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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 -
Pharmacological Reports : PR Dec 2023Treatment-resistant depression (TRD) is a subgroup of major depressive disorder in which the use of classical antidepressant treatments fails to achieve satisfactory... (Review)
Review
Treatment-resistant depression (TRD) is a subgroup of major depressive disorder in which the use of classical antidepressant treatments fails to achieve satisfactory treatment results. Although there are various definitions and grading models for TRD, common criteria for assessing TRD have still not been established. However, a common feature of any TRD model is the lack of response to at least two attempts at antidepressant pharmacotherapy. The causes of TRD are not known; nevertheless, it is estimated that even 60% of TRD patients are so-called pseudo-TRD patients, in which multiple biological factors, e.g., gender, age, and hormonal disturbances are concomitant with depression and involved in antidepressant drug resistance. Whereas the phenomenon of TRD is a complex disorder difficult to diagnose and successfully treat, the search for new treatment strategies is a significant challenge of modern pharmacology. It seems that despite the complexity of the TRD phenomenon, some useful animal models of TRD meet the construct, the face, and the predictive validity criteria. Based on the literature and our own experiences, we will discuss the utility of animals exposed to the stress paradigm (chronic mild stress, CMS), and the Wistar Kyoto rat strain representing an endogenous model of TRD. In this review, we will focus on reviewing research on existing and novel therapies for TRD, including ketamine, deep brain stimulation (DBS), and psychedelic drugs in the context of preclinical studies in representative animal models of TRD.
Topics: Rats; Animals; Humans; Depression; Depressive Disorder, Major; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Rats, Inbred WKY
PubMed: 37882914
DOI: 10.1007/s43440-023-00542-9 -
The Journal of Clinical Psychiatry Aug 2023Among the greatest unmet needs in major depressive disorder (MDD) is a lack of effective pharmacotherapies for patients who do not respond to first- and second-line...
Among the greatest unmet needs in major depressive disorder (MDD) is a lack of effective pharmacotherapies for patients who do not respond to first- and second-line antidepressant medications. After decades of muted progress, optimism regarding the future of MDD therapy rose after scientists serendipitously uncovered the antidepressant effects of ketamine. The discovery of ketamine's antidepressant effects inspired the search for related newer medications, such as -ketamine. Orally administered NMDA antagonists have also demonstrated considerable promise in recently concluded, late-stage clinical trials. Researchers evaluating an extended-release combination of bupropion (105 mg) and dextromethorphan (45 mg) found that recipients experienced a decline in MADRS total score. Neurosteroids, such as brexanolone and zuranolone, appear to represent another class of antidepressants. These drugs appear to modulate GABA neurotransmission, which has long been known to be a pathway for drugs that are used to treat insomnia and anxiety. After nearly 50 years of legal injunctions against their use, psychedelic drugs have attracted interest among researchers seeking alternative antidepressants. Psilocybin, derived from mushrooms, remains under investigation for its benefits in treatment-resistant depression.
Topics: Humans; Depressive Disorder, Major; Ketamine; Antidepressive Agents; Hallucinogens; Depressive Disorder, Treatment-Resistant
PubMed: 37585245
DOI: 10.4088/JCP.mulmdd3048sho -
Psychiatria Danubina Oct 2023There is a lot of evidence for a bidirectional communication between the gut and brain. Dysbiosis and increase intestinal permeability may lead to a systemic low-grade... (Review)
Review
BACKGROUND
There is a lot of evidence for a bidirectional communication between the gut and brain. Dysbiosis and increase intestinal permeability may lead to a systemic low-grade inflammatory response or various neuroactive bacterial metabolite may cross gut barrier. Pro-inflammatory cytokines or bacterial metabolites such as short-chain fatty acid (SCFA) are known to pass through blood brain barrier and altered neurotransmitter metabolism or increase production of neurotoxic pathways. In this review we hypothesized that restoring the gut microbiota ecosystem could improve mental disorders. We reviewed literature for human evidence proving clinical relevance of probiotics intake in mental disorders.
SUBJECTS AND METHODS
We searched literature with keywords "depression" or "major depressive disorder" and "probiotic". We selected randomized control trial and we considered having both outcomes concerning impact on depressive symptoms but also on inflammation biomarkers, microbiota composition, cerebral nervous system or cognition.
