Andressa Bortoluzzi - Academia.edu (original) (raw)

Papers by Andressa Bortoluzzi

Research paper thumbnail of Anxiety disorders in childhood are associated with youth IL-6 levels: A mediation study including metabolic stress and childhood traumatic events

Journal of Psychiatric Research

Research paper thumbnail of DNA methylation in adolescents with anxiety disorder: a longitudinal study

Scientific reports, Jan 14, 2018

Anxiety disorders (AD) typically manifest in children and adolescents and might persist into adul... more Anxiety disorders (AD) typically manifest in children and adolescents and might persist into adulthood. However, there are still few data concerning epigenetic mechanisms associated with onset, persistence or remission of AD over time. We investigated a cohort of adolescents and young adults at baseline (age; 13.19 ± 2.38) and after 5 years and classified them according to the AD diagnosis and their longitudinal trajectories into 4 groups: (1) Typically Developing Comparisons (TDC; control group, n = 14); (2) Incident (AD in the second evaluation only, n = 11); (3) Persistent (AD in both evaluations, n = 14) and (4) Remittent (AD in the first evaluation only, n = 8). DNA methylation was evaluated with the Infinium HumanMethylation450 BeadChip from saliva samples collected at both evaluations. Gene set enrichment analysis was applied to consider biological pathways. We found decreased DNA methylation in TDC group while the chronic cases of AD presented hypermethylation in central ner...

Research paper thumbnail of Decreased comfort food intake and allostatic load in adolescents carrying the A3669G variant of the glucocorticoid receptor gene

Appetite, Sep 8, 2017

The A3669G single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene NR3C1 is... more The A3669G single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene NR3C1 is associated with altered tissue sensitivity to glucocorticoids (GCs). GCs modulate the food reward circuitry and are implicated in increased intake of palatable foods, which can lead to the metabolic syndrome and obesity. We hypothesized that presence of the G variant of the A3669G SNP would affect preferences for palatable foods and alter metabolic, behavioural, and neural outcomes. One hundred thirty-one adolescents were genotyped for the A3669G polymorphism, underwent anthropometric assessment and nutritional evaluations, and completed behavioural measures. A subsample of 74 subjects was followed for 5 years and performed a brain functional magnetic resonance imaging (fMRI) paradigm to verify brain activity in response to food cues. Sugar and total energy consumption were lower in A3669G G allele variant carriers. On follow-up, this group also had reduced serum insulin concentrations,...

Research paper thumbnail of Cytokine Levels in Panic Disorder

Psychosomatic Medicine, 2016

Research paper thumbnail of A estimulação elétrica da musculatura periférica melhora a concentração de glut-4 em um modelo experimental de infarto agudo do miocárdio

Research paper thumbnail of Eletroestimulação aumenta a concentração de GLUT-4 em ratos submetidos a infarto do miocárdio

Brazilian Journal of Physical Therapy, 2008

Research paper thumbnail of Efeitos da eletroestimulação sobre diferentes parâmetros histofisiológicos na musculatura de ratos com infarto do miocárdio

