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Psychiatry Research Oct 2023Positive allosteric modulators of γ-aminobutyric acid-A (GABA) receptors, or GABAkines, play important roles in the treatment of depression, epilepsy, insomnia, and... (Meta-Analysis)
Meta-Analysis
Positive allosteric modulators of γ-aminobutyric acid-A (GABA) receptors, or GABAkines, play important roles in the treatment of depression, epilepsy, insomnia, and other disorders. Recently, some new GABAkines (zuranolone and brexanolone) have been administrated to patients with major depressive disorder (MDD) or postpartum depression (PPD) in randomized controlled trials (RCTs). This study aims to systematically review and examine the efficacy and safety of zuranolone or brexanolone for treatment of depression. A systematic literature retrieval was conducted through August 20, 2023. RCTs evaluating the efficacy and safety of zuranolone or brexanolone for treatment of depression were included. Eight studies (nine reports) were identified in the study. The percentages of patients with PPD achieving Hamilton Depression Rating Scale (HAM-D) response and remission were significantly higher after brexanolone or zuranolone administration compared with placebo at different points. The percentages of patients with MDD achieving HAM-D response and remission were significantly increased during the zuranolone treatment period compared with placebo. In addition, zuranolone caused more adverse events in patients with MDD compared with placebo. Our findings support the effects of brexanolone on improving the core symptoms of depression in patients with PPD, and the potential of zuranolone in treating patients with MDD or PPD.
Topics: Female; Humans; Antidepressive Agents; Depression, Postpartum; Depression; Randomized Controlled Trials as Topic; Depressive Disorder, Major
PubMed: 37683318
DOI: 10.1016/j.psychres.2023.115450 -
Australian Dental Journal Dec 2023
Topics: Humans; Depression; Depressive Disorder, Treatment-Resistant
PubMed: 37961004
DOI: 10.1111/adj.13001 -
Nature Oct 2023Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD). However, achieving stable... (Clinical Trial)
Clinical Trial
Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD). However, achieving stable recovery is unpredictable, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.
Topics: Humans; Artificial Intelligence; Biomarkers; Deep Brain Stimulation; Depression; Depressive Disorder, Major; Electrophysiology; Treatment Outcome; Local Field Potential Measurement; White Matter; Limbic Lobe; Facial Expression
PubMed: 37730990
DOI: 10.1038/s41586-023-06541-3 -
Science Translational Medicine Jul 2023Depression associated with traumatic brain injury (TBI) is believed to be clinically distinct from primary major depressive disorder (MDD) and may be less responsive to...
Depression associated with traumatic brain injury (TBI) is believed to be clinically distinct from primary major depressive disorder (MDD) and may be less responsive to conventional treatments. Brain connectivity differences between the dorsal attention network (DAN), default mode network (DMN), and subgenual cingulate have been implicated in TBI and MDD. To characterize these distinctions, we applied precision functional mapping of brain network connectivity to resting-state functional magnetic resonance imaging data from five published patient cohorts, four discovery cohorts ( = 93), and one replication cohort ( = 180). We identified a distinct brain connectivity profile in TBI-associated depression that was independent of TBI, MDD, posttraumatic stress disorder (PTSD), depression severity, and cohort. TBI-associated depression was independently associated with decreased DAN-subgenual cingulate connectivity, increased DAN-DMN connectivity, and the combined effect of both. This effect was stronger when using precision functional mapping relative to group-level network maps. Our results support the possibility of a physiologically distinct "TBI affective syndrome," which may benefit from individualized neuromodulation approaches to target its distinct neural circuitry.
Topics: Humans; Depressive Disorder, Major; Brain Mapping; Depression; Brain Injuries, Traumatic; Brain; Magnetic Resonance Imaging; Neural Pathways
PubMed: 37406139
DOI: 10.1126/scitranslmed.abn0441 -
Frontiers in Endocrinology 2023According to World Health Organization estimates, 5% of the adult population worldwide suffers from depression. In addition to the affective, psychomotor and cognitive... (Review)
Review
According to World Health Organization estimates, 5% of the adult population worldwide suffers from depression. In addition to the affective, psychomotor and cognitive symptoms which characterize this mood disorder, sexual dysfunction has been frequently reported among men suffering from depression. The most common sexual manifestations are decreased libido, erectile dysfunction and orgasmic disorder. In addition, epidemiological studies have documented a reduction of testosterone concentrations in men with depression and, for these reasons, depressive disorders appear as one possible cause of male functional hypogonadism. Moreover, some largely used antidepressant medications can cause or worsen sexual complaints, thus depression and its treatments rise several andrological-relevant issues. The other way round, men with hypogonadism can manifest depressed mood, anxiety, insomnia, memory impairment which, if mild, may respond to testosterone replacement therapy (TRT). However, the prevalence of functional hypogonadism in depression, and of depressive symptoms in hypogonadal men, is not known. Severe depressive symptoms do not respond to TRT, while the effect of treating major depression on functional hypogonadism, has not been investigated. Overall, the clinical relevance of each condition to the other, as well as the physiopathological underpinnings of their relationship, are still to be clarified. The present review summarizes current evidence on the influence of testosterone on mood and of depression on the hypothalamic-pituitary-testis axis; the clinical association between male hypogonadism and depression; and the reciprocal effects of respective treatments.
