Ego-defense mechanisms and brief psychotherapies for the management of major depressive disorder in adults: A longitudinal and quasi-experimental study.

OBJECTIVE: To evaluate the effect of psychotherapies on ego defense mechanisms and the reduction of depressive symptoms in a 12-month follow-up period. METHODS: This longitudinal and quasi-experimental study nested within a randomized clinical trial included a clinical sample of adults (18-60 years) diagnosed with major depressive disorder using the Mini-International Neuropsychiatric Interview. Two models of psychotherapy were used: Supportive Expressive Dynamic Psychotherapy (SEDP) and Cognitive Behavioral Therapy (CBT). Defense Style Questionnaire 40 was used to analyze defense mechanisms and the Beck Depression Inventory was used to measure the depressive symptoms. RESULTS: The total sample comprised 195 patients (113 SEDP and 82 CBT), with the mean age was 35.63 (11.44) years. After adjustments, increased mature defenses was significantly associated with reduced depressive symptoms at all follow-up times (p < 0.001) and the decrease in immature defenses was significantly associated with the reduction of depressive symptoms at all follow-up times (p < 0.001). While neurotic defenses were not associated with a reduction in depressive symptoms at any time of follow-up (p > 0.05). CONCLUSION: Both models of psychotherapy were effective in increasing mature defenses and decreasing immature ones, as well as decreasing depressive symptoms at all evaluation times. With this, it is understood that a greater understanding of these interactions will allow a more adequate diagnostic and prognostic evaluation and the design of useful strategies that adapt to the patient's reality.

BDNF Levels According to Variations in the CACNA1C Gene: Sex-Based Disparity.

The CACNA1C gene encodes the pore-forming alpha-1c subunit of L-type voltage-gated calcium channels. The calcium influx through these channels regulates the transcription of the brain-derived neurotrophic factor (BDNF). Polymorphisms in this gene have been consistently associated with psychiatric disorders, and alterations in BDNF levels are a possible biological mechanism to explain such associations. Here, we sought to investigate the effect of the CACNA1C rs1006737 and rs4765913 polymorphisms and their haplotypes on serum BDNF concentration. We further aim to investigate the regulatory function of these SNPs and the ones linked to them. The study enrolled 641 young adults (362 women and 279 men) in a cross-sectional population-based survey. Linear regression was used to test the effects of polymorphisms and haplotypes on BDNF levels adjusted for potential confounders. Moreover, regulatory putative functional roles were assessed using in silico approach. BDNF levels were not associated with CACNA1C polymorphisms/haplotype in the total sample. When the sample was stratified by sex, checking the effect of polymorphisms on men and women separately, the A-allele of rs4765913 was associated with lower BDNF levels in women compared with the TT genotype (p = 0.010). The AA (rs1006737-rs4765913) haplotype was associated with BDNF levels in opposite directions regarding sex, with lower levels of BDNF in women (p = 0.040) compared to those without this haplotype, while with higher levels in men (p = 0.027). These findings were supported by the presence of regulatory marks only on the male fetal brain. Our results suggest that the BDNF levels regulation may be a potential mechanism underpinning the association between CACNA1C and psychiatric disorders, with a differential role in women and men.

Interaction between COMT Val158 Met polymorphism and childhood trauma predicts risk for depression in men.

Depression is a disabling illness with complex etiology. While the catechol-O-methyltransferase (COMT) gene, in particular the functional Val158 Met polymorphism, has been related to depression, the mechanisms underlying this gene-disease association are not completely understood. Therefore, we explore the association of COMT Val158 Met polymorphism with depression as well as its interaction with childhood trauma in 1136 young adults from a population-based study carried out in the city of Pelotas, Brazil. The diagnosis was performed through the Mini International Neuropsychiatric Interview 5.0 (MINI 5.0), and trauma was assessed with the Childhood Trauma Questionnaire (CTQ). Total DNA was extracted and genotyped by real-time PCR, and the QTLbase dataset was queried to perform large-scale quantitative trait locus (QTL) analysis. Our research showed no direct association between the Val158 Met polymorphism and the diagnosis of depression (women: χ2  = 0.10, d = 1, p = 0.751; men: χ2  = 0.003, df = 1, p = 0.956). However, the Met-allele of the Val158 Met polymorphism modified the effect of childhood trauma in men (OR = 2.58 [95% CI: 1.05-6.29]; p = 0.038) conferring risk for depression only on those who suffer from trauma. The conditional effect from moderation analysis showed that trauma impacts the risk of depression only in men carrying the Met-allele (effect: 0.9490, standard error [SE]: 0.2570; p = 0.0002). QTLbase and dataset for Val158 Met polymorphism were consistent for markers that influence chromatin accessibility transcription capacity including histone methylation and acetylation. The changes caused in gene regulation by childhood trauma exposure and polymorphism may serve as evidence of the mechanism whereby the interaction increases susceptibility to this disorder in men.