Dall'ago (orient.) (PUCRS). Introdução: A insuficiência cardíaca (IC), após infarto do miocárdio,... more Dall'ago (orient.) (PUCRS). Introdução: A insuficiência cardíaca (IC), após infarto do miocárdio, caracteriza-se por diminuição da capilarização periférica e da massa muscular esquelética. Uma alternativa para atenuar os efeitos da IC é a estimulação elétrica (EE). Neste trabalho avaliamos os efeitos da EE sobre a área da secção transversa do músculo (AM), área da secção transversa da fibra (AF), a densidade de fibras (DF) e a densidade de vasos (DV). Metodologia: 40 ratos Wistar foram divididos em 4 grupos: 1-Controle (C); 2-Infarto do miocárdio (IM); 3-Controle submetido a EE (C+EE); 4-Infarto do miocárdio submetido a EE (IM+EE). Nos grupos IM o infarto foi realizado pela ligação da artéria coronária esquerda. Três semanas após o infarto, foram implantados eletrodos na pata esquerda de todos os animais. Para EE, foi utilizado um protocolo de (30Hz, 15 s de contração e 30 s de repouso, 30 min/20 dias). Após a EE, os animais foram sacrificados e os músculos tibial anterior esquerdo (TAE) e direito (TAD) foram processados histologicamente com HE. Os cortes foram analisados no software IPP 6.1. Para a análise estatística foi realizado um teste t pareado comparando TAE e TAD considerando a pata direita como controle (100%). Resultados: A AM foi menor na pata esquerda quando comparada à direita nos grupos C e IM (C:-34% P = 0, 006; IM:-20%; P = 0, 045). Da mesma forma, a AF mostrou-se reduzida na pata esquerda comparada com a direita (C:-29% P = 0, 01; IM:-18% P = 0, 04). Nos grupos submetidos à EE, a atrofia do músculo e da fibra não foi observada. A DF foi significativamente maior no TAE nos grupos C e IM (S P = 0, 02; IM P = 0, 007), esta diferença não foi observada nos grupos EE. A EE foi capaz de normalizar a DV no grupo IM+EE. Conclusão: Nossos resultados mostram que a EE reverte a atrofia muscular e aumenta a DV no tibial anterior, neste modelo de IC. (Fapergs).

Research paper thumbnail of Estudo de associação entre os transtornos de ansiedade e seus endofenótipos e o polimorfismo da região promotora do gene transportador de serotonina (5-HTTLPR) em adolescentes e suas famílias

Research paper thumbnail of Eletroestimulação aumenta a densidade vascular de ratos submetidos a infarto do miocárdio

Brazilian Journal of Physical Therapy, 2008

Research paper thumbnail of What can HPA axis-linked genes tell us about anxiety disorders in adolescents?

Trends in psychiatry and psychotherapy, 2015

Anxiety disorders (AD) share features of both anxiety and fear linked to stress response. The hyp... more Anxiety disorders (AD) share features of both anxiety and fear linked to stress response. The hypothalamic-pituitary-adrenal (HPA) axis is considered the core biological pathway of the stress system and it is known that an inappropriate response to environmental stimuli may be related to individual genetic vulnerability in HPA-linked genes. Despite the biological plausibility of a relationship between the HPA axis and AD, few studies have investigated associations between genetic polymorphisms linked to the HPA axis and this complex disorder. To investigate whether AD are associated with genetic polymorphisms in HPA-linked genes in adolescents. Our study consisted of a cross-sectional evaluation of a community sample comprising a total of 228 adolescents (131 cases of AD). We extracted DNA from saliva and genotyped polymorphisms in HPA-linked genes (FKBP5: rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916; NR3C1: rs6198; CRHR1: rs878886; and SERPINA6: rs746530) with real time...

Research paper thumbnail of Estudo de associação entre transtornos de ansiedade e seus endofenótipos e o polimorfismo da região promotora do gene do transportador de serotonina (5-HTTLPR) em adolescentes

Introduction: Anxiety disorders (AD) are prevalent in childhood and adolescence and results in si... more Introduction: Anxiety disorders (AD) are prevalent in childhood and adolescence and results in significant impairments. It usually persists into adulthood. Anxiety traits such as behavioral inhibition and harm avoidance may also be considered. The serotonin neurotransmitter plays an important role in the development and the plasticity of the brain. The serotonin transporter gene (5-HTT) is considered a strong candidate and the Serotonin Transporter Gene-linked Polymorphic Region (5-HTTLPR) functional and, therefore, relevant in studies concerning the association between genetic and psychiatric disorders. Objectives: To investigate the association between 5-HTTLPR (biallelic and triallelic classification) and AD and anxiety related phenotypes (behavioral inhibition and harm avoidance) in a sample of adolescents and their families. Methodology: A total of 510 subjects participated in this study. Participants were 225 adolescents (129 anxiety cases and 96 community controls) and their biological families (194 mothers, 66 fathers and 22 siblings). We assessed psychiatric diagnosis throughout a clinical interview and using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version Diagnostic Interview (K-SADS-PL). The Temperament and Character Inventory (TCI) and an adaptation of the Resnick Behavioral Inhibition Scale were used in order to measure harm avoidance and behavioral inhibition, respectively. The molecular analysis resulted in the extraction of DNA from saliva sample of the adolescents and their families, followed by DNA amplification by PCR and enzymatic digestion with the MspI. The genotypes were grouped by level of expression: low

