•Chronic fatigue syndrome (CFS) and atypical MDE (A-MDE) share several clinical and neurobiological features, such as low short-term cortisol output, using saliva samples.•Decreased short-term ...cortisol level may be transient since cortisol levels were normal when long-term cortisol level, using hair specimen was studied.•Both disorders may be part of the wider group of somatic symptom disorder (SSD), given the similar cortisol and clinical results.
Several diagnostic criteria for major depressive disorder (MDE) overlap with those of Chronic Fatigue Syndrome (CFS). Furthermore, atypical MDE (A-MDE), a subtype of MDE characterised by profound fatigue and which has frequently been linked with CFS, exhibits similar low cortisol levels to CFS. However, this result has been only found in specimens designed for measuring acute cortisol levels. In this study, we measure cortisol levels in subjects with CFS and in subjects with A-MDE, without psychiatric comorbidity, using both hair and saliva specimens, to gain a measure of both short and long-term cortisol levels in these two conditions.
Hair cortisol concentration, representing the cortisol concentration of the previous three months, and salivary cortisol, measured at six time-points across one day and including the cortisol awakening response (CAR), post-awakening delta cortisol and the total daily output, were assessed in an age and gender matched group of 34 controls, 15 subjects with A-MDE and 17 with CFS.
CFS (mean 92.2 nmol/l.h, s.d. 33.2 nmol/l.h) and A-MDE (mean 89.1 nmol/l.h, s.d. 22.6 nmol/l.h) subjects both showed lower cortisol total daily output in saliva (AUCg) in comparison to healthy controls (mean 125.5 nmol/l.h, s.d. 40.6 nmol/l.h). However, hair cortisol concentration was not lower than that of controls in either patient group. CFS and A-MDE did not differ from one another on any cortisol measures. CFS subjects reported fewer daily hassles and less severe psychic anxiety symptoms in comparison to A-MDE subjects (all p < 0.05). However, they did not differ in the severity of somatic anxiety symptoms. There was also no difference in the presence of overlapping symptoms such as fatigability and concentration/memory problems between A-MDE and CFS subjects.
Low levels of cortisol found using short-term measures of daily output may be transient, since cortisol levels were normal when a long-term measure (hair) was studied. This might be explained by a potential cortisol rhythm alteration. Although these disorders have their distinctive depressive and somatic features, they may from part of a wider group of Somatic Symptom Disorders (SSD), given the findings of the same pattern of cortisol secretion in both disorders and increased frequency of overlapping clinical features.
Summary Background and aims Childhood trauma may have longstanding effects on individuals’ propensity to react adversely to stress, and also predisposes individuals to suffer from depression. The ...current study aimed to examine stress reactivity in individuals with and without a history of childhood trauma by measuring cortisol responses to the passive viewing of stressful images, specifically including images relevant to childhood trauma. In addition, participants with and without a diagnosis of current depression were studied to investigate whether cortisol stress reactivity may underlie resilience or vulnerability to depression. Methods The study involved 17 healthy participants with and 24 without a history of childhood trauma; and 21 depressed patients with and 18 without a history of childhood trauma. Salivary cortisol was measured before, during and after participants were shown affectively laden images, including standardised scenes from the International Affective Picture System and also images suggestive of childhood abuse. Cortisol stress reactivity to the passive image viewing was compared between groups. Results In those who had experienced childhood trauma, cortisol stress responses were overall low and the same in those who were depressed and those who were not (mean stress reactivity variable – depressed: 0.8 nmol/l; non-depressed: 0.72 nmol/l). In contrast, cortisol stress reactivity was raised in depressed subjects relative to those who were not depressed in those without a history of childhood trauma (mean stress reactivity variable – depressed: 3.75 nmol/l; non-depressed: 0.1 nmol/l). Conclusions A history of childhood trauma has longstanding effects on adulthood cortisol responses to stress, particularly in that depressed individuals with a history of childhood trauma show blunted cortisol responses. However, there were no differences between abused depressed and abused non-depressed subjects on cortisol stress responses, suggesting that such a finding does not explain subsequent susceptibility to depression. On the other hand, patients who experience depression without a history of childhood trauma show enhanced cortisol stress reactivity, which could help explain the aetiology of their depressive illnesses. Differences between the current findings and those using other pharmacological and stress challenge paradigms may relate to the type of stimuli used and to dysfunction at different levels of the hypothalamic–pituitary–adrenal (HPA) axis.
Treatment resistance is a common clinical phenomenon in depression. However, current unitary models of staging fail to represent its complexity. We aimed to devise a model to stage ...treatment-resistant depression, taking into account the core factors contributing to treatment failure.
