Maramycin, a Cytotoxic Isoquinolinequinone Terpenoid Produced through Heterologous Expression of a Bifunctional Indole Prenyltransferase/Tryptophan Indole-Lyase in S. albidoflavus.

Isoquinolinequinones represent an important family of natural alkaloids with profound biological activities. Heterologous expression of a rare bifunctional indole prenyltransferase/tryptophan indole-lyase enzyme from Streptomyces mirabilis P8-A2 in S. albidoflavus J1074 led to the activation of a putative isoquinolinequinone biosynthetic gene cluster and production of a novel isoquinolinequinone alkaloid, named maramycin (1). The structure of maramycin was determined by analysis of spectroscopic (1D/2D NMR) and MS spectrometric data. The prevalence of this bifunctional biosynthetic enzyme was explored and found to be a recent evolutionary event with only a few representatives in nature. Maramycin exhibited moderate cytotoxicity against human prostate cancer cell lines, LNCaP and C4-2B. The discovery of maramycin (1) enriched the chemical diversity of natural isoquinolinequinones and also provided new insights into crosstalk between the host biosynthetic genes and the heterologous biosynthetic genes in generating new chemical scaffolds.

Pepticinnamins N, O, and P, Nonribosomal Peptides from the Soil-Derived Streptomyces mirabilis P8-A2.

Cinnamoyl moiety containing nonribosomal peptides represented by pepticinnamin E are a growing family of natural products isolated from different Streptomyces species and possess diverse bioactivities. The soil bacterium Streptomyces mirabilis P8-A2 harbors a cryptic pepticinnamin biosynthetic gene cluster, producing azodyrecins as major products. Inactivation of the azodyrecin biosynthetic gene cluster by CRISPR-BEST base editing led to the activation and production of pepticinnamin E (1) and its analogues, pepticinnamins N, O, and P (2-4), the structures of which were determined by detailed NMR spectroscopy, HRMS data, and Marfey's reactions. These new compounds did not show a growth inhibitory effect against the LNCaP and C4-2B prostate cancer lines, respectively.

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.

5-year incidence of suicide-risk in youth: A gradient tree boosting and SHAP study.

BACKGROUND: Machine learning methods for suicidal behavior so far have failed to be implemented as a prediction tool. In order to use the capabilities of machine learning to model complex phenomenon, we assessed the predictors of suicide risk using state-of-the-art model explanation methods. METHODS: Prospective cohort study including a community sample of 1,560 young adults aged between 18 and 24. The first wave took place between 2007 and 2009, and the second wave took place between 2012 and 2014. Sociodemographic and clinical characteristics were assessed at baseline. Incidence of suicide risk at five-years of follow-up was the main outcome. The outcome was assessed using the Mini Neuropsychiatric Interview (MINI) at both waves. RESULTS: The risk factors for the incidence of suicide risk at follow-up were: female sex, lower socioeconomic status, older age, not studying, presence of common mental disorder symptoms, and poor quality of life. The interaction between overall health and socioeconomic status in relation to suicide risk was also captured and shows a shift from protection to risk by socioeconomic status as overall health increases. LIMITATIONS: Proximal factors associated with the incidence of suicide risk were not assessed. CONCLUSIONS: Our findings indicate that factors related to poor quality of life, not studying, and common mental disorder symptoms of young adults are already in place prior to suicide risk. Most factors present critical non-linear patterns that were identified. These findings are clinically relevant because they can help clinicians to early detect suicide risk.

Sex-dependent role of CD300f immune receptor in generalized anxiety disorder.