Research paper thumbnail of Mineralocorticoid receptor genotype moderates the association between physical neglect and serum BDNF

Journal of Psychiatric Research, 2014

The objective of this study is to investigate if a polymorphism in the NR3C2 gene moderates the a... more The objective of this study is to investigate if a polymorphism in the NR3C2 gene moderates the association between childhood trauma on serum levels of brain derived neurothrophic factor (sBDNF). sBDNF was used here as a general marker of alteration in brain function. This is a community cross sectional study comprising 90 adolescents (54 with anxiety disorders). DNA was extracted from saliva in order to genotype the MR-2G/C (rs2070951) polymorphism using real time PCR. Blood was collected for sBDNF Elisa immunoassay. The Childhood Trauma Questionnaire (CTQ) was used to evaluate childhood abuse and neglect. Main effects and gene environment interactions were tested using linear regression models. Anxiety disorders were not associated with the MR-2G/C polymorphism or with sBDNF levels, but the number of C alleles of the MR-2G/C polymorphism was significantly associated with higher sBDNF levels (b ¼ 8.008; p-value ¼ 0.001). Subjects with intermediate and high exposure to physical neglect showed higher sBDNF levels if compared to subjects non-exposed (b ¼ 11.955; p ¼ 0.004 and b ¼ 16.186; p ¼ 0.009, respectively). In addition, we detected a significant physical neglect by MR-2G/C C allele interaction on sBDNF levels (p ¼ 0.005), meaning that intermediate and high exposure to childhood neglect were only associated with increased sBDNF levels in subjects with the CC genotype, but not in subjects with other genotypes. Our findings suggest that genetic variants in NR3C2 gene may partially explain plastic brain vulnerability to traumatic events. Further studies are needed to investigate the moderating effects of NR3C2 gene in more specific markers of alteration in brain function.

Research paper thumbnail of Anxiety disorders and anxiety-related traits and serotonin transporter gene-linked polymorphic region (5-HTTLPR) in adolescents

Psychiatric Genetics, 2014

The role of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in anxiety disord... more The role of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in anxiety disorder and anxiety-related traits is controversial. Besides this study, few studies have evaluated the triallelic genotype in adolescents. The aim of this study was to investigate whether anxiety disorders and anxiety-related traits are associated with 5-HTTLPR (biallelic and triallelic) in adolescents, integrating both case-control-based and family-based designs in a community sample. This is a cross-sectional community study of 504 individuals and their families: 225 adolescents (129 adolescents with anxiety disorder and 96 controls) and their biological families. We assessed psychiatric diagnosis using the Kiddie Schedule for Affective Disorders and Schizophrenia. The Temperament and Character Inventory and the Resnick Behavioral Inhibition Scale were used to evaluate harm avoidance and behavioral inhibition. DNA was extracted from saliva and genotyped, including biallelic and triallelic 5-HTTLPR classification, by PCR-RFLP followed by agarose gel electrophoresis. We were not able to find any associations between 5-HTTLPR and anxiety-related phenotypes in both case-control and trio analyses. Further investigation and meta-analytic studies are needed to better clarify the inconsistent results with regard to the association between 5-HTTLPR and anxiety-related phenotypes in adolescents.

Research paper thumbnail of Evidence of association between Val66Met polymorphism at BDNF gene and anxiety disorders in a community sample of children and adolescents

Neuroscience Letters, 2011

Research paper thumbnail of Is puberty a trigger for 5HTTLPR polymorphism association with depressive symptoms?

