Maternal expression of miR-let-7d-3p and miR-451a during gestation influences the neuropsychomotor development of 90 days old babies: "Pregnancy care, healthy baby" study.

INTRODUCTION: Studies on maternal microRNA expression have emerged to better understand regulatory mechanisms during the gestational period, since microRNA expression has been associated with pregnancy disorders. OBJECTIVES: This study aims to investigate the association between the expression of the maternal microRNAs miR-let-7d-3p and miR-451a during the second gestational trimester and neuropsychomotor development at 90 days of life of infants. METHODS: This is a case-control study nested within a cohort, with the groups being divided into dyads in which pregnant women presented Major Depressive Episode (MDE) (n = 64), these being the cases, and their respective controls (no MDE; n = 64). The Bayley Scale III was used to assess the outcome of child development, and MDE was assessed through the Mini International Neuropsychiatric Interview Plus. The analysis of miR-let-7d-3p and miR-451a was done via serum from the pregnant women, utilizing the qRT-PCR (n = 128). RESULTS: The results indicated a negative association between expression levels of miR-451a (ß -3.3 CI95% -6.4;-0.3) and a positive associated of the miR-let-7d-3p with the cognitive development domain (ß 1.7 CI95% 0.1; 3.0), and a positive association between expression of miR-let-7d-3p with motor development of the infants (ß 1.6 CI95% 0.3; 2.9). CONCLUSION: This is a pioneering study on the topic that indicates a biological interrelationship between the miRNAs miR-let-7d-3p and miR-451a evaluated during the pregnancy and the motor and cognitive domains of infant development at 90 days postpartum.

BDNF Val66Met polymorphism and resilience in major depressive disorder: the impact of cognitive psychotherapy

Objective: Clinical and biological correlates of resilience in major depressive disorder are scarce. We aimed to investigate the effect of the Val66Met polymorphism in the BDNF gene on resilience scores in major depressive disorder patients and evaluate the polymorphism's moderation effect on resilience scores in response to cognitive therapy. Method: A total of 106 major depressive disorder patients were enrolled in this clinical randomized study. The Resilience Scale and the Hamilton Rating Scale for Depression were applied at baseline, post-treatment, and at six months of follow-up. Blood samples were obtained at baseline for molecular analysis. Results: The baseline resilience scores were higher in patients with the Met allele (114.6±17.6) than in those with the Val/Val genotype (104.04±21.05; p = 0.037). Cognitive therapy treatment increased resilience scores (p ≤ 0.001) and decreased depressive symptoms (p ≤ 0.001). In the mixed-effect model, the Val/Val genotype represented a decrease in resilience scores (t218 = -1.98; p = 0.048), and the Val66Met polymorphism interacted with sex to predict an increase in total resilience scores during cognitive treatment (t218 = 2.69; p = 0.008). Conclusion: Our results indicate that cognitive therapy intervention could improve resilience in follow-up, considering that gender and genetic susceptibility are predicted by the Val66Met polymorphism.

BDNF Val66Met polymorphism and resilience in major depressive disorder: the impact of cognitive psychotherapy.

OBJECTIVE: Clinical and biological correlates of resilience in major depressive disorder are scarce. We aimed to investigate the effect of the Val66Met polymorphism in the BDNF gene on resilience scores in major depressive disorder patients and evaluate the polymorphism's moderation effect on resilience scores in response to cognitive therapy. METHOD: A total of 106 major depressive disorder patients were enrolled in this clinical randomized study. The Resilience Scale and the Hamilton Rating Scale for Depression were applied at baseline, post-treatment, and at six months of follow-up. Blood samples were obtained at baseline for molecular analysis. RESULTS: The baseline resilience scores were higher in patients with the Met allele (114.6±17.6) than in those with the Val/Val genotype (104.04±21.05; p = 0.037). Cognitive therapy treatment increased resilience scores (p ≤ 0.001) and decreased depressive symptoms (p ≤ 0.001). In the mixed-effect model, the Val/Val genotype represented a decrease in resilience scores (t218 = -1.98; p = 0.048), and the Val66Met polymorphism interacted with sex to predict an increase in total resilience scores during cognitive treatment (t218 = 2.69; p = 0.008). CONCLUSION: Our results indicate that cognitive therapy intervention could improve resilience in follow-up, considering that gender and genetic susceptibility are predicted by the Val66Met polymorphism.