Generalized Anxiety Disorder (GAD) presents a high prevalence in the population, leading to distress and disability. Immune system alterations have been associated with anxiety-related behaviors in rodents and GAD patients. CD300f immune receptors are highly expressed in microglia and participate not only in the modulation of immune responses but also in pruning and reshaping synapses. It was recently demonstrated that CD300f might be influential in the pathogenesis of depression in a sex-dependent manner. Here, we evaluated the role of CD300f immune receptor in anxiety, using CD300f knockout mice (CD300f-/-) and patients with GAD. We observed that male CD300f-/- mice had numerous behavioral changes associated with a low-anxiety phenotype, including increased open field central locomotion and rearing behaviors, more exploration in the open arms of the elevated plus-maze test, and decreased latency to eat in the novelty suppressed feeding test. In a cross-sectional population-based study, including 1111 subjects, we evaluated a common single-nucleotide polymorphism rs2034310 (C/T) in the cytoplasmatic tail of CD300f gene in individuals with GAD. Notably, we observed that the T allele of the rs2034310 polymorphism conferred protection against GAD in men, even after adjusting for confounding variables. Overall, our data demonstrate that CD300f immune receptors are involved in the modulation of pathological anxiety behaviors in a sex-dependent manner. The biological basis of these sex differences is still poorly understood, but it may provide significant clues regarding the neuropathophysiological mechanisms of GAD and can pave the way for future specific pharmacological interventions.

Molecular Profiling of Docetaxel-Resistant Prostate Cancer Cells Identifies Multiple Mechanisms of Therapeutic Resistance.

Docetaxel-a taxane-based chemotherapeutic agent-was the first treatment to demonstrate significant improvements in overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, the response to docetaxel is generally short-lived, and relapse eventually occurs due to the development of resistance. To explore the mechanisms of acquired docetaxel resistance in prostate cancer (PCa) and set these in the context of androgen deprivation therapy, we established docetaxel-resistant PCa cell lines, derived from the androgen-dependent LNCaP cell line, and from the LNCaP lineage-derived androgen-independent C4-2B sub-line. We generated two docetaxel-resistant LNCaPR and C4-2BR sub-lines, with IC50 values 77- and 50-fold higher than those of the LNCaP and C4-2B parental cells, respectively. We performed gene expression analysis of the matched sub-lines and found several alterations that may confer docetaxel resistance. In addition to increased expression of ABCB1, an ATP-binding cassette (ABC) transporter, and a well-known gene associated with development of docetaxel resistance, we identified genes associated with androgen signaling, cell survival, and overexpression of ncRNAs. In conclusion, we identified multiple mechanisms that may be associated with the development of taxane drug resistance in PCa. Actioning these mechanisms could provide a potential approach to re-sensitization of docetaxel-resistant PCa cells to docetaxel treatment and thereby further add to the life-prolonging effects of this drug in men with mCRPC.

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.

Childhood trauma and bipolar spectrum: a population-based sample of young adults.

Introduction Childhood trauma has been suggested to be involved in susceptibility to bipolar disorder (BP). However, it remains unclear whether the occurrence of childhood trauma is differently distributed in subthreshold bipolar disorder (SBP). Objective To assess childhood trauma in young adults with SBP, as compared to young adults with BP and population controls (PC). Method This was a cross-sectional, population-based study. The Mini International Neuropsychiatric Interview (MINI) was used to define the groups with BP (subjects with a lifetime or current manic episode or lifetime or current hypomania with a history of a depressive episode), SBP (subjects with a history of hypomanic episode without lifetime or current depressive episode), and subjects without mood disorders (PC). Childhood trauma was assessed using de Childhood Trauma Questionnaire (CTQ). We investigated differences regarding childhood trauma across the three groups (BP, SBP and PC). Result Except for sexual abuse, all subtypes of childhood trauma remained associated with the BP group as compared to PC. Additionally, when we compared SBP and BP, significant differences were found only for emotional abuse. No significant differences were found in relation to childhood trauma between the SBP and PC groups after adjusting for confounding factors. Conclusion These findings suggest that investigating childhood trauma, with a particular focus on emotional abuse, could be considered a preventive measure and potentially improve the prognosis.

