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The American Journal of Psychiatry Jul 2024
Topics: Humans; Depressive Disorder, Treatment-Resistant; Medical Records
PubMed: 38946279
DOI: 10.1176/appi.ajp.20240377 -
The American Journal of Psychiatry Jul 2024
Topics: Humans; Brain; Multimodal Imaging; Neuroimaging; Magnetic Resonance Imaging; Brain Mapping; Depressive Disorder, Major; Stress, Psychological
PubMed: 38946274
DOI: 10.1176/appi.ajp.20240400 -
Nihon Yakurigaku Zasshi. Folia... 2024Major depressive disorder (MDD) is a psychiatric disorder that affects more than 300 million people worldwide and has a serious impact on society. Conventional... (Review)
Review
Major depressive disorder (MDD) is a psychiatric disorder that affects more than 300 million people worldwide and has a serious impact on society. Conventional antidepressants targeting monoamines in the brain based on the monoamine hypothesis are known to take a prolonged time to be effective or less effective in 30% of MDD patients. Hence, there is a need to develop antidepressants that are effective against treatment-resistant depression and have a new mechanism different from the monoamine hypothesis. An increasing number of research groups including us have been establishing that pituitary adenylate cyclase-activating polypeptide (PACAP) and one of its receptors, PAC1 receptor, are closely related to the etiology of stress-related diseases such as MDD. Therefore, it is strongly suggested that the PAC1 receptor is a promising target in the treatment of psychiatric disorders. We developed a novel, non-peptidic, small-molecule, high-affinity PAC1 receptor antagonists and conducted behavioral pharmacology experiments in mice to characterize a novel PAC1 receptor antagonist as a new option for MDD therapy. The results show that our novel PAC1 receptor antagonist has the potential to be a new antidepressant with a high safety profile. In this review, we would like to present the background of developing our novel PAC1 receptor antagonist and its effects on mouse models of acute stress.
Topics: Antidepressive Agents; Animals; Humans; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Drug Development; Depressive Disorder, Major; Molecular Targeted Therapy
PubMed: 38945904
DOI: 10.1254/fpj.24008 -
Nihon Yakurigaku Zasshi. Folia... 2024Major Depressive Disorder (MDD) poses a significant global health burden, with 30-40% patients developing resistance to standard clinical antidepressants, such as... (Review)
Review
Major Depressive Disorder (MDD) poses a significant global health burden, with 30-40% patients developing resistance to standard clinical antidepressants, such as selective serotonin reuptake inhibitors and tricyclic antidepressants. In 2016, Carhart-Harris and colleagues reported that psilocybin, the hallucinogenic compound derived from magic mushrooms, exhibits rapid and enduring antidepressant effects in patients with treatment-resistant depression. Subsequent clinical studies have found the therapeutic potential of psilocybin in MDD, depressive episode in bipolar disorder, anorexia, and drug addiction. In 2018 and 2019, the U.S. Food and Drug Administration designated psilocybin as a "breakthrough medicine" for treatment-resistant depression and MDD, respectively. Notably, the side effects of psilocybin are limited to transient and mild issues, such as headache and fatigue, suggesting its safety. In 2023, we published a review on the role of serotonin 5-HT receptors in the antidepressant effects of serotonergic psychedelics (Nihon Yakurigaku Zasshi, Volume 158, Issue 3, Page 229-232). Here, we present our study alongside the latest clinical and preclinical research on the antidepressant effects of psilocybin and provide an overview of the potential and issues related to psilocybin therapy.
Topics: Psilocybin; Humans; Animals; Antidepressive Agents; Hallucinogens; Depressive Disorder, Major; Receptor, Serotonin, 5-HT2A
PubMed: 38945903
DOI: 10.1254/fpj.24007 -
Science Bulletin Jun 2024
PubMed: 38945750
DOI: 10.1016/j.scib.2024.06.021 -
Journal of Affective Disorders Jun 2024Major depressive disorder (MDD) is characterized by increased T helper (Th)1 polarization, T cell activation (e.g., CD71+ and CD40L+), and cannabinoid receptor type 2...
