The link between the abnormalities of the Hypothalamic-pituitary-adrenal (HPA) axis and depression has been one of the most consistently reported findings in psychiatry. At the same time, multiple ...studies have demonstrated a stronger association between the increased activation of HPA-axis and melancholic, or endogenous depression subtype. This association has not been confirmed for the atypical subtype, and some researchers have suggested that as an antinomic depressive subtype, it may be associated with the opposite type, i.e. hypo-function, of the HPA-axis, similarly to PTSD. The purpose of this systematic review is to summarise existing studies addressing the abnormalities of the HPA-axis in melancholic and/or atypical depression.
We conducted a systematic review in the literature by searching MEDLINE, PsycINFO, OvidSP and Embase databases until June 2017. The following search items were used: "hypothalamic-pituitary-adrenal" OR "HPA" OR "cortisol" OR "corticotropin releasing hormone" OR "corticotropin releasing factor" OR "glucocorticoid*" OR "adrenocorticotropic hormone" OR "ACTH" AND "atypical depression" OR "non-atypical depression" OR "melancholic depression" OR "non-melancholic depression" OR "endogenous depression" OR "endogenomorphic depression" OR "non-endogenous depression". Search limits were set to include papers in English or German language published in peer-reviewed journals at any period. All studies were scrutinized to determine the main methodological characteristics, and particularly possible sources of bias influencing the results reported.
We selected 48 relevant studies. Detailed analysis of the methodologies used in the studies revealed significant variability especially regarding the samples’ definition comparing the HPA axis activity of melancholic patients to atypical depression, including healthy controls. The results were subdivided into 4 sections: (1) 27 studies which compared melancholic OR endogenous depression vs. non-melancholic or non-endogenous depression or controls; (2) 9 studies which compared atypical depression or atypical traits vs. non-atypical depression or controls; (3) 7 studies which compared melancholic or endogenous and atypical depression subtypes and (4) 5 studies which used a longitudinal design, comparing the measures of HPA-axis across two or more time points. While the majority of studies did confirm the association between melancholic depression and increased post-challenge cortisol levels, the association with increases in basal cortisol and basal ACTH were less consistent. Some studies, particularly those focusing on reversed vegetative symptoms, demonstrated a decrease in the activity of the HPA axis in atypical depression compared to controls, but the majority did not distinguish it from healthy controls.
In conclusion, our findings indicate that there is a difference in the activity of the HPA-axis between melancholic and atypical depressive subtypes. However, these are more likely explained by hypercortisolism in melancholia; and most often normal than decreased function in atypical depression. Further research should seek to distinguish a particular subtype of depression linked to HPA-axis abnormalities, based on symptom profile, with a focus on vegetative symptoms, neuroendocrine probes, and the history of adverse childhood events. New insights into the dichotomy addressed in this review might be obtained from genetic and epigenetic studies of HPA-axis related genes in both subtypes, with an emphasis on the presence of vegetative symptoms.
•Different depressive subtype classification criteria may influence severity and treatment.•The depressive subtype is an important factor influencing Hypothalamus-Pituitary-Adrenal (HPA) axis activity.•Melancholic patients has increased post-challenge cortisol levels than Atypical Depressive patients.•Studies focusing on reversed vegetative symptoms, demonstrated a decrease in the activity of the HPA axis in atypical depressives compared to controls, but the majority did not distinguish it from healthy controls.•Future studies should consider epigenetic studies of HPA-axis related to both subtypes, with an emphasis on vegetative symptom and standardized methodologies.
Abstract Background Anxiety and related disorders (AD) disproportionately affect women, and are the most prevalent of all mental health conditions. The current research represents the first study of ...maternal postpartum AD prevalence in which all of the AD are assessed, and one of few studies of this type in which maternal prenatal AD incidence is assessed. Methods A Canadian sample of pregnant women (N=310) was recruited from a defined geographical area between November 2007 and November 2010. Participants were first administered postnatal mood and anxiety screening measures. Those who scored at or above cutoff on one or more of these measures were administered a diagnostic interview for depression and anxiety at approximately three months postpartum ( n =115). Findings from the diagnostic interview were used to estimate the prevalence and incidence of mood and AD in pregnancy, as well as at and during the first three months postpartum. Period prevalence and incidence estimates were obtained retrospectively from interview data collected postnatally. Results The prevalence of AD during pregnancy and the early postpartum period (15.8% and 17.1% respectively) exceeded that of depression (3.9% and 4.8% respectively). The prevalence of OCD in our sample exceeded that of OCD among adults aged 18-64. Parity was unrelated to AD prevalence. Slightly less than 5% of participants were comorbid for both AD, and depression. Limitations This study is limited by a relatively small sample size for a prevalence study, and non-random sample selection. As only women who scored above cutoff on one or more screening measures were interviewed, prevalence estimates are conservative. Finally, prenatal prevalence estimates are based on retrospective report provided postpartum. Conclusions This study provides evidence that, as a group, anxiety and related conditions affect a significant proportion of postpartum women, and are more prevalent than is postpartum depression.