Childhood trauma and bipolar spectrum: a population-based sample of young adults

Abstract Introduction Childhood trauma has been suggested to be involved in susceptibility to bipolar disorder (BP). However, it remains unclear whether the occurrence of childhood trauma is differently distributed in subthreshold bipolar disorder (SBP). Objective To assess childhood trauma in young adults with SBP, as compared to young adults with BP and population controls (PC). Method This was a cross-sectional, population-based study. The Mini International Neuropsychiatric Interview (MINI) was used to define the groups with BP (subjects with a lifetime or current manic episode or lifetime or current hypomania with a history of a depressive episode), SBP (subjects with a history of hypomanic episode without lifetime or current depressive episode), and subjects without mood disorders (PC). Childhood trauma was assessed using de Childhood Trauma Questionnaire (CTQ). We investigated differences regarding childhood trauma across the three groups (BP, SBP and PC). Result Except for sexual abuse, all subtypes of childhood trauma remained associated with the BP group as compared to PC. Additionally, when we compared SBP and BP, significant differences were found only for emotional abuse. No significant differences were found in relation to childhood trauma between the SBP and PC groups after adjusting for confounding factors. Conclusion These findings suggest that investigating childhood trauma, with a particular focus on emotional abuse, could be considered a preventive measure and potentially improve the prognosis.

Lifetime cocaine use is a potential predictor for conversion from major depressive disorder to bipolar disorder: A prospective study.

AIM: We aimed to identify whether lifetime cocaine use is a risk factor for conversion from major depressive disorder (MDD) to bipolar disorder (BD) in an outpatient sample of adults. METHODS: This prospective cohort study included 585 subjects aged 18 to 60 years who had been diagnosed with MDD as assessed by the Mini International Neuropsychiatric Interview (MINI-Plus) at baseline (2012-2015). Subjects were reassessed a mean of 3 years later (2017-2018) for potential conversion to BD as assessed by the MINI-Plus. Lifetime cocaine use was assessed using the Alcohol, Smoking, and Substance Involvement Screening Test. RESULTS: In the second wave, we had 117 (20%) losses, and 468 patients were reassessed. The rate of conversion from MDD to BD in 3 years was 12.4% (n = 58). A logistic regression analysis showed that the risk for conversion from MDD to BD was 3.41-fold higher (95% confidence interval, 1.11-10.43) in subjects who reported lifetime cocaine use at baseline as compared to individuals who did not report lifetime cocaine use at baseline, after adjusting for demographic and clinical confounders. CONCLUSION: These findings showed that lifetime cocaine use is a potential predictor of conversion to BD in an MDD cohort. Further studies are needed to assess the possible underlying mechanisms linking exposure to cocaine with BD conversion.

Effect of cognitive-behavioral therapy after treatment for adults with major depression / Efeito da terapia cognitivo-comportamental um ano após tratamento para adultos com transtorno depressivo maior / Efecto de la terapia cognitiva comportamental un año después tratamiento para transtorno depresivo mayor

In Brazil, little is known about the maintenance of results after treatment of cognitive-behavioral therapy (CBT) for major depressive disorder (MDD). The objective of this study was to verify the effectiveness of individual psychotherapeutic treatment from CBT for depressive symptoms within 6 and 12 months after the intervention. We evaluated 94 participants with MDD from the Beck Depression Inventory (BDI-II). There was significant posttreatment response (p < 0.001), with no difference between the end of the treatment and the symptom assessment at 6 (p = 0.486) and 12 months (p = 0.098). A significant positive correlation was observed between the intensity of depressive symptoms at the baseline and the reduction of initial symptoms for 12-month follow-up (r = 0.49; p < 0.001). CBT significantly reduces depressive symptoms by maintaining this condition up to 12 months post-intervention without significant influence of other characteristics beyond the intensity of depressive symptoms at the beginning of the therapeutic process.

