Late-life depression (LLD) arises from a complex interplay among biological, psychological, and social factors. Biologically, three main hypotheses have been proposed to explain the distinct clinical features of LLD. The vascular hypothesis supports vascular-related white matter changes in the development of LLD, while the neurodegenerative hypothesis suggests that LLD might be a prodrome of neurodegenerative diseases. The inflammatory hypothesis, which is the main focus of this review, posits that heightened inflammation underlies LLD directly or indirectly through neurodegenerative and microvascular alterations.

This is a non-systematic review on the role played by inflammation in the pathophysiology of LLD and the related opportunities to define biomarkers and therapeutic targets. We searched PubMed from January 2010 through March 2025 for relevant English-language studies.

Patients with LLD have elevated circulating levels of inflammatory biomarkers (e.g., C-reactive protein and interleukin-6) as well as evidence of neuroinflammation. Although the exact origin of this inflammatory profile remains unclear, it is thought to be exacerbated by immune cell senescence and the presence of physical comorbidities, including cardiovascular and metabolic diseases. Pharmacological (e.g., selective serotonin receptor inhibitors) and non-pharmacological (e.g., diet, physical interventions) approaches for LLD seem to exert their therapeutic effect, at least in part, through inflammation-related mechanisms.

Recognizing the unique features of LLD compared to depression in other periods of life is an important step toward its proper management. More specifically, understanding the role of inflammation in LLD holds both theoretical and practical implications, including anti-inflammatory or immune-based strategies as potential therapeutic interventions.

Previous studies on the aetiology of attention-deficit/hyperactivity disorder (ADHD) emphasise high heritability and the influence of maternal smoking during pregnancy, highlighting the role of gene–environment interactions. Additionally, low-grade peripheral inflammation is frequently observed in individuals with ADHD. However, the underlying neurobiological mechanisms remain unclear. We aimed to investigate neuroinflammatory signalling contributing to ADHD and explore behavioural and molecular changes in a mouse model.

We examined neuroinflammatory signalling using a perinatal nicotine exposure (PNE) model via immunohistochemistry combined with cortical thickness (CT) measurement in the subregions of the prefrontal cortex (PFC). Mice were exposed to nicotine via drinking water containing 300 μg/ml nicotine and 2% sucrose starting 2 weeks before mating until weaning to induce ADHD-like symptoms, as opposed to controls receiving drinking water containing 2% sucrose alone. Behavioural tests were conducted to assess ADHD-like behaviours and accompanying anxiety on postnatal week 5. Inflammatory pathways in the anterior cingulate cortex (ACC), prelimbic cortex (PL), and infralimbic cortex (IL) were examined using Iba-1 and NF-κB immunolabelling, and microglial morphology was analyzed.

Findings showed increased CT, microglial cell number, activity, and NF-κB activation in the ACC, which correlated with attention-related impairment in PNE mice. Increased Iba-1 levels in the PL and IL, along with elevated NF-κB activation in the IL, were observed in PNE mice, which corresponded with a significant increase in anxiety-like behaviours compared to controls. PNE mice also morphologically exhibited microglia activation in all three subregions.

PNE contributes to ADHD development through neuroinflammatory signalling, a common end pathway.

Cognitive function plays a pivotal role in assessing an individual’s quality of life. This research aimed to investigate how azelaic acid (AzA), a natural dicarboxylic acid with antioxidant and anti-inflammatory properties, affects aluminium chloride (AlCl3)-induced behavioural changes and biochemical alterations in the hippocampus of rats.

Thirty-two male Wistar rats divided into four groups received distilled water, AzA 50 mg/kg, AlCl3 100 mg/kg and AzA plus AlCl3, respectively, by oral gavage for 6 weeks. Behavioural changes were evaluated using open-field maze, elevated plus maze, novel object recognition (NOR), passive avoidance task, and Morris water maze (MWM) tests. Also, malondialdehyde (MDA), carbonyl protein, tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), nuclear factor-kappa B (NF-κB), C/EBP homologous protein (CHOP), glycogen synthase kinase-3 beta (GSK-3β), brain-derived neurotrophic factor (BDNF) and acetylcholinesterase (AChE) activity were examined.

AzA significantly affected AlCl3-provoked anxiety-like behaviours and learning and memory impairments. It also reduced the toxic effect of AlCl3 on MDA, carbonyl protein, TNF-α, IL-1β, NF-κB and GSK-3β status; however, its beneficial effects on AlCl3-induced changes of CHOP, BDNF and AChE activity were not significant.

These findings disclosed that AzA could improve behavioural and cognitive function and almost limit the oxidative stress and neuroinflammation caused by AlCl3.

Inflammation is increasingly recognised as a fundamental component of the pathophysiology of major depressive disorder (MDD), with a variety of inflammatory biomarkers playing pivotal roles. These markers are closely linked to both the severity of symptoms and the responsiveness to treatments in MDD.

This scoping review aims to explore the scientific literature investigating the complex relationships between inflammatory biomarkers and depression, by identifying new studies and critical issues in current research.

Following the PRISMA Extension for Scoping Reviews guidelines, we systematically searched databases including PubMed, Scopus, PsycINFO, Open Grey and Cochrane Library. Our search focused on articles published from 1 January 2020 to 1 May 2024. We included studies evaluating inflammatory biomarkers in adult patients with MDD, utilising observational and randomised controlled trial designs, and review studies.

Our analysis examined 44 studies on the complex interplay between inflammation and its multiple effects on MDD. Significant associations between specific inflammatory biomarkers and depression severity were found, requiring cautious interpretation. We also highlight several methodological limitations in the current studies, which warrant caution in directly applying these findings to clinical practice. However, identified methodologies show potential for using these biomarkers as diagnostic tools or therapeutic targets, including anti-inflammatory interventions.

