites on the conjugate, which was proportional to numbers of cortisol in liquid phase. Biotinylated secondary anti-rabbit antibody was used to detect primary antibodies by addition of streptavidin peroxidase and substrate, respectively. Color formation was stopped and yellow color was read by a plate-reader spectrophotometer. Additionally, validated test was used to met all validation criteria including. Test developed was used to establish cortisol awakening response (CAR) in saliva samples collected in the morning after awakening (0, 15, 30, and 60th min) from women (n = 4) and men (n = 4) at 8 or 4 different days, respectively. Diurnal cortisol levels were assessed (n = 8) at after awaking 60 min at morning, 12:00, 19:00, and 22:00 hr. In conclusion, an enzyme immunoassay test was successfully produced, validated and used for cortisol measurement in saliva samples.

Effect of the interaction between childhood abuse and rs1360780 FKBP5 gene on cortisol awakening response and diurnal cortisol levels in first episode psychosis

Effect of the interaction between childhood abuse and rs1360780 FKBP5 gene on cortisol awakening response and diurnal cortisol levels in first episode psychosis

Neuroanatomical correlates of HPA axis biomarkers among children at elevated risk for schizophrenia

Background: The hypothalamic-pituitary-adrenal (HPA) axis disturbances observed in psychosis might feasibly contribute to some of the structural brain abnormalities associated with the disorder (i.e., via the potentially toxic effects of elevated glucocorticoid levels on the brain). However, the association between brain structure and cortisol has rarely been investigated. The current study examined relationships between salivary cortisol and regional brain volumes among at-risk children aged 11-14 years, who present multiple antecedents of schizophrenia (ASz=30) or a family history of illness (FHx=22), and typically-developing children (TD=32). Methods: Volumes of specific brain regions known to express glucocorticoid receptors were extracted from structural brain images using FreeSurfer. Diurnal cortisol levels and the cortisol awakening response (CAR) were determined from multiple salivary cortisol samples obtained throughout the day. Results: In the FHx group only, higher diurnal cortisol was correlated with smaller right amygdala and white matter hypointensity volumes (r=-0.51 and -0.62, respectively, p<0.05). In post-hoc analyses, a higher CAR was associated with smaller bilateral cerebellum, bilateral hippocampus, right ventral diencephalon, and total subcortical grey matter volumes among FHx children with a first-degree relative with schizophrenia. In FHx children with an affected second-degree relative, increased diurnal cortisol levels were associated with smaller left hippocampal and white matter hypointensity volumes. Conclusions: Our findings are consistent with the few previous studies examining cortisol and brain structure among adults with established psychosis. These associations may not necessarily reflect a direct effect of cortisol on the developing brain; indeed, abnormal neurodevelopment affecting these brain regions may contribute to HPA-axis dysregulation. Funding: This work was supported by a Sir Henry Wellcome Postdoctoral Fellowship (107395/Z/15/Z) and a Waterloo Foundation Child Development Fund grant (164/1719)

Exploring the relationship between disease-related pain and cortisol levels in women with osteoarthritis

To determine if (1) Osteoarthritis (OA)-related pain is associated with the diurnal cortisol pattern and cortisol levels; (2) the diurnal pattern of cortisol varies with severity of OA pain and (3) the association between OA pain and cortisol is mediated by daily experience variables (DEV). In a community-based study of changes in regional and widespread pain among women with OA, participants (n=31) completed daily diaries and collected three saliva samples daily for 7 days. Severity of OA-related pain was assessed by the validated Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Multilevel regression analyses estimated associations between OA pain and diurnal cortisol levels and slopes, controlling for body mass index (BMI), medication use, time and day. Mediation analyses examined DEV as potential mediators of the association between OA pain and cortisol. The mean age was 57 years and average BMI 31kg/m2. Mean WOMAC pain subscale score was 8.8. Women with higher WOMAC pain scores had higher cortisol throughout the day. The estimated association of WOMAC with cortisol [β 0.083(0.02, 0.15) P=0.009] represents a ∼9% increase in cortisol for every unit increase in WOMAC pain score. Women with WOMAC pain scores ≥9 had higher cortisol levels than those with scores <9. Examination of DEV revealed no significant mediated associations between these relationships at the daily level. In women with OA, disease-related pain is positively associated with cortisol production, particularly with greater pain severity. Future studies should explore biologic mediating variables between OA pain and cortisol.