T cell activation and lowered T regulatory cell numbers are key processes in severe major depressive disorder: Effects of recurrence of illness and adverse childhood experiences.
BACKGROUND
Major depressive disorder (MDD) is characterized by increased T helper (Th)1 polarization, T cell activation (e.g., CD71+ and CD40L+), and cannabinoid receptor type 2 bearing CD20+ B cells; and lower T regulatory (Treg) numbers.
AIMS
To delineate the effects of adverse childhood experiences (ACEs) and recurrence of illness (ROI) on activated T and CB2-bearing B populations, and Tregs, including FoxP3 + CD152+, FoxP3 + GARP+, and FoxP3 + CB1+ cells.
METHODS
We measured ROI, ACEs, the number of activated T cells, Tregs, and CD20 + CB2+ B cells, in 30 MDD patients and 20 healthy controls.
RESULTS
A larger part of the variance in the depression phenome (40.8 %) was explained by increased CD20 + CB2+ and activated T cells, and lowered Tregs. ROI and lifetime suicidal behaviors were significantly and positively associated with CD20 + CB2+, CD3 + CD71+, CD3 + CD40L+, CD4 + CD71+, CD4 + CD40L+, and CD4HLADR+ numbers. ROI was significantly correlated with CD8 + CD40L+ numbers. The sum of ACEs was significantly associated with CD20 + CB2+, CD3 + CD40L+, CD4 + 40 L+ numbers, T cell activation (positively) and Treg (inversely) indices. One replicable latent vector could be extracted from activated T cells, lifetime and current suicidal behaviors, number of depressive episodes, and severity of depression, and 48.8 % of its variance was explained by ACEs.
CONCLUSIONS
ACE-induced activation of T effector and cytotoxic cells and B cells with autoimmune potential, coupled with lowered Treg numbers are a key component of depression. The findings indicate that increasing ROI, the phenome of depression and suicidal behaviors, are caused by autoimmune processes, which are the consequence of ACEs and increasing sensitization of immune responses.
PubMed: 38945402
DOI: 10.1016/j.jad.2024.06.097 -
Behavioural Brain Research Jun 2024Major depressive disorder (MDD) affects millions of people worldwide, with women at a higher risk during the childbearing age. Vortioxetine (VOX) and Vilazodone (VLZ)...
Major depressive disorder (MDD) affects millions of people worldwide, with women at a higher risk during the childbearing age. Vortioxetine (VOX) and Vilazodone (VLZ) are newer antidepressants with improved therapeutic profile commonly used, but their safety during pregnancy and long-term effects on offspring are poorly understood due to paucity of literature in preclinical and clinical studies. This study aimed to investigate whether prenatal exposure to VOX and VLZ impacts depressive- and anxiety-like neurobehavioral alterations in offspring, focusing on neurotransmitter-mediated mechanisms. Pregnant Wistar dams received either VOX or VLZ, 1mg/day and 2mg/day of the drug orally from gestation day (GD) 6 to 21. The dams naturally delivered their offspring and reared until they reached postnatal day (PND) 21. Offspring of both sexes were tested for display of depressive-and anxiety-like behaviors from PND 56 to 70. After PND 70, offspring were sacrificed, and their brains were collected to estimate neurotransmitter levels. As per protocol, controls were maintained simultaneously for each experimental design. Prenatal exposure to VOX or VLZ induced an increased state of depressive- and anxiety-like behaviors in both male and female offspring. Additionally, neurotransmitter (serotonin, dopamine, and nor-epinephrine) levels in the prefrontal cortex region of the brain were substantially reduced in exposed offspring. No sex specific neurobehavioral and neurochemical implications were observed in the present study. Our findings suggest that prenatal exposure to VOX and VLZ disrupts neurochemical balance in the fetal brain, leading to long-lasting neurobehavioral impairments in offspring of both sexes.