We reviewed the literature to identify factors consistently associated with treatment resistance. We also analyzed data from a subgroup of patients discharged from a specialist inpatient unit for whom adequate data were obtainable.
We present a points-based staging model incorporating 3 factors: treatment, severity of illness, and duration of presenting episode. In this model, the rating of symptom severity ranges from subsyndromal depression (score 1) to severe syndromal depression with psychosis (score 5). Antidepressant treatment is rated on a 5-point subscale based on number of medications used, while duration of the presenting episode is rated on a 3-point subscale. The overall level of resistance estimated using this model varies from minimal resistance (score of 3) to severe resistance (score of 15). The rating system allows the overall severity of treatment resistance to be summarized either as a single numeric score or under a single descriptive category. It may also be possible to specify categories (mild, moderate, and severe) based on severity of resistance. Analysis of inpatient data indicates that the factors incorporated in the model and the model itself have some predictive validity.
This staging model has reasonable face and predictive validity and may have better utility in staging treatment resistance than currently available methods.
Pharmacological augmentation is a recommended strategy for patients with treatment-resistant depression. A range of guidelines provide advice on treatment selection, prescription, monitoring and ...discontinuation, but variation in the content and quality of guidelines may limit the provision of objective, evidence-based care. This is of importance given the side effect burden and poorer long-term outcomes associated with polypharmacy and treatment-resistant depression. This review provides a definitive overview of pharmacological augmentation recommendations by assessing the quality of guidelines for depression and comparing the recommendations made.
A systematic literature search identified current treatment guidelines for depression published in English. Guidelines were quality assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Data relating to the prescription of pharmacological augmenters were extracted from those developed with sufficient rigor, and the included recommendations compared.
Total of 1696 records were identified, 19 guidelines were assessed for quality, and 10 were included. Guidelines differed in their quality, the stage at which augmentation was recommended, the agents included, and the evidence base cited. Lithium and atypical antipsychotics were recommended by all 10, though the specific advice was not consistent. Of the 15 augmenters identified, no others were universally recommended.
This review provides a comprehensive overview of current pharmacological augmentation recommendations for major depression and will support clinicians in selecting appropriate treatment guidance. Although some variation can be accounted for by date of guideline publication, and limited evidence from clinical trials, there is a clear need for greater consistency across guidelines to ensure patients receive consistent evidence-based care.
•Systematic review on polymorphisms in HPA axis genes and antidepressant response•No relationship between SNPs in AVP and AVPR1A and treatment response•Equivocal findings in terms of NR3C1, NR3C2, ...and FKBP5•Specific polymorphisms in CRHBP, CRHR1, and POMC predicted non-response
Around 50% of depressed patients do not respond to antidepressants. Evidence from familial studies suggests a genetic component to this. This study investigated whether patients with polymorphisms in genes related to the hypothalamic-pituitary-adrenal (HPA) axis were less likely to respond to antidepressants.
EMBASE, MEDLINE, PsycINFO, and the Cochrane Library were searched. Inclusionary criteria were: 1) patients with depression, 2) study of HPA axis-related candidate genes, 3) at least four weeks of antidepressants, and 4) assessment of depressive symptoms dividing patients into non-responders and responders.
Nineteen studies were identified. Non-responders and responders did not differ in single nucleotide polymorphisms (SNPs) in genes encoding arginine vasopressin. Findings were equivocal regarding genes encoding the FK506 binding protein 5 and glucocorticoid and mineralocorticoid receptors. Specific SNPs and haplotypes within genes related to corticotropin-releasing hormone (CRHBP, CRHR1) and melanocortins (POMC) predicted non-responder status.
Replication studies and additional investigations exploring gene x environment and drug x environment interactions are necessary before pharmacological treatments may be adjusted based on a patient’s genetic profile.
Depression is one of the commonest mental disorders in primary care but is poorly identified. The objective of this review was to determine the level of detection of depression by primary care ...clinicians and its determinants in studies from low- to middle-income countries (LMICs).
A systematic review and meta-analysis was conducted using PubMed, PsycINFO, MEDLINE, EMBASE, LILAC, and AJOL with no restriction of year of publication. Risk of bias within studies was evaluated with the Effective Public Health Practice Project (EPHPP). "Gold standard" diagnosis for the purposes of this review was based on the 9-item Patient Health Questionnaire (PHQ-9; cutoff scores of 5 and 10), other standard questionnaires and interview scales or expert diagnosis. Meta-analysis was conducted excluding studies on special populations. Analyses of pooled data were stratified by diagnostic approaches.
