Sodium nitroprusside as an adjunctive treatment for schizophrenia reduces the Ndel1 oligopeptidase activity.

OBJECTIVE: Schizophrenia (SCZ) is a disabling disorder that continues to defy clinicians and researchers. We investigated the effects of sodium nitroprusside (sNP) in an animal model of SCZ and as an add-on therapy in patients and the relationship between treatment with sNP and activity of the nDel1 enzyme, whose involvement in the pathophysiology of the disorder has been suggested earlier. METHODS: Ndel1 activity was measured following sNP infusions in spontaneously hypertensive rats (SHR; 2.5 or 5.0 mg/kg) and in a double-blind trial with SCZ patients (0.5 µg/kg/min). RESULTS: Ndel1 activity was significantly reduced after sNP infusion in blood of SHR compared to controls, and in patients receiving sNP (t = 7.756, df = 97, p < 0.0001, dcohen = 1.44) compared to placebo. Reduced Ndel1 activity between baseline and the end of the infusion was only seen in patients after treatment with sNP. CONCLUSION: Our findings suggest that SCZ patients may benefit from adjunctive therapy with sNP and that the Ndel1 enzyme is a candidate biomarker of psychopathology in the disorder. Future research should look into the role of Ndel1 in SCZ and the potential effects of sNP and drugs with similar profiles of action in both animals and patients.

Progression of the COVID-19 pandemic, Brazilian healthcare workers' emotional burden and the effects on professional fulfillment at the end of the third wave: a longitudinal study.

Introduction: Even though the long-term effects of the COVID-19 pandemic on healthcare workers' mental health remain unknown, such effects might negatively impact health services and patient safety, especially in countries like Brazil, where there is little investment in public health policies. Objectives: To assess how the mental health indicators of Brazilian healthcare workers progressed between the beginning and 2 years after the pandemic (at the end of the third wave when there was a significant decrease in the number of new cases and deaths). Methods: The sample comprised healthcare workers whose mental health indicators have been monitored since the beginning of the pandemic in Brazil. The potential participants were addressed via social media and contacted through class councils and health institutions across Brazil. A total of 165 participants answered instruments at the baseline and 2 years after the pandemic. Data were collected online using the Redcap platform and addressed symptoms of anxiety, depression, post-traumatic stress, insomnia, and burnout (emotional exhaustion, depersonalization, and professional fulfillment). Results: Brazilian healthcare workers faced three periods of intensified incidence of new cases and deaths due to COVID-19 for 2 years. Approximately one-third of the sample still experiences high levels of anxiety, depression, and post-traumatic stress. Insomnia indicators remained the most prevalent compared to the baseline assessment, while post-traumatic stress symptoms (p = 0.04) and professional fulfillment (p = 0.005) decreased. Conclusion: The lack of positive changes in mental health indicators coupled with decreased professional fulfillment over time highlights the pandemic's chronic effects and the need for organizations to monitor these workers' mental health, especially in developing countries like Brazil, where there is a high demand for health services and public policies are poorly structured and unstable.

Interventions for deficits in recognition of emotions in facial expressions in major depressive disorder: An updated systematic review of clinical trials.

The recognition of emotions in facial expressions (REFE) is a core construct of social cognition. In the last decades, studies have showed that REFE is altered in major depressive disorder (MDD), but the evidence is conflicting. Thus, we conducted a systematic review of clinical trials involving therapeutic interventions in MDD and any evaluation of REFE to update (2018-2023) and systematically evaluate the evidence derived from controlled clinical trials on the effects of therapeutic strategies to MDD on the REFE. Eleven studies were included in the final review. Some interventions, including drugs (ketamine, bupropion, psylocibin) and non-pharmacological strategies (psychotherapy) seem to be able to reduce pre-existing REFE biases in MDD patients. However, there was a high heterogeneity in the evaluated studies, in terms of sample, interventions, tasks and results. Further studies and more consistent evaluation tools are highly needed to better understand nuanced deficits and specific actions of different treatment options.

Pharmacological Interaction Between Cannabidiol and Tramadol on Experimental Diabetic Neuropathic Pain: An Isobolographic Analysis.

