Technical Report: Efficacy and Safety of Low-Intensity Transcranial Magnetic Stimulation in the Remission of Depressive Symptoms in Patients With Treatment-Resistant Depression in Mexico.

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that induces action potentials in the stimulated cortical area and has been approved by the Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). The prevalence of MDD in Mexico almost tripled after the COVID-19 pandemic. In this study, we evaluated the safety and therapeutic effects of low-intensity TMS (Li-TMS) - characterized by inducing electric currents below the action potential threshold on the cerebral cortex - in 41 subjects diagnosed with treatment-resistant depression (TRD). A Li-TMS device dispensed repetitive magnetic pulses at 30 mT for 60 minutes during 20 sessions (once daily from Monday to Saturday) with the theta burst pattern. Our results suggest that Li-TMS is a safe therapy with antidepressant effects, demonstrated by the decrease in Beck Depression Inventory (BDI) scores and lessening of depressive symptoms.

Polysomnographic parameters associated with cognitive function in patients with major depression and insomnia.

OBJECTIVE: To examine whether objective sleep parameters are associated with cognitive function (CF) in patients with major depressive disorder (MDD) with chronic insomnia (CI) and whether the severity of these disorders is related to CF. METHOD: Thirty patients with MDD with CI attending a tertiary care institution underwent two consecutive nights of polysomnographic (PSG) recording and a battery of neuropsychological tests, which included episodic memory, sustained attention, working memory, and executive function. The severity of MDD and CI was assessed by clinical scales. We examined the relationship between PSG parameters and CF, as well as whether the severity of the disorders is related to CF. RESULTS: Linear regression analysis revealed that total sleep time (TST) was positively associated with higher learning and recall of episodic memory, as well as better attention. Slow-wave sleep (SWS) showed a positive association with better working memory. Furthermore, wake after sleep onset (WASO) was negatively associated with episodic memory and lower attention. No significant relationships were found between the severity of MDD or CI with CF. CONCLUSION: Both sleep duration and depth are positively associated with several aspects of CF in patients with MDD with CI. Conversely, a lack of sleep maintenance is negatively related to CF in these patients. These findings could help identify modifiable therapeutic targets to reduce CF impairment.

Human olfactory neural progenitor cells reveal differences in IL-6, IL-8, thrombospondin-1, and MCP-1 in major depression disorder and borderline personality disorder.

Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC). Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression. Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD. Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders.

Pharmacological and computational analysis of the involvement of the 5-HT4 receptor in the antidepressant-like effect of N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide in mice.

The serotonin type 4 receptor (5-HT4R)shows promise as a target for treating major depressive disorder (MDD). Studies have demonstrated that 5-HT4R agonists have a faster antidepressant-like effect compared to conventional medications. Developing drugs that modulate this receptor could lead to faster and more effective MDD treatments. The compound N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide (SePB) induces an antidepressant-like effect in mice. The present study explored if the 5-HT4R mediates SePB's antidepressant effect. For this, male Swiss mice were treated with GR113808 (0.1 mg/kg, intraperitoneally - i.p.), a 5-HT4R antagonist, and SePB (10 mg/kg, intragastrically - i.g), and then subjected to the tail-suspension test (TST) and open-field test (OFT). In silico tests were conducted to analyze SePB's binding affinity to the 5-HT4R and identify participating amino acid residues. The administration of GR113808 blocked the antidepressant-like effect of SePB in the TST without changing locomotor activity in the OFT. Moreover, SePB exhibited a high binding affinity between the 5-HT4R (-7.9 kcal/mol) and the amino acid residues Leu298, Asp100, Thr97, Arg96, Glu80, Leu81, Cys184, Val185, and Phe186 seem to be important for this interaction. The involvement of the 5-HT4R in the antidepressant-like effect of SePB suggests potential for novel therapies in MDD.

Brain-Derived Neurotrophic Factor (BDNF) as a Predictor of Treatment Response in Major Depressive Disorder (MDD): A Systematic Review.

Brain-derived neurotrophic factor (BDNF) has been studied as a biomarker of major depressive disorder (MDD). Besides diagnostic biomarkers, clinically useful biomarkers can inform response to treatment. We aimed to review all studies that sought to relate BDNF baseline levels, or BDNF polymorphisms, with response to treatment in MDD. In order to achieve this, we performed a systematic review of studies that explored the relation of BDNF with both pharmacological and non-pharmacological treatment. Finally, we reviewed the evidence that relates peripheral levels of BDNF and BDNF polymorphisms with the development and management of treatment-resistant depression.