Ketamine: A tale of two enantiomers Jelen, Luke A; Young, Allan H; Stone, James M
Journal of Psychopharmacology,
02/2021, Letnik:
35, Številka:
2
Book Review, Journal Article
Recenzirano
Odprti dostop
The discovery of the rapid antidepressant effects of the dissociative anaesthetic ketamine, an uncompetitive N-Methyl-D-Aspartate receptor antagonist, is arguably the most important breakthrough in ...depression research in the last 50 years. Ketamine remains an off-label treatment for treatment-resistant depression with factors that limit widespread use including its dissociative effects and abuse potential. Ketamine is a racemic mixture, composed of equal amounts of (S)-ketamine and (R)-ketamine. An (S)-ketamine nasal spray has been developed and approved for use in treatment-resistant depression in the United States and Europe; however, some concerns regarding efficacy and side effects remain. Although (R)-ketamine is a less potent N-Methyl-D-Aspartate receptor antagonist than (S)-ketamine, increasing preclinical evidence suggests (R)-ketamine may have more potent and longer lasting antidepressant effects than (S)-ketamine, alongside fewer side effects. Furthermore, a recent pilot trial of (R)-ketamine has demonstrated rapid-acting and sustained antidepressant effects in individuals with treatment-resistant depression. Research is ongoing to determine the specific cellular and molecular mechanisms underlying the antidepressant actions of ketamine and its component enantiomers in an effort to develop future rapid-acting antidepressants that lack undesirable effects. Here, we briefly review findings regarding the antidepressant effects of ketamine and its enantiomers before considering underlying mechanisms including N-Methyl-D-Aspartate receptor antagonism, γ-aminobutyric acid-ergic interneuron inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor activation, brain-derived neurotrophic factor and tropomyosin kinase B signalling, mammalian target of rapamycin complex 1 and extracellular signal-regulated kinase signalling, inhibition of glycogen synthase kinase-3 and inhibition of lateral habenula bursting, alongside potential roles of the monoaminergic and opioid receptor systems.
AbstractObjectiveTo estimate the comparative clinical efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults.DesignSystematic ...review with pairwise and network meta-analysis.Data sourcesElectronic search of Embase, PubMed/Medline, and PsycINFO up to 8 May 2018, supplemented by manual searches of bibliographies of several reviews (published between 2009 and 2018) and included trials.Eligibility criteria for selecting studiesClinical trials with random allocation to electroconvulsive therapy (ECT), transcranial magnetic stimulation (repetitive (rTMS), accelerated, priming, deep, and synchronised), theta burst stimulation, magnetic seizure therapy, transcranial direct current stimulation (tDCS), or sham therapy.Main outcome measuresPrimary outcomes were response (efficacy) and all cause discontinuation (discontinuation of treatment for any reason) (acceptability), presented as odds ratios with 95% confidence intervals. Remission and continuous depression severity scores after treatment were also examined.Results113 trials (262 treatment arms) that randomised 6750 patients (mean age 47.9 years; 59% women) with major depressive disorder or bipolar depression met the inclusion criteria. The most studied treatment comparisons were high frequency left rTMS and tDCS versus sham therapy, whereas recent treatments remain understudied. The quality of the evidence was typically of low or unclear risk of bias (94 out of 113 trials, 83%) and the precision of summary estimates for treatment effect varied considerably. In network meta-analysis, 10 out of 18 treatment strategies were associated with higher response compared with sham therapy: bitemporal ECT (summary odds ratio 8.91, 95% confidence interval 2.57 to 30.91), high dose right unilateral ECT (7.27, 1.90 to 27.78), priming transcranial magnetic stimulation (6.02, 2.21 to 16.38), magnetic seizure therapy (5.55, 1.06 to 28.99), bilateral rTMS (4.92, 2.93 to 8.25), bilateral theta burst stimulation (4.44, 1.47 to 13.41), low frequency right rTMS (3.65, 2.13 to 6.24), intermittent theta burst stimulation (3.20, 1.45 to 7.08), high frequency left rTMS (3.17, 2.29 to 4.37), and tDCS (2.65, 1.55 to 4.55). Network meta-analytic estimates of active interventions contrasted with another active treatment indicated that bitemporal ECT and high dose right unilateral ECT were associated with increased response. All treatment strategies were at least as acceptable as sham therapy.ConclusionsThese findings provide evidence for the consideration of non-surgical brain stimulation techniques as alternative or add-on treatments for adults with major depressive episodes. These findings also highlight important research priorities in the specialty of brain stimulation, such as the need for further well designed randomised controlled trials comparing novel treatments, and sham controlled trials investigating magnetic seizure therapy.