Introduction: Diabetic neuropathies are the most prevalent chronic complications of diabetes, characterized by pain and substantial morbidity. Although many drugs have been approved for the treatment of this type of pain, including gabapentin, tramadol (TMD), and classical opioids, it is common to report short-term results or potentially severe side effects. TMD, recommended as a second-line treatment can lead to unwanted side effects. Cannabidiol (CBD) has been gaining attention recently due to its therapeutic properties, including pain management. This study aimed to characterize the pharmacological interaction between CBD and TMD over the mechanical allodynia associated with experimental diabetes using isobolographic analysis. Materials and Methods: After diabetes induction by streptozotocin (STZ), diabetic rats were systemically treated with CBD or TMD alone or in combination (doses calculated based on linear regression of effective dose 40% [ED40]) and had the mechanical threshold evaluated using the electronic Von Frey apparatus. Both experimental and theoretical additive ED40 values (Zmix and Zadd, respectively) were determined for the combination of CBD plus TMD in this model. Results: Acute treatment with CBD (3 or 10 mg/kg) or TMD (2.5, 5, 10, or 20 mg/kg) alone or in combination (0.38+1.65 or 1.14+4.95 mg/kg) significantly improved the mechanical allodynia in STZ-diabetic rats. Isobolographic analysis revealed that experimental ED40 of the combination (Zmix) was 1.9 mg/kg (95% confidence interval [CI]=1.2-2.9) and did not differ from the theoretical additive ED40 2.0 mg/kg (95% CI=1.5-2.8; Zadd), suggesting an additive antinociceptive effect in this model. Conclusions: Using an isobolographic analysis, these results provide evidence of additive pharmacological interaction between CBD and TMD over the neuropathic pain associated with experimental diabetes induced by STZ.

Mental health trajectories of Brazilian health workers during two waves of the COVID-19 pandemic (2020-2021).

This study aimed to: (a) monitor the progression of symptoms of mental health burden among frontline workers caring for COVID-19 patients in Brazil during the two waves of the pandemic, considering the number of new cases and deaths, and; (b) to verify the different mental health outcomes and potential associations with current burnout symptoms. A non-probabilistic sample of health professionals was assessed as the pandemic progressed in Brazil (May/2020 August/2021). Standardized instruments focusing on anxiety, depression, insomnia, post-traumatic stress, and burnout symptoms were applied online. The results indicate a decrease in anxiety levels, what was related to when the number of new cases declined (end 1th-wave); symptoms returned to higher levels later. Emotional exhaustion increased when there was a higher incidence of cases, returning to the baseline levels at the end of the second wave. Depersonalization symptoms increased in this phase, characterized by a further decrease in new cases, while professional accomplishment decreased during the follow-up. The highest number of new cases was associated with a higher frequency of anxiety (OR = 1.467;95%CI = 1.109-1.941; p = 0.007) and professional accomplishment (OR = 1.490;95%CI = 1.098-2.023; p = 0.011). The subjects with trajectory of resilience against anxiety presented the lowest level of emotional exhaustion and depersonalization (p < 0.05). The conclusion is that the pressure experienced by healthcare professionals throughout the pandemic caused different impacts on their mental health, emphasizing the dynamic nature of this condition and the need for constant monitoring and care. This finding directly affects mental health prevention and intervention measures, which remain a priority and require continuous reinforcement, especially among the most vulnerable groups.

Stroke: An electromyographic approach to the masseter and temporal muscles, orofacial soft tissue pressure, and occlusal force.

Stroke is a cerebrovascular disease that triggers changes in the central and peripheral nervous systems, and can compromise human body function. This cross-sectional observational study aimed to analyze the electromyographic (EMG) activity of the masseter and temporal muscles, orofacial soft tissue pressure, and strength of occlusal contacts in patients who had suffered a stroke. Twenty-four patients were divided into two groups: stroke (n = 12) and control (n = 12). The EMG of the masseter and temporal muscles was evaluated during mandibular rest, protrusion, right laterality, left laterality, and maximal voluntary contraction. The Iowa Oral Pressure Instrument (IOPI) was used to measure pressure from the tongue, lips, and buccinator muscles. A computerized system for occlusal analysis (T-Scan III) was used to measure the occlusal contact points of the right and left hemiarches (upper and lower) and the upper and lower first molars. Data were subjected to Student's t-test (p < 0.05). The stroke group had lower normalized electromyographic activity, with a significant difference in the left temporal muscle during rest (p = 0.03) when compared to the control group. There was a significant difference between the groups in tongue pressure (p = 0.004) with a lower mean value in the stroke group. There was a significant difference between the groups in the evaluation of the occlusal contact points of the first permanent molars, with a lower mean percentage in the stroke group. The results indicate that stroke negatively affects functional performance of the stomatognathic system.