Journal of Psychiatric Research, 2012

Adolescence is not only a critical period for depression onset, but also the period that gender b... more Adolescence is not only a critical period for depression onset, but also the period that gender became a risk factor for depression susceptibility (Hankin et al., 1998). Puberty is one of the most important landmarks of adolescence with clear consequences in emotion regulation, thinking and behavior. During puberty, steroid hormones trigger various brain circuits remodeling responses for functional and structural changes (Sisk and Zehr, 2005). The serotonin transporter gene promoter polymorphism (5HTTLPR) has been implicated as a moderator of the effects of psychosocial stressors in depression in several studies (Karg et al., 2011). Furthermore, there is clinical (Bridge et al., 2007) and animal (Ansorge et al., 2004) evidence for age-related developmental moderation of serotonergic pathways. The aim of this study was to test whether the 5HTTLPR polymorphism would be associated with depressive symptoms in adolescents in different stages of development. We hypothesized that low functional variants would be associated with higher depressive symptoms only in post-pubertal adolescents. This sample was primarily designed in order to investigate anxiety disorders in the community and involves an oversampling of anxious adolescents. Detailed description of the sample selection can be found elsewhere (Salum et al., 2010). The current study addresses a sub-sample of 121 adolescents who accepted and have completed the whole evaluation protocol, including genetic evaluation. This study was approved by the ethical committee of Hospital de Clínicas de Porto Alegre. We collected separate informed consent from primary caretakers and assent from adolescents. Psychiatric diagnoses were assessed throughout clinical and structured interview using the K-SADS-PL based on the DSM-IV criteria (Kaufman et al., 1997). We measured depressive symptoms with the Childhood Depressive Inventory (CDI) (Golfeto et al., 2002). Pubertal stage was evaluated with a self-report instrument (Morris and Udry, 1980) consisting of schematic drawings based on Tanner's Sexual Maturity Scale (Tanner, 1962). The ratings Contents lists available at SciVerse ScienceDirect

Research paper thumbnail of The multidimensional evaluation and treatment of anxiety in children and adolescents: rationale, design, methods and preliminary findings= Avaliação multidimensional e tratamento da ansiedade em crianças e adolescentes

Objective: This study aims to describe the design, methods and sample characteristics of the Mult... more Objective: This study aims to describe the design, methods and sample characteristics of the Multidimensional Evaluation and Treatment of Anxiety in Children and Adolescents-the PROTAIA Project. Method: Students between 10 and 17 years old from all six schools belonging to the catchment area of the Primary Care Unit of Hospital de Clínicas de Porto Alegre were included in the project. It comprises five phases: (1) a community screening phase; (2) a psychiatric diagnostic phase; (3) a multidimensional assessment phase evaluating environmental, neuropsychological, nutritional, and biological factors; (4) a treatment phase, and (5) a translational phase. Results: A total of 2,457 subjects from the community were screened for anxiety disorders. From those who attended the diagnostic interview, we identified 138 individuals with at least one anxiety disorder (apart from specific phobia) and 102 individuals without any anxiety disorder. Among the anxiety cases, generalized anxiety disorder (n = 95; 68.8%), social anxiety disorder (n = 57; 41.3%) and separation anxiety disorder (n = 49; 35.5%) were the most frequent disorders. Conclusion: The PROTAIA Project is a promising research project that can contribute to the knowledge of the relationship between anxiety disorders and anxiety-related phenotypes with several genetic and environmental risk factors.

Research paper thumbnail of Neuromuscular electrical stimulation improves GLUT-4 and morphological characteristics of skeletal muscle in rats with heart failure

Acta Physiologica, 2011

Changes in skeletal muscle morphology and metabolism are associated with limited functional capac... more Changes in skeletal muscle morphology and metabolism are associated with limited functional capacity in heart failure, which can be attenuated by neuromuscular electrical stimulation (ES). The purpose of the present study was to analyse the effects of ES upon GLUT-4 protein content, fibre structure and vessel density of the skeletal muscle in a rat model of HF subsequent to myocardial infarction. Forty-four male Wistar rats were assigned to one of four groups: sham (S), sham submitted to ES (S+ES), heart failure (HF) and heart failure submitted to ES (HF+ES). The rats in the ES groups were submitted to ES of the left leg during 20 days (2.5 kHz, once a day, 30 min, duty cycle 50%- 15 s contraction/15 s rest). After this period, the left tibialis anterior muscle was collected from all the rats for analysis. HF+ES rats showed lower values of lung congestion when compared with HF rats (P = 0.0001). Although muscle weight was lower in HF rats than in the S group, thus indicating hypotro...

