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1.
Neuroimage Clin ; 22: 101735, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30878610

RESUMO

Anticipation of potentially threatening social situations is a key process in social anxiety disorder (SAD). In other anxiety disorders, recent research of neural correlates of anticipation of temporally unpredictable threat suggests a temporally dissociable involvement of amygdala and bed nucleus of the stria terminalis (BNST) with phasic amygdala responses and sustained BNST activation. However, the temporal profile of amygdala and BNST responses during temporal unpredictability of threat has not been investigated in patients suffering from SAD. We used functional magnetic resonance imaging (fMRI) to investigate neural activation in the central nucleus of the amygdala (CeA) and the BNST during anticipation of temporally unpredictable aversive (video camera observation) relative to neutral (no camera observation) events in SAD patients compared to healthy controls (HC). For the analysis of fMRI data, we applied two regressors (phasic/sustained) within the same model to detect temporally dissociable brain responses. The aversive condition induced increased anxiety in patients compared to HC. SAD patients compared to HC showed increased phasic activation in the CeA and the BNST for anticipation of aversive relative to neutral events. SAD patients as well as HC showed sustained activity alterations in the BNST for aversive relative to neutral anticipation. No differential activity during sustained threat anticipation in SAD patients compared to HC was found. Taken together, our study reveals both CeA and BNST involvement during threat anticipation in SAD patients. The present results point towards potentially SAD-specific threat processing marked by elevated phasic but not sustained CeA and BNST responses when compared to HC.


Assuntos
Tonsila do Cerebelo/diagnóstico por imagem , Antecipação Psicológica/fisiologia , Fobia Social/diagnóstico por imagem , Estimulação Luminosa/métodos , Núcleos Septais/diagnóstico por imagem , Comportamento Social , Adulto , Tonsila do Cerebelo/metabolismo , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Fobia Social/metabolismo , Fobia Social/psicologia , Núcleos Septais/metabolismo , Fatores de Tempo , Adulto Jovem
2.
Depress Anxiety ; 36(3): 198-212, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30479005

RESUMO

BACKGROUND: We aimed to examine the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) for anxiety disorders examining overall symptom improvement, likelihood of treatment response, time course of treatment response, individual pharmacological agent, diagnostic indication dose, and tolerability. METHODS: We searched PubMed and Cochrane Central Register of Controlled Trials. We included randomized placebo-controlled clinical trials of SSRIs/SNRIs in adult patients with anxiety disorders that provided data at three or more time points. Extracted data included trial duration, weekly/biweekly anxiety scores for 12 weeks. RESULTS: Meta-analysis included 57 trials (N = 16,056). A linear mixed model analysis based on weekly outcome data suggested that for SNRI a logarithmic model offered the best fit compared to placebo (indicating the greatest incremental improvement from baseline occurred early in treatment); whereas for SSRI a linear model provided the best fit (indicating a similar improvement over the duration of the acute treatment phase). There were no significant differences in efficacy between pharmacological agents within each class or when comparing SSRIs to SNRIs. The greatest treatment benefits were observed for social anxiety disorder for both medication classes. Higher doses of SSRIs, but not SNRIs, were associated with significantly greater symptom improvement and likelihood of treatment response. For both medical classes, higher doses were associated with an increased likelihood of dropout due to side effects. CONCLUSIONS: SSRIs and SNRIs are effective in treating anxiety disorders. Higher doses of SSRIs within the therapeutic range are associated with greater treatment benefit, whereas higher doses of SNRIs are not.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Transtornos de Ansiedade/metabolismo , Humanos , Norepinefrina/metabolismo , Fobia Social/tratamento farmacológico , Fobia Social/metabolismo , Serotonina/metabolismo , Inibidores de Captação de Serotonina/farmacologia , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacologia
3.
Int J Dev Neurosci ; 71: 52-60, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30165174

RESUMO

Children with Autism Spectrum Disorder (ASD) show dysregulation of the expected Hypothalamus-Pituitary-Adrenal (HPA) axis and elevated cortisol responses to stress and response patterns, but little has been reported regarding their recovery from stress in terms of cortisol concentrations. This response was investigated in a sample of 32 young males with ASD aged between 9 and 18 years (M = 14.3 yr, SD = 2.7 yr), using a standardised experimental protocol combined with individualised stressor and non-stressor tasks. Results indicated that about half of the sample demonstrated unexpected HPA axis response patterns, and that recovery from stress cortisol concentrations were significantly associated with a single symptom of Social Phobia and Morning cortisol. These findings suggest that one of the key diagnostic criteria for ASD may be strongly influential in the HPA axis responses of boys with ASD and that training regimesto assist them to form less fearful associations with their non-ASD peers may be central to the academic and social progress of these boys.