The Effect of Cannabidiol for Restless Legs Syndrome/Willis-Ekbom Disease in Parkinson's Disease Patients with REM Sleep Behavior Disorder: A Post Hoc Exploratory Analysis of Phase 2/3 Clinical Trial.

Background: Cannabidiol (CBD) is one of the main nonpsychoactive components of Cannabis sativa and may represent an alternative treatment for Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) in patients with Parkinson's disease (PD) and REM (Rapid Eye Movement) sleep behavior disorder (RBD). Objective: Our purpose was a post hoc exploratory analysis to evaluate the CBD's efficacy to improve the severity of RLS/WED symptoms in patients with PD and RBD. Methods: A post hoc exploratory analysis of a phase II/III, a parallel, double-blind, placebo-controlled clinical trial was conducted in 18 patients with RLS/WED and PD plus RBD associated. Six patients were randomized to the CBD group in doses of 75-300 mg, and twelve received placebo capsules. They were followed up for 14 weeks. The primary outcome was the severity of RLS/WED by Restless Legs Syndrome Rating Scale of the International Restless Legs Syndrome Study Group (IRLSSG). Results: CBD showed no difference in relationship to placebo for primary and secondary outcomes. Conclusion: CBD showed no reduction in the severity of RLS/WED manifestation in patients with PD and RBD.

Mundo de Pólus serious game for people with bipolar disorder.

BACKGROUND: Serious games are play-based technologies designed to teach users a wide range of concepts and skills applicable in the non-virtual environment. OBJECTIVES: This paper describes the process of developing a serious game for people with bipolar disorder to promote symptom recognition and the safe use of medications. METHODS: This study was based on the User-Centered Design methodological model and the theoretical framework for Participatory Design. We conducted interviews with health professionals and discussion circles with people with bipolar disorder and their family members in order to identify the learning needs related to symptom recognition and safe medication use. A categorical analysis was completed of the participants' reports and the scientific literature and formed the basis for the design of Mundo de Pólus. RESULTS: The game development process had three pillars (detailed in this manuscript): missions, simulation, and journal. The serious game focuses on the users' perceptions about their experience with the disorder, their interpersonal relationships, coping strategies, use of medications, and non-pharmacological treatments. CONCLUSIONS: These scientific and technological outcomes are useful to promote literacy and safety in medication therapy for people with bipolar disorder.

Amyotrophic Lateral Sclerosis: An Analysis of the Electromyographic Fatigue of the Masticatory Muscles.

Amyotrophic lateral sclerosis is a chronic degenerative disease that affects motor neurons, thereby promoting functional changes in the human body. The study evaluated the electromyographic fatigue threshold of the masseter and temporal muscles of subjects with amyotrophic lateral sclerosis. A total of eighteen subjects were divided into two groups: amyotrophic lateral sclerosis (n=9) and disease-free control (n=9). The groups were equally divided according to gender (7 males, 2 females). The fatigue threshold was analysed using median frequencies obtained during the 5-second window (initial [IP], mid [MP], and final [FP] periods) of electromyographic signalling of the masseter and temporal muscles bilaterally, with reduction in muscle force during maximal voluntary dental clenching. Significant difference (p<0.05) in the left temporal muscle: IP (p=0.05) and MP (p=0.05) periods was demonstrated. The amyotrophic lateral sclerosis group showed a decrease in median frequency of the electromyographic signal of the masseter and temporal muscles compared to the control group. Amyotrophic lateral sclerosis promotes functional impairment of the stomatognathic system, especially at the electromyographic fatigue threshold of the masticatory muscles.

Prophylactic action of ayahuasca in a non-human primate model of depressive-like behavior.