Research paper thumbnail of Anxiety disorders in childhood are associated with youth IL-6 levels: A mediation study including metabolic stress and childhood traumatic events

Journal of Psychiatric Research

Research paper thumbnail of DNA methylation in adolescents with anxiety disorder: a longitudinal study

Scientific reports, Jan 14, 2018

Anxiety disorders (AD) typically manifest in children and adolescents and might persist into adul... more Anxiety disorders (AD) typically manifest in children and adolescents and might persist into adulthood. However, there are still few data concerning epigenetic mechanisms associated with onset, persistence or remission of AD over time. We investigated a cohort of adolescents and young adults at baseline (age; 13.19 ± 2.38) and after 5 years and classified them according to the AD diagnosis and their longitudinal trajectories into 4 groups: (1) Typically Developing Comparisons (TDC; control group, n = 14); (2) Incident (AD in the second evaluation only, n = 11); (3) Persistent (AD in both evaluations, n = 14) and (4) Remittent (AD in the first evaluation only, n = 8). DNA methylation was evaluated with the Infinium HumanMethylation450 BeadChip from saliva samples collected at both evaluations. Gene set enrichment analysis was applied to consider biological pathways. We found decreased DNA methylation in TDC group while the chronic cases of AD presented hypermethylation in central ner...

Research paper thumbnail of Decreased comfort food intake and allostatic load in adolescents carrying the A3669G variant of the glucocorticoid receptor gene

Appetite, Sep 8, 2017

The A3669G single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene NR3C1 is... more The A3669G single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene NR3C1 is associated with altered tissue sensitivity to glucocorticoids (GCs). GCs modulate the food reward circuitry and are implicated in increased intake of palatable foods, which can lead to the metabolic syndrome and obesity. We hypothesized that presence of the G variant of the A3669G SNP would affect preferences for palatable foods and alter metabolic, behavioural, and neural outcomes. One hundred thirty-one adolescents were genotyped for the A3669G polymorphism, underwent anthropometric assessment and nutritional evaluations, and completed behavioural measures. A subsample of 74 subjects was followed for 5 years and performed a brain functional magnetic resonance imaging (fMRI) paradigm to verify brain activity in response to food cues. Sugar and total energy consumption were lower in A3669G G allele variant carriers. On follow-up, this group also had reduced serum insulin concentrations,...

Research paper thumbnail of Cytokine Levels in Panic Disorder

Psychosomatic Medicine, 2016

Research paper thumbnail of A estimulação elétrica da musculatura periférica melhora a concentração de glut-4 em um modelo experimental de infarto agudo do miocárdio

Research paper thumbnail of Eletroestimulação aumenta a concentração de GLUT-4 em ratos submetidos a infarto do miocárdio

Brazilian Journal of Physical Therapy, 2008

Research paper thumbnail of Efeitos da eletroestimulação sobre diferentes parâmetros histofisiológicos na musculatura de ratos com infarto do miocárdio

Dall'ago (orient.) (PUCRS). Introdução: A insuficiência cardíaca (IC), após infarto do miocárdio,... more Dall'ago (orient.) (PUCRS). Introdução: A insuficiência cardíaca (IC), após infarto do miocárdio, caracteriza-se por diminuição da capilarização periférica e da massa muscular esquelética. Uma alternativa para atenuar os efeitos da IC é a estimulação elétrica (EE). Neste trabalho avaliamos os efeitos da EE sobre a área da secção transversa do músculo (AM), área da secção transversa da fibra (AF), a densidade de fibras (DF) e a densidade de vasos (DV). Metodologia: 40 ratos Wistar foram divididos em 4 grupos: 1-Controle (C); 2-Infarto do miocárdio (IM); 3-Controle submetido a EE (C+EE); 4-Infarto do miocárdio submetido a EE (IM+EE). Nos grupos IM o infarto foi realizado pela ligação da artéria coronária esquerda. Três semanas após o infarto, foram implantados eletrodos na pata esquerda de todos os animais. Para EE, foi utilizado um protocolo de (30Hz, 15 s de contração e 30 s de repouso, 30 min/20 dias). Após a EE, os animais foram sacrificados e os músculos tibial anterior esquerdo (TAE) e direito (TAD) foram processados histologicamente com HE. Os cortes foram analisados no software IPP 6.1. Para a análise estatística foi realizado um teste t pareado comparando TAE e TAD considerando a pata direita como controle (100%). Resultados: A AM foi menor na pata esquerda quando comparada à direita nos grupos C e IM (C:-34% P = 0, 006; IM:-20%; P = 0, 045). Da mesma forma, a AF mostrou-se reduzida na pata esquerda comparada com a direita (C:-29% P = 0, 01; IM:-18% P = 0, 04). Nos grupos submetidos à EE, a atrofia do músculo e da fibra não foi observada. A DF foi significativamente maior no TAE nos grupos C e IM (S P = 0, 02; IM P = 0, 007), esta diferença não foi observada nos grupos EE. A EE foi capaz de normalizar a DV no grupo IM+EE. Conclusão: Nossos resultados mostram que a EE reverte a atrofia muscular e aumenta a DV no tibial anterior, neste modelo de IC. (Fapergs).