Investigating biological rhythms disruptions across the menstrual cycle in women with comorbid bipolar disorder and premenstrual dysphoric disorder.

We investigated whether women diagnosed with comorbid bipolar disorder (BD) and premenstrual dysphoric disorder (PMDD) experience higher disruptions in biological rhythms in two independent study samples. The first study has a population-based sample of 727 women, including 104 women with PMDD only, 43 women with BD only, 24 women with comorbid PMDD and BD, and 556 women without BD or PMDD (controls). Biological rhythm disruptions were cross-sectionally evaluated using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). The second study enrolled 77 outpatient women who completed prospective assessments at two timepoints: during the mid-follicular and the late-luteal phases of their menstrual cycles, using the BRIAN, and included 19 women with PMDD, 16 with BD, 17 with comorbid PMDD and BD, and 25 controls. In the population-based sample, all the diagnostic groups (BD, PMDD, BDPMDD) presented greater biological rhythm disruption than controls. In addition, women with BD presented greater overall biological rhythms disruption, and greater disruption in sleep, activity, and eating patterns, than women with PMDD. In the outpatient sample study, women with BDPMDD showed greater disruption in the social domain than women with PMDD. In the outpatient sample, women with BDPMDD reported significantly higher disruptions in biological rhythms across both the follicular and the luteal phases of the menstrual cycle. The comorbidity between BD and PMDD may affect biological rhythms beyond the luteal phase of the menstrual cycle. These results support previous literature on the increased illness burden of women diagnosed with comorbid BD and PMDD.

Dropout in brief psychotherapy for major depressive disorder: Randomized clinical trial.

The aim of this paper is to analyse the factors associated with the dropout from brief psychotherapy for adults with major depressive disorder (MDD) treated at a mental health outpatient clinic. This is a randomized clinical trial with two models of psychotherapy: cognitive behavioural therapy (CBT) and supportive expressive dynamic psychotherapy (SEDP). MDD and anxiety disorders were evaluated through the Mini International Neuropsychiatric Interview-Plus. The personality disorders were evaluated by the Millon Clinical Multiaxial Inventory-III. The severity of depressive symptoms was measured using the Beck Depression Inventory-II and resilience through Resilience Scale. Of the 215 participants, 41.9% abandoned psychotherapy (n = 90), and, of these, 54.4% (n = 49) abandoned after the fourth session. The proportion of psychotherapy dropout was higher among those with nonwhite skin colour, belonging to economic classes C and D, who had children and whose depressive symptoms were moderate. Presence of obsessive-compulsive personality trait was protective against dropout. The damage caused by this abrupt interruption is evident for all those involved in the psychotherapeutic process, so the clinician should pay attention to the predictors found in this study in order to develop strategies that promote therapeutic adherence.

The role of CACNA1C gene and childhood trauma interaction on bipolar disorder.

Studies on gene x environment interaction (GxE) have provided vital information for uncovering the origins of complex diseases. When considering the etiology of bipolar disorder (BD), the role of such interactions is unknown. Here, we tested whether trauma during childhood could modify the effect of two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) in terms of susceptibility to BD. The study enrolled 878 Caucasian young adults in a cross-sectional population-based survey. BD diagnosis was performed using a clinical interview MINI 5.0, and trauma was assessed with the childhood trauma questionnaire (CTQ). Binary logistic regression models were employed to test the main effects of polymorphisms, haplotypes, and GxE interactions using sex as a confounder. We did not observe an association between the polymorphisms and diagnosis of BD. However, we noted that childhood trauma modified the effect of the rs4765913 polymorphism (p = .018) and the AA haplotype (rs1006737 - rs4765913) (p = .018) on BD susceptibility. A allele carriers of the rs4765913 polymorphism or the AA haplotype exposed to childhood trauma are more likely to develop BD compared to the individuals without a genetic risk. Thus, this study showed that the risk of developing BD in individuals exposed to childhood trauma was influenced by the individual's genetic background, varying according to the CACNA1C genotypes.