Observational studies of long-term users of ayahuasca, an Amazonian psychedelic brew, suggest an increase in resilience via improvements in emotion and cognition. Ayahuasca has also demonstrated clinical antidepressant effects in human and animal studies; however, its potential prophylactic action in depression has not been previously studied. Therefore, this experimental study sought to evaluate the potential prophylactic effects of repeated and long-term ayahuasca use, via the modulation of resilience, in a non-human primate animal model, Callithrix jacchus, subjected to a protocol for induction of depressive-like behavior. For the formation of the study groups, some juvenile marmosets were kept in their family groups (GF = 7), while for the two experimental groups, the animals were removed from the family and kept socially isolated. Then, part of the isolated animals made up the group in which ayahuasca was administered (AG, n = 6), while for others, no intervention was made (IG, n = 5). AG animals took ayahuasca (1.67 mL/300g body weight) at weeks 4 (before isolation), 8, and 12 (during isolation) of the study. More adaptive stress response was observed for the AG when compared to the IG. The AG showed higher cortisol reactivity and fecal cortisol levels than IG, while both measures were similar to FG. Moreover, AG animals showed no signs of anhedonia and no increase in chronic stress-related behaviors, which were expressed by the IG. Thus, ayahuasca seems to promote the expression of resilient responses, indicating a prophylactic action, buffering the emergence of depressive-like behaviors and cortisol alterations associated with major depression. These results are encouraging for further research on the prophylactic use of psychedelics to prevent psychopathologies associated with chronic stress.

Workplace Protections and Burnout Among Brazilian Frontline Health Care Professionals During the COVID-19 Pandemic.

Health care workers from low- and middle-income countries have been playing a critical role in overcoming the challenges related to the COVID-19 pandemic; yet little is known about the relationship between workplace protections and wellbeing of Brazilian health care workers during the pandemic. This study aimed to evaluate whether Brazilian health care workers were satisfied with their workplace measures to protect their physical and mental health during the pandemic, and to assess the associations of such levels of satisfaction with indicators of burnout. Licensed Brazilian health care professionals were recruited via popular media between 5/19/2020 and 8/23/2020 to complete an online survey including questions about their demographic/professional characteristics, satisfaction with their workplace protective measures during the pandemic, and validated questionnaires assessing neuroticism, resilient coping, and symptoms of burnout. Most participants reported being dissatisfied with their workplace measures to protect their physical (516, 56.3%) and mental health (756, 82.5%). In multivariable analysis adjusted for personal and environmental factors, dissatisfaction with workplace physical health protections was significantly associated with higher levels of emotional exhaustion (B = 1.08, 95% CI = 0.47-1.69) and depersonalization (B = 0.61, 95% CI = 0.10-1.12), and dissatisfaction with workplace mental health protections significantly associated with higher levels emotional exhaustion (B = 1.17, 95% CI = 0.40-1.95). Efforts to improve both physical and mental health protective measures are critical to guarantee that health care workers continue to provide care at their maximum capacity.

The anxiolytic effect of cannabidiol depends on the nature of the trauma when patients with post-traumatic stress disorder recall their trigger event

Objectives: We assessed whether administering cannabidiol (CBD) before recalling the traumatic event that triggered their disorder attenuates anxiety in patients with post-traumatic stress disorder (PTSD). As an exploratory pilot analysis, we also investigated whether this effect depends on the nature of the event (sexual vs. nonsexual trauma). Methods: Thirty-three patients of both sexes with PTSD were recruited and randomized 1:1 into two groups. One group received oral CBD (300 mg), and the other received a placebo before listening to a digital audio playback of their previously recorded report of the trigger event. Subjective and physiological measurements were taken before and after recall. We analyzed the data in two subsamples: trigger events involving sexual and nonsexual trauma. Results: In the nonsexual trauma group, the differences between measurements before and after recall were significantly smaller with CBD than placebo; this held true for anxiety and cognitive impairment. However, in the sexual trauma group, the differences were non-significant for both measurements. Conclusion: A single dose of CBD (300mg) attenuated the increased anxiety and cognitive impairment induced by recalling a traumatic event in patients with PTSD when the event involved nonsexual trauma.

Monitoring the Mental Health and Professional Overload of Health Workers in Brazil: A Longitudinal Study Considering the First Wave of the COVID-19 Pandemic.