Psychoactive substance abuse and dependence and its association with anxiety disorders: a population-based study of young adults in Brazil

Objective: To evaluate the association between abuse of and dependence on different psychoactive substances and the presence of anxiety disorders in a sample of young adults from a city in southern Brazil. Methods: Between 2007 and 2009, we carried out a cross-sectional, population-based study of individuals aged 18-24 years who lived in Pelotas, a city in southern Brazil. We evaluated anxiety disorders using the Mini International Neuropsychiatric Interview 5.0 (MINI), and use of psychoactive substances with the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST 2.0/0MS). We used Fisher's exact test for univariate analysis, and Poisson regression models with robust variance for multivariable analysis. Results: The sample consisted of 1,560 young adults. The overall prevalence of abuse/dependence was 26.9% for alcohol, 24.9% for tobacco, and 7.3% for illicit substances. Individuals with agoraphobia had a 32% higher prevalence of tobacco abuse/dependence (prevalence ratio [PR] = 1.32 [95%CI 1.01-1.74]). Individuals with posttraumatic stress disorder (PTSD) or generalized anxiety disorder (GAD) had a 2.41-fold (95%CI 1.22-4.77) and 1.76-fold (95%CI 1.00-3.11) higher prevalence of illicit substance abuse/dependence, respectively. Conclusion: In this population-based sample, we found associations between GAD, PTSD, and increased prevalence of illicit substance abuse/dependence. In addition, individuals with agoraphobia seem to have increased tobacco abuse/dependence.

Psychoactive substance abuse and dependence and its association with anxiety disorders: a population-based study of young adults in Brazil.

OBJECTIVE: To evaluate the association between abuse of and dependence on different psychoactive substances and the presence of anxiety disorders in a sample of young adults from a city in southern Brazil. METHODS: Between 2007 and 2009, we carried out a cross-sectional, population-based study of individuals aged 18-24 years who lived in Pelotas, a city in southern Brazil. We evaluated anxiety disorders using the Mini International Neuropsychiatric Interview 5.0 (MINI), and use of psychoactive substances with the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST 2.0/0MS). We used Fisher's exact test for univariate analysis, and Poisson regression models with robust variance for multivariable analysis. RESULTS: The sample consisted of 1,560 young adults. The overall prevalence of abuse/dependence was 26.9% for alcohol, 24.9% for tobacco, and 7.3% for illicit substances. Individuals with agoraphobia had a 32% higher prevalence of tobacco abuse/dependence (prevalence ratio [PR] = 1.32 [95%CI 1.01-1.74]). Individuals with posttraumatic stress disorder (PTSD) or generalized anxiety disorder (GAD) had a 2.41-fold (95%CI 1.22-4.77) and 1.76-fold (95%CI 1.00-3.11) higher prevalence of illicit substance abuse/dependence, respectively. CONCLUSION: In this population-based sample, we found associations between GAD, PTSD, and increased prevalence of illicit substance abuse/dependence. In addition, individuals with agoraphobia seem to have increased tobacco abuse/dependence.

Anxiety symptoms have a direct effect on oral health perception in young women.