Is suicide risk a predictor of diagnosis conversion to bipolar disorder?

To assess predictors of the diagnosis of bipolar disorder is important since it is known that the early diagnosis is associated with a better response to the treatment. Thus, the aim of this systematic review is to assess the role of the suicide risk in the diagnosis conversion to bipolar disorder. We searched Pubmed, Bireme, Scopus, and PsycINFO with no year restriction for articles containing the words (suicidal or suicide or suicide risk or suicide attempt) and (conversion or switch) and (bipolar disorder or mania or hypomania or bipolar disorders). The review included four studies, with only one confirming that subjects who converted to bipolar disorder had higher rates of suicide risk than subjects who did not convert to bipolar disorder. The main limitation of this review is that few longitudinal studies assessed the predictors of conversion to bipolar disorders. In conclusion, suicide risk appears to be a predictor of bipolar disorder; nevertheless, more studies are needed to confirm this association.

Serum brain-derived neurotrophic factor levels in subjects with major depressive disorder with previous suicide attempt: A population-based study.

Major depressive disorders (MDD) and suicide are significant public health concerns. Recent studies have been demonstrated that alterations in Brain Derived Neurotrophic Factor (BDNF) can be associated with this psychiatric disorders, MDD and suicide. Thus, the aim of this study was to evaluate differences in serum levels in individuals with MDD and with or without suicide attempt (SA), from a population-based sample. This was a paired cross-sectional study nested in a population-based study. The psychopathology screen was performed with the Mini-International Neuropsychiatric Interview (MINI). The total population of the sample consisted of 147 subjects distributed in three groups: 49 healthy controls, 49 subjects with MDD and 49 subjects with MDD and SA (MDD + SA). The BDNF serum levels were significantly reduced in subjects with MDD and MDD + SA compared to the healthy controls. However, there were no significant differences between the MDD and MDD + SA groups with respect to BDNF serum levels. These results suggest that SA did not interfere in the serum levels of BDNF, indicating that this neurotrophin may be related to the diagnosis of MDD and not to suicide attempt.

Brief psychoeducation for bipolar disorder: Evaluation of trophic factors serum levels in young adults.

The aim of this study was to evaluate the impact of psychoeducation in serum levels of BDNF, NGF and GDNF in young adults presenting bipolar disorder (BD). This is a randomized clinical trial including 39 young adults (18-29 years) diagnosed with BD through the Structured Clinical Interview for DSM-IV (SCID-CV). Participants were randomized in two treatment groups: usual treatment (medication) and combined intervention (medication plus psychoeducation). Depressive symptoms were assessed using the Hamilton Depression Rating Scale (HDRS) and severity of manic and hypomanic symptoms was evaluated through the Young Mania Rating Scale (YMRS). The serum levels of trophic factors were measured with an ELISA kit. In both intervention groups, there was an improvement in depressive symptoms significantly between baseline and post-intervention. In the combined intervention, GDNF serum levels increased significantly from baseline to post-intervention. However, there were no differences in BDNF and NGF serum levels. In the usual treatment group, no changes were observed in serum levels of GDNF, BDNF, and NGF the post-intervention in individuals. Our data suggests that only combined intervention was effective in improving depressive symptoms and increasing GDNF levels in a sample of young adults with bipolar disorder.

Inflammatory cytokines and functional impairment in drug-free subjects with mood disorder.

OBJECTIVE: To assess the association between peripheral levels of inflammatory cytokines and functional impairment in subjects with Bipolar Disorder (BD), Major Depressive Disorder (MDD) and population controls. METHODS: This was a cross-sectional study with a matched sample of drug-free young adults with BD (n=48), MDD (n=48) and population controls (n=48). Mood disorder was confirmed by a certified psychologist using the Structured Clinical Interview for DSM-IV (SCID-I). Functional impairment was assessed using the Functional Assessment Short Test (FAST). Serum levels of IL-6 and IL-10 were measured by ELISA. RESULTS: Peripheral levels of IL-6 and IL-10 were not significantly different between subjects with BD, MDD compared to controls. Higher levels of functional impairment were verified in subjects with BD and MDD compared to population controls (p≤0.001). In addition, IL-6 and IL-10 levels were positively correlated with functional impairment in subjects with BD (IL-6: r=0.349, p=0.016; and IL-10: r=0.351, p=0.016). CONCLUSION: Inflammatory dysregulation was associated with functional impairment among drug-free subjects with BD. This finding suggests that inflammatory dysregulation may be involved in the neuroprogression of BD.

