Chronic stress significantly contributes to the development of depressive disorders, with the hypothalamic–pituitary–adrenal (HPA) axis playing a central role in mediating stress responses. This review examines the neurobiological alterations in the hippocampus linked to HPA axis dysregulation in chronic stress-associated depressive disorders. The prolonged activation of the HPA axis disrupts cortisol regulation, leading to the decline of both physical and mental health. The chronic stress-induced HPA axis dysfunction interacts with inflammatory pathways and generates oxidative stress, contributing to cellular damage and neuroinflammation that further aggravates depressive symptoms. These processes result in structural and functional alterations in the hippocampus, which is essential for emotional regulation and cognitive function. Comprehending the impact of chronic stress on the HPA axis and associated neurobiological pathways is essential for formulating effective interventions for depressive disorders. This review summarises the existing findings and underscores the necessity for future investigations into intervention strategies to improve physical and psychological wellbeing targeting at HPA axis dysregulation for the betterment of psychological wellbeing and human health.

Perimenopausal depression, occurring shortly before or after menopause, is characterized by symptoms such as emotional depression, anxiety, and stress, often accompanied by endocrine dysfunction, particularly hypogonadism and senescence. Current treatments for perimenopausal depression primarily provide symptomatic relief but often come with undesirable side effects. The development of agents targeting the specific pathologies of perimenopausal depression has been relatively slow. The erratic fluctuations in estrogen and progesterone levels during the perimenopausal stage expose women to the risk of developing perimenopausal-associated depression. These hormonal changes trigger the production of proinflammatory mediators and induce oxidative stress, leading to progressive neuronal damage. This review serves as a comprehensive overview of the underlying mechanisms contributing to perimenopausal depression. It aims to shed light on the complex relationship between perimenopausal hormones, neurotransmitters, brain-derived neurotrophic factors, chronic inflammation, oxidative stress, and perimenopausal depression. By summarizing the intricate interplay between hormonal fluctuations, neurotransmitter activity, brain-derived neurotrophic factors, chronic inflammation, oxidative stress, and perimenopausal depression, this review aims to stimulate further research in this field. The hope is that an increased understanding of these mechanisms will pave the way for the development of more effective therapeutic targets, ultimately reducing the risk of depression during the menopausal stage for the betterment of psychological wellbeing.

Major depressive disorder (MDD) is a common neuropsychiatric disorder affecting the mood and mental well-being. Its pathophysiology remains elusive due to the complexity and heterogeneity of this disorder that affects millions of individuals worldwide. Chronic stress is frequently cited as the one of the risk factors for MDD. To date, the conventional monoaminergic theory (serotonin, norepinephrine, and/or dopamine dysregulation) has received the most attention in the treatment of MDD, and all available classes of antidepressants target these monoaminergic systems. However, the contributions of other neurotransmitter systems in MDD have been widely reported. Emerging preclinical and clinical findings reveal that maladaptive glutamatergic neurotransmission might underlie the pathophysiology of MDD, thus revealing its critical role in the neurobiology of MDD and as the therapeutic target. Aiming beyond the monoaminergic hypothesis, studies of the neurobiological mechanisms underlying the stress-induced impairment of AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-glutamatergic neurotransmission in the brain could provide novel insights for the development of a new generation of antidepressants without the detrimental side effects. Here, the authors reviewed the recent literature focusing on the role of AMPA-glutamatergic neurotransmission in stress-induced maladaptive responses in emotional and mood-associated brain regions, including the hippocampus, amygdala, prefrontal cortex, nucleus accumbens and periaqueductal gray.

Interferons (IFNs) are important in controlling the innate immune response to viral infections. Besides that, studies have found that IFNs also have antimicrobial, antiproliferative/antitumor and immunomodulatory effects. IFNs are divided into Type I, II and III. Type I IFNs, in particular IFN-α, is an approved treatment for hepatitis C. However, patients developed neuropsychological disorders during treatment. IFN-α induces proinflammatory cytokines, indoleamine 2,3-dioxygenase (IDO), oxidative and nitrative stress that intensifies the body’s inflammatory response in the treatment of chronic inflammatory disease. The severity of the immune response is related to behavioral changes in both animal models and humans. Reactive oxygen species (ROS) is important for synaptic plasticity and long-term potentiation (LTP) in the hippocampus. However, excess ROS will generate highly reactive free radicals which may lead to neuronal damage and neurodegeneration. The limbic system regulates memory and emotional response, damage of neurons in this region is correlated with mood disorders. Due to the drawbacks of the treatment, often patients will not complete the treatment sessions, and this affects their recovery process. However, with proper management, this could be avoided. This review briefly describes the different types of IFNs and its pharmacological and clinical usages and a focus on IFN-α and its implications on depression.

Recreational use of alcohol is a social norm in many communities worldwide. Alcohol use in moderation brings pleasure and may protect the cardiovascular system. However, excessive alcohol consumption or alcohol abuse are detrimental to one’s health. Three million deaths due to excessive alcohol consumption were reported by the World Health Organization. Emerging evidence also revealed the danger of moderate consumption, which includes the increased risk to cancer. Alcohol abuse and periods of withdrawal have been linked to depression and anxiety. Here, we present the effects of alcohol consumption (acute and chronic) on important brain structures—the frontal lobe, the temporal lobe, the limbic system, and the cerebellum. Apart from this, we also present the link between alcohol abuse and withdrawal and mood disorders in this review, thus drawing a link to oxidative stress. In addition, we also discuss the positive impacts of some pharmacotherapies used. Due to the ever-rising demands of life, the cycle between alcohol abuse, withdrawal, and mood disorders may be a never-ending cycle of destruction. Hence, through this review, we hope that we can emphasise the importance and urgency of managing this issue with the appropriate approaches.