Hypothalamic-pituitary-adrenal axis measures and cognitive abilities in early psychosis: Are there sex differences?

IntroductionMeasures of hypothalamic-pituitary-adrenal (HPA) axis activity such as increased diurnal cortisol levels or a blunted cortisol awakening response (CAR) have been associated with cognitive impairments in people with psychotic disorders. We aimed to explore whether there are sex differences in the relationship between HPA axis measures and cognition in early psychosis (EP). Methods60 EP outpatients and 50 healthy subjects (HS) were assessed with the MATRICS Consensus Cognitive Battery. Saliva cortisol levels were determined at the neuropsychological assessment and on another day at 6 sampling times: awakening; 30′ and 60′ post-awakening; and 10:00h, 23:00h and 10:00h the day after the administration of 0.25mg of dexamethasone, which occurred at 23:00h. Three HPA axis measures were calculated: CAR, cortisol diurnal slope and cortisol suppression ratio of the dexamethasone suppression test (DST). Multiple linear regression analyses were conducted to explore the relationship between HPA axis measures and cognitive tasks while adjusting for covariates (education level, smoking, cannabis use, and cortisol levels at the cognitive assessment). Interactions between female sex, EP diagnosis and HPA axis measures were examined. ResultsAn increased CAR was associated with a poorer cognitive performance in EP women in processing speed and verbal memory. In contrast, a more flattened diurnal cortisol slope was associated with poorer functioning in the spatial working memory of EP women. DST suppression ratio was associated with better visual memory, without sex differences. ConclusionsOur study suggests that there are sex differences in the relationship between HPA axis measures and cognitive abilities in EP.

Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in elderly men and women.

Elevated cortisol levels with aging have been associated with atrophy of the hippocampus and prefrontal cortex (PFC), as well as with impaired cognitive functions in men. However, coexisting diseases have confounded many studies examining these relationships. Studies in women are lacking. Our objective was to test whether salivary cortisol levels were related to morphology of the hippocampus and the PFC, and to cognitive performance. A cross-sectional study including 200 elderly (55-80 years old) men and women. We used magnetic resonance imaging, tests of episodic-, semantic-, and working memory, visuospatial ability, and cortisol levels in four saliva samples collected during 1 day. Area under the curve (AUC) for cortisol levels was negatively related to cortical surface area of the left anterior cingulate gyrus (caudal P<0.001; rostral P=0.006), right lateral orbitofrontal cortex (P=0.004), and right rostral middle frontal gyrus (P=0.003). In women, there was also a negative relationship with cortical surface area in the left rostral middle frontal gyrus (P=0.006). No relationship was found between cortisol levels and hippocampal volume. This study suggests that the structure of the medial PFC is related to cortisol levels in both elderly women and men.

Associations between psychiatric symptoms and cortisol levels in Nicaraguan young school-age children

The regulation of the Hypothalamus-Pituitary-Adrenal axis (HPA-axis) with its end product cortisol seems to be affected in several psychiatric disorders. Although findings are not conclusive, internalizing symptoms have primarily been associated with higher diurnal cortisol levels and externalizing symptoms with lower cortisol levels. In this study on nine-year-olds in Nicaragua (n=111), we investigated associations between child psychiatric symptoms, using the Child Behavior Check List (CBCL), and saliva cortisol levels collected in the morning and afternoon, also adjusting for potential confounders. In line with previous findings, internalizing symptoms were significantly associated with higher morning, but not afternoon cortisol levels. Surprisingly, externalizing symptoms were also significantly associated with higher morning cortisol levels. Possibly, this association between externalizing symptoms and cortisol levels may be characteristic of early ages, representing a higher exposure to external stressors. The study highlights the need for prospective studies, following the development of the HPA-axis and its association with psychiatric symptoms.

Multidimensional assessment of neuroendocrine and psychopathological profiles in maltreated youth.