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder.

The pharmacological treatment of depression consists of taking antidepressant drugs for prolonged periods; its modest therapeutic effect can often be associated with significant adverse effects, while its discontinuation can lead to relapses. Psilocybin is today a novel and breakthrough therapy for major depression. It is a natural alkaloid in Psilocybe mushrooms, which are endemic to Mexico. Research on a larger scale is lacking in various populations, including the Mexican people. This proposal contemplates the experimental design of a preclinical (toxicity and pharmacological evaluation of an extract in mice) and clinical study by including the chemical analysis of a species of Psilocybe cubensis mushroom to characterize its main constituents. The clinical study will consider the safety evaluation by exploring tolerated doses of Psilocybe cubensis by measuring pharmacokinetic parameters after oral administration in healthy adults and an open trial on a sample of patients with major depressive disorder to assess the safety and efficacy of fully characterized Psilocybe cubensis in a two-single doses treatment, (with assisted psychotherapy), compared with the traditional care model at the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz in Mexico City. This report presents the design of a research project with preclinical and clinical experimental components.

Arketamine as adjunctive therapy for treatment-resistant depression: A placebo-controlled pilot study.

BACKGROUND: Racemic ketamine is a mixture of (R)-ketamine (arketamine) and (S)-ketamine (esketamine), with the latter regarded as the main isomer for antidepressant effects. However, preclinical data and one open-label human trial suggest arketamine might exert a more potent and longer-lasting antidepressant effect with fewer side effects. We aimed to explore the feasibility of a randomized controlled trial of arketamine for treatment-resistant depression (TRD) and to assess its efficacy and safety compared to placebo. METHODS: This is a, randomized, double-blind, crossover, pilot trial (n = 10). All participants received saline and arketamine (0.5 mg/kg) with a one-week interval. Treatment effects were analyzed with a linear mixed effects (LME) model. RESULTS: Our analysis suggested the presence of a carryover effect, so the main efficacy analysis was limited to the first week, which demonstrated a main effect of time (p = 0.038) but not for treatment (p = 0.40) or their interaction (p = 0.95). This indicates that depression improved over time, but without significant difference between arketamine and placebo. Analyzing the two weeks together, findings were the same. Dissociation and other adverse events were minimal. LIMITATIONS: This was a pilot study with a small sample and underpowered. CONCLUSIONS: Arketamine was not superior to placebo for TRD but demonstrated to be extremely safe. Our findings reinforce the importance of continuing studies with this drug, with better powered clinical trials, perhaps considering a parallel design with higher or flexible doses and repeated administrations.

DNA methylation in regulatory elements of the FKBP5 and NR3C1 gene in mother-child binomials with depression.

BACKGROUND: The FKBP5 and NR3C1 genes play an important role in stress response, thus impacting mental health. Stress factor exposure in early life, such as maternal depression, may contribute to epigenetic modifications in stress response genes, increasing the susceptibility to different psychopathologies. The present study aimed to evaluate the DNA methylation profile in maternal-infant depression in regulatory regions of the FKBP5 gene and the alternative promoter of the NR3C1 gene. METHODS: We evaluated 60 mother-infant pairs. The levels of DNA methylation were analyzed by the MSRED-qPCR technique. RESULTS: We observed an increased DNA methylation profile in the NR3C1 gene promoter in children with depression and children exposed to maternal depression (p < 0.05). In addition, we observed a correlation of DNA methylation between mothers and offspring exposed to maternal depression. This correlation shows a possible intergenerational effect of maternal MDD exposure on the offspring. For FKBP5, we found a decrease in DNA methylation at intron 7 in children exposed to maternal MDD during pregnancy and a correlation of DNA methylation between mothers and children exposed to maternal MDD (p < 0.05). LIMITATIONS: Although the individuals of this study are a rare group, the sample size of the study was small, and we evaluated the DNA methylation of only one CpG site for each region. CONCLUSION: These results indicate changes in DNA methylation levels in regulatory regions of FKBP5 and NR3C1 in the mother-child MDD context and represent a potential target of studies to understand the depression etiology and how it occurs between generations.

