Serotonergic neurons in the median raphe nucleus regulate inhibitory avoidance but not escape behavior in the rat elevated T-maze test of anxiety

Rationale: A wealth of evidence supports the involvement of the serotonergic neurons of the median raphe nucleus (MRN) in anxiety. However, it is presently unclear whether serotonergic pathways arising from this nucleus play distinguishing regulatory roles in defensive behaviors that have been associated with specific subtypes of anxiety disorders. Objectives: To evaluate the role of the MRN serotonergic neurons in the regulation of two defensive behaviors, inhibitory avoidance and escape, which have been related, respectively, to generalized anxiety and panic disorders. Methods: Male Wistar rats were submitted to the elevated T-maze test of anxiety after intra-MRN administration of drugs that either non-selectively or selectively change the activity of the serotonergic neurons. Results: Intra-MRN injection of FG 7142 (0.04 and 0.08 nmol) and kainic acid (0.03 and 0.06 nmol), drugs that non-selectively stimulate the MRN serotonergic neurons, facilitated inhibitory avoidance acquisition, but impaired escape performance. Microinjection of muscimol (0.11 and 0.22 nmol), a compound that non-selectively inhibits the activity of the MRN serotonergic neurons, impaired inhibitory avoidance and facilitated escape performance. Both kainic acid and muscimol also changed rat locomotion in the open-field test. Intra-MRN injection of 8-OH-DPAT (0.6-15 nmol) and WAY-100635 (0.18-0.74 nmol), respectively an agonist and an antagonist of somatodendritic 5-HT1A receptors located on serotonergic neurons of the MRN, only affected inhibitory avoidance-while the former inhibited the acquisition of this behavior, the latter facilitated it. Conclusion: MRN serotonergic neurons seem to be selectively involved in the regulation of inhibitory avoidance in the elevated T-maze. This result supports the proposal that 5-HT pathways departing from this nucleus play an important role in anxiety processing, with implications for pathologies such as generalized anxiety disorder.

Treatment seeking by individuals with obsessive-compulsive disorder from the British Psychiatric Morbidity Survey of 2000

Objective: For several reasons, many individuals with obsessive-compulsive disorder (OCD) do not seek treatment. However, data on treatment seeking from community samples are scant. This study analyzed service use by adults with OCD living in private households in Great Britain. Methods: Data from the British Survey of Psychiatric Morbidity of 2000, in which 8,580 individuals were surveyed, were analyzed. Service use was compared for those with OCD, with other neuroses, with different subtypes of OCD (only obsessions, only compulsions, or both), and with OCD and comorbid neuroses. Results: Persons with OCD (N=114) were more likely than persons with other neuroses (N=1,395) to be receiving treatment (40% compared with 23%, p<.001). However, those with OCD alone (N=38) were much less likely than those with OCD and a comorbid disorder to be in treatment (14% compared with 56%, p<.001). In the previous year, 9.4% of persons with OCD had seen a psychiatrist and 4.6% had seen a psychologist. Five percent were receiving cognitive-behavioral therapy, 2% were taking selective serotonin reuptake inhibitors, and 10% were taking tricyclics. Conclusions: Most persons with OCD were not in contact with a mental health professional, and apparently very few were receiving appropriate treatments. Very few persons with noncomorbid OCD were receiving treatment. Individuals with OCD who are in treatment may not be disclosing their obsessions and compulsions and may be discussing other emotional symptoms, leading to inappropriate treatment strategies. Public awareness of OCD symptoms should be raised, and primary care professionals should inquire about them with all patients who have depressive or anxiety disorders.

BODY DYSMORPHIC DISORDER IN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER: PREVALENCE and CLINICAL CORRELATES

Background The prevalence, sociodemographic aspects, and clinical features of body dysmorphic disorder (BDD) in patients with obsessivecompulsive disorder (OCD) have been previously addressed in primarily relatively small samples. Methods We performed a cross-sectional demographic and clinical assessment of 901 OCD patients participating in the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders. We used the Structured Clinical Interview for DSM-IV Axis I Disorders; Yale-Brown Obsessive-Compulsive Scale; Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS); Brown Assessment of Beliefs Scale; Clinical Global Impression Scale; and Beck Depression and Anxiety Inventories. Results The lifetime prevalence of BDD was 12.1%. The individuals with comorbid BDD (OCD-BDD; n = 109) were younger than were those without it. In addition, the proportions of single and unemployed patients were greater in the OCD-BDD group. This group of patients also showed higher rates of suicidal behaviors; mood, anxiety, and eating disorders; hypochondriasis; skin picking; Tourette syndrome; and symptoms of the sexual/religious, aggressive, and miscellaneous dimensions. Furthermore, OCD-BDD patients had an earlier onset of OC symptoms; greater severity of OCD, depression, and anxiety symptoms; and poorer insight. After logistic regression, the following features were associated with OCD-BDD: current age; age at OCD onset; severity of the miscellaneous DY-BOCS dimension; severity of depressive symptoms; and comorbid social phobia, dysthymia, anorexia nervosa, bulimia nervosa, and skin picking. Conclusions Because OCD patients might not inform clinicians about concerns regarding their appearance, it is essential to investigate symptoms of BDD, especially in young patients with early onset and comorbid social anxiety, chronic depression, skin picking, or eating disorders. Depression and Anxiety 29: 966-975, 2012. (C) 2012 Wiley Periodicals, Inc.