RESULTS
Seven out of fourteen randomized control trial reported significant improvement on depressive symptoms in patients taking probiotics. Besides improvement in depressive symptoms, we found decrease in inflammatory markers such as IL-6, decrease in serum kynurenine level, changes in microbiota diversity and abundance of species correlated to depressive disorder and higher cognitive performance.
CONCLUSIONS
Probiotic seems to be secure and more effective on depression when used in supplement to usual antidepressant and in mild to moderate depression. We highlighted positive impact on vulnerability factors prevent further worsening. Probiotics could have anti-inflammatory effect acting on inflammatory markers well known to have a role on pathogenesis of depression. A strong correlation between neuroactive metabolites and a relative abundance of microbiota bacterial species underlined importance to consider the gut-brain axis in mental disorders.
Topics: Humans; Depressive Disorder, Major; Probiotics; Microbiota; Inflammation; Brain
PubMed: 37800206
DOI: No ID Found -
The World Journal of Biological... Nov 2023Melancholia is a severe form of depression that is typified by greater genetic and biological influence, distinct symptomatology, and preferential response to physical... (Review)
Review
OBJECTIVES
Melancholia is a severe form of depression that is typified by greater genetic and biological influence, distinct symptomatology, and preferential response to physical treatment. This paper sought to broadly overview potential biomarkers of melancholia to benefit differential diagnosis, clinical responses and treatment outcomes. Given nuances in distinguishing melancholia as its own condition from other depressive disorder, we emphasised studies directly comparing melancholic to non-melancholic depression.
METHODS
A comprehensive literature search was conducted. Key studies were identified and summarised qualitatively.
RESULTS
105 studies in total were identified. These studies covered a wide variety of biomarkers, and largely fell into three domains: endocrinological (especially cortisol levels, particularly in response to the dexamethasone suppression test), neurological, and immunological (particularly inflammatory markers). Less extensive evidence also exists for metabolic, genetic, and cardiovascular markers.
CONCLUSIONS
Definitive conclusions were predominantly limited due to substantial heterogeneity in how included studies defined melancholia. Furthermore, this heterogeneity could be responsible for the between- and within-group variability observed in the candidate biomarkers that were examined. Therefore, clarifying these definitional parameters may help identify underlying patterns in biomarker expression to improve diagnostic and therapeutic precision for the depressive disorders.
Topics: Humans; Depression; Depressive Disorder; Diagnosis, Differential; Biomarkers
PubMed: 37259772
DOI: 10.1080/15622975.2023.2219725 -
Journal of Affective Disorders Nov 2023Adjustment disorder has three main subtypes: adjustment disorder with depressed mood, adjustment disorder with anxiety, and adjustment disorder with disturbance of...
Adjustment disorder has three main subtypes: adjustment disorder with depressed mood, adjustment disorder with anxiety, and adjustment disorder with disturbance of conduct. The disorder is moderately heritable and has lifetime comorbidities with major depressive disorder (MDD), anxiety disorders, or risk-tolerant personality. However, it remains unclear whether the degrees of genetic correlations between adjustment disorder and other psychiatric disorders and intermediate phenotypes are similar or different to those between MDD, anxiety disorders or risk-tolerant personality and these other psychiatric disorders and intermediate phenotypes. To compare patterns of genetic correlations, we utilized large-scale genome-wide association study summary statistics for adjustment disorder-related disorders and personality trait, eleven other psychiatric disorders and fifteen intermediate phenotypes. Adjustment disorder had highly positive genetic correlations with MDD, anxiety disorders, and risk-tolerant personality. Among other psychiatric disorders, adjustment disorder, MDD, anxiety disorders and risk-tolerant personality were positively correlated with risks for schizophrenia (SCZ), bipolar disorder (BD), SCZ + BD, attention-deficit/hyperactivity disorder, and cross disorders. In contrast, adjustment disorder was not significantly correlated with risks for obsessive-compulsive disorder, Tourette syndrome, or posttraumatic stress disorder despite significant genetic correlations of MDD or anxiety disorders with these disorders. Among intermediate phenotypes, adjustment disorder, MDD, anxiety disorders, and risk-tolerant personality commonly had a younger age at first sexual intercourse, first birth, and menopause, lower cognitive ability, and higher rate of smoking initiation. Adjustment disorder was not genetically correlated with extraversion, although the related disorder and personality were correlated with extraversion. Only adjustment disorder was correlated with a higher smoking quantity. These findings suggest that adjustment disorder could share a genetic etiology with MDD, anxiety disorders and risk-tolerant personality trait, as well as have a disorder-specific genetic etiology.