PURPOSE: Assess the influence of anxiety symptoms on oral health related-quality of life in young women from a cohort study in Southern Brazil. METHODS: A sample of 535 young mothers were analyzed. Interviews and psychological evaluations were carried out by trained psychologists. The Brazilian version of the Corah's dental anxiety scale and the Beck anxiety inventory were used to evaluate dental anxiety and anxiety symptoms, respectively. The oral health-related quality of life (OHRQoL) was assessed by the Oral Impacts on Daily Performance instrument. Dental examinations were performed by trained dentists to assess oral health status (DMFT). The effect of anxiety symptoms on oral health-related quality of life was estimated using the parametric g-formula. RESULTS: The prevalence of negative impact on OHRQoL was of 46.3 and 28% of the women presented anxiety symptoms. Unadjusted analysis showed that women with anxiety symptoms had 2.5 higher impact on OHRQoL (OR 2.55; CI 95% 1.72-3.79). The parametric g-formula revealed that anxiety had a direct effect on oral health perception (OR 1.16; CI 95% 1.04-1.30), not mediated by dental anxiety. CONCLUSION: Oral health-related quality of life is influenced by anxiety symptoms, regardless of dental anxiety.

Association between perceived social support and anxiety in pregnant adolescents

Objective: To evaluate the association between perceived social support and anxiety disorders in pregnant adolescents. Methods: We conducted a cross-sectional study with a sample of 871 pregnant women aged 10 to 19 years who received prenatal care in the national public health care system in the urban area of Pelotas, state of Rio Grande do Sul, southern Brazil. We assessed perceived social support and anxiety disorders using the Medical Outcomes Study Social Support Survey and the Mini International Neuropsychiatric Interview. A self-report questionnaire was used to obtain sociodemographic information. Results: The prevalence of any anxiety disorder was 13.6%. Pregnant adolescents with an anxiety disorder reported less perceived social support in all domains (affectionate, emotional, tangible, informational, and positive social interaction). Older teenagers reported lower perceived support in the emotional, informational, and positive social interaction domains, whereas those with low socioeconomic status reported lower perceived social support in the material domain. Women who did not live with a partner had less perceived social support in the affectionate and positive social interaction domains. Conclusion: Perceived social support seems to be a protective factor against anxiety disorders in pregnant adolescents, with a positive effect on mental health.

Polymorphism in CRHR1 gene affects the IL-1ß levels in suicidal attempters.

Approximately one million people commit suicide every year, being suicide attempts and ideation even more common. Changes in stress response and activation of the immune system have been associated with suicide risk. Here we investigated the interaction between immune system and HPA axis alterations in the suicide risk, looking for the influence of rs110402 CRHR1 SNP in the IL-1ß levels according to suicide ideation and attempt. This study evaluated 171 subjects of which 15 had suicidal ideation, 20 had suicide attempt and 136 were controls. Genotyping was performed by real-time PCR and IL-1ß levels were measured by ELISA. Our data showed that for each point increase in IL-1ß levels the risk of suicide attempt increased 5% [relative risk = 1.05 (95% CI: 1.0-1.10)]. After sample stratification by rs110402 SNP genotypes, we observed that in subjects carrying the A allele the risk raised to 15% [relative risk = 1.15 (95% CI: 1.03-1.28)], suggesting an apparent effect modification. Thus, this study showed that alterations in CRHR1 gene were associated with higher levels of IL-1ß, and increased risk for suicide, reinforcing the importance of multifactorial interactions of biological markers for psychiatric disorders.

Association between perceived social support and anxiety in pregnant adolescents.

OBJECTIVE:: To evaluate the association between perceived social support and anxiety disorders in pregnant adolescents. METHODS:: We conducted a cross-sectional study with a sample of 871 pregnant women aged 10 to 19 years who received prenatal care in the national public health care system in the urban area of Pelotas, state of Rio Grande do Sul, southern Brazil. We assessed perceived social support and anxiety disorders using the Medical Outcomes Study Social Support Survey and the Mini International Neuropsychiatric Interview. A self-report questionnaire was used to obtain sociodemographic information. RESULTS:: The prevalence of any anxiety disorder was 13.6%. Pregnant adolescents with an anxiety disorder reported less perceived social support in all domains (affectionate, emotional, tangible, informational, and positive social interaction). Older teenagers reported lower perceived support in the emotional, informational, and positive social interaction domains, whereas those with low socioeconomic status reported lower perceived social support in the material domain. Women who did not live with a partner had less perceived social support in the affectionate and positive social interaction domains. CONCLUSION:: Perceived social support seems to be a protective factor against anxiety disorders in pregnant adolescents, with a positive effect on mental health.