It has been debated whether children who have experienced early life stress (ELS), such as early caregiver separation show elevated risk for stress-related psychiatric disorders and a multi-symptom psychopathological profile that is not fully reflected in categorical assessments. In this study, we investigated dimensional measures of stress-related psychopathology in children in permanent out-of-home care, taking into account potential neuroendocrine interactions. In the current study, 25 children who had been placed in permanent out-of-home care before age 3 (years) and 26 controls (aged 10.6 ± 1.75 years) were investigated with categorical (DSM-IV) and dimensional assessments (CBCL) of psychopathology and diurnal salivary cortisol levels were assessed. Semi-structured interviews (K-DIPS) revealed no significant group differences in full-scale psychiatric diagnoses, whereas dimensional assessment (CBCL) revealed significant group differences in externalizing and total problem behaviours within the clinical range for children with ELS. Only children with ELS showed a combined symptom profile of clinical-range internalizing and externalizing problems. Lower morning cortisol values and subsequent flatter decline was found in subjects with ELS children compared to controls, showing group differences in diurnal cortisol secretion. Lower morning cortisol values were associated with more problem behaviour in the ELS group. Results show that ELS children exhibited increased psychopathological symptom severity and complexity associated with lower morning cortisol levels, which was not fully reflected in categorical assessments. This highlights the importance of incorporating dimensional assessments and neurobiological factors into psychopathological evaluations of children in out-of-home care in order to facilitate early identification of children at high risk for stress-related disorders.

Endocrine dysregulation in women with irritable bowel syndrome according to Rome II criteria.

The etiology of the irritable bowel syndrome (IBS) is unexplained: biological, psychological and social factors must be considered. This study examined if differences in HPA-axis activity already exist in those who do not yet fulfill IBS criteria (i.e. "subthreshold IBS"). We also investigated whether there were differences between those who reported clinically relevant (i.e. distressing) IBS symptoms and those who did not. Thirty-six women were subdivided into three groups (IBS group, subthreshold IBS group, control group). Results showed differences in morning cortisol levels (U=11.58; p<0.05), with IBS patients showing a lower cortisol response compared to controls. Subthreshold IBS patients were comparable to controls regarding endocrine function. Diurnal cortisol levels did not differ between groups. Group comparisons between distressed subjects and non-distressed subjects regarding cortisol levels did not reach significance. The finding of endocrine abnormalities (at least in a sub-set of patients) is important since these might be associated with deficient pain processing in IBS.

Salivary Cortisol Levels and Depressive Symptomatology in Consumers and Nonconsumers of Self-Help Books: A Pilot Study.

The self-help industry generates billions of dollars yearly in North America. Despite the popularity of this movement, there has been surprisingly little research assessing the characteristics of self-help books consumers, and whether this consumption is associated with physiological and/or psychological markers of stress. The goal of this pilot study was to perform the first psychoneuroendocrine analysis of consumers of self-help books in comparison to nonconsumers. We tested diurnal and reactive salivary cortisol levels, personality, and depressive symptoms in 32 consumers and nonconsumers of self-help books. In an explorative secondary analysis, we also split consumers of self-help books as a function of their preference for problem-focused versus growth-oriented self-help books. The results showed that while consumers of growth-oriented self-help books presented increased cortisol reactivity to a psychosocial stressor compared to other groups, consumers of problem-focused self-help books presented higher depressive symptomatology. The results of this pilot study show that consumers with preference for either problem-focused or growth-oriented self-help books present different physiological and psychological markers of stress when compared to nonconsumers of self-help books. This preliminary study underlines the need for additional research on this issue in order to determine the impact the self-help book industry may have on consumers' stress.

Polymorphisms in the FK506 binding protein 5 gene are associated with attention deficit hyperactivity disorder and diurnal cortisol levels.

目的 之前的研究显示儿童注意缺陷多动障碍(attention deficit hyperactivity disorder，ADHD)和肾上腺皮质轴(hypothalamus-pituitary-adrenal axis，HPA轴)受抑制的低皮质醇水平相关。鉴于FK506结合蛋白5(FK506 binding protein 5，FKBP5)作为一个重要的调节因子调控HPA轴负反馈系统，我们试图研究FKBP5单核酸多态性(single nucleotide polymorphisms，SNP)与ADHD和日间皮质醇水平之间可能的相关性。 方法 在正常上学日收集ADHD患儿(n＝81)和健康对照儿童(n＝88)的唾液应用放射免疫法分析日间皮质醇水平和FKBP5中五个SNP(rs9296158、rs1360780、rs9470080、rs7748266和rs9394309)。 结果 SNP基因型和ADHD之间以及SNP基因型和多动症和日间皮质醇之间存在相关性。rs9470080，与多动症和低皮质醇水平都显著相关。 结论 本研究通过证实ADHD、低皮质醇水平和FKBP5基因SNPs的相关性有助于之前关于ADHD儿童HPA轴下调的发现。这些发现与发育和ADHD临床症候群的形成的关系还需要较大样本的研究，最好考虑到应激反应。