The findings emphasise the need for sophisticated, integrative research to understand inflammation's role in MDD. Future studies should identify specific biomarker panels for diagnosing depression and bridging peripheral biomarker measurements with central neuroinflammatory processes, leading to better diagnostic and treatment strategies.

To investigate the effects of cannabidiol (CBD) on emotional and cognitive symptoms in rats with intra-nigral 6-hydroxydopamine (6-OHDA) lesions.

Adult male Wistar rats received bilateral intranigral 6-OHDA infusions and were tested in a battery of behavioural paradigms to evaluate non-motor symptoms. The brains were obtained to evaluate the effects of CBD on hippocampal neurogenesis.

6-OHDA-lesioned rats exhibited memory impairments and despair-like behaviour in the novelty-suppressed feeding test and forced swim test, respectively. The animals also exhibited dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), striatum, and ventral tegmental area and a reduction of hippocampal neurogenesis. CBD decreased dopaminergic neuronal loss in the SNpc, reduced the mortality rate and decreased neuroinflammation in 6-OHDA-lesioned rats. In parallel, CBD prevented memory impairments and attenuated despair-like behaviour that were induced by bilateral intranigral 6-OHDA lesions. Repeated treatment with CBD favoured the neuronal maturation of newborn neurons in the hippocampus in Parkinsonian rats.

The present findings suggest a potential beneficial effect of CBD on non-motor symptoms induced by intra-nigral 6-OHDA infusion in rats.

The s100b inflammatory protein is involved in schizophrenia pathophysiology. We aim at studying the evolution of the s100b serum levels in acutely relapsed paranoid schizophrenia patients at three different time points (admission, discharge and 3 months after hospital discharge 3MAHD).

Twenty-three paranoid schizophrenia inpatients meeting DSM-IV criteria participated in the research. Twenty-three healthy subjects matched by age, gender and season acted as the control group. Psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS). Serum s100b levels were determined at 12:00 and 24:00 h with an enzyme-linked immunoassay kit.

Patients had significant higher serum s100b levels at admission and discharge (12:00 h) than the group of healthy subjects. At admission and discharge, s100b serum levels at 24 h had decreased compared to the 24:00 h s100b levels of the healthy subjects. At 3MAHD patients and healthy subjects had similar levels of serum s100b protein. Positive and negative PANSS scores decreased significantly between admission and discharge. Positive and negative PANSS scores decreased between discharge and 3MAHD, but these changes had no statistical significance.

Our study confirms that the acute inflammatory response produced in acutely relapsed patients is reversed after 3 month of hospital discharge. The variations of serum s100b concentrations when the patients suffer from an acute relapse may be a useful predictor of disease evolution.

Suicide is the second leading cause of death (8.5% of all deaths) in adolescents. The search for neurobiological markers of suicidal behavior seems to be highly actual. Such markers may include quantitative EEG parameters and signs of neuroinflammation that plays an important role in the pathogenesis of various mental disorders.

The aim of the study was to reveal the relationships between pre-treatment clinical, EEG, and neuroimmunological parameters in depressive adolescents with suicidal attempts in their history.

35 female depressive patients (all right-handed, age 16–25, mean 18,7±2.9 years old) were enrolled in the study. Total HDRS-17 scores varied from 13 to 43 (mean 27,7±8.1). Multichannel resting EEG was recorded with spectral power (SP) measurements in narrow frequency sub-bands. Functional activities of leukocyte elastase (LE) and of its antagonist α1-proteinase inhibitor (α1-PI), as neuroinflammation markers, were measured in the blood plasma. Leukocyte/inhibitory index (LII=LE/α1-PI) was calculated. Spearman’s correlations between clinical, EEG, and neuroimmunological parameters were analyzed.

Sum of anxiety cluster of HDRS-17 scale (items 9, 10, 11) correlated positively (p<0.02) with LE and α1-PI values, as well as with theta1 (4-6 Hz) and theta2 (6-8 Hz) SP in EEG leads of the right hemisphere. In turn, α1-PI values correlated negatively and LII values correlated positively with alpha3 (11-13 Hz) SP in majority of EEG leads.

The data obtained confirm the contribution of neuroinflammation to clinical conditions, especially to anxiety level, and to EEG pattern in depressive female adolescents with suicidal attempts. The study supported by RBRF grant No.20-013-00129a.

No significant relationships.

Schizophrenia affects approximately 1% of the world population, having a devastating impact not only in patients but in all society. As a result, it has been subject of extensive investigation and the presence of certain genes was associated with an increased risk of developing schizophrenia. However, the presence of these genes is not sufficient, therefore, other factors are necessarily involved.Observation of the association between schizophrenia and inflammatory states of the Central Nervous System led to the hypothesis that a dysfunction of the immune system may play a central role in this process.

In this work we intend to make a brief review of the existing literature related to the immunological theory of schizophrenia.

A bibliographic research was conducted in Medline library using the following terms: “schizophrenia and immune system”; “schizophrenia and inflammation” and “schizophrenia and neuroinflammation”.

The survey results reveal increasing evidence of the key role of the immune system in schizophrenia. Several studies show benefits of treatment with anti-inflammatory drugs in patients at an early stage of the disease. In the same way, it was verified that pro and anti-inflammatory cytokines influence glutamatergic transmission and tryptophan metabolism. Furthermore, the decrease in microglial activity appears to have a beneficial effect on schizophrenia.

Future will say if neuroimmunology mechanisms are primary or a secondary consequence in Schizophrenia. Recent discoveries in this area are encouraging and open the possibility of new therapeutic targets and new therapeutic approaches to this disease.

No significant relationships.