Assuntos
Transtorno do Espectro Autista , Fobia Social/metabolismo , Recuperação de Função Fisiológica/fisiologia , Saliva/metabolismo , Adolescente , Análise de Variância , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/psicologia , Criança , Humanos , Masculino , Fobia Social/diagnóstico , Fobia Social/etiologia , Escalas de Graduação Psiquiátrica , Restrição Física/fisiologia
4.
Cogn Emot ; 32(7): 1487-1498, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-28397544

RESUMO

Individual differences in the habitual use of emotion regulation strategies may play a critical role in understanding psychological and biological stress reactivity and recovery in depression and anxiety. This study investigated the relation between the habitual use of different emotion regulation strategies and cortisol reactivity and recovery in healthy control individuals (CTL; n = 33) and in individuals diagnosed with social anxiety disorder (SAD; n = 41). The tendency to worry was associated with increased cortisol reactivity to a stressor across the full sample. Rumination was not associated with cortisol reactivity, despite its oft-reported similarities to worry. Worry and rumination, however, were associated with increased cortisol during recovery from the stressor. The only difference between CTL and SAD participants was observed for reappraisal. In the CTL but not in the SAD group, reappraisal predicted recovery, such that an increased tendency to reappraise was associated with greater cortisol recovery. These results suggest an important role of the habitual use of emotion regulation strategies in understanding biological stress reactivity and recovery.


Assuntos
Ansiedade/psicologia , Hidrocortisona/metabolismo , Fobia Social/psicologia , Ruminação Cognitiva , Estresse Fisiológico , Adulto , Estudos de Casos e Controles , Depressão/psicologia , Feminino , Humanos , Individualidade , Masculino , Fobia Social/metabolismo , Saliva/metabolismo , Adulto Jovem
5.
Brain Res ; 1662: 16-22, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28232064

RESUMO

The aim of our study was to detect white matter (WM) regions being involved in the pathophysiology of SAD. We applied diffusion tensor imaging in 22 consecutive adult patients (11 women and 11 men) with SAD and 22 age and sex-matched healthy control subjects. We examined white matter (WM) alterations between the patients with social anxiety disorder (SAD) and healthy controls by a whole-brain analysis. We found that fractional anisotropy (FA) was reduced in patients with SAD compared with controls in the temporal part of right inferior longitudinal fasciculus (ILF) and the occipito-temporal part of the right superior longitudinal fasciculus (SLF). We also identified that in these regions FA was negatively correlated with the severity of anxiety. Our results suggest that the lateral temporal and occipito-temporal WM microstructure plays a role in mediating social interactions, and a pattern of WM abnormality in the right ILF and SLF may be implicated in the pathophysiology of SAD plausibly through leading to deficits in face processing mechanisms.


Assuntos
Fobia Social/fisiopatologia , Substância Branca/fisiopatologia , Adulto , Anisotropia , Encéfalo/fisiopatologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética/métodos , Masculino , Fibras Nervosas Mielinizadas , Rede Nervosa/fisiopatologia , Fobia Social/metabolismo
6.
Brain Imaging Behav ; 11(3): 797-807, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27180247