A total of 3159 non-duplicate publications were screened. Nine publications, 2 multi-country studies, and 7 single-country studies, making 12 country-level reports, were included. Overall methodological quality of the studies was good. Depression detection was 0.0% in four of the twelve reports and < 12% in another five. PHQ-9 was the main tool used: the pooled detection in two reports that used PHQ-9 at a cutoff point of 5 (combined sample size = 1426) was 3.9% (95% CI = 2.3%, 5.5%); in four reports that used PHQ-9 cutoff score of 10 (combined sample size = 5481), the pooled detection was 7.0% (95% CI = 3.9%, 10.2%). Severity of depression and suicidality were significantly associated with detection.
While the use of screening tools is an important limitation, the extremely low detection of depression by primary care clinicians poses a serious threat to scaling up mental healthcare in LMICs. Interventions to improve detection should be prioritized.
PROSPERO CRD42016039704 .
•It would be desirable to screen large cohorts online for vulnerability to psychiatric illness.•Conventional psychiatric screening tools risk overmedicalizing normal emotional reactions.•The Trait ...Self-Description Inventory (TSDI) is a brief, free-to-use, online non-clinical personality questionnaire designed for occupational use.•We show the TSDI is sensitive to affective disorder symptoms when administered online in a sample of 8,470 individuals.
Online assessments allow cost-effective, large-scale screening for psychiatric vulnerability (e.g., university undergraduates or military recruits). However, conventional psychiatric questionnaires may worsen mental health outcomes due to overmedicalizing normal emotional reactions. Personality questionnaires designed for occupational applications could circumvent this problem as they utilise non-clinical wording and it is well-established that personality traits influence susceptibility to psychiatric illness. Here we present a brief, free-to-use occupational personality questionnaire, and test its sensitivity to symptoms of Bipolar Disorder (BD) and Major Depressive Disorder (MDD) in an online sample. Our study used a cross-sectional, self-report design to assess the relationship between self-reported symptoms of affective disorders and scores on the personality dimensions of openness, conscientiousness, extraversion, agreeableness and neuroticism. We used SEM to compare affective symptoms in 8,470 individuals (mean age 25.6 ± 7.0 years; 4,717 male) with scores on an online adaption of the TSDI, a public-domain ‘Big Five’ personality questionnaire. ROC curve analyses assessed cut off scores for the best predictors of overall vulnerability to affective disorders (represented by a composite screening score). Neuroticism was the most robust predictor of QIDS-16 depression symptoms and MDQ Hypomania symptoms (β = 0.68 and 0.39 respectively, p < .0001). Extraversion was the most robust predictor of HCL-16 Hypomania symptoms (β = 0.34, p < .0001). ROC curve analyses suggest if the TSDI was used for screening in this sample, neuroticism cut offs of approximately 58 for men and 70 for women would provide the most useful classification of overall vulnerability to affective disorders.
There is uncertainty as to whether alterations in glutamatergic function in affective disorders differ between unipolar and bipolar disorders and between depressive and euthymic states. Additionally, ...there are currently no available blood-based markers of central glutamatergic function to support clinical diagnosis and aid brain based investigations.
In this study, we measured levels of glutamate in the dorsal anterior cingulate cortex in-vivo using 1H-Magnetic Resonance Spectroscopy in medication free unipolar and bipolar patients (n = 29, 20 unipolar and 9 bipolar) experiencing a major depressive episode, in comparison with a group of matched healthy controls (n = 20). We also analysed peripheral glutaminase measured in serum to examine the relationship between central and peripheral measures.
Anterior cingulate glutamate levels were reduced in both unipolar and bipolar depression groups relative to healthy controls, although this only reached significance in the unipolar group. Peripheral glutaminase levels did not differentiate bipolar from unipolar depression and a positive correlation with central glutamate levels did not reach statistical significance.
The sample of bipolar disorder patients was relatively small due to the difficulties involved in finding medication-free patients experiencing a depressive episode.
These results suggest that glutamatergic hypofunction might represent a state marker for a depressive episode irrespective of diagnosis. Peripheral glutaminase did not index central glutamate levels in this study, which could potentially reflect a small magnitude of the effect requiring larger samples for detection.
•Glutamate has been implicated in the pathology and treatment of both unipolar and bipolar depression.•We quantified glutamate levels in the anterior cingulate cortex of patients with unmedicated unipolar and bipolar depression.•Glutamate levels were similarly reduced in both patient groups relative to healthy individuals.•A reduction in glutamatergic neurotransmission may explain the efficacy of ketamine in treating both unipolar and bipolar depression.
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