Association between perception of maternal bonding styles and social anxiety disorder among young women.

OBJECTIVE: To evaluate the association between social anxiety disorder (SAD) and perceived maternal bonding styles among young women during pregnancy and 30 months after childbirth. METHODS: A cohort of young women from the city of Pelotas, Brazil was followed up from pregnancy to 30 months postpartum. The Mini Neuropsychiatric Interview Plus was used to assess SAD and the Parental Bonding Instrument was administered to measure maternal bonding styles. Poisson regression with robust variance was used for multivariable analysis. RESULTS: After adjusting for potential confounding factors, SAD prevalence was 6.39 times higher among young women who perceived their mothers as neglectful (prevalence ratio [PR] 6.39; 95% confidence interval [95%CI] 1.2-32.0), and 5.57 times higher in women who perceived their mothers as affectionless controlling (PR = 5.57; 95%CI 1.5-19.7) when compared with those who received optimal care. CONCLUSION: Maternal bonding style may have an influence on the development of SAD. Therefore, support and early prevention strategies should be offered to the family.

Quality of life, social functioning, family structure, and treatment history associated with crack cocaine use in youth from the general population

Objective:To assess the relationship between crack cocaine use and dimensions of quality of life and social functioning in young adults.Methods:This was a cross-sectional, population-based study involving 1,560 participants in Pelotas, Brazil. Crack cocaine use and abuse were investigated using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) inventory. Outcomes of interest were quality of life, religiosity, and social functioning in terms of education, occupational status, family structure, and medical treatment history.Results:Lifetime crack cocaine use was associated with poor quality of life, worse functioning, impaired academic performance, and lower religious involvement. A greater maternal presence and higher paternal absence were more also more pronounced in crack cocaine users, who were also more likely to seek psychological and psychiatric treatment than the general population.Conclusion:Quality of life was severely impacted by crack cocaine use, especially in terms of general and physical health. Social functioning also differed between the general population and crack users, who had lower educational attainment and religious involvement. Maternal presence, paternal absence, and mental health-seeking behaviors were also more frequent among crack cocaine users, although these individuals reported lower rates of treatment satisfaction. Crack cocaine users also had significant social impairment, so that interventions involving family management and a greater focus on general health, quality of life, and functioning may make crucial contributions to the recovery of this group.

Cognitive psychotherapy treatment decreases peripheral oxidative stress parameters associated with major depression disorder.

INTRODUCTION: Studies have already pointed out the contribution of oxidative stress in the pathophysiology of major depressive disorder (MDD). The aim of the present study was to investigate the oxidative-antioxidative systems in MDD and in response to cognitive psychotherapies. Oxidative stress were analyzed in 49 MDD patients at baseline, post-treatment, and follow-up; and 49 control subjects without history of psychiatric disorders. RESULTS: MDD subjects presented an increase in oxidative damage related to control subjects for thiobarbituric acid reactive species (TBARS), nitric oxide, and a decrease in total thiol content. Cognitive psychotherapies were able to counteract peripheral oxidative stress in MDD patients, reducing TBARS levels (p<0.001) in the follow-up, nitric oxide (p<0.001) in the post-treatment and follow-up, and increasing the total thiol content (p<0.01) in the post-treatment and follow-up. CONCLUSION: Oxidative stress was associated with MDD and the regulation of these parameters might represent an important mechanism associated with the clinical improvement of cognitive psychotherapy.

The Met allele of BDNF Val66Met polymorphism is associated with increased BDNF levels in generalized anxiety disorder.