RESUMO

Functional near-infrared (fNIR) spectroscopy is a promising new technology that has demonstrated utility in the study of normal human cognition. We utilized fNIR spectroscopy to examine the effect of social anxiety and performance on hemodynamic activity in the dorsolateral prefrontal cortex (DLPFC). Socially phobic participants and non-clinical participants with varying levels of social anxiety completed a public speaking task in front of a small virtual audience while the DLPFC was being monitored by the fNIR device. The relationship between anxiety and both blood volume (BV) and deoxygenated hemoglobin (Hb) varied significantly as a function of speech performance, such that individuals with low social anxiety who performed well showed an increase in DLPFC activation relative to those who did not perform well. This result suggests that effortful thinking and/or efficient top-down inhibitory control may have been required to complete an impromptu speech task with good performance. In contrast, good performers who were highly socially anxious showed lower DLPFC activation relative to good performers who were low in social anxiety, suggesting autopilot thinking or less-effortful thinking. In poor performers, slight increases in DLPFC activation were observed from low to highly anxious individuals, which may reflect a shift from effortless thinking to heightened self-focused attention. Heightened self-focused attention, poor inhibitory control resulting in excessive fear or anxiety, or low motivation may lower performance. These results suggest that there can be different underlying mechanisms in the brain that affect the level of speech performance in individuals with varying degrees of social anxiety. This study highlights the utility of the fNIR device in the assessment of changes in DLPFC in response to exposure to realistic phobic stimuli, and further supports the potential utility of this technology in the study of the neurophysiology of anxiety disorders.


Assuntos
Ansiedade/diagnóstico por imagem , Ansiedade/metabolismo , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho , Fala/fisiologia , Volume Sanguíneo , Circulação Cerebrovascular , Estudos de Viabilidade , Feminino , Neuroimagem Funcional , Humanos , Masculino , Testes Neuropsicológicos , Oxiemoglobinas/metabolismo , Personalidade , Fobia Social/diagnóstico por imagem , Fobia Social/metabolismo , Autoimagem , Percepção Social , Realidade Virtual , Adulto Jovem
7.
Eur Neuropsychopharmacol ; 26(11): 1775-1783, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27642077

RESUMO

Social anxiety disorder (SAD) is associated with increased fear-related neural activity in the amygdala and we recently found enhanced serotonin synthesis rate in the same region. Anxiolytic agents like selective serotonin re-uptake inhibitors (SSRIs) and neurokinin-1 receptor (NK1R) antagonists reduce amygdala activity and may attenuate serotonin formation according to animal studies. Here, we examined the effects of SSRI pharmacotherapy, NK1R antagonism, and placebo on serotonin synthesis rate in relation to neural activity, measured as regional cerebral blood flow (rCBF), and symptom improvement in SAD. Eighteen SAD patients were randomized to receive daily double-blind treatment for six weeks either with the SSRI citalopram (n=6; 40mg), the NK1R antagonist GR205171 (n=6; 5mg; 4 weeks following 2 weeks of placebo), or placebo (n=6). Serotonin synthesis rate at rest and rCBF during stressful public speaking were assessed, before and after treatment, using positron emission tomography with the tracers [11C]5-hydroxytryptophan and [15O]water respectively. The Liebowitz Social Anxiety Scale (LSAS-SR) indexed symptom severity. All groups exhibited attenuated amygdala serotonin synthesis rate after treatment, which was associated with reduced amygdala rCBF during public speaking and accompanied by symptom improvement. These results are consistent with the notion that serotonin in the amygdala exerts an anxiogenic influence and, conversely, that anxiolysis is achieved through decreased serotonin formation in the amygdala.


Assuntos
Ansiolíticos/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Fobia Social/tratamento farmacológico , Fobia Social/metabolismo , Serotonina/biossíntese , Adulto , Tonsila do Cerebelo/efeitos dos fármacos , Citalopram/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Cinética , Masculino , Antagonistas do Receptor de Neuroquinina-1/farmacologia , Fobia Social/diagnóstico por imagem , Piperidinas/uso terapêutico , Tomografia por Emissão de Pósitrons , Escalas de Graduação Psiquiátrica , Inibidores de Captação de Serotonina/uso terapêutico , Meio Social , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Tetrazóis/uso terapêutico
8.
Genes Brain Behav ; 15(8): 722-732, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27535696