Qualidade de vida no transtorno obsessivo-compulsivo: uma revisão

CONTEXTO: O transtorno obsessivo-compulsivo (TOC) foi considerado pela Organização Mundial da Saúde como a 10ª causa de anos vividos com incapacidade, mas pesquisas sobre qualidade de vida (QV) nesse transtorno ainda são relativamente raras. OBJETIVOS: O objetivo deste trabalho foi fazer uma revisão convencional da literatura a respeito de estudos sobre qualidade de vida no TOC, publicados em português e inglês. MÉTODOS: A busca de artigos foi feita pelos sistemas MEDLINE, PsicoInfo e LILACS, cobrindo o período de 1980 a 2007, utilizando-se como palavras-chave: qualidade de vida, transtorno obsessivo-compulsivo, prejuízo funcional e incapacidade. RESULTADOS: Estudos populacionais apresentam indicadores indiretos de comprometimento na QV em pessoas com TOC, como mais desemprego, menor renda e menor índice de união conjugal estável, além de taxas relativamente altas de ideação e tentativas de suicídio. Estudos clínicos encontraram mais comprometimento na QV no TOC em comparação com algumas doenças clínicas crônicas, outros transtornos de ansiedade, quadros depressivos e mesmo esquizofrenia, em alguns aspectos. CONCLUSÃO: O impacto negativo do TOC sobre a QV de seus portadores pode ser grande, afetando vários domínios da vida e repercutindo também nos familiares. A reabilitação psicossocial deve ser vista como parte integrante essencial do tratamento e é preciso aumentar a conscientização da população sobre o problema, assim como o acesso a tratamentos adequados, para minimizar tal impacto, por vezes devastador.

Clinical features of tic-related obsessive-compulsive disorder: results from a large multicenter study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Epidemiologia do transtorno obsessivo-compulsivo: uma revisão

Os inquéritos populacionais são importantes, pois amostras clínicas tendem a apresentar vieses de seleção. Aspectos sociodemográficos e relacionados à própria condição mórbida podem interferir na procura por tratamento. Pela natureza egodistônica do transtorno obsessivo-compulsivo, seus portadores tendem a ocultar o problema, podendo não procurar ou demorar a procurar tratamento. Porém, a maior parte do conhecimento atual sobre o transtorno obsessivo-compulsivo advém de amostras clínicas, que não representam a totalidade dos casos. Foi feita uma revisão convencional da literatura através do Medline, PsicoInfo e Lilacs de inquéritos populacionais sobre o transtorno obsessivo-compulsivo, cobrindo o período de 1980 a 2004, utilizando-se como palavras-chave epidemiologia, transtorno obsessivo-compulsivo, inquéritos populacionais e prevalência. Estudos realizados em diferentes países indicam para o transtorno obsessivo-compulsivo uma prevalência atual em torno de 1,0% e ao longo da vida de 2,0 a 2,5%. Diferentemente de amostras clínicas, em quase todas as amostras populacionais há predomínio de mulheres e portadores que têm apenas obsessões. A freqüente comorbidade com outros transtornos mentais, particularmente depressão e outros transtornos ansiosos, repete-se em casos da população geral, que apresentam ainda uma associação com abuso de substâncias. Muitos portadores não estão em tratamento, particularmente os casos puros. Indicadores de incapacitação funcional demonstram um considerável impacto negativo do transtorno obsessivo-compulsivo. É preciso melhorar o conhecimento da população e dos profissionais de saúde sobre os sintomas do transtorno obsessivo-compulsivo para aumentar a procura de atendimento, assim como a correta identificação e abordagem terapêutica deste grave problema de saúde.

Obsessive-compulsive disorder: Influence of age at onset on comorbidity patterns

Purpose: This study investigates the influence of age at onset of OCS on psychiatric comorbidities, and tries to establish a cut-off point for age at onset. Methods: Three hundred and thirty OCD patients were consecutively recruited and interviewed using the following structured interviews: Yale-Brown Obsessive Compulsive Scale; Yale Global Tic Severity Scale and the Structured Clinical Interview for DSM-IV. Data were analyzed with regression and cluster analysis. Results: Lower age at onset was associated with a higher probability of having comorbidity with tic, anxiety, somatoform, eating and impulse-control disorders. Longer illness duration was associated with lower chance of having tics. Female gender was associated with anxiety, eating and impulse-control disorders. Tic disorders were associated with anxiety disorders and attention-deficit/hyperactivity disorder. No cut-off age at onset was found to clearly divide the sample in homogeneous subgroups. However, cluster analyses revealed that differences started to emerge at the age of 10 and were more pronounced at the age of 17, suggesting that these were the best cut-off points on this sample. Conclusions: Age at onset is associated with specific comorbidity patterns in OCD patients. More prominent differences are obtained when analyzing age at onset as an absolute value. © 2008 Elsevier Masson SAS. All rights reserved.