A systematic mini-review of epigenetic mechanisms associated with electroconvulsive therapy in humans.

Introduction: Electroconvulsive therapy (ECT) is one of the most effective strategies for treating resistant major depression. Although the mechanism of action is not fully understood and studies are limited, epigenetics is a promising area for the development of biomarkers associated with ECT treatment response. Aim: We reviewed studies available in the literature that explored the epigenetics of ECT in peripheral samples from patients with major depressive disorder (MDD). Methods: A systematic review was performed following The PRISMA guidelines. The search was performed in seven electronic databases: Scopus, Web of Science, Medline, PsycINFO, Embase, Cochrane, and Cinahl. Results: Nine studies were included. Seven assessed DNA methylation and three investigated microRNAs (miR). Overall, most studies were exploratory, with small sample sizes, and we found high heterogeneity between the study's design, ECT protocols, molecular biology methods, and epigenetic findings. Investigated candidates with some evidence of association with ECT treatment response were BDNF, S100A10, RNF213M, TNKS, FKBP5, miR-126, miR-106a, and miR-24. Conclusion: The present findings seem to support previous preclinical research, suggesting that epigenetic mechanisms play an important role in the molecular mechanism underlying ECT effects.

Increased insulin resistance due to Long COVID is associated with depressive symptoms and partly predicted by the inflammatory response during acute infection.

OBJECTIVE: Some months after the remission of acute COVID-19, some individuals show depressive symptoms, which are predicted by increased peak body temperature (PBT) and decreased blood oxygen saturation (SpO2). The present study aimed to examine data on whether long COVID is associated with increased insulin resistance (IR) in association with neuroimmune and oxidative (NIO) processes during the acute infectious and long COVID phases. METHODS: This case-control, retrospective cohort study used the Homeostasis Model Assessment 2 (HOMA2) calculator© to compute ß-cell function (HOMA2%B) and insulin sensitivity (HOMA2%S) and resistance (HOMA2-IR) and administered the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAMD) to 86 patients with long COVID and 39 controls. RESULTS: Long COVID (3-4 months after the acute infection) is accompanied by increased HOMA2-IR, fasting blood glucose (FBG), and insulin levels; 33.7% of the patients vs. 0% of the controls had HOMA2-IR values > 1.8, suggesting IR. Increased IR was predicted by PBT during acute infection and associated with depressive symptoms above and beyond the effects of NIO pathways (nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 [NLRP3] inflammasome, myeloperoxidase [MPO], protein oxidation). There were no significant associations between increased IR and the activated NIO pathways during long COVID. CONCLUSION: Long COVID is associated with new-onset IR, which may contribute to onset of depressive symptoms due to long COVID by enhancing overall neurotoxicity.

Serum cytokine variations among inpatients with major depression, bipolar disorder, and schizophrenia versus healthy controls: a prospective 'true-to-life' study.

Background: There is increasing evidence of the association between chronic low-grade inflammation and severe mental illness (SMI). The objective of our study was to assess serum cytokine levels (SCLs) at admission and discharge in a true-to-life-setting population of inpatients with major depression (MD), bipolar disorder (BD), and schizophrenia (Sz), as well as of healthy controls. Methods: We considered MD, BD, and Sz to be SMIs. We evaluated 206 inpatients [MD, N = 92; BD, N = 26; mania (Ma), N = 44; Sz, N = 44). Generalized estimating equations were used to analyze variations in SCL [interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17] at hospital admission and discharge. Results of 100 healthy controls were compared with those of SMI patients at both time points. We evaluated patients' improvement during in-hospital treatment in terms of general psychiatric symptoms, global clinical impression, functionality, and manic and depressive symptoms with validated scales. Results: In all, 68.9% of patients completed the study. Overall, SMI inpatients had higher SCL when compared with controls regardless of diagnosis. There was a significant decrease in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity Scale (CGI-S) scores, and an increase in Global Assessment of Functioning (GAF) scores for all disorders evaluated (p < 0.001), as well as a significant decrease in HDRS-17 scores among MD inpatients (p < 0.001) and in YMRS scores among Ma inpatients (p < 0.001). IL-2 and IL-6 levels decreased significantly between admission and discharge only among MD inpatients (p = 0.002 and p = 0.03, respectively). We found no further statistically significant changes in SCL among the remaining disorders (BD, Ma, and Sz). There was no significant decrease in IFN-γ (p = 0.64), TNF-α (p = 0.87), IL-4 (p = 0.21), IL-10 (p = 0.88), and IL-17 (p = 0.71) levels in any of the evaluated diagnoses. Conclusion: MD inpatients had a decrease in IL-2 and IL-6 levels during hospitalization, which was accompanied by clinical improvement. No associations were found for the remaining SMIs (BD, Ma, and Sz).