RESUMO

Female-emitted pheromonal inputs possess an intrinsic rewarding value for conspecific males, promoting approach and investigation of the potential mating partner. In mice these inputs are detected mainly by the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). We investigated the role of VNO-mediated inputs in experience-dependent plasticity of reproductive responses. We applied a sex-specific conditioned odor aversion (COA) paradigm on adult, wild-type (WT) male mice and on male mice impaired in VNO-mediated signal transduction (TrpC2-/- ). We found that WT males, which underwent COA to female-soiled bedding, lost their innate preference to female odors and presented lower motivation to approach a sexually receptive female. COA also abolished the testosterone surge normally seen following exposure to female odors. Moreover, the conditioned males displayed impairments in copulatory behaviors, which lasted for several weeks. Surprisingly, these males also exhibited phobic behaviors towards receptive females, including freezing and fleeing responses. In contrast, WT males which underwent COA specifically to male pheromones showed no change in olfactory preference and only a marginally significant elevation in intermale aggression. Finally, we show that TrpC2-/- males were able to acquire aversion to female-soiled bedding and presented similar behavioral alterations following COA in their responses to female cues. Our results demonstrate that the intrinsic rewarding value of female pheromones can be overridden through associative olfactory learning, which occurs independently of VNO inputs, probably through MOE signaling.


Assuntos
Feromônios/fisiologia , Fobia Social/genética , Fobia Social/psicologia , Comportamento Sexual Animal/fisiologia , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo , Agressão/fisiologia , Animais , Ansiedade/genética , Ansiedade/metabolismo , Medo , Feminino , Masculino , Camundongos , Camundongos Knockout , Neurônios/fisiologia , Odorantes , Fobia Social/metabolismo , Recompensa , Olfato/fisiologia , Canais de Cátion TRPC/deficiência
9.
Psychoneuroendocrinology ; 73: 51-62, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27464065

RESUMO

Generalized Social Phobia (GSP) is a common anxiety disorder that produces clear social life disruptions. There is no consensus on the specific processes involved in its development, but the role of the hypothalamic-pituitary-adrenal (HPA) axis has been suggested. This study analyzed the effects of the cortisol response to the Trier Social Stress Test (TSST) on the memory retrieval of pictures with different emotional valences in 45 non-treated young students with GSP and 50 non-anxious (NA) subjects (mean=19.35years, SD=0.18). No differences were found in the cortisol response of GSP and NA subjects to the TSST and control sessions. In addition, psychosocial stress impaired memory retrieval in both the GSP and NA groups, with no differences between them. Regarding the sex factor, no effects were found in the cortisol response to the TSST. However, during the encoding session, GSP men had higher cortisol levels than GSP women and NA subjects. There was also a significant interaction between sex and stress exposure on memory retrieval. Women recognized more unpleasant and neutral pictures than men; however, under stress, the women's advantage disappeared, and the men's performance improved. Sex also interacted with social phobia on positive mood, with GSP women exposed to the TSST showing the lowest positive mood. These results suggest that GSP subjects do not present an HPA axis sensitization to psychosocial stress, and they emphasize the importance of Sex in understanding stress effects on memory.


Assuntos
Afeto/fisiologia , Hidrocortisona/metabolismo , Rememoração Mental/fisiologia , Fobia Social/metabolismo , Fobia Social/fisiopatologia , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Reconhecimento Visual de Modelos/fisiologia , Saliva/química , Fatores Sexuais , Adulto Jovem
10.
J Psychopharmacol ; 30(10): 1028-35, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27189957

RESUMO

It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[ß -(11)C]tryptophan, [(11)C]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [(11)C]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.


Assuntos
Transtornos de Ansiedade/genética , Transtornos de Ansiedade/metabolismo , Fobia Social/genética , Fobia Social/metabolismo , Polimorfismo Genético/genética , Serotonina/metabolismo , Triptofano Hidroxilase/genética , Adulto , Alelos , Tonsila do Cerebelo/metabolismo , Gânglios da Base/metabolismo , Feminino , Genótipo , Giro do Cíngulo/metabolismo , Hipocampo/metabolismo , Humanos , Masculino , Adulto Jovem
11.
Psychoneuroendocrinology ; 69: 35-40, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27017431

