Major depressive disorder (MDD) is associated with inflammation and a high level of comorbidities. Atypical depression (AD) is a MDD subtype based on DSM criteria, that could have specific underlying biological mechanisms. AD is associated with elevated cardiovascular (CVD) comorbidities, higher risk of suicide attempts, hypersomnia, and anxiety disorder. In this study, we aim to investigate if AD and polysomnographic parameters could be associated with low-grade inflammation (LGI). LGI is defined by a range from 3 to 10 mg/L of C-reactive protein levels. We carried out a retrospective cohort study in which 765 individuals with MDD were split into two groups: with and without LGI. Our results exhibit differences between the groups for the polysomnographic parameters, with the LGI group showing parameters already associated with inflammation such as reduced rapid eye movement sleep and elevated hypoxemia markers (identified as CVD risk factor). We found that AD is associated with LGI (OR 1.48; p = 0.047) after adjustment. Likewise, we found an LGI prevalence in AD higher (34.8%) than in MDD without atypical features (26.8%). Overall, these results confirm the low-grade inflammation feature of AD and highlight polysomnographic parameters associated with LGI that could also act as risk factors in this context.

Women exhibit unique vulnerabilities in health, especially regarding mental health and neurodegenerative diseases. Biological, hormonal, and metabolic differences contribute to sex-specific risks that remain underrepresented in clinical studies. Diseases such as major depressive disorder (MDD) and Alzheimer’s disease (AD) are more prevalent in women and may be influenced by hormonal transitions, particularly during menopause. Chronic low-grade inflammation is emerging as a shared mechanism underlying both conditions, and this inflammatory state can be worsened by dietary habits. During menopause, mood and sleep disturbances can influence dietary behavior, leading to enhanced snacking and consumption of high-glycemic and comfort foods. Such foods, low in nutritional value, promote weight gain and elevated inflammatory markers. Their consumption combined (or not) with a preexisting Western diet pattern—already linked to inflammation—could reinforce systemic inflammation involving the gut–brain axis. Moreover, the symptoms “per se” could act on inflammation as well. Peripheral inflammation may cross the blood–brain barrier, sustaining mood disorders and promoting neurodegenerative changes. Finally, MDD and AD are both associated with conditions such as obesity and diabetes, which occur more frequently in women. The review highlights how menopause-related changes in mood, sleep, and diet may heighten susceptibility to mental and neurodegenerative diseases.

Background and Objectives: Anhedonia is a core symptom of major depressive disorder (MDD) and worsens its prognosis. Inflammation has been associated with MDD, contributing to the severity of this pathology despite no clear clinical guidance on whether it should be integrated into the diagnosis or treatment of the MDD symptomatology. Notably, the neural basis of anhedonia is associated with alterations in the reward neural circuit, where inflammation may also interfere. In this study, we investigate whether recent change in anhedonia was associated with low-grade inflammation (defined as C-Reactive Protein levels between 3 and 10 mg/L) in MDD subjects. Materials and Methods: A retrospective study was conducted on 496 MDD subjects and drawn from the database of the sleep laboratory. Recent change in anhedonia was assessed via the Anhedonia Subscale of the 21-items Beck Depression Inventory (BDI-II), with scores > 3 indicating its presence. Recent change in anhedonia was defined as the recent onset or worsening of anhedonia complaints within the past 2 weeks. Anxiety and sleep disturbances were also evaluated and inflammatory status was determined based on CRP levels. Results: After adjusting for the main confounding factors, the multivariate logistic regression confirms a clear association between recent change in anhedonia and low-grade inflammation, thereby contributing to a detrimental context underlying the symptom. Conclusions: A better understanding of anhedonia in the context of inflammation could enable treatment adjustments and improve the poor prognosis of anhedonia-type depression.