Effects of exercise training on inflammatory, neurotrophic and immunological markers and neurotransmitters in people with depression: A systematic review and meta-analysis.

BACKGROUND: Major depressive disorder is the most common type of mental disorder. The biological pathway by which exercise promotes its antidepressant effects remains uncleared. This study aimed to systematically review the chronic effect of exercise on blood biomarkers and its association with changes in depressive symptoms in adults with major depressive disorder. METHODS: Randomized controlled trials (RCT) published until February 2020 were screened in seven databases. Studies were systematically reviewed by two independent reviewers. Random effect meta-analysis was performed and reported as standardized mean differences (SMD) and 95 % confidence interval (CI). The meta- analysis protocol was registered with PROSPERO (CRD42021221177). RESULTS: From 3865 records, 12 studies (N = 757 participants, mean age [SD]: 43.0 [11.0], 66.2 % women) were included in this review. Exercise training resulted in superior increase in circulating BDNF (SMD: 0.44, 95%CI: 0.15, 0.73) and kynurenine (SMD: 0.29, 95%CI: 0.04, 0.54), and decrease depressive symptoms (SMD: -0.72, 95%CI: -1.08, -0.37) in adults with major depression disorder compared to control groups. Multivariate meta-regression analysis showed that improvements in circulating levels of BDNF, kynurenine and interleukyn-6 were associated with decreases in depressive symptoms. LIMITATIONS: Results were not stratified by the type of medication used by participants due to the lack of reporting of the included studies. Few studies provided data on other biomarkers (e.g., TNF-α and IL-10) besides BNDF and kynurenine. CONCLUSIONS: Antidepressant effect of exercise may be triggered by improved circulating levels of BNDF, kynurenine, and interleukine-6 in adults with major depressive disorder.

Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression.

Major depressive disorder (MDD) is a major cause of disability in adults. MDD is both a comorbidity and a risk factor for Alzheimer's disease (AD), and regular physical exercise has been associated with reduced incidence and severity of MDD and AD. Irisin is an exercise-induced myokine derived from proteolytic processing of fibronectin type III domain-containing protein 5 (FNDC5). FNDC5/irisin is reduced in the brains of AD patients and mouse models. However, whether brain FNDC5/irisin expression is altered in depression remains elusive. Here, we investigate changes in fndc5 expression in postmortem brain tissue from MDD individuals and mouse models of depression. We found decreased fndc5 expression in the MDD prefrontal cortex, both with and without psychotic traits. We further demonstrate that the induction of depressive-like behavior in male mice by lipopolysaccharide decreased fndc5 expression in the frontal cortex, but not in the hippocampus. Conversely, chronic corticosterone administration increased fndc5 expression in the frontal cortex, but not in the hippocampus. Social isolation in mice did not result in altered fndc5 expression in either frontal cortex or hippocampus. Finally, fluoxetine, but not other antidepressants, increased fndc5 gene expression in the mouse frontal cortex. Results indicate a region-specific modulation of fndc5 in depressive-like behavior and by antidepressant in mice. Our finding of decreased prefrontal cortex fndc5 expression in MDD individuals differs from results in mice, highlighting the importance of carefully interpreting observations in mice. The reduction in fndc5 mRNA suggests that decreased central FNDC5/irisin could comprise a shared pathologic mechanism between MDD and AD.

Serum plasminogen activator inhibitor-1 levels in patients with major depressive disorder vs. healthy controls: a systematic review and meta-analysis.