The predictive value of cortisol levels on 2-year course of depression in older persons

BackgroundDepressive disorders in older persons are associated with an altered functioning of the Hypothalamic–Pituitary–Adrenal (HPA)-axis. In adults, a lower cortisol awakening response is a predictor of a worse prognosis of depression, but to date longitudinal studies in older depressed persons are lacking. We hypothesised that a lower cortisol awakening response is also associated with poorer course of depression in later life. MethodsData were derived from the Netherlands Study of Depression in Older Persons (NESDO). Participants with a 6-month Major Depressive Disorder (MDD), who provided 2-year follow-up data, were included (n=246). Logistic regression analyses were conducted to examine the association between diurnal cortisol levels and depressive status at 2-year follow-up. ResultsBoth lower (OR=3.54; 95% CI=1.59–7.89) and higher evening cortisol levels (OR=2.41; 95% CI=1.09–5.35) at baseline were associated with poorer prognosis of MDD. Low dexamethasone suppression was associated with poorer course (OR=2.37; 95% CI=1.09–5.16), but failed to reach significance after additional adjustment for severity and chronicity of MDD (OR=1.98; 95% CI=0.89–4.42). Cortisol awakening response was not significantly associated with course. Since smoking has a great impact on cortisol levels, we conducted post-hoc analyses including non-smokers only, indicating that lower evening cortisol levels (OR=2.83, 95% CI=1.31–6.13) predicted unfavourable course. ConclusionsThis first longitudinal study on cortisol and prognosis of depression in older persons demonstrates that in particular lower evening cortisol levels may predict poorer course in MDD. This finding may have clinical implications. Evening cortisol values may serve as a marker to identify persons at risk for an unfavourable course.

Bad sleep? Don't blame the moon! A population-based study

IntroductionThe aim of this study was to evaluate if there is a significant effect of lunar phases on subjective and objective sleep variables in the general population. MethodsA total of 2125 individuals (51.2% women, age 58.8 ± 11.2 years) participating in a population-based cohort study underwent a complete polysomnography (PSG) at home. Subjective sleep quality was evaluated by a self-rating scale. Sleep electroencephalography (EEG) spectral analysis was performed in 759 participants without significant sleep disorders. Salivary cortisol levels were assessed at awakening, 30 min after awakening, at 11 am, and at 8 pm. Lunar phases were grouped into full moon (FM), waxing/waning moon (WM), and new moon (NM). ResultsOverall, there was no significant difference between lunar phases with regard to subjective sleep quality. We found only a nonsignificant (p = 0.08) trend toward a better sleep quality during the NM phase. Objective sleep duration was not different between phases (FM: 398 ± 3 min, WM: 402 ± 3 min, NM: 403 ± 3 min; p = 0.31). No difference was found with regard to other PSG-derived parameters, EEG spectral analysis, or in diurnal cortisol levels. When considering only subjects with apnea/hypopnea index of <15/h and periodic leg movements index of <15/h, we found a trend toward shorter total sleep time during FM (FM: 402 ± 4, WM: 407 ± 4, NM: 415 ± 4 min; p = 0.06) and shorter-stage N2 duration (FM: 178 ± 3, WM: 182 ± 3, NM: 188 ± 3 min; p = 0.05). ConclusionOur large population-based study provides no evidence of a significant effect of lunar phases on human sleep.

Pituitary gland volume and psychosocial stress among children at elevated risk for schizophrenia.