Few longitudinal studies assessed the less immediate consequences of the COVID-19 pandemic on health workers' mental health, especially in less developed countries. The objective was to assess the evolution of mental health indicators of Brazilian health workers providing care to COVID-19 patients, considering the beginning and first wave of the pandemic, identifying risk and protective factors. A non-probabilistic sample of health professionals was assessed for 6 months at seven different points in time using standardized instruments to measure anxiety, depression, insomnia, posttraumatic stress, and burnout symptoms. Risk and protective factors were assessed using a questionnaire addressing socio-demographic, clinical, occupational variables, and COVID-19 risk perception. The results indicate high rates for all the indicators (>30%) throughout the follow-up; only anxiety symptoms decreased in the different phases compared to the baseline. Depression and insomnia symptoms showed a significant drop in isolated points of the assessment, which were not maintained at the final follow-up. Burnout indicators concerning emotional exhaustion and depersonalization remained stable (40 and 20%), while professional achievement decreased by approximately 19%. Occupational and personal characteristics (profession and work setting), perceptions regarding protective measures imposed by the institutions, and future professional prospects stood out as risk/protective factors in mental health. Unlike European and Asian countries, where mental distress symptoms tended to decrease over the pandemic, this study's results suggest alarming indicators of mental health problems remaining stable with burnout symptoms on the rise. Hence, the different contexts across countries, with different management resources and investments in health actions, seem to influence workers' mental health differently, demanding constant attention and monitoring and measures to minimize the impacts on individuals and collectives, especially in less developed countries like Brazil.

The anxiolytic effect of cannabidiol depends on the nature of the trauma when patients with post-traumatic stress disorder recall their trigger event.

OBJECTIVES: We assessed whether administering cannabidiol (CBD) before recalling the traumatic event that triggered their disorder attenuates anxiety in patients with post-traumatic stress disorder (PTSD). As an exploratory pilot analysis, we also investigated whether this effect depends on the nature of the event (sexual vs. nonsexual trauma). METHODS: Thirty-three patients of both sexes with PTSD were recruited and randomized 1:1 into two groups. One group received oral CBD (300 mg), and the other received a placebo before listening to a digital audio playback of their previously recorded report of the trigger event. Subjective and physiological measurements were taken before and after recall. We analyzed the data in two subsamples: trigger events involving sexual and nonsexual trauma. RESULTS: In the nonsexual trauma group, the differences between measurements before and after recall were significantly smaller with CBD than placebo; this held true for anxiety and cognitive impairment. However, in the sexual trauma group, the differences were non-significant for both measurements. CONCLUSION: A single dose of CBD (300mg) attenuated the increased anxiety and cognitive impairment induced by recalling a traumatic event in patients with PTSD when the event involved nonsexual trauma.

Effects of cannabidiol on symptoms induced by the recall of traumatic events in patients with posttraumatic stress disorder.

Studies with cannabidiol (CBD) suggest that this compound has anxiolytic properties and may mediate the reconsolidation and extinction of aversive memories. The objective of this study was to test whether the administration of CBD 300 mg before the recall of traumatic events attenuated symptoms usually induced by recall in subjects diagnosed with posttraumatic stress disorder (PTSD) and if its potential effects interfere with the reconsolidation of aversive memories. The double-blind trial included 33 participants of both sexes, aged between 18 and 60 years, diagnosed with PTSD according to the SCID-5 and randomly allocated to two groups treated with CBD (n = 17) and placebo (n = 16). In the first experimental section, participants were matched by sex, age, body mass index (BMI), and PTSD symptoms as assessed with the Posttraumatic Stress Disorder Checklist (PCL-5). On the same day, participants prepared the behavior test, recording accounts of their traumas in digital audio for a minute and a half and then imagining the trauma for 30 s. After 7 days, participants received CBD (300 mg) or placebo and performed the behavioral test, listening to the trauma account and imagining themselves in that situation. Before and after the behavioral test, subjective changes in mood and anxiety were recorded (Visual and Analogical Mood Scale - VAMS and STAI-state), along with physiological correlates of anxiety blood pressure (BP), heart rate (HR), and salivary cortisol (SC). Seven days later, participants underwent the same procedures as the previous session, but without the pharmacological intervention, to assess the effect on reconsolidation of traumatic memories. We found that CBD significantly attenuated the increase in the VAMS scale cognitive impairment factor scores, under the CBD's effect, with this effect remaining 1 week after drug administration. No significant differences between the effects of CBD and placebo on anxiety, alertness, and discomfort induced by the recall of the traumatic event during the pharmacological intervention and in the subsequent week, in the absence of it. There were no significant differences between the CBD and placebo groups regarding physiological data (BP, HR, and SC). The attenuation of cognitive impairments during trauma recall under the effect of CBD may have interfered with the reconsolidation of traumatic memories concerning its association with cognitive impairments.

