The role of oxidative stress in the pathomechanism of major mood disorders: a narrative review with a special focus on uric acid.

Major mood disorder (i.e. major depressive disorder [MDD] and bipolar disorders [BPDs]) are among the most prevalent and disabling mental illnesses. Several, frequently intertwining theories (such as the monoamine, neuroinflammatory and neurotrophic theories) exist to explain the etiopathogenic background of mood disorders. A lesser-known hypothesis addresses the role of oxidative stress (OS; i.e. the overproduction and accumulation of free radicals) in the pathogenesis of these mental disorders. Free radicals are capable of damaging phospholipids, polyunsaturated fatty acids, proteins and nucleic acids. In the brain, OS impairs inter alia synaptic signalling and neuroplasticity. In the current paper, in addition to a brief description of the aforementioned pathophysiological processes involved in mood disorders (with a special focus on OS), we discuss in detail the results of studies on changes in non-enzymatic antioxidant uric acid (UA) levels in major mood disorders. Findings to date indicate that UA - a routinely measured laboratory parameter - may be a candidate biomarker to distinguish between MDD and BPD. Since the diagnostic criteria are identical for major depressive episodes regardless of whether the episode occurs in the context of MDD or BPD and also bearing in mind that the treatment for those two disorders is different, we may conclude that the identification of biomarkers to enable MDD to be distinguished from BPD would be of great clinical relevance.

Lysophosphatidic Acid (LPA) and Its Receptors in Mood Regulation: A Systematic Review of the Molecular Mechanisms and Therapeutic Potential.

Mood disorders affect over 300 million individuals worldwide, often characterized by their chronic and refractory nature, posing significant threats to patient life. There has been a notable increase in mood disorders among American adolescents and young adults, with a rising number of suicide attempts and fatalities, highlighting a growing association between mood disorders and suicidal outcomes. Dysregulation within the neuroimmune-endocrine system is now recognized as one of the fundamental biological mechanisms underlying mood and mood disorders. Lysophosphatidic acid (LPA), a novel mediator of mood behavior, induces anxiety-like and depression-like phenotypes through its receptors LPA1 and LPA5, regulating synaptic neurotransmission and plasticity. Consequently, LPA has garnered substantial interest in the study of mood regulation. This study aimed to elucidate the molecular mechanisms of lysophosphatidic acid and its receptors, along with LPA receptor ligands, in mood regulation and to explore their potential therapeutic efficacy in treating mood disorders. A comprehensive literature search was conducted using the PubMed and Web of Science databases, identifying 208 articles through keyword searches up to June 2024. After excluding duplicates, irrelevant publications, and those restricted by open access limitations, 21 scientific papers were included in this review. The findings indicate that LPA/LPA receptor modulation could be beneficial in treating mood disorders, suggesting that pharmacological agents or gintonin, an extract from ginseng, may serve as effective therapeutic strategies. This study opens new avenues for future research into how lysophosphatidic acid and its receptors, as well as lysophosphatidic acid receptor ligands, influence emotional behavior in animals and humans.

A novel method for quantifying affective sensitivity to endogenous ovarian hormones.

Increased sensitivity to ovarian hormone changes is implicated in the etiology of reproductive mood disorders across the female lifespan, including menstrually-related mood disorders, perinatal mood disorders, and perimenopausal depression. Developing a method to accurately quantify sensitivity to endogenous hormone fluctuations may therefore facilitate the prediction and prevention of these mental health conditions. Here, we propose one such method applying a synchrony analysis to compute time-lagged cross-correlations between repeated assessments of endogenous hormone levels and self-reported affect. We apply this method to a dataset containing frequent repeated assessments of affective symptoms and the urinary metabolites of estradiol (E2) and progesterone (P4) in 94 perimenopausal females. These preliminary findings suggest that, with further refinement and validation, the proposed method holds promise as a diagnostic tool to be used in clinical practice and to advance research investigating the etiology of reproductive mood disorders.

High-intensity interval training ameliorates postnatal immune activation-induced mood disorders through KDM6B-regulated glial activation.

Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme - histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders.