Pituitary volume enlargements have been observed among individuals with first-episode psychosis. These abnormalities are suggestive of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, which may contribute to the development of psychosis. However, the extent to which these abnormalities characterize individuals at elevated risk for schizophrenia prior to illness onset is currently unclear, as volume increases, decreases and no volume differences have all been reported relative to controls. The current study aimed to determine whether antipsychotic-naive, putatively at-risk children who present multiple antecedents of schizophrenia (ASz) or a family history of illness (FHx) show pituitary volume abnormalities relative to typically developing (TD) children. An additional aim was to explore the association between pituitary volume and experiences of psychosocial stress. ASz (n = 30), FHx (n = 22) and TD (n = 32) children were identified at age 9-12 years using a novel community-screening procedure or as relatives of individuals with schizophrenia. Measures of pituitary volume and psychosocial stress were obtained at age 11-14 years. Neither ASz nor FHx children showed differences in pituitary volume relative to TD children. Among FHx children only, pituitary volume was negatively associated with current distress relating to negative life events and exposure to physical punishment. The lack of pituitary volume abnormalities among ASz and FHx children is consistent with our previous work demonstrating that these children are not characterized by elevated diurnal cortisol levels. The findings imply that these biological markers of HPA axis hyperactivity, observed in some older samples of high-risk individuals, may emerge later, more proximally to disease onset.

Polymorphisms in the FK506 binding protein 5 gene are associated with attention deficit hyperactivity disorder and diurnal cortisol levels.

Previous studies have shown an association between childhood attention deficit hyperactivity disorder (ADHD) and a down-regulated hypothalamus-pituitary-adrenal axis (HPA axis) with low diurnal cortisol levels. Given the role of the FK506 binding protein 5 (FKBP5) as an important regulator of the negative feedback system of the HPA axis, we set out to investigate possible associations between single nucleotide polymorphisms (SNPs) in FKBP5 in relation to ADHD and diurnal cortisol levels. Children with ADHD (n=81) and healthy comparisons (n=88) collected saliva four times during a regular school day for radioimmunoassay analysis of cortisol and for genotyping of five SNPs in FKBP5 (rs9296158, rs1360780, rs9470080, rs7748266 and rs9394309). We found associations between SNP genotypes and ADHD as well as between genotypes and diurnal cortisol levels. One of these SNPs, rs9470080, was significantly associated with both ADHD and lower cortisol levels. This study contributes to previous findings on a down-regulated HPA axis in children with ADHD by demonstrating an association between ADHD, lower cortisol levels and SNPs of the FKBP5-gene. The relevance of these findings for the development and shaping of ADHD symptoms needs to be approached in larger samples, preferably also taking stress reactivity into consideration.

Association of Sleep Duration and Quality With Alterations in the Hypothalamic-Pituitary Adrenocortical Axis: The Multi-Ethnic Study of Atherosclerosis (MESA).

Short sleep duration and poor sleep quality are associated with cardiovascular outcomes. One mechanism proposed to explain this association is altered diurnal cortisol secretion. The objective of the study was to examine the associations of sleep duration and sleep quality with diurnal salivary cortisol levels. This was a cross-sectional analysis using data from examination 5 (2010-2012) of the Multi-Ethnic Study of Atherosclerosis. Actigraphy-based measures of sleep duration and efficiency were collected over 7 days, and salivary cortisol samples were collected over 2 days from participants aged 54-93 years (n = 600 with analyzable data). Shorter average sleep duration (<6 h/night) was associated with less pronounced late decline in cortisol [2.2% difference in slope; 95% confidence interval (CI) 0.8-3.7; P ≤ .01] and less pronounced wake-to-bed slope (2.2% difference; 95% CI 1.0-3.4; P ≤ .001) compared with longer sleep duration (≥6 h/night). Lower sleep efficiency (<85%) was associated with less pronounced early decline in cortisol (29.0% difference in slope; 95% CI 4.1-59.7; P < .05) compared with higher sleep efficiency (≥85%). Subjects reporting insomnia had a flatter cortisol awakening response (-16.1% difference in slope; 95% CI -34.6 to -0.1; P < .05) compared with those not reporting insomnia. Shorter sleep duration, lower sleep efficiency, and insomnia are associated with alterations in diurnal cortisol levels consistent with changes in hypothalamic-pituitary-adrenal regulation.

Income, cumulative risk, and longitudinal profiles of hypothalamic–pituitary–adrenal axis activity in preschool-age children

Environmental risk predicts disrupted basal cortisol levels in preschool children. However, little is known about the stability or variability of diurnal cortisol morning levels or slope patterns over time in young children. This study used latent profile analysis to identify patterns of the hypothalamic-pituitary-adrenal axis activity during the preschool period. Using a community sample (N = 306), this study measured income, cumulative risk, and children's diurnal cortisol (morning level and slope) four times across 2.5 years, starting when children were 36 months old. Latent profile analysis profiles indicated that there were predominantly stable patterns of diurnal cortisol level and slope over time and that these patterns were predicted by income and cumulative risk. In addition, there were curvilinear relations of income and cumulative risk to profiles of low morning cortisol level and flattened diurnal slope across time, suggesting that both lower and higher levels of income and cumulative risk were associated with a stress-sensitive physiological system. Overall, this study provides initial evidence for the role of environmental risk in predicting lower, flattened basal cortisol patterns that remain stable over time.