Topics: Adult; Humans; Male; Depression; Testosterone; Behavior Therapy; Depressive Disorder, Major; Hypogonadism
PubMed: 37635965
DOI: 10.3389/fendo.2023.1198437 -
Journal of Affective Disorders Oct 2023Children and adolescents with major depressive disorder (MDD) are at increased risk for premature cardiovascular disease (CVD). Whether adolescents with MDD manifest...
BACKGROUND
Children and adolescents with major depressive disorder (MDD) are at increased risk for premature cardiovascular disease (CVD). Whether adolescents with MDD manifest evidence of dyslipidemia, a key risk factor for CVD, is unknown.
METHODS
Youth recruited through an ambulatory psychiatry clinic and the community, were categorized following diagnostic interview as MDD or as healthy controls [HC]. CVD risk factors including high density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride concentrations were collected. Depression severity was measured using the Center for Epidemiological Studies Depression Scale for Children. The associations of diagnostic group as well as depressive symptom severity with lipid concentrations were examined using multiple regression analyses. Models were adjusted for age, sex, and standardized Body Mass Index.
RESULTS
Participants (n = 243) were 68 % female with a mean age of 15.04 ± 1.81 years. MDD and HC participants had comparable levels of dyslipidemia (MDD: 48 %, HC: 46 %, p > .7) and hypertriglyceridemia (MDD: 34 %, HC: 30 %, p > .7). Among depressed adolescents, greater depressive symptoms were associated with higher total cholesterol concentrations in unadjusted models only. Greater depressive symptoms were associated with higher HDL concentrations and a lower triglyceride-to-HDL ratio, after adjusting for covariates.
LIMITATIONS
Cross-sectional design.
CONCLUSIONS
Adolescents with clinically significant depressive symptoms manifested similar levels of dyslipidemia as healthy youth. Future studies examining the prospective trajectories of depressive symptoms and lipid concentrations are needed to determine the point at which dyslipidemia emerges in the course of MDD, and the mechanism of the association that imparts increased CVD risk for depressed youth.
Topics: Child; Humans; Adolescent; Female; Male; Depressive Disorder, Major; Depression; Prospective Studies; Cross-Sectional Studies; Triglycerides; Dyslipidemias; Cardiovascular Diseases; Lipoproteins, HDL; Cholesterol, HDL
PubMed: 37302507
DOI: 10.1016/j.jad.2023.06.017 -
The American Journal of Psychiatry Oct 2023
Topics: Humans; Depression; Depressive Disorder, Major
PubMed: 37777851
DOI: 10.1176/appi.ajp.20230574 -
Journal of Affective Disorders Oct 2023Debate is ongoing as to whether burnout can be differentiated from depression. This study evaluated whether burnout and depression could be distinguished using a new...
BACKGROUND
Debate is ongoing as to whether burnout can be differentiated from depression. This study evaluated whether burnout and depression could be distinguished using a new burnout measure and other variables.
METHODS
Scores on the Sydney Burnout Measure (SBM) were compared between participants with self-diagnosed burnout (BO-all group; n = 622) and clinically-diagnosed depression (DEP-all group; n = 90). The latter group was split into melancholic (DEP-mel; n = 56) and non-melancholic (DEP-nonmel; n = 34) depression subgroups for subsequent analyses. Differences in reporting of depressive symptoms and causal attributions were also evaluated.
RESULTS
While total SBM scores showed poor differentiation, the BO-all group had lower social withdrawal and higher empathy loss subscale scores than the depression groups. Odds ratios were significant for several of the depressive symptoms and causal attribution items when comparing the BO-all group to the DEP-all and DEP-mel groups, while only a few items were significant when comparing the BO-all and DEP-nonmel groups.