Substantial evidence from various studies suggests a preeminent role for early adverse experiences in the development of psychopathology. The most recent studies reviewed here suggest that early life ...stressors are associated with an increased risk for anxiety disorders in adulthood. Early life stress predisposes individuals to develop a number of psychiatric syndromes, particularly affective disorders, including anxiety disorders, and is therefore a significant health problem.This review examines the emerging literature on the relationship between stress, hypothalamic-pituitary-adrenal (HPA) axis function, and generalized anxiety disorder (GAD), panic disorder, and phobias and the role of early life stress as an important risk factor for HPA axis dysfunction.The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolemia and reduced inhibitory feedback. In addition to melancholic depression, a spectrum of other conditions may be associated with increased and prolonged activation of the HPA axis, including panic, GAD, phobias and anxiety. Moreover, HPA axis changes appear to be state-dependent, tending to improve upon resolution of the anxiety syndrome. Interestingly, persistent HPA hyperactivity has been associated with higher rates of relapse. These studies suggest that an evaluation of the HPA axis during treatment may help identify patients who are at a higher risk for relapse. These findings suggest that this dysfunction of the HPA axis is partially attributable to an imbalance between glucocorticoid and mineralocorticoid receptors. Evidence has consistently demonstrated that glucocorticoid receptor function is impaired in anxiety disorders. Moreover, normal basal cortisol levels and hyper-responsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. Early stressful life events may provoke alterations of the stress response and thus of the HPA axis that can endure during adulthood, predisposing individuals to develop psychopathology.
Abstract Background Identification of white matter microstructure differences and similarities between major depression and bipolar disorder is a necessary step to better understand the underlying ...brain abnormalities in affective disorders and target more effective treatments. However, research has not yet yielded robust conclusions. We report here a meta-analysis of diffusion tensor imaging studies in these conditions. Methods A comprehensive literature search was conducted up to 2014 to identify studies comparing fractional anisotropy (FA) between patients and control subjects. Results were combined to identify white matter abnormalities in major depression (736 patients vs. 668 control subjects) and bipolar disorder (536 patients vs. 489 control subjects). Effect size comparison and conjunction analysis allowed identification of similarities and differences between the disorders. Results A significant decrease in FA in the genu of the corpus callosum characterized both conditions. The comparison between unipolar and bipolar disorders revealed a greater decrease in FA in the left posterior cingulum in bipolar disorder. Studies that adopted tract-based spatial statistics methodology showed more pronounced reductions in these regions compared with voxel-based analyses. Conclusions Major depression and bipolar disorder are characterized by abnormalities in white matter tracts of the genu of the corpus callosum that connect the two hemispheres of the prefrontal cortex implicated in mood regulation. Bipolar disorder was associated with reduced white matter integrity in the left posterior cingulum, which may contribute to cognitive impairment described in this condition. Tract-based spatial statistics may be a more sensitive technique to detect white matter abnormalities in these regions compared with voxel-based analyses.
Rohde et al present the results of a "target trial emulation" designed to assess the risk of antidepressant-induced mania in bipolar depression. Although double-blind RCTs remain the gold standard in ...research, the execution of RCTs has many challenges. Especially with longer follow-up periods, RCTs can be prohibitively expensive, recruitment may be uncertain, retaining participants can be difficult, and generalizability of the results may be dubious. A target trial emulation using longitudinal observational data may solve some of these challenges. For this study, the authors defined the target trial, created comprehensive eligibility criteria, and followed the appropriate methods to adjust for baseline confounding factors, all of which are key elements of a robust target trial emulation. However, target trial emulations are not without their own limitations. Data that are not collected for research purposes may include inconsistencies, such as ambiguous medical coding and a lack of standardized measurements. Additionally, they are unable to emulate RCTs with regard to placebo control or tight monitoring of treatment adherence.
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