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.

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.

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.

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.

Functional impairment and cognitive performance in mood disorders: A community sample of young adults.

The aim of this study was to compare the global functioning and cognitive performance in a community sample of young adults with mood disorders versus community controls. This was a cross-sectional study nested in a cohort study with a community sample. Data was collected from February 2012 to June 2014; specifically, at a mean of five years after the first phase, all young adults were invited to participate in a re-evaluation. Mini International Neuropsychiatric Interview - PLUS (MINI-PLUS) was used for the diagnosis of mood disorders. The Functional Assessment Short Test (FAST) and the Montreal Cognitive Assessment (MoCA) were used to assess the global functioning, and cognitive performance, respectively. Were included 1258 subjects. Functional impairment was greater in subjects with bipolar disorder when compared to community controls, and there were no differences between major depressive disorder and community controls. There were no significant differences in cognitive performance between young adults with mood disorders when compared to community controls. Functional impairment is a marker for bipolar disorder in young adults; however, gross cognitive impairment assessed by a screening test is not, possibly because cognition is impaired in more advanced stages of the disorder.

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.

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.

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.

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.