INTRODUCTION: Major depressive disorder (MDD) is a severe mental health condition that affects millions of people worldwide. Etiologically, several factors may play a role in its development. Previous studies have reported elevated plasminogen activator inhibitor-1 (PAI-1) levels in patients with depression, suggesting that PAI-1 levels might be linked to the etiology of MDD. METHODS: We systematically searched the following online databases: MEDLINE, Scopus, and Web of Science up to September 10, 2020, to identify studies in which PAI-1 levels were reported in subjects with MDD. Subsequently we used RevMan 5.3 to perform a meta-analysis of data extracted from the included studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and PICO criteria for the search and analysis. RESULTS: Six studies that reported mean ± standard deviation (SD) were included in the analysis, with a total of 507 MDD patients and 3,453 controls. The overall standardized mean difference (SMD) was 0.27 (95% confidence interval [95% CI] 0.01-0.53). PAI-1 serum levels were 0.27 SDs higher in MDD patients than in controls. The test for overall effect was significant (z = 2.04, p = 0.04). Substantial heterogeneity was detected among the studies, demonstrated by the inconsistency test (I² = 72%) and the chi-square test (χ² = 18.32; p = 0.003). CONCLUSIONS: This systematic review and meta-analysis showed that MDD might be related to elevated PAI-1 levels. We propose larger prospective clinical studies to further investigate this clinical correlation and validate the clinical significance of these observations.

Therapeutic Potential of the Purinergic System in Major Depressive Disorder Associated with COVID-19.

Neuroinflammation is closely related to the development of depression, since the latter is caused, among other factors, by inflammatory processes, mainly related to the activation of microglia and expression of specific genes, which occurs during the neuroinflammatory process. Thus, COVID-19 is an important risk factor for the development of depression, since in addition to generating the feeling of stress, which also increases the activity of the immune system, it is also the cause of pathological processes and physiological ones that lead to the development of neuroinflammation, microglial activation, gene expression dysfunction and decreased concentration of available serotonin. That said, drugs are being used to combat COVID-19 to reduce the oxidative stress presented in the disease. Thus, tramadol and fluoxetine are highlighted as drugs used, however, although they present some positive results, such as the reduction of pro-inflammatory cytokines, they are also associated with negative effects such as dependence, pulmonary, cardiac and brain impairment. From this, the purinergic system is highlighted in the literature as a possible therapeutic target. This is because its mechanisms are related to the regulation of microglia, astrocytes and the physiology of important neurotransmitters and hormones. Added to this, there is a modulation of inflammatory activity, especially with regard to the P2X7 receptors of this system. The latter is an important target for the treatment of depression and COVID-19, since positive results were obtained through the genetic exclusion of this receptor and the use of selective antagonists.

Increased insulin resistance due to long COVID is associated with depressive symptoms and partly predicted by the inflammatory response during acute infection

Objective: Some months after the remission of acute COVID-19, some individuals show depressive symptoms, which are predicted by increased peak body temperature (PBT) and decreased blood oxygen saturation (SpO2). The present study aimed to examine data on whether long COVID is associated with increased insulin resistance (IR) in association with neuroimmune and oxidative (NIO) processes during the acute infectious and long COVID phases. Methods: This case-control, retrospective cohort study used the Homeostasis Model Assessment 2 (HOMA2) calculator© to compute β-cell function (HOMA2%B) and insulin sensitivity (HOMA2%S) and resistance (HOMA2-IR) and administered the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAMD) to 86 patients with long COVID and 39 controls. Results: Long COVID (3-4 months after the acute infection) is accompanied by increased HOMA2-IR, fasting blood glucose (FBG), and insulin levels; 33.7% of the patients vs. 0% of the controls had HOMA2-IR values > 1.8, suggesting IR. Increased IR was predicted by PBT during acute infection and associated with depressive symptoms above and beyond the effects of NIO pathways (nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 [NLRP3] inflammasome, myeloperoxidase [MPO], protein oxidation). There were no significant associations between increased IR and the activated NIO pathways during long COVID. Conclusion: Long COVID is associated with new-onset IR, which may contribute to onset of depressive symptoms due to long COVID by enhancing overall neurotoxicity.