Topics: Female; Humans; Depressive Disorder, Major; Adjustment Disorders; Genome-Wide Association Study; Depression; Anxiety; Anxiety Disorders; Personality
PubMed: 37557993
DOI: 10.1016/j.jad.2023.08.019 -
Current Opinion in Psychiatry Jan 2024Major depressive disorder (MDD) is a common and burdensome severe mental disorder, which is expected to become the leading cause of disease burden worldwide. Most... (Review)
Review
PURPOSE OF REVIEW
Major depressive disorder (MDD) is a common and burdensome severe mental disorder, which is expected to become the leading cause of disease burden worldwide. Most patients with MDD remain untreated/undertreated. For many decades "a trial and error" approach has been adopted for selecting the best treatment plan for each individual patient, but more recently a personalized treatment approach has been proposed, by taking into account several individual and clinical factors (e.g., clinical stage, comorbidity, duration of illness). Therefore, the aim of this study is to address the most relevant innovations in the personalized treatment plan for patients with MDD.
RECENT FINDINGS
In recent years, several pharmacological and nonpharmacological innovations have been introduced in the treatment of patients with MDD. As regards pharmacological treatments, the newly developed drugs have an innovative mechanism of action, targeting the glutamatergic systems. These drugs are highly effective in improving depressive symptoms, with a good level of safety and tolerability. As regards nonpharmacological interventions, innovations include both new strategies targeting different domains (e.g., lifestyle interventions aiming to improve the physical symptoms of depression or virtual reality) and classical interventions provided through innovative mechanisms (e.g., web-based psychotherapies and use of digital approaches). Patients globally report a good level of acceptability of these interventions.
SUMMARY
Depression is a heterogeneous, complex and multidimensional disorder, representing one of the leading causes of disability worldwide. The final aim of the management of patients is functional recovery, which can be achieved by using personalized, integrated and recovery-oriented interventions. Several innovative pharmacological and nonpharmacological treatments are now available; interventions should be selected on the basis of the patient's needs and preferences in order to tailor the treatment, according to a shared decision-making approach.
Topics: Humans; Depressive Disorder, Major; Depression; Precision Medicine; Psychotherapy; Comorbidity
PubMed: 37865845
DOI: 10.1097/YCO.0000000000000903 -
The Journal of Clinical Psychiatry Dec 2023Zuranolone is a positive allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors and a neuroactive steroid approved in the...
Long-Term Safety and Efficacy of Initial and Repeat Treatment Courses With Zuranolone in Adult Patients With Major Depressive Disorder: Interim Results From the Open-Label, Phase 3 SHORELINE Study.
Zuranolone is a positive allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors and a neuroactive steroid approved in the United States as an oral, once-daily, 14-day treatment course for adults with postpartum depression and under investigation for adults with major depressive disorder (MDD). Interim results from the open-label, longitudinal, phase 3 SHORELINE Study (NCT03864614) that evaluated the long-term safety and efficacy of zuranolone in adults with MDD are reported. This interim report includes patients who were enrolled and had the opportunity to be on study for up to 1 year between February 2019 and September 2021. Adults aged 18-75 years with MDD diagnosed per criteria and a 17-item Hamilton Rating Scale for Depression (HAMD-17) total score ≥ 20 received an initial 30-mg or 50-mg 14-day zuranolone course. HAMD-17 responders (≥ 50% reduction from baseline) at Day (D)15 of the initial treatment period were allowed to continue in the study beyond D28 and were followed up for ≤ 1 year, during which repeat treatment courses were permitted. The primary endpoint was safety and tolerability of the initial and repeat treatment courses through 1 year. Secondary endpoints included change from baseline (CFB) in HAMD-17 total score and need for repeat treatment course(s). As of September 2021, among patients in the 30-mg (n = 725) and 50-mg (n = 199) Cohorts who received a zuranolone dose, 493 (68.0%) and 137 (68.8%), respectively, reported a treatment-emergent adverse event (TEAE); most patients who experienced TEAEs reported mild/moderate events (30-mg Cohort, 90.9% [448/493]; 50-mg Cohort, 85.4% [117/137]). Mean (standard deviation) CFB HAMD-17 total score at D15 of the initial treatment period was -15.2 (7.1) and -16.0 (6.0) for the 30-mg and 50-mg Cohorts, respectively; similar improvements were observed after repeat treatment courses. The proportion of patients who received only 1 treatment course during their time on study was 42.9% (210/489) in the 30-mg Cohort and 54.8% (80/146) in the 50-mg Cohort; 57.1% (279/489) and 45.2% (66/146) patients, respectively, received 2-5 total treatment courses. The majority of patients who initially responded to zuranolone received ≤ 2 total treatment courses (30-mg Cohort, 68.5% [335/489]; 50-mg Cohort, 79.5% [116/146]). Of patients who experienced TEAEs, most reported mild or moderately severe events, and responders to zuranolone experienced improvements in depressive symptoms with initial and repeat treatment courses. ClinicalTrials.gov identifier: NCT03864614.