Research paper thumbnail of Estudo de associação entre os transtornos de ansiedade e seus endofenótipos e o polimorfismo da região promotora do gene transportador de serotonina (5-HTTLPR) em adolescentes e suas famílias

Research paper thumbnail of Eletroestimulação aumenta a densidade vascular de ratos submetidos a infarto do miocárdio

Brazilian Journal of Physical Therapy, 2008

Research paper thumbnail of What can HPA axis-linked genes tell us about anxiety disorders in adolescents?

Trends in psychiatry and psychotherapy, 2015

Anxiety disorders (AD) share features of both anxiety and fear linked to stress response. The hyp... more Anxiety disorders (AD) share features of both anxiety and fear linked to stress response. The hypothalamic-pituitary-adrenal (HPA) axis is considered the core biological pathway of the stress system and it is known that an inappropriate response to environmental stimuli may be related to individual genetic vulnerability in HPA-linked genes. Despite the biological plausibility of a relationship between the HPA axis and AD, few studies have investigated associations between genetic polymorphisms linked to the HPA axis and this complex disorder. To investigate whether AD are associated with genetic polymorphisms in HPA-linked genes in adolescents. Our study consisted of a cross-sectional evaluation of a community sample comprising a total of 228 adolescents (131 cases of AD). We extracted DNA from saliva and genotyped polymorphisms in HPA-linked genes (FKBP5: rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916; NR3C1: rs6198; CRHR1: rs878886; and SERPINA6: rs746530) with real time...

Research paper thumbnail of Estudo de associação entre transtornos de ansiedade e seus endofenótipos e o polimorfismo da região promotora do gene do transportador de serotonina (5-HTTLPR) em adolescentes

Introduction: Anxiety disorders (AD) are prevalent in childhood and adolescence and results in si... more Introduction: Anxiety disorders (AD) are prevalent in childhood and adolescence and results in significant impairments. It usually persists into adulthood. Anxiety traits such as behavioral inhibition and harm avoidance may also be considered. The serotonin neurotransmitter plays an important role in the development and the plasticity of the brain. The serotonin transporter gene (5-HTT) is considered a strong candidate and the Serotonin Transporter Gene-linked Polymorphic Region (5-HTTLPR) functional and, therefore, relevant in studies concerning the association between genetic and psychiatric disorders. Objectives: To investigate the association between 5-HTTLPR (biallelic and triallelic classification) and AD and anxiety related phenotypes (behavioral inhibition and harm avoidance) in a sample of adolescents and their families. Methodology: A total of 510 subjects participated in this study. Participants were 225 adolescents (129 anxiety cases and 96 community controls) and their biological families (194 mothers, 66 fathers and 22 siblings). We assessed psychiatric diagnosis throughout a clinical interview and using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version Diagnostic Interview (K-SADS-PL). The Temperament and Character Inventory (TCI) and an adaptation of the Resnick Behavioral Inhibition Scale were used in order to measure harm avoidance and behavioral inhibition, respectively. The molecular analysis resulted in the extraction of DNA from saliva sample of the adolescents and their families, followed by DNA amplification by PCR and enzymatic digestion with the MspI. The genotypes were grouped by level of expression: low