BACKGROUND: Generalized anxiety disorder (GAD) is a common psychiatric disorder characterized by long-term worry, tension, nervousness, fidgeting, and symptoms of autonomic system hyperactivity. The neurobiology of this disorder is still unclear, although it has been shown consistently that the environment and the genetic profile could increase its risk. We examined whether a polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which plays a role in neuroplasticity and memory, could increase the vulnerability to this disorder. PARTICIPANTS AND METHODS: In our study, 816 participants from a population-based study were genotyped by qPCR for the BDNF functional variant rs6265 (Val66Met) and the BDNF serum levels were measured by ELISA. RESULTS: Our results showed a significant association between the Met allele and risk for GAD (P=0.014), but no differences were observed in the serum levels of BDNF according to diagnosis (P=0.531) or genotype distribution (P=0.197). However, after stratification according to the GAD diagnosis, the Met allele was associated significantly with an increase in serum BDNF levels compared with the Val/Val genotype in GAD participants (F=3.93; P=0.048). The logistic regression analysis confirmed the independent association of Met allele as a risk factor for development of GAD after adjusting for confounder variables (ß=0.528; 95% confidence interval: 0.320-0.871; P=0.012). CONCLUSION: These results suggest that BDNF could be involved in the neurobiology of GAD and might represent a useful marker associated with the disease.

Quality of life, social functioning, family structure, and treatment history associated with crack cocaine use in youth from the general population.

OBJECTIVE: To assess the relationship between crack cocaine use and dimensions of quality of life and social functioning in young adults. METHODS: This was a cross-sectional, population-based study involving 1,560 participants in Pelotas, Brazil. Crack cocaine use and abuse were investigated using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) inventory. Outcomes of interest were quality of life, religiosity, and social functioning in terms of education, occupational status, family structure, and medical treatment history. RESULTS: Lifetime crack cocaine use was associated with poor quality of life, worse functioning, impaired academic performance, and lower religious involvement. A greater maternal presence and higher paternal absence were more also more pronounced in crack cocaine users, who were also more likely to seek psychological and psychiatric treatment than the general population. CONCLUSION: Quality of life was severely impacted by crack cocaine use, especially in terms of general and physical health. Social functioning also differed between the general population and crack users, who had lower educational attainment and religious involvement. Maternal presence, paternal absence, and mental health-seeking behaviors were also more frequent among crack cocaine users, although these individuals reported lower rates of treatment satisfaction. Crack cocaine users also had significant social impairment, so that interventions involving family management and a greater focus on general health, quality of life, and functioning may make crucial contributions to the recovery of this group.

Increased serum neurotrophin levels related to alcohol use disorder in a young population sample.

BACKGROUND: The diagnosis of alcohol use disorder is based on clinical signs and on the measurement of biological markers. However, these markers are neither sufficiently sensitive, nor specific enough, for determining the effects of alcohol abuse on the central nervous system. Serum neurotrophins are important regulators of neural survival, development, function, and plasticity and have been found to be reduced in alcohol use disorder. The aim of this study was to investigate the alterations in serum neurotrophin levels (brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF], and nerve growth factor [NGF]) in alcohol use disorder in a young population, and thus possibly representing the early stages of the illness. METHODS: This is a cross-sectional study, nested in a population-based study of people aged 18 to 35, involving 795 participants. The participants responded to the CAGE questionnaire, and a CAGE score of ≥2 was considered to be a positive screen for the abuse/dependence or moderate to severe alcohol use disorder. Serum BDNF, GDNF, and NGF levels were measured by ELISA. RESULTS: In the CAGE ≥ 2 group, GDNF (p ≤ 0.001) and NGF (p ≤ 0.001) serum levels were significantly increased, and the BDNF elevation was near a statistical significance (p = 0.068) when compared to the CAGE < 2 group. A significantly positive correlation was observed only in the CAGE ≥ 2 group for BDNF/GDNF (r = 0.37, p < 0.001) and GDNF/NGF (r = 0.84, p < 0.001) levels. The correlation between the NGF and BDNF levels was significantly positive in both groups (r = 0.28, p < 0.001 for the CAGE < 2 group, and r = 0.30, p = 0.008 for the CAGE ≥ 2 group). CONCLUSIONS: These results suggest that elevated neurotrophins are candidate markers for the early stages of alcohol misuse.