Evaluation of a hospital-based day-structuring exercise programme on exacerbated behavioural and psychological symptoms in dementia--the exercise carrousel: study protocol for a randomised controlled trial.

BackgroundConceptual reviews and observational studies describe a link between physical inactivity and behavioural disturbances in people with dementia. Consequently, treatment of these symptoms requires physical activation and pharmacological or physical immobilization should be avoided. The few trials that have been conducted in inpatient dementia care to investigate the effects of exercise on behavioural and psychological symptoms revealed inconsistent results. Due to a lack of evidence, there is a paucity of recommendations for physical activation in this stage of care. Therefore, this trial seeks to investigate the effects of a day-structuring exercise programme on behavioural and psychological symptoms as well as on circadian rhythms of patients with dementia, hospitalized because of their behavioural and psychological disturbances.Methods/DesignA single-centre randomised controlled trial will be conducted in three special dementia care units of an old age psychiatry hospital. Enrolled patients will receive either a 2-week exercise programme, or a 2-week social stimulation programme in addition to usual care. Due to the provision of four day-structuring exercise-sessions in the course of an intervention day, the exercise programme for the study group is called exercise-carrousel. Baseline and post-intervention assessment for the primary outcome variable - the overall effects on behavioural and psychological symptoms - will be measured by the Alzheimer's disease Cooperative Study-Clinical Global Impression of Change. The following objectives are set up as secondary outcomes: dimensions of the behavioural and psychological symptoms of dementia (BPSD) and caregiver burden, routine and on-demand psychotropic medication, patients’ motor behaviour, diurnal cortisol-levels from saliva probes and brain-derived neurotrophic factor-levels from blood serum.DiscussionIn order to be regarded as an important treatment option for behavioural and psychological symptoms, physical activation in inpatient hospital dementia care requires more evidence and appropriate recommendations. Respecting hospital routines and the intra-daily variability of the patients’ motivation and behavioural disturbances in the provision of exercise sessions could lead to higher exercise adherence and better effects on patients’ behavioural and psychological symptoms than former trials have presented. The concealment of allocation throughout the trial and the rating of individual exercise exertion present the key challenges and main limitations of this trial.Trial registrationDRKS00006740 (German Clinical Trial Register, date of registration: 28 October 2014).

Cortisol and Inflammatory Biomarkers Predict Poor Treatment Response in First Episode Psychosis.

Background: Cortisol and inflammatory markers have been increasingly reported as abnormal at psychosis onset. The main aim of our study was to investigate the ability of these biomarkers to predict treatment response at 12 weeks follow-up in first episode psychosis. Methods: In a longitudinal study, we collected saliva and blood samples in 68 first episode psychosis patients (and 57 controls) at baseline and assessed response to clinician-led antipsychotic treatment after 12 weeks. Moreover, we repeated biological measurements in 39 patients at the same time we assessed the response. Saliva samples were collected at multiple time points during the day to measure diurnal cortisol levels and cortisol awakening response (CAR); interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ (IFN-γ) levels were analyzed from serum samples. Patients were divided into Non-Responders (n = 38) and Responders (n = 30) according to the Remission symptom criteria of the Schizophrenia Working Group Consensus. Results: At first onset, Non-Responders had markedly lower CAR (d = 0.6, P = .03) and higher IL-6 and IFN-γ levels (respectively, d = 1.0, P = .003 and d = 0.9, P = .02) when compared with Responders. After 12 weeks, Non-Responders show persistent lower CAR (P = .01), and higher IL-6 (P = .04) and IFN-γ (P = .05) when compared with Responders. Comparison with controls show that these abnormalities are present in both patients groups, but are more evident in Non-Responders. Conclusions: Cortisol and inflammatory biomarkers at the onset of psychosis should be considered as possible predictors of treatment response, as well as potential targets for the development of novel therapeutic agents.