Research paper thumbnail of Mineralocorticoid receptor genotype moderates the association between physical neglect and serum BDNF

Journal of Psychiatric Research, 2014

The objective of this study is to investigate if a polymorphism in the NR3C2 gene moderates the a... more The objective of this study is to investigate if a polymorphism in the NR3C2 gene moderates the association between childhood trauma on serum levels of brain derived neurothrophic factor (sBDNF). sBDNF was used here as a general marker of alteration in brain function. This is a community cross sectional study comprising 90 adolescents (54 with anxiety disorders). DNA was extracted from saliva in order to genotype the MR-2G/C (rs2070951) polymorphism using real time PCR. Blood was collected for sBDNF Elisa immunoassay. The Childhood Trauma Questionnaire (CTQ) was used to evaluate childhood abuse and neglect. Main effects and gene environment interactions were tested using linear regression models. Anxiety disorders were not associated with the MR-2G/C polymorphism or with sBDNF levels, but the number of C alleles of the MR-2G/C polymorphism was significantly associated with higher sBDNF levels (b ¼ 8.008; p-value ¼ 0.001). Subjects with intermediate and high exposure to physical neglect showed higher sBDNF levels if compared to subjects non-exposed (b ¼ 11.955; p ¼ 0.004 and b ¼ 16.186; p ¼ 0.009, respectively). In addition, we detected a significant physical neglect by MR-2G/C C allele interaction on sBDNF levels (p ¼ 0.005), meaning that intermediate and high exposure to childhood neglect were only associated with increased sBDNF levels in subjects with the CC genotype, but not in subjects with other genotypes. Our findings suggest that genetic variants in NR3C2 gene may partially explain plastic brain vulnerability to traumatic events. Further studies are needed to investigate the moderating effects of NR3C2 gene in more specific markers of alteration in brain function.

Research paper thumbnail of Anxiety disorders and anxiety-related traits and serotonin transporter gene-linked polymorphic region (5-HTTLPR) in adolescents

Psychiatric Genetics, 2014

The role of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in anxiety disord... more The role of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in anxiety disorder and anxiety-related traits is controversial. Besides this study, few studies have evaluated the triallelic genotype in adolescents. The aim of this study was to investigate whether anxiety disorders and anxiety-related traits are associated with 5-HTTLPR (biallelic and triallelic) in adolescents, integrating both case-control-based and family-based designs in a community sample. This is a cross-sectional community study of 504 individuals and their families: 225 adolescents (129 adolescents with anxiety disorder and 96 controls) and their biological families. We assessed psychiatric diagnosis using the Kiddie Schedule for Affective Disorders and Schizophrenia. The Temperament and Character Inventory and the Resnick Behavioral Inhibition Scale were used to evaluate harm avoidance and behavioral inhibition. DNA was extracted from saliva and genotyped, including biallelic and triallelic 5-HTTLPR classification, by PCR-RFLP followed by agarose gel electrophoresis. We were not able to find any associations between 5-HTTLPR and anxiety-related phenotypes in both case-control and trio analyses. Further investigation and meta-analytic studies are needed to better clarify the inconsistent results with regard to the association between 5-HTTLPR and anxiety-related phenotypes in adolescents.

Research paper thumbnail of Evidence of association between Val66Met polymorphism at BDNF gene and anxiety disorders in a community sample of children and adolescents

Neuroscience Letters, 2011

Research paper thumbnail of Is puberty a trigger for 5HTTLPR polymorphism association with depressive symptoms?