Towards a post-traumatic subtype of obsessive-compulsive disorder

We evaluated whether traumatic events are associated with a distinctive pattern of socio-demographic and clinical features of obsessive-compulsive disorder (OCD). We compared socio-demographic and clinical features of 106 patients developing OCD after post-traumatic stress disorder (PTSD; termed post-traumatic OCD), 41 patients developing OCD before PTSD (pre-traumatic OCD), and 810 OCD patients without any history of PTSD (non-traumatic OCD) using multinomial logistic regression analysis. A later age at onset of OCD, self-mutilation disorder, history of suicide plans, panic disorder with agoraphobia, and compulsive buying disorder were independently related to post-traumatic OCD. In contrast, earlier age at OCD onset, alcohol-related disorders, contamination-washing symptoms, and self-mutilation disorder were all independently associated with pre-traumatic OCD. In addition, patients with post-traumatic OCD without a previous history of obsessive-compulsive symptoms (OCS) showed lower educational levels, greater rates of contamination-washing symptoms, and more severe miscellaneous symptoms as compared to post-traumatic OCD patients with a history of OCS. © 2011 Elsevier Ltd.

Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT1A-receptors and reduces cholesterol after repeated oral treatment

Background: The current treatments for anxiety disorders and depression have multiple adverse effects in addition to a delayed onset of action, which has prompted efforts to find new substances with potential activity in these disorders. Citrus aurantium was chosen based on ethnopharmacological data because traditional medicine refers to the Citrus genus as useful in diminishing the symptoms of anxiety or insomnia, and C. aurantium has more recently been proposed as an adjuvant for antidepressants. In the present work, we investigated the biological activity underlying the anxiolytic and antidepressant effects of C. aurantium essential oil (EO), the putative mechanism of the anxiolytic-like effect, and the neurochemical changes in specific brain structures of mice after acute treatment. We also monitored the mice for possible signs of toxicity after a 14-day treatment.Methods: The anxiolytic-like activity of the EO was investigated in a light/dark box, and the antidepressant activity was investigated in a forced swim test. Flumazenil, a competitive antagonist of benzodiazepine binding, and the selective 5-HT1A receptor antagonist WAY100635 were used in the experimental procedures to determine the mechanism of action of the EO. To exclude false positive results due to motor impairment, the mice were submitted to the rotarod test.Results: The data suggest that the anxiolytic-like activity observed in the light/dark box procedure after acute (5 mg/kg) or 14-day repeated (1 mg/kg/day) dosing was mediated by the serotonergic system (5-HT1A receptors). Acute treatment with the EO showed no activity in the forced swim test, which is sensitive to antidepressants. A neurochemical evaluation showed no alterations in neurotransmitter levels in the cortex, the striatum, the pons, and the hypothalamus. Furthermore, no locomotor impairment or signs of toxicity or biochemical changes, except a reduction in cholesterol levels, were observed after treatment with the EO.Conclusion: This work contributes to a better understanding of the biological activity of C. aurantium EO by characterizing the mechanism of action underlying its anxiolytic-like activity. © 2013 Costa et al; licensee BioMed Central Ltd.

Bateria sequencial de procedimentos para avaliação da atividade ansiolítica e antidepressiva em camundongos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo da ação ansiolítica e sedativa de preparações obtidas de Cymbopogon citratus (D.C.) Stapf

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo farmacológico e neuroquímico dos óleos essenciais de Cymbopogon citratus (D.C) Stapf e Citrus ayrantium L

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Extrato hidroalcoólico de Erithryna mulungu, composições farmacêuticas e processos para produzir essas substâncias

The present invention provides the use of molecules for cholinergic and/or serotonergic system models, revealing pharmaceutical compositions comprising 11-OH-erythravine, erythravine, erythrartine, pharmaceutically acceptable isotherals, salts, byproducts and/or solvates thereof, optionally containing other erythrina byproducts, for the treatment of anxiety disorders; processes for obtaining said pharmaceutical compositions are also revealed.

Uso na modulação dos sistemas colinérgico e/ou serotonérgico e/ou gabaérgico de vertebrados, de um extrato bruto vegetal padronizado, composição farmacêutica para o tratamento de disturbios associados a disfunções do sistema colinérgico e/ou serotonérgico e/ou gabaérgico, e processo de produção de medicamento para a modulação dos sistemas colinérgico e/ou serotonérgico e/ou gabaérgico de vertebrados

The present invention provides the use of molecules for cholinergic serotonergic and/or gabaergic system models, revealing pharmaceutical compositions comprising 11-OH-erythravine, erythravine, erythrartine, pharmaceutically acceptable isotherals, salts, byproducts and/or solvates thereof, optionally containing other Erythrine byproducts, for the treatment of anxiety disorders; processes for obtaining said pharmaceutical compositions...