Endocannabinoid System Attenuates Oxaliplatin-Induced Peripheral Sensory Neuropathy Through the Activation of CB1 Receptors.

Oxaliplatin-induced neurotoxicity is expressed as a dose-limiting peripheral sensory neuropathy (PSN). Cannabinoid substances have been investigated for the analgesic effect. This study aimed to investigate the role of cannabinoid receptors in oxaliplatin-associated PSN. Swiss male mice received nine oxaliplatin injections (2 mg/kg, i.v.). Mechanical and thermal nociceptive tests were performed for 56 days. CB1, CB2, and c-Fos expression were assessed in dorsal root ganglia (DRG), spinal cord (SC), trigeminal ganglia (TG), spinal trigeminal nucleus caudalis (Sp5C), and periaqueductal gray (PAG). Iba-1 expression was assessed in DRG and ATF3 in TG. Cannabidiol (10 mg/kg, p.o.) or a CB1/CB2 non-selective agonist (WIN 55,212-2; 0.5 mg/kg, s.c.) or AM251 (CB1 antagonist) or AM630 (CB2 antagonist) (3 mg/kg, i.p.) were injected before oxaliplatin. Oxaliplatin increased CB1 in DRG, SC, TG, Sp5C, and ventrolateral PAG, with no interference in CB2 expression. Cannabidiol increased CB1 in DRG, reduced mechanical hyperalgesia and c-Fos expression in DRG and SC. Additionally, WIN 55,212-2 increased CB1 in DRG, reduced mechanical hyperalgesia, cold allodynia and c-Fos expression in DRG and SC. CB1 blockage hastened the cold allodynia response, but the CB2 antagonist failed to modulate the oxaliplatin-induced nociceptive behavior. Oxaliplatin also increased Iba-1 in DRG, suggesting immune response modulation which was reduced by cannabidiol and enhanced by AM630. The modulation of the endocannabinoid system, through the CB1 receptor, attenuates the oxaliplatin-associated PNS. The activation of the endocannabinoid system could be considered as a therapeutic target for controlling oxaliplatin-associated neuropathy.

Does Systemic Arterial Hypertension Change the Function of the Stomatognathic System?

The aim of this study was to evaluate the stomatognathic system of individuals with controlled systemic hypertension through comparison with a disease-free control group. Seventy individuals (44 female and 26 male) were divided into two groups: a controlled systemic hypertension (n=35) and a disease-free control (n=35). The individuals were evaluated on the basis of masticatory cycle efficiency of the value of the ensemble-averaged integrated linear envelope to the electromyographic signal of the masseter and temporalis muscles in the habitual (peanuts and raisins) and non-habitual chewing (Parafilm M); molar bite force (right and left) and ultrasound images from the bilateral masseter and temporal muscles at rest and maximum voluntary contraction. The data obtained were tabulated and submitted to statistical analysis (p<0.05). There was a significant difference between groups in the habitual (peanuts and raisins) and non-habitual (Parafilm M) chewing with reduced muscle activity to controlled systemic hypertension group. Muscle thickness occurred significant difference between groups at rest and maximum voluntary contraction of the temporalis muscles. There was no significant difference between groups in maximum molar bite force. The present study findings indicate that the controlled systemic hypertension promotes functional changes of the masticatory system, especially with respect to its masticatory efficiency and muscle thickness.

Potential biomarkers of major depression diagnosis and chronicity.

BACKGROUND: Molecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence and morbidity. METHODS: We tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease's chronicity using regression models, and ROC curve. RESULTS: For diagnosis model, two groups were analyzed: patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity. CONCLUSION: These results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practice.