Serum plasminogen activator inhibitor-1 levels in patients with major depressive disorder vs. healthy controls: a systematic review and meta-analysis

Abstract Introduction Major depressive disorder (MDD) is a severe mental health condition that affects millions of people worldwide. Etiologically, several factors may play a role in its development. Previous studies have reported elevated plasminogen activator inhibitor-1 (PAI-1) levels in patients with depression, suggesting that PAI-1 levels might be linked to the etiology of MDD. Methods We systematically searched the following online databases: MEDLINE, Scopus, and Web of Science up to September 10, 2020, to identify studies in which PAI-1 levels were reported in subjects with MDD. Subsequently we used RevMan 5.3 to perform a meta-analysis of data extracted from the included studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and PICO criteria for the search and analysis. Results Six studies that reported mean ± standard deviation (SD) were included in the analysis, with a total of 507 MDD patients and 3,453 controls. The overall standardized mean difference (SMD) was 0.27 (95% confidence interval [95% CI] 0.01-0.53). PAI-1 serum levels were 0.27 SDs higher in MDD patients than in controls. The test for overall effect was significant (z = 2.04, p = 0.04). Substantial heterogeneity was detected among the studies, demonstrated by the inconsistency test (I2 = 72%) and the chi-square test (χ2 = 18.32; p = 0.003). Conclusion This systematic review and meta-analysis showed that MDD might be related to elevated PAI-1 levels. We propose larger prospective clinical studies to further investigate this clinical correlation and validate the clinical significance of these observations.

Manejo farmacológico del episodio depresivo bipolar en adolescentes: actualización bibliográfica / Pharmacological management of bipolar depressive episode in adolescents: bibliographic update

El manejo farmacológico del episodio depresivo en contexto del trastorno bipolar constituye un desafío para el clínico tanto en psiquiatría adultos como infantoadolescente. El presente trabajo tiene por objetivo actualizar y sintetizar la evidencia disponible respecto al manejo farmacológico para la depresión bipolar en población pediátrica. Metodología: Se realizó una búsqueda de las publicaciones de los últimos 5 años en bases de datos. Resultados: La evidencia muestra como primera línea el uso de antipsicóticos de segunda generación por sobre los estabilizadores del ánimo en este grupo etario; demostrando lurasidona y lanzapina/fluoxetina eficacia similares. Lurasidona es una opción con mejor perfil de seguridad por asociarse a menos efectos adversos y mejor adherencia. El uso de antidepresivos debe considerarse dentro de los pasos iniciales del manejo, asociado a un antipsicótico de segunda generación. Conclusiones: Se destaca la importancia de la sospecha, evaluación y diagnóstico adecuado para guiar la decisión de manejo integral. A pesar de los riesgos y consideraciones existentes, es importante considerar el uso en primera línea de antipsicóticos de segunda generación y de antidepresivos en el manejo de un cuadro depresivo en contexto de la enfermedad bipolar. La escasez de estudios en el tratamiento farmacológico de la depresión bipolar en general y especialmente en población pediátrica limita la generalización y extrapolación de los resultados a la realidad local.

The pharmacological management of the depressive episode in the context of bipolar disorder constitutes a challenge for the clinician both in adult and child-adolescent population. The objective of this paper is to update and synthesize the available evidence regarding the pharmacological management of bipolar depression in the pediatric population. Methodology: A search of the publications of the last 5 years in databases was carried out. Results: The evidence shows the use of second generation antipsychotics over mood stabilizers as the first line in this age group; demonstrating similar efficacy. Results: The evidence shows the use of second generation antipsychotics over mood stabilizers as the first line in this age group; demonstrating similar efficacy lurasidone and lanzapine/fluoxetine. Lurasidone is an option with a better safety profile as it is associated with fewer adverse effects and better adherence. The use of antidepressants should be considered within the initial steps of management, associated with a second generation antipsychotic. Conclusions: The importance of suspicion, evaluation and adequate diagnosis to guide the decision of comprehensive management is highlighted. Despite the existing risks and considerations, it is important to consider the first-line use of second-generation antipsychotics and antidepressants in the management of a depressive episode in the context of bipolar illness. The scarcity of studies on the pharmacological treatment of bipolar depression in general and especially in the pediatric population limits the generalization and extrapolation of the results to the local reality.