Topics: Adult; Female; Humans; Depressive Disorder, Major; Double-Blind Method; Treatment Outcome; Longitudinal Studies
PubMed: 38153320
DOI: 10.4088/JCP.23m14845 -
Journal of Affective Disorders Nov 2023Osteomyelitis and major depressive disorder (MDD) are significant health concerns with potential interconnections. However, the underlying mechanisms linking these...
BACKGROUND
Osteomyelitis and major depressive disorder (MDD) are significant health concerns with potential interconnections. However, the underlying mechanisms linking these conditions remain unknown. This study aimed to investigate the potential mediating role of non-steroidal anti-inflammatory drug (NSAID) medication in the association between MDD and the risk of osteomyelitis.
METHODS
We utilized summary data from large-scale genome-wide association studies (GWAS) to perform Mendelian randomization (MR) mediation analysis. Instrumental variables were selected based on genome-wide significance, and instrumental strength was assessed using F-statistics. Univariable and multivariable MR analyses were conducted to estimate causal effects and proportions mediated by NSAID medication.
RESULTS
The univariable MR analysis revealed significant associations between MDD and osteomyelitis (odds ratio [OR] = 1.44, 95 % confidence interval [CI]: 1.18-1.874) and between MDD and NSAID medication (OR = 1.36, 95 % CI 1.24-1.49). In the multivariable MR analysis, the direct effect of MDD on osteomyelitis was OR 1.35 (95 % CI: 1.09, 1.67) after adjusting for NSAID medication. The proportion of mediation by NSAID medication was 23 % (95 % CI: 0.05 %, 38.6 %).
CONCLUSION
This MR study provides evidence for a genetically predicted causal association between MDD, NSAID medication, and osteomyelitis. The findings emphasize the need for a comprehensive approach in managing individuals with comorbid depression and osteomyelitis, considering the potential risks and benefits of NSAID medication. Future research should address limitations and explore additional mediators and confounding factors to enhance understanding of this complex relationship.
Topics: Humans; Depressive Disorder, Major; Genome-Wide Association Study; Mendelian Randomization Analysis; Osteomyelitis; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37634817
DOI: 10.1016/j.jad.2023.08.121 -
International Journal of Molecular... Nov 2023Major depressive disorder (MDD) has a high prevalence and is a major contributor to the global burden of disease. This psychiatric disorder results from a complex... (Review)
Review
Major depressive disorder (MDD) has a high prevalence and is a major contributor to the global burden of disease. This psychiatric disorder results from a complex interaction between environmental and genetic factors. In recent years, the role of the gut microbiota in brain health has received particular attention, and compelling evidence has shown that patients suffering from depression have gut dysbiosis. Several studies have reported that gut dysbiosis-induced inflammation may cause and/or contribute to the development of depression through dysregulation of the gut-brain axis. Indeed, as a consequence of gut dysbiosis, neuroinflammatory alterations caused by microglial activation together with impairments in neuroplasticity may contribute to the development of depressive symptoms. The modulation of the gut microbiota has been recognized as a potential therapeutic strategy for the management of MMD. In this regard, physical exercise has been shown to positively change microbiota composition and diversity, and this can underlie, at least in part, its antidepressant effects. Given this, the present review will explore the relationship between physical exercise, gut microbiota and depression, with an emphasis on the potential of physical exercise as a non-invasive strategy for modulating the gut microbiota and, through this, regulating the gut-brain axis and alleviating MDD-related symptoms.
Topics: Humans; Gastrointestinal Microbiome; Depressive Disorder, Major; Dysbiosis; Inflammation; Exercise
PubMed: 38069198
DOI: 10.3390/ijms242316870