Mental disorders, functional impairment, and nerve growth factor.

Nerve growth factor (NGF) is an important member of the neurotrophin family and its alteration has been associated with psychiatric disorders. Functionality consists of the activities that an individual can perform, as well as their social participation, which is an important factor in analyzing the carrier living conditions of subjects with psychiatric suffering. Several studies have evaluated functionality in bipolar disorder; however, no studies have evaluated the functionality in other mental disorders. There are also few studies investigating the association between functionality and the biological bases of mental disorders. This study aimed to evaluate the serum NGF levels in psychiatric patients and to verify a possible association between the serum neurotrophic levels and functionality. This was a cross-sectional study with a convenient sample obtained from the Public Mental Health Service from the south of Brazil. The final sample was composed of 286 patients enrolled from July 2013 to October 2014. Data was collected using a sociodemographic questionnaire, and the diagnosis was confirmed using the Mini International Neuropsychiatric Interview (M.I.N.I) and a Functioning Assessment Short Test. The serum NGF levels were determined using the enzyme-linked immunosorbent assay method. Statistical analyses were performed using IBM SPSS Statistic 21.0 software. NGF serum levels were increased significantly in patients with obsessive-compulsive disorder compared with patients with no obsessive-compulsive disorder (P=0.015). An increase in serum NGF levels in generalized anxiety disorder patients was observed compared with patients with no generalized anxiety disorder (P=0.047). NGF was negatively associated with autonomy (P=0.024, r=-0.136), work (P=0.040, r=-0.124), and cognition (P=0.024, r=-0.137), thereby showing that changes in serum levels of NGF are associated with functionality in mental disorders.

Risk Factors for the Incidence of Perceived Voice Disorders in Elementary and Middle School Teachers.

OBJECTIVE/HYPOTHESIS: This study aimed to identify risk factors for the incidence of perceived voice disorders in teachers, specifically related to the influence of common mental disorders. DESIGN: This is a longitudinal quantitative study conducted in municipal schools. METHOD: We performed a data analysis of 469 teachers, reassessed 3 years after an initial study. The Voice Handicap Index was used to measure the impact of a probable voice problem with a cutoff value of 19 points. Mental disorder symptomatology was measured by the Self-Reporting Questionnaire (20 items), with a cutoff value of eight points. Bivariate analysis was conducted through Poisson regression to verify proportion differences in the occurrence of perceived voice disorders among the study's different categories of independent variables. The same technique of Poisson regression was used to assess risk factors for perceived voice disorder incidence in a specific hierarchic model. RESULTS: The incidence of a perceived voice disorder was 17.1%. Teachers who lectured in fourth grade and below presented a risk of 20% less than those who lectured from the fifth grade up (P = 0.046). Teachers who reported taking a leave of absence because of their voice had a 32% more chance of a probable perceived voice disorder (P = 0.024). Teachers who presented a common mental disorder had twice the risk of perceived voice disorder (P > 0.001). CONCLUSIONS: This study concluded that teachers presented a higher risk of developing a perceived voice disorder when they have the following features: lectured from fifth grade up, have gone on leave because of their voice, and showed behavior indicative of common mental disorder.

Circadian preferences, oxidative stress and inflammatory cytokines in bipolar disorder: A community study.