No Brasil, pouco se sabe sobre a manutenção dos resultados pós-tratamento da terapia cognitivo-comportamental (TCC) para o transtorno depressivo maior (TDM). Objetivou-se verificar a efetividade do tratamento psicoterápico individual a partir da TCC para os sintomas depressivos em um período de 6 e 12 meses pós-intervenção. Avaliaram-se 94 participantes com TDM a partir do Inventário Beck de Depressão (BDI-II). Houve resposta significativa pós-tratamento (p < 0,001), não ocorrendo diferenças entre o final do tratamento e a avaliação dos sintomas aos 6 (p = 0,486) e 12 meses (p = 0,098). Uma correlação positiva significativa foi observada entre a intensidade dos sintomas depressivos no baseline e a redução de sintomas iniciais para o acompanhamento de 12 meses (r = 0,49; p < 0,001). A TCC reduz significativamente os sintomas depressivos mantendo essa condição até 12 meses pós-intervenção sem influência significativa de outras características além da intensidade dos sintomas depressivos no início do processo terapêutico.

Este estudio verificó la efectividad del tratamiento psicoterápico individual a partir de la terapia cognitiva conductual (TCC) para los síntomas depresivos dentro de los 6 y 12 meses post-intervención. Se evaluaron 94 participantes con TDM a partir del Inventario Beck de depresión (BDI-II). Se observó una respuesta significativa post-tratamiento (p < 0,001), no ocurrieron diferencias entre el final del tratamiento y la evaluación de los síntomas a los 6 (p = 0,486) y 12 meses (p = 0,098). Había una correlación positiva significativa entre la intensidad de los síntomas depresivos en el baseline y la reducción de los síntomas iniciales para el seguimiento de 12 meses (r = 0,49; p < 0,001). La TCC reduce significativamente los síntomas depresivos manteniendo esa condición hasta 12 meses después de la intervención sin influencia significativa de otras características además de la intensidad de los síntomas depresivos al inicio del proceso terapéutico.

Serum level of nerve growth factor is a potential biomarker of conversion to bipolar disorder in women with major depressive disorder.

AIM: The aim of this study was to identify biomarkers associated with major depressive disorder (MDD) and conversion from MDD to bipolar disorder (BD) in an outpatient sample of women. METHODS: This was a longitudinal study including women diagnosed with MDD and aged 18 to 60 years. The follow-up was 3 years. The diagnosis was performed using the Mini International Neuropsychiatric Interview Plus. Blood collection was just performed in the first phase. Serum interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and nerve growth factor (NGF) levels were measured using a commercial immunoassay kit. RESULTS: We included 156 women. The conversion rate from MDD to BD was 15.4% (n = 24). NGF serum levels were increased in patients who converted to BD compared to the remitted MDD group and current MDD group (P = 0.013). The Bonferroni post-hoc test for multiple comparisons revealed significant differences for higher NGF levels in patients who converted to BD compared to patients with current MDD (P = 0.037). Interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor serum levels did not differ among the groups. CONCLUSION: Our results suggest that NGF might be a useful biomarker associated with early detection of conversion to BD, helping clinicians in the clinical diagnosis.

Metabolic syndrome and psychiatric disorders: a population-based study

Objective: To identify the association of metabolic syndrome (MetS) and psychiatric disorders in young adults in southern Brazil. Methods: This population based cross-sectional study involved a total of 1,023 young adults between the ages of 21 and 32 years. Current episodes of psychiatric disorders were assessed using the Mini International Neuropsychiatric Interview - Plus version. MetS was evaluated using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). Results: Of the 1,023 participants, 24.3% were identified with MetS, 13.5% were diagnosed with anxiety disorders, 7.5% with current depression, 3.9% with bipolar disorders and 10.1% were at risk of suicide. MetS was associated with ethnicity (p = 0.022), excess weight (p < 0.001), current anxiety disorders (p < 0.001), current mood disorders (bipolar disorder in mood episode and current depression) (p < 0.001), and suicide risk (p < 0.001). Conclusions: MetS was associated with psychiatric disorders. Awareness of factors associated with MetS can help identify high-risk individuals and stimulate disease prevention and control programs, as well as lifestyle changes.

