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INTRODUCTION: Major Depressive Disorder (MDD) is a common mental health disorder marked by sadness, hopelessness, and anhedonia. Various therapies exist, but their effectiveness is limited. Dextromethorphan hydrobromide combined with bupropion hydrochloride (Auvelity®) is a recently approved alternative for treating this condition in adults. AREAS COVERED: This review summarizes the neurobiology of major depression and delves into the pharmacology, efficacy, safety, and tolerability of dextromethorphan plus bupropion in adult patients. It is based on observational studies, clinical trials, and other secondary studies obtained through systematic literature searches. EXPERT OPINION: The combination of bupropion and dextromethorphan as a new pharmacotherapy for mental health is an interesting addition to the treatment options that can be used for MDD. The combination can be used in a range of scenarios, including as a first line therapy, as a second option when a patient has failed to achieve remission with a serotonin targeting agent, and for treatment resistant depression. Further research for other indications, including addiction disorders, may provide exciting results. Although a new combination, clinicians will be very familiar with both agents, increasing their acceptability. This pharmacotherapy also may bring increased impetus for discovering other combinations that may have beneficial synergistic effects.

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Major Depressive Disorder (MDD) is a global problem. Currently, the most common diagnosis is based on criteria susceptible to the subjectivity of the patient and the clinician. A possible solution to this problem is to look for diagnostic biomarkers that can accurately and early detect this mental condition. Some researchers have focused on electroencephalogram (EEG) analysis to identify biomarkers. In this study we used a dataset composed of EEG recordings from 24 subjects with MDD and 29 healthy controls (HC), during the execution of affective priming tasks with three different emotional stimuli (images): fear, sadness, and happiness. We investigated abnormalities in depressed patients using a novel technique, by directly comparing Event-Related Potential (ERP) waveforms to find statistically significant differences between the MMD and HC groups. Compared to the control group (healthy subjects), we found out that for the emotions fear and happiness there is a decrease in cortical activity at temporal regions in MDD patients. Just the opposite, for the emotion sadness, an increase in MDD brain activity occurs in frontal and occipital regions. Our findings suggest that emotions regulate the attentional control of cognitive processing and are promising for clinical application in diagnosing patients with MDD more objectively.

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Severe mental illnesses (SMI) collectively affect approximately 20% of the global population, as estimated by the World Health Organization (WHO). Despite having diverse etiologies, clinical symptoms, and pharmacotherapies, these diseases share a common pathophysiological characteristic: the misconnection of brain areas involved in reality perception, executive control, and cognition, including the corticolimbic system. Dendritic spines play a crucial role in excitatory neurotransmission within the central nervous system. These small structures exhibit remarkable plasticity, regulated by factors such as neurotransmitter tone, neurotrophic factors, and innate immunity-related molecules, and other mechanisms - all of which are associated with the pathophysiology of SMI. However, studying dendritic spine mechanisms in both healthy and pathological conditions in patients is fraught with technical limitations. This is where animal models related to these diseases become indispensable. They have played a pivotal role in elucidating the significance of dendritic spines in SMI. In this review, the information regarding the potential role of dendritic spines in SMI was summarized, drawing from clinical and animal model reports. Also, the implications of targeting dendritic spine-related molecules for SMI treatment were explored. Specifically, our focus is on major depressive disorder and the neurodevelopmental disorders schizophrenia and autism spectrum disorder. Abundant clinical and basic research has studied the functional and structural plasticity of dendritic spines in these diseases, along with potential pharmacological targets that modulate the dynamics of these structures. These targets may be associated with the clinical efficacy of the pharmacotherapy.

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Abstract Introduction Major depressive disorder (MDD) is a prevalent disease affecting women more than men worldwide. Various factors are involved in the genesis of depression, including hormones such as testosterone and certain metabolic factors Objective To evaluate hormone levels and metabolic variables in women with major depression and healthy controls. Method A cross-sectional, comparative analytical study was conducted in 40 participants, 23 patients with an MDD diagnosis and 17 controls, all of women in reproductive age between the ages of 18 and 45. Sociodemographic variables, hormonal profile, and metabolic variables were assessed and the 17-item Hamilton Depression Scale was used to evaluate depressive symptoms. Results No statistically significant differences were observed between the groups in the hormonal and metabolic variables explored. Nevertheless, it was observed that the lower the testosterone levels and the higher the serum glucose levels, the more intense depressive symptoms were. Discussion and conclusion Testosterone is associated with a lower depressive symptoms score on the Hamilton Depression scale, suggesting a potential antidepressant effect, whereas high glucose levels are associated with a higher score on this scale. We believe that the measurement of hormonal and metabolic variables in women can contribute to a better understanding of the pathophysiology of depression.

Resumen Introducción El trastorno depresivo mayor (TDM) es una enfermedad prevalente a nivel mundial, que afecta más a mujeres que a hombres. En la génesis de la depresión se consideran diversos factores, entre ellos algunas hormonas como la testosterona y ciertos factores metabólicos Objetivo Evaluar los niveles de hormonas y variables metabólicas en mujeres con depresión mayor y controles sanas. Método Se realizó un estudio transversal, comparativo y analítico en 40 participantes, 23 pacientes con diagnóstico de TDM y 17 controles, todas ellas mujeres de 18 a 45 años en periodo reproductivo. Se evaluaron variables sociodemográficas, perfil hormonal y variables metabólicas, y se aplicó la Escala de Depresión de Hamilton de 17 reactivos para evaluar los síntomas depresivos. Resultados No se observaron diferencias estadísticamente significativas entre los grupos en las variables hormonales y metabólicas exploradas. Sin embargo, se observó que, cuanto menores eran los niveles de testosterona y mayores los de glucosa sérica, los síntomas depresivos eran de mayor intensidad. Discusión y conclusión La testosterona se asocia con un menor puntaje de síntomas depresivos en la Escala Hamilton, lo que sugiriere un potencial efecto antidepresivo, mientras que los niveles altos de glucosa se asocian con un mayor puntaje en dicha escala. Consideramos que la medición de variables hormonales y metabólicas en la mujer puede contribuir a mejorar el conocimiento de la fisiopatología de la depresión.

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BACKGROUND: Studies have shown the relationship between neuroinflammation and depressive- like parameters. However, research still has not been carried out to evaluate neuroinflammation in the neonatal period and psychiatric disorders in adulthood. OBJECTIVE: To verify the association between neonatal immune activation and depressive-like parameters in adulthood using an animal model. METHODS: Two days old C57BL/6 animals were exposed to lipopolysaccharides (LPS) or phosphate- buffered saline (PBS). When the animals were 46 days old, they received PBS or Imipramine at 14 days. At 60 days, the consumption of sucrose; immobility time; adrenal gland and the hippocampus weight; levels of plasma corticosterone and hippocampal Brain-derived neurotrophic factor (BDNF) were evaluated. RESULTS: It was observed that the animals exposed to LPS in the neonatal period and evaluated in adulthood decreased the consumption of sucrose and had reducted hippocampus weight. Also, the exposed animals presented an increase of immobility time, adrenal gland weight and plasma levels of corticosteroids. The use of imipramine did not only modify the decreased hippocampal weight. On the other hand, there were no alterations in the BDNF levels in the hippocampus with or without the use of imipramine. CONCLUSION: These results suggest that neonatal immune activation may be associated with depressive- like parameters in adulthood. It is believed that endotoxemia may trigger physiological and behavioral alterations, increasing vulnerability for the development of depression in adulthood.

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