OBJECTIVE: To assess circadian preference among a community sample of people with bipolar disorder, major depression and without any mood disorders. Secondly, we investigated the association of circadian preference with cytokines interleukin-6 (IL-6), interleukin-10 (IL-10) and, tumor necrosis factor alpha (TNF-α) and oxidative stress assessed by thiobarbituric acid reactive substances (TBARS), uric acid and Protein Carbonyl Content (PCC). METHOD: A cross-sectional study nested in a population-based sample. Caseness was confirmed with the Structured Clinical Interview for DSM-IV. A sample of 215 participants, in whom we measured circadian preferences, IL-6, IL-10, TNF-α, TBARS, uric acid, PCC. Biological rhythms were evaluated using the Biological Interview of Assessment in Neuropsychiatry. RESULTS: Bipolar group presented a higher alteration in biological rhythms (40.40±9.78) when compared with the major depression group (36.35±9.18) and control group (27.61±6.89) p<0.001. Subjects with bipolar disorder who were active at night and had a day/night cycle reverse showed decreased levels of IL-6 (t, 44=2.096; p=0.042), (t, 44=2.213; p=0.032), respectively. In the bipolar disorder group subjects who presented day/night cycle reverse had lower TBARS levels (t, 41=2.612; p=0.013). TNF-α were decreased in subjects more active at night with bipolar disorder. CONCLUSION: Lower serum levels of IL-6, TNF-α and TBARS were associated with evening preference in bipolar disorder group. These findings suggest that chronotype may alter the levels of interleukins and oxidative stress levels in bipolar and healthy subjects. A better understanding of the role of circadian preferences in levels of interleukins and oxidative stress are needed.

Neuron-specific enolase levels in drug-naïve young adults with major depressive disorder.

The aim of this study is to assess neuron-specific enolase (NSE) levels and clinical features in subjects with major depressive disorder (MDD). This is a cross-sectional study with drug-naïve young adults with MDD (aged 18-29 years). Serum levels of NSE were assessed using the electrochemiluminescence method. MDD diagnosis, suicidal ideation, and time of disease were assessed using the Structured Clinical Interview for DSM-IV (SCID). The Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were used to assess depressive and anxiety symptoms. No relationship was observed between NSE levels and severity of depressive and anxiety symptoms, time of disease, and suicidal ideation. These results suggest that NSE serum levels were not associated with clinical features of MDD among drug-naïve young adults.

Six-session caregiver psychoeducation on bipolar disorder: Does it bring benefits to caregivers?

AIM: To evaluate the impact of psychoeducational intervention on the levels of burden, of self-esteem and quality of life in caregivers of patients diagnosed with Bipolar Disorders. METHOD: In this randomized clinical trial, changes in degree of burden, levels of self-esteem and quality of life were evaluated. Caregivers could participate in the group of psychoeducation (six sessions) or usual treatment (without psychoeducation following a manual). RESULTS: There were no significant differences regarding levels of objective burden between groups. Both groups presented improvement in subjective burden scores throughout the interventions. Objective burden scores showed significant reduction in the usual treatment group (p = .003) and a trend toward decrease in the psychoeducational intervention (p = .081). There are no differences regarding improvement in perceived self-esteem and quality of life when comparing means between the groups with and without intervention. CONCLUSION: A six-session caregiver psychoeducational intervention on bipolar disorder did not bring benefits to caregiver's health. A longer longitudinal follow-up study would be crucial to see whether there were differences in degree of burden, perceived self-esteem and quality of life over time in caregivers.

Serum levels of nerve growth factor (NGF) in patients with major depression disorder and suicide risk.

Nerve growth factor (NGF) is an important member of the neurotrophins group and their involvement in the pathophysiology of major depression disorder (MDD) and suicide risk (SR) has been recently suggested. The aim of this study is to evaluate the changes in NGF serum levels in individuals with MDD and with or without risk of suicide, in subjects from a young population-based sample. This is a paired cross-sectional study nested in a population-based study. Individuals were rated for MDD and SR by a diagnostic interview--Mini International Neuropsychiatric Interview (M.I.N.I). The total population of the sample was comprised of 141 subjects distributed in three groups: 47 healthy controls, 47 subjects with current depressive episode without SR (MDD) and 47 subjects with current depressive episode and with SR (MDD + SR). NGF serum levels were significantly reduced in the MDD and MDD + SR groups when compared with controls (p ≤ 0.001). However, there were no differences in NGF levels between the MDD and MDD + SR groups (p = 1.000). These results suggest that reduced NGF serum levels can be a possible biomarker of MDD.

Practice of leisure-time physical activities and episodes of mood alteration amongst men and women.