PubMed: 38945303
DOI: 10.1016/j.bbr.2024.115128 -
Archives of Suicide Research : Official... Jun 2024Nearly 50,000 Americans die each year from suicide, despite suicide death being a rare event in the context of health risk assessment and modeling. Prior research has...
OBJECTIVE
Nearly 50,000 Americans die each year from suicide, despite suicide death being a rare event in the context of health risk assessment and modeling. Prior research has underscored the need for contextualizing suicide risk models in terms of their potential uses and generalizability. This sensitivity analysis makes use of the Maryland Suicide Data Warehouse (MSDW) and illustrates how results inform clinical decision support.
METHOD
A cohort of 1 million living control patients were extracted from the MSDW in addition to 1,667 patients who had died by suicide between the years 2016 and 2019 according to the Maryland Office of the Medical Examiner (OCME). Data were extracted and aggregated as part of a 4-year retrospective design. Binary logistic and two penalized regression models were deployed in a repeated fivefold cross-validation. Model performances were evaluated using sensitivity, positive predictive value (PPV), and F1, and model coefficients were ranked according to coefficient size.
RESULTS
Several features were significantly associated with patients having died by suicide, including male sex, depressive and anxiety disorder diagnoses, social needs, and prior suicidal ideation and suicide attempt. Cross-validated binary logistic regression outperformed either ridge or LASSO (least absolute shrinkage and selection operator) models but generally achieved low-to-moderate PPV and sensitivity across most thresholds and a peak F1 of 0.323.
CONCLUSIONS
Suicide death prediction is constrained by the context of use, which determines the best balance of precision and recall. Predictive models must be evaluated close to the level of intervention. They may not hold up to different needs at different levels of care.
PubMed: 38945167
DOI: 10.1080/13811118.2024.2363227 -
Maternal Postpartum Depression Screening and Early Intervention in the Neonatal Intensive Care Unit.Advances in Pediatrics Aug 2024Families with infants admitted to the neonatal intensive care unit (NICU) are at a markedly increased risk of developing postpartum depression (PPD) because of the... (Review)
Review
Families with infants admitted to the neonatal intensive care unit (NICU) are at a markedly increased risk of developing postpartum depression (PPD) because of the stressors they experience by having an infant in this intensive setting. Routine screening for PPD is not regularly performed for these families because many NICUs do not offer it and well-child visits are missed while the infant is hospitalized. Because the identification and treatment of PPD is often missed in these families, screening needs to be administered in the NICU to ensure improved outcomes.
Topics: Humans; Depression, Postpartum; Female; Intensive Care Units, Neonatal; Infant, Newborn; Mass Screening; Risk Factors
PubMed: 38944489
DOI: 10.1016/j.yapd.2024.01.004 -
Journal of Affective Disorders Jun 2024Trying to better define Bipolar Disorder (BD) progression, different staging models have been conceptualized, each one emphasizing different aspects of illness. In a...
BACKGROUND
Trying to better define Bipolar Disorder (BD) progression, different staging models have been conceptualized, each one emphasizing different aspects of illness. In a previous article we retrospectively applied the main staging models to a sample of 100 bipolar patients at four time points over a ten-year observation. In the present study, focusing on Kupka & Hillegers's model, we aimed to assess the transition of the same sample through the different stages of illness and to explore the potential role of clinical variables on the risk of progression.
METHODS
Multistate Model using the mstate package in R and Markov model with stratified hazards were used for statistical analysis.
RESULTS
A high hazard of transition from stage 2 to 3 emerged, with a probability of staying in stage 2 decreasing to 14 % after 3 years. BD II and depressive predominant polarity were significantly associated with transition from stage 1 to 2, whereas the number of lifetime episodes >3 and the elevated predominant polarity with transition from stage 3 to 4.
CONCLUSION
Our results corroborated the evidence on BD progression and contributed to outline its trajectory over time. Further effort may help to define a standardized staging approach towards ever increasing tailored interventions.
PubMed: 38944295
DOI: 10.1016/j.jad.2024.06.094