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Background Functional neuroimaging studies have consistently shown abnormal limbic activation patterns in socially anxious individuals, but structural data on the amygdala and hippocampus of these patients are scarce. This study explored the existence of structural differences in the whole brain, amygdala, and hippocampus of subjects with clinical and subthreshold social anxiety compared to healthy controls. We hypothesized that there would be volumetric differences across groups, without predicting their direction (i.e. enlargement or reduction). Methods Subjects classified as having social anxiety disorder (n = 12), subthreshold social anxiety (n = 12) and healthy controls (n = 14) underwent structural magnetic resonance imaging scans. The amygdala and hippocampus were defined a priori as regions of interest and volumes were calculated by manual tracing. Whole brain volume was calculated using voxel-based morphometry. Results The bilateral amygdala and left hippocampus were enlarged in socially anxious individuals relative to controls. The volume of the right hippocampus was enlarged in subthreshold social anxiety participants relative to controls. No differences were found across groups in