OBJECTIVE: To evaluate the prevalence of leisure-time physical activity and episodes of mood alteration in a population-based sample of adults, and its relation with gender. METHOD: This is a cross-sectional population-based study with young adults aged between 18 and 35 years old. Sample selection was performed by clusters. The practice of physical activity was evaluated through the International Physical Activity Questionnaire (IPAQ), whereas mood disorders were evaluated using a short structured diagnostic interview-the Mini International Neuropsychiatric Interview (MINI) for DSM-IV and ICD-10 psychiatric disorders. LIMITATION: Causal inferences are limited due the study׳s design. RESULTS: Sample consisted of 1953 young adults. The prevalence of leisure-time physical activity and of depressive episodes in the total sample was 25.3% and 17.2%, respectively. The prevalence of activity amongst men was 1.18 (CI 95% 1.18-1.32) times higher than in the women׳s group, whereas depression was 1.87 (CI 95% 1.41-2.47) times more prevalent amongst women than men. The prevalence of physical activity was not different between women (p=0.287), nor between men (p=0.895) regarding the presence of mania/hypomania episode. CONCLUSION: The prevalence of physical activity and depression was different concerning gender. The prevalence of physical activity is lower amongst women, whereas the prevalence of depression is higher amongst women when compared to men.

The impact of anxious symptoms in the remission of depressive symptoms in a clinical trial for depression: follow-up of six months.

BACKGROUND: Studies show high comorbidity between anxiety disorder and depression. Little is known regarding how anxiety symptoms affect prognosis in depression treatment, suggesting the importance of studying the impact of anxiety symptoms in the treatment of depression. We evaluated the impact of anxiety symptoms in the remission of depressive symptoms after brief psychotherapies for depression. METHODS: This randomized clinical trial of 18-29-year-old adults included individuals who met the diagnostic criteria for depression as assessed by the Structured Clinical Interview for DSM (SCID). Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HRSD); anxiety symptoms were assessed using the Hamilton Anxiety Rating Scale (HARS). The protocols of psychotherapy used were: Cognitive Narrative Psychotherapy (CNP) and Cognitive Behavioral Psychotherapy (CBP). Both treatments included seven sessions. At the end of the treatment and six-month follow-up, an evaluation was made with the HRSD and HARS. The sample included 97 patients divided between the protocols of psychotherapy. RESULTS: There was a significant, positive, moderate correlation between the severity of anxiety symptoms at baseline and the remission of depressive symptoms at post-intervention (r=0.38 p<0.001) as well as a significant, positive, low correlation at follow up (r=0.20 p=0.049). We found remission of anxiety symptoms and depressive symptoms after brief psychotherapies, and the remission persisted at follow up. LIMITATION: We did not evaluate the diagnosis of anxiety disorders. CONCLUSION: The severity of anxiety symptoms did not compromise the treatment focused primarily on depressive symptoms.

The influence of psychoeducation on regulating biological rhythm in a sample of patients with bipolar II disorder: a randomized clinical trial.

INTRODUCTION: Changes in biological rhythm are among the various characteristics of bipolar disorder, and have long been associated with the functional impairment of the disease. There are only a few viable options of psychosocial interventions that deal with this specific topic; one of them is psychoeducation, a model that, although it has been used by practitioners for some time, only recently have studies shown its efficacy in clinical practice. AIM: To assess if patients undergoing psychosocial intervention in addition to a pharmacological treatment have better regulation of their biological rhythm than those only using medication. METHOD: This study is a randomized clinical trial that compares a standard medication intervention to an intervention combined with drugs and psychoeducation. The evaluation of the biological rhythm was made using the Biological Rhythm Interview of Assessment in Neuropsychiatry, an 18-item scale divided in four areas (sleep, activity, social rhythm, and eating pattern). The combined intervention consisted of medication and a short-term psychoeducation model summarized in a protocol of six individual sessions of 1 hour each. RESULTS: The sample consisted of 61 patients with bipolar II disorder, but during the study, there were 14 losses to follow-up. Therefore, the final sample consisted of 45 individuals (26 for standard intervention and 19 for combined). The results showed that, in this sample and time period evaluated, the combined treatment of medication and psychoeducation had no statistically significant impact on the regulation of biological rhythm when compared to standard pharmacological treatment. CONCLUSION: Although the changes in biological rhythm were not statistically significant during the time period evaluated in this study, it is noteworthy that the trajectory of the score showed a trend towards improvement, which may indicate a positive impact on treatment, though it may take a longer time than expected.