Journal of Psychiatric Research, 2012

Adolescence is not only a critical period for depression onset, but also the period that gender b... more Adolescence is not only a critical period for depression onset, but also the period that gender became a risk factor for depression susceptibility (Hankin et al., 1998). Puberty is one of the most important landmarks of adolescence with clear consequences in emotion regulation, thinking and behavior. During puberty, steroid hormones trigger various brain circuits remodeling responses for functional and structural changes (Sisk and Zehr, 2005). The serotonin transporter gene promoter polymorphism (5HTTLPR) has been implicated as a moderator of the effects of psychosocial stressors in depression in several studies (Karg et al., 2011). Furthermore, there is clinical (Bridge et al., 2007) and animal (Ansorge et al., 2004) evidence for age-related developmental moderation of serotonergic pathways. The aim of this study was to test whether the 5HTTLPR polymorphism would be associated with depressive symptoms in adolescents in different stages of development. We hypothesized that low functional variants would be associated with higher depressive symptoms only in post-pubertal adolescents. This sample was primarily designed in order to investigate anxiety disorders in the community and involves an oversampling of anxious adolescents. Detailed description of the sample selection can be found elsewhere (Salum et al., 2010). The current study addresses a sub-sample of 121 adolescents who accepted and have completed the whole evaluation protocol, including genetic evaluation. This study was approved by the ethical committee of Hospital de Clínicas de Porto Alegre. We collected separate informed consent from primary caretakers and assent from adolescents. Psychiatric diagnoses were assessed throughout clinical and structured interview using the K-SADS-PL based on the DSM-IV criteria (Kaufman et al., 1997). We measured depressive symptoms with the Childhood Depressive Inventory (CDI) (Golfeto et al., 2002). Pubertal stage was evaluated with a self-report instrument (Morris and Udry, 1980) consisting of schematic drawings based on Tanner's Sexual Maturity Scale (Tanner, 1962). The ratings Contents lists available at SciVerse ScienceDirect

Research paper thumbnail of The multidimensional evaluation and treatment of anxiety in children and adolescents: rationale, design, methods and preliminary findings= Avaliação multidimensional e tratamento da ansiedade em crianças e adolescentes

Objective: This study aims to describe the design, methods and sample characteristics of the Mult... more Objective: This study aims to describe the design, methods and sample characteristics of the Multidimensional Evaluation and Treatment of Anxiety in Children and Adolescents-the PROTAIA Project. Method: Students between 10 and 17 years old from all six schools belonging to the catchment area of the Primary Care Unit of Hospital de Clínicas de Porto Alegre were included in the project. It comprises five phases: (1) a community screening phase; (2) a psychiatric diagnostic phase; (3) a multidimensional assessment phase evaluating environmental, neuropsychological, nutritional, and biological factors; (4) a treatment phase, and (5) a translational phase. Results: A total of 2,457 subjects from the community were screened for anxiety disorders. From those who attended the diagnostic interview, we identified 138 individuals with at least one anxiety disorder (apart from specific phobia) and 102 individuals without any anxiety disorder. Among the anxiety cases, generalized anxiety disorder (n = 95; 68.8%), social anxiety disorder (n = 57; 41.3%) and separation anxiety disorder (n = 49; 35.5%) were the most frequent disorders. Conclusion: The PROTAIA Project is a promising research project that can contribute to the knowledge of the relationship between anxiety disorders and anxiety-related phenotypes with several genetic and environmental risk factors.

Research paper thumbnail of Neuromuscular electrical stimulation improves GLUT-4 and morphological characteristics of skeletal muscle in rats with heart failure

Acta Physiologica, 2011

Changes in skeletal muscle morphology and metabolism are associated with limited functional capac... more Changes in skeletal muscle morphology and metabolism are associated with limited functional capacity in heart failure, which can be attenuated by neuromuscular electrical stimulation (ES). The purpose of the present study was to analyse the effects of ES upon GLUT-4 protein content, fibre structure and vessel density of the skeletal muscle in a rat model of HF subsequent to myocardial infarction. Forty-four male Wistar rats were assigned to one of four groups: sham (S), sham submitted to ES (S+ES), heart failure (HF) and heart failure submitted to ES (HF+ES). The rats in the ES groups were submitted to ES of the left leg during 20 days (2.5 kHz, once a day, 30 min, duty cycle 50%- 15 s contraction/15 s rest). After this period, the left tibialis anterior muscle was collected from all the rats for analysis. HF+ES rats showed lower values of lung congestion when compared with HF rats (P = 0.0001). Although muscle weight was lower in HF rats than in the S group, thus indicating hypotro...