Metabolic syndrome and psychiatric disorders: a population-based study.

OBJECTIVE: To identify the association of metabolic syndrome (MetS) and psychiatric disorders in young adults in southern Brazil. METHODS: This population based cross-sectional study involved a total of 1,023 young adults between the ages of 21 and 32 years. Current episodes of psychiatric disorders were assessed using the Mini International Neuropsychiatric Interview - Plus version. MetS was evaluated using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). RESULTS: Of the 1,023 participants, 24.3% were identified with MetS, 13.5% were diagnosed with anxiety disorders, 7.5% with current depression, 3.9% with bipolar disorders and 10.1% were at risk of suicide. MetS was associated with ethnicity (p = 0.022), excess weight (p < 0.001), current anxiety disorders (p < 0.001), current mood disorders (bipolar disorder in mood episode and current depression) (p < 0.001), and suicide risk (p < 0.001). CONCLUSIONS: MetS was associated with psychiatric disorders. Awareness of factors associated with MetS can help identify high-risk individuals and stimulate disease prevention and control programs, as well as lifestyle changes.

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.

Effects of cognitive-behavioral therapy on neurotrophic factors in patients with major depressive disorder

Objective: To correlate neurotrophic factors - brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and beta-nerve growth factor (beta-NGF) - and severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD) undergoing cognitive-behavioral therapy (CBT). Methods: In this quasi-experimental study, participants were selected by convenience and received 16 sessions of CBT. The outcomes of interest were severity of depressive symptoms and changes in neurotrophic factor levels after CBT. The differences between variables before and after treatment (deltas) were analyzed. Results: Patients had significant changes in symptom severity after treatment. No significant associations were found between Beck Depression Inventory II (BDI-II) scores and any independent variable. No correlations were observed between BDNF or GDNF levels and BDI scores before or after treatment, although there was a trend toward significant differences in beta-NGF levels. Conclusion: BDNF, beta-NGF, and GDNF were not influenced by the effects of CBT on depressive symptoms.

Effects of cognitive-behavioral therapy on neurotrophic factors in patients with major depressive disorder.

OBJECTIVE: To correlate neurotrophic factors - brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and beta-nerve growth factor (beta-NGF) - and severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD) undergoing cognitive-behavioral therapy (CBT). METHODS: In this quasi-experimental study, participants were selected by convenience and received 16 sessions of CBT. The outcomes of interest were severity of depressive symptoms and changes in neurotrophic factor levels after CBT. The differences between variables before and after treatment (deltas) were analyzed. RESULTS: Patients had significant changes in symptom severity after treatment. No significant associations were found between Beck Depression Inventory II (BDI-II) scores and any independent variable. No correlations were observed between BDNF or GDNF levels and BDI scores before or after treatment, although there was a trend toward significant differences in beta-NGF levels. CONCLUSION: BDNF, beta-NGF, and GDNF were not influenced by the effects of CBT on depressive symptoms.

Gender differences of cannabis smoking on serum leptin levels: population-based study

Objective: To evaluate the serum leptin levels in cannabis smokers. Methods: This was a cross-sectional population-based study of participants between the ages of 18 and 35 years. The data were collected through a self-administered questionnaire covering sociodemographic data and the use of psychoactive substances. Leptin levels were measured using a commercial ELISA kit. Results: Of the 911 participants, 6.7% were identified as cannabis smokers and had significantly lower leptin levels (p = 0.008). When stratified by gender, there was a significant decrease in leptin levels among male smokers (p = 0.039). Conclusion: Cannabis smoking was linked to leptin levels in men, suggesting that the response to biological signals may be different between men and women.

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.