RESUMO

Arch et al. (2014) demonstrated that brief self-compassion meditation training (SCT) dampened sympathetic (salivary alpha-amylase) and subjective anxiety responses to the Trier Social Stress Test (TSST), relative to attention and no-instruction control conditions. The present study examined baseline predictors and moderators of these SCT intervention effects. Baseline characteristics included two stress vulnerability traits (social anxiety and rumination) and two potential resiliency traits (non-attachment and self-compassion). We investigated how these traits moderated the effects of SCT on response to the TSST, relative to the control conditions. We also tested how these individual differences predicted TSST responses across conditions in order to uncover characteristics that confer increased vulnerability and resiliency to social stressors. Trait non-attachment, rumination (for sympathetic TSST response only), and social anxiety (for subjective TSST response only) interacted with training condition to moderate TSST responses such that following SCT, lower attachment and lower social anxiety predicted lower TSST stress responses, relative to those scoring higher on these traits. In contrast, trait self-compassion neither moderated nor predicted responses to the TSST. Thus, although SCT had robust effects on buffering stress across individuals with varying levels of trait self-compassion, other psychological traits enhanced or dampened the effect of SCT on TSST responses. These findings support the importance of examining the role of relevant baseline psychological traits to predict sympathetic and subjective responses to social evaluative threat, particularly in the context of resiliency training.


Assuntos
Meditação/psicologia , Estresse Psicológico/metabolismo , Estresse Psicológico/prevenção & controle , Adulto , Ansiedade/psicologia , Empatia/genética , Empatia/fisiologia , Feminino , Previsões , Humanos , Hidrocortisona , Fobia Social/metabolismo , Fobia Social/psicologia , Saliva , alfa-Amilases Salivares/análise , Estresse Psicológico/psicologia
12.
J Neuropsychiatry Clin Neurosci ; 28(2): 138-42, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26569150

RESUMO

In the present study, 24 nonmedicated patients with social anxiety disorder (SAD) were compared with 24 healthy control subjects to assess metabolite levels in the anterior cingulate, insula, caudate, and putamen using proton magnetic resonance spectroscopy. The ratio of N-acetylaspartate (NAA)/creatine (Cr) was significantly higher in patients with SAD than in healthy control subjects in the anterior cingulate and insula. NAA/Cr ratios in the insula correlated positively with the Liebowitz Social Anxiety Scale total scores in patients with SAD. Our results support the significance and biochemical involvement of the anterior cingulate and insula in the pathophysiology of SAD.


Assuntos
Encéfalo/diagnóstico por imagem , Fobia Social/diagnóstico por imagem , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/metabolismo , Colina/metabolismo , Creatina/metabolismo , Feminino , Humanos , Masculino , Fobia Social/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Adulto Jovem
13.
Psychoneuroendocrinology ; 64: 31-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26600008

RESUMO

Early timing of adrenarche, associated with relatively high levels of dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) in children, has been linked with mental health problems, particularly anxiety. However, little is known about possible neurobiological mechanisms underlying this association. The pituitary gland is a key component of the hypothalamic-pituitary-adrenal (HPA) axis, the activation of which triggers the onset of adrenarche. The purpose of this study was to examine the extent to which pituitary gland volume mediated the relationship between levels of DHEA/DHEA-S relative to age (i.e., adrenarcheal timing) and symptoms of anxiety in 95 children (50 female, M age 9.50 years, SD 0.34 years). Relatively high DHEA and DHEA-S (DHEA/S) levels were found to be associated with larger pituitary gland volumes. There was no significant direct effect of relative DHEA/S levels on overall symptoms of anxiety. However, results supported an indirect link between relatively high DHEA/S levels and symptoms of social anxiety, mediated by pituitary gland volume. No sex differences were observed for any relationship. Our findings suggest that neurobiological mechanisms may be partly responsible for the link between relatively early adrenarche and anxiety symptoms in children. One possible mechanism for this finding is that an enlarged pituitary gland in children experiencing relatively advanced adrenarche might be associated with hyper-activity/reactivity of the HPA axis. Further research is needed to understand the role of stress in the link between adrenarcheal timing and HPA-axis function, especially in relation to the development of anxiety symptoms in children and adolescents.


Assuntos
Adrenarca/metabolismo , Adrenarca/psicologia , Ansiedade/metabolismo , Desidroepiandrosterona/metabolismo , Fobia Social/metabolismo , Hipófise/anatomia & histologia , Ansiedade/diagnóstico , Índice de Massa Corporal , Criança , Feminino , Cabelo/metabolismo , Humanos , Hidrocortisona/metabolismo , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão , Fobia Social/diagnóstico , Hipófise/metabolismo , Saliva/metabolismo , Caracteres Sexuais , Testosterona/metabolismo
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