Social defeat protocol and relevant biomarkers, implications for stress response physiology, drug abuse, mood disorders and individual stress vulnerability: a systematic review of the last decade / Protocolo de derrota social e biomarcadores relevantes, implicações para a fisiologia de resposta ao estresse, abuso de drogas, transtornos do humor e vulnerabilidade individual ao estresse: revisão sistemática de estudos na última década

Introduction: Social defeat (SD) in rats, which results from male intraspecific confrontations, is ethologically relevant and useful to understand stress effects on physiology and behavior. Methods: A systematic review of studies about biomarkers induced by the SD protocol and published from 2002 to 2013 was carried out in the electronic databases PubMed, Web of Knowledge and ScienceDirect. The search terms were: social defeat, rat, neurotrophins, neuroinflammatory markers, and transcriptional factors. Results: Classical and recently discovered biomarkers were found to be relevant in stress-induced states. Findings were summarized in accordance to the length of exposure to stress: single, repeated, intermittent and continuous SD. This review found that the brain-derived neurotrophic factor (BDNF) is a distinct marker of stress adaptation. Along with glucocorticoids and catecholamines, BDNF seems to be important in understanding stress physiology. Conclusion: The SD model provides a relevant tool to study stress response features, development of addictive behaviors, clinic depression and anxiety, as well as individual differences in vulnerability and resilience to stress. .

Introdução: A derrota social (social defeat, SD) entre ratos, resultado da confrontação intraespecífica entre machos, é etologicamente relevante e útil para o entendimento dos efeitos do estresse na fisiologia e no comportamento. Métodos: Foi realizada uma revisão sistemática de estudos sobre biomarcadores induzidos pelo protocolo de SD publicados entre 2002 e 2013, usando as bases de dados PubMed, Web of Knowledge e ScienceDirect. Os termos usados na busca foram: derrota social, neurotrofinas, marcadores neuroinflamatórios e fatores de transcrição. Resultados: Biomarcadores clássicos ou recentemente descobertos mostraram-se relevantes nos estados induzidos pelo estresse. Os achados foram resumidos de acordo com o tempo de exposição ao estresse: SD única, repetida, intermitente ou contínua. O fator neurotrófico derivado do cérebro se mostrou um marcador específico de adaptação ao estresse. Assim como glicocorticóides e catecolaminas, o BDNF parece ser importante para o entendimento da fisiologia do estresse. Conclusão: O modelo de SD oferece uma ferramenta importante para estudar características da resposta ao estresse, desenvolvimento de comportamentos aditivos, depressão clínica e ansiedade, bem como diferenças individuais de vulnerabilidade e resiliência ao estresse. .

Hormônios sexuais femininos e transtornos do humor / Female sexual hormones and mood disorders

Objetivo: Descrever o conhecimento atual sobre a relação entre transtornos do humor e hormônios sexuais femininos. Método: Levantamento, pelo PubMed/Medline, do período entre 1990 e 2004 utilizando os unitermos mulher, hormônios femininos, transtorno do humor, depressão, neurotransmissores e hormônios sexuais. As referências foram usadas como fonte de consulta. Resultados: Na menarca, chama a atenção a grande influência do meio ambiente sobre o ciclo reprodutivo e dessa fase sobre o estado psíquico da mulher. A interação entre os sistemas hormonais gonadal e adrenal vem sendo apontada como um dos sensibilizadores para a ocorrência da depressão no período reprodutivo da vida feminina. Alterações do humor próprias da mulher, como a disforia pré-menstrual, ainda carecem de dados para a explicação de sua fisiopatogenia. Porém parece muito sugestivo o papel da serotonina no desenvolvimento desse transtorno. Ainda menos clara está a fisiopatogenia dos transtornos do hunmor relacionados a parto e puerpério. Têm-se encontrado diversas alterações hormonais e de neurotransmissores, mas ainda não existe uma teoria unificadora. A menopausa é o período em que as pesquisas atuais trazem perspectivas terapêuticas mais concretas. Conclusão: As alterações fisiológicas dos hormônios sexuais ocorrem em todas as mulheres, o que nos sugere qua a alta prevalência de transtornos de humor pode ser resultado de mudanças hormonais associadas a um fator genético predisponente. O padrão de alterações neuroendócrinas relacionadas aos hormônios femininos e o ciclo reprodutivo tornam as mulheres mais vulneráveis a mudanças de humor e sensíveis a fatores sociais, psicológicos e fisiológicos.

Hipótesis de las catecolaminas en los trastornos afectivos: Revisión de las pruebas en su apoyo

La hipótesis de las catecolaminas en los trastornos afectivos propone que algunas, si no la totalidad de las depresiones, están asociadas con una disminución relativa o absoluta de las catecolaminas, en particular la noreprinefrina, disponibles en los sitios centrales de recepción adrenérgica. La elevación, por el contrario, puede estar asociada con un exceso de tales aminas. Se revisaron los indicios que le dan apoyo a esta hipótisis. Los datos de los estudios farmacológicos realizados mayormente en animales, sugieren que las acciones de las dos principales clases de drogas antidepresoras son influidas por las catecolaminas. Los inhibidores de la monoamina oxidasa aumentan las concentraciones encefálicas de noreprinefrina, mientras que los agentes semejantes a la imipramina potencian los efectos fisiológicos de la norepinefrina (AU)