Leptin in depressive episodes: is there a difference between unipolar and bipolar depression?

OBJECTIVE: The present study investigated whether peripheral leptin levels are associated with current depressive episodes in a cross-sectional study nested within a population-based study. METHODS: The Mini-International Neuropsychiatric Interview (MINI) 5.0 was used to assess the presence of current depressive episodes. The sample was composed of 206 subjects (103 controls and 103 subjects with a current depressive episode) paired by gender, BMI and age. Medication use and lifestyle characteristics were self-reported. RESULTS: Serum leptin levels were lower in currently depressive subjects (10.9 ± 12.0 ng/ml) than in the control group (20.3 ± 24.0 ng/ml; p = 0.023). According to the clinical diagnosis, individuals with bipolar depression present lower leptin levels (8.4 ± 8.1 ng/ml) than those with unipolar depression (12.0 ± 13.4 ng/ml) and the control group (20.3 ± 24.0 ng/ml; p = 0.031). In addition, ANCOVA showed that leptin is an independent factor associated with current depressive episodes (p = 0.018). CONCLUSION: A decreased leptin level might be a useful peripheral marker associated with depressive episodes in the context of bipolar disorder.

Psychiatric and substance-use comorbidities associated with lifetime crack cocaine use in young adults in the general population.

OBJECTIVE: To assess the association between lifetime crack cocaine use and psychiatric (post-traumatic stress disorder, current depression, current dysthymia, generalized anxiety disorder, panic disorder with agoraphobia, social phobia, as well as SRQ scores and suicide risk) and substance-use disorders (tobacco, alcohol, cannabis, cocaine, amphetamine, inhalants, sedatives, hallucinogens and opioids) in youth in the general population of the city of Pelotas, RS. METHOD: This was a cross-sectional population-based study, involving 1560 participants between 18 and 24 ears old. Lifetime substance use and abuse were investigated using the ASSIST inventory. Psychiatric comorbidities were assessed using the Mini-International Neuropsychiatric Interview and symptoms of common mental disorders were evaluated with the Self-Reported Questionnaire (SRQ). RESULTS: The prevalence of lifetime crack cocaine use in the sample was 2.5%. Its use was associated with total SRW scores and the presence of post-traumatic stress disorder, antisocial personality disorder and suicide risk in the final regression model. Tobacco, alcohol, cannabis, cocaine, amphetamine and cocaine dependence were also associated with lifetime use of crack cocaine. DISCUSSION: Youth with a history of crack cocaine use had a higher prevalence of psychiatric conditions such as post-traumatic stress disorder, as well as an increased risk of tobacco, alcohol, cannabis, cocaine, amphetamine and inhalant use and dependence.

Immune dysfunction in bipolar disorder and suicide risk: is there an association between peripheral corticotropin-releasing hormone and interleukin-1ß?

OBJECTIVE: The aim of the present study was to investigate the relationship between peripheral levels of corticotropin-releasing hormone (CRH) and interleukin-1ß (IL-1ß) in individuals with bipolar disorder (BD) with and without suicide risk (SR), and controls. METHODS: A total of 120 young adults (40 controls, 40 subjects with BD without SR, and 40 subjects with BD with SR) were enrolled from a population-based study carried out in the city of Pelotas, Brazil. BD and SR were assessed through the Mini International Neuropsychiatric Interview (MINI 5.0), and peripheral markers were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Levels of CRH were significantly lower both in subjects with BD without SR (p = 0.04) and subjects with BD with SR (p = 0.02) when compared to controls. However, levels of IL-1ß were increased in subjects with BD with SR (p = 0.05) when compared to controls. Sociodemographic and clinical variables, current mood episode, and use of psychiatric medications were not associated with changes in these markers. No correlation was found between peripheral levels of CRH and IL-1ß (p = 0.60) in the population or in the BD with SR group (p = 0.88). CONCLUSIONS: These results suggest that peripheral mechanisms linking stress hormones and the immune system might be critical patterns involved in suicidal behavior associated with BD.