LIMITATIONS
Participants in the depression group were assigned by clinician-based depression diagnoses, rather than by a standardised diagnostic interview, and the group had a relatively small sample size. Participants in the burnout group were self-diagnosed and not assessed for comorbid psychiatric diagnoses.
CONCLUSIONS
There were some nuanced symptoms differences between burnout and depression, but many of the SBM symptoms were not specific to burnout. Results also suggested that burnout overlaps more with non-melancholic than melancholic depression, and that differentiation of burnout and depression may rely more on weighting causal factors over symptoms.
Topics: Humans; Depression; Depressive Disorder; Comorbidity; Burnout, Professional; Sample Size
PubMed: 37479038
DOI: 10.1016/j.jad.2023.07.095 -
The Journal of Clinical Psychiatry Nov 2023To systematically review the literature to identify and categorize the predictors and risk factors for treatment-resistant depression (TRD). Online databases (PubMed,...
To systematically review the literature to identify and categorize the predictors and risk factors for treatment-resistant depression (TRD). Online databases (PubMed, MEDLINE, Embase, and APA PsycNet) and relevant conference sources were searched from inception up to January 24, 2022. The following keywords were used: , , , , and . All studies that included a definition of TRD were included. A total of 1,686 abstracts were screened, and 57 studies were included in the final data synthesis. Data were extracted using a data extraction form developed for this study. The most frequently reported mental predictors/risk factors were greater symptom severity (9 studies), suicidality (8 studies), and recurrent depression (6 studies). Cardiovascular disease (4 studies), pain (3 studies), and thyroid dysfunction (3 studies) were the most common physical predictors/risk factors, while younger age (7 studies) and female gender (6 studies) were the most common demographic predictors/risk factors. Higher levels of neuroticism appeared twice in the literature. Several articles reported on genetic, biological, and imaging variables, but results were too heterogenous to identify common predictors/risk factors. TRD is a complex disorder with many contributing factors that need to be identified and addressed earlier in the disease course to prevent its development or facilitate better treatment outcomes. Future work should focus on replicating the key predictors/risk factors identified in this review.
Topics: Humans; Female; Antidepressive Agents; Depression; Treatment Outcome; Depressive Disorder, Treatment-Resistant; Pain
PubMed: 37967334
DOI: 10.4088/JCP.23r14885 -
Journal of Affective Disorders Oct 2023Maternal and paternal perinatal depression and anxiety are theorised to adversely impact infant development. Yet, few studies have assessed both mental health symptoms...
BACKGROUND
Maternal and paternal perinatal depression and anxiety are theorised to adversely impact infant development. Yet, few studies have assessed both mental health symptoms and clinical diagnoses within the one study. Moreover, research on fathers is limited. This study therefore aimed to examine the association between symptoms and diagnoses of maternal and paternal perinatal depression and anxiety with infant development.
METHOD
Data were from the Triple B Pregnancy Cohort Study. Participants included 1539 mothers and 793 partners. Depressive and anxiety symptoms were assessed using the Edinburgh Postnatal Depression Scale and Depression Anxiety Stress Scales. Major depressive disorder, generalized anxiety disorder, social anxiety disorder, panic disorder, and agoraphobia were assessed using the Composite International Diagnostic Interview in trimester three. Infant development was assessed at 12-months using the Bayley Scales of Infant and Toddler Development.
RESULTS
Antepartum, maternal depressive and anxiety symptoms were associated with poorer infant social-emotional (d = -0.11, p = .025) and language development (d = -0.16, p = .001). At 8-weeks postpartum, maternal anxiety symptoms were associated with poorer overall development (d = -0.11, p = .030). No association was observed for clinical diagnoses in mothers, nor paternal depressive and anxiety symptoms or clinical diagnoses; albeit risk estimates were largely in the expected direction of adverse effects on infant development.
CONCLUSIONS
Evidence suggests that maternal perinatal depression and anxiety symptoms may adversely impact infant development. Effects were small but findings underscore the importance of prevention, early screening and intervention, alongside consideration of other risk factors during early critical periods.
Topics: Male; Female; Pregnancy; Infant; Humans; Longitudinal Studies; Depression; Cohort Studies; Depressive Disorder, Major; Anxiety; Anxiety Disorders; Fathers; Mothers; Depression, Postpartum
PubMed: 37302506
DOI: 10.1016/j.jad.2023.06.020