Sleep hygiene practices in patients with major depression with comorbid insomnia, primary insomnia, and good sleepers / Prácticas de higiene de sueño en pacientes con depresión mayor con insomnio comórbido, insomnio primario y buenos durmientes

Abstract Introduction Inadequate sleep hygiene (SH) is considered factor contributing to insomnia. However, the practice of SH by depressed patients with comorbid insomnia has not been explored. Objective We aimed to compare the practice of SH between patients with major depression, comorbid insomnia, primary insomnia, and good sleepers. Method One hundred and eighty-two adult individuals participated: 62 outpatients with major depressive disorder with comorbid insomnia (MDD), 56 outpatients with primary insomnia (PI), and 64 good sleepers (GS). All participants were assessed with a structured psychiatric interview, an insomnia interview, the Pittsburgh Sleep Quality Index, the Insomnia Severity Index, and the Sleep Hygiene Practice Scale. We compared the practice of SH as a whole and by domains between the groups and the relation between SH practice, insomnia, and sleep quality. Results Patients with PI and MDD showed a significantly worse practice of global SH. In the comparison by SH domains, MDD and PI groups had significantly worse scores than GS in all domains. Individuals with MDD showed a significantly worse practice of sleep schedule and arousal related behaviors than PI group. Although, SH practice was significantly related with insomnia and sleep quality in the whole sample, this association remained significant only in the PI. The arousal-related behaviors domain was the main predictor of insomnia and sleep quality. Discussion and conclusion Although patients with insomnia comorbid with MDD or with PI have a worse SH practice than GS, only arousal-related behaviors and drinking/eating habits contribute significantly to insomnia severity and sleep quality.

Resumen Introducción Una inadecuada higiene de sueño (HS) se considera como un factor que contribuye al insomnio, incluido el insomnio comórbido con trastornos mentales. Sin embargo, no se ha estudiado la práctica de HS en pacientes con depresión e insomnio comórbido. Objetivo Comparar la práctica de HS entre pacientes con depresión mayor con insomnio comórbido, insomnio primario y buenos durmientes. Método Participaron 182 individuos: 62 pacientes ambulatorios con trastorno depresivo mayor con insomnio comórbido (TDM), 56 pacientes con insomnio primario (IP) y 64 buenos durmientes (BD). A todos se les realizó una entrevista psiquiátrica estructurada, una entrevista sobre insomnio, el Índice de Calidad de Sueño de Pittsburgh, el Índice de Severidad de Insomnio y la Escala de Prácticas de Higiene de Sueño. Comparamos la práctica de HS tanto global como por dominios entre los grupos, y la relación entre la práctica de HS, el insomnio y la calidad de sueño. Resultados Los pacientes con IP y con TDM mostraron una práctica global de la HS significativamente peor. En la comparación por dominios, los grupos con TDM e IP alcanzaron peores calificaciones que los BD en todos. La práctica de HS se relacionó significativamente con el insomnio y calidad de sueño en la muestra total, sin embargo, solamente en el grupo con IP se mantuvo significativa. El dominio de conductas relacionadas con el alertamiento fue el principal predictor de insomnio y calidad de sueño. Discusión y conclusión Aunque los pacientes con insomnio comórbido con TDM o con IP tienen peores hábitos de HS que los BD, solamente las conductas relacionadas con el alertamiento y los hábitos de alimentación contribuyen significativamente a la gravedad del insomnio y calidad de sueño.

Functional Cognitive Disorder Presents High Frequency and Distinct Clinical Profile in Patients With Low Education.

Introduction: Functional Cognitive Disorder (FCD) is a non-degenerative, common cause of memory complaint in patients with high educational levels. FCD has been insufficiently described in individuals with low education. Here, we investigated the frequency of FCD among individuals with low education. Methods: We analyzed retrospectively all new referrals from primary care to a tertiary memory clinic from 2014 to 2021. Final diagnosis, diagnostic work-up, clinical and cognitive testing data were compared between FCD and other diagnoses, grouped as Neurodegenerative Disorders (NDD). A regression model was used to assess the effect of education on the diagnosis. Data is shown in Mean [SD]. Results: A total of 516 individuals (70.76 [10.3] years) with low educational attainment (4.5 [3.94] years) were divided into FCD (146, 28.3%) and NDD. Compared with NDD, FCD patients showed lower age at presentation (66.2 [9.4] vs. 72.6 [10.2], p < 0.001), higher Mini-Mental State Examination (MMSE) scores (22.4 [6.2] vs. 14.7 [7.8], p < 0.001) and Geriatric Depression Scale (GDS) scores (7.4 [5.4] vs. 5.3 [3.7], p = 0.0001). Discussion: Surprisingly, FCD was the most frequent diagnosis in a low educational setting. However, education was not associated with FCD. Individuals presenting FCD showed a distinct clinical profile, including younger age and higher depressive scores. Strategies to identify FCD in primary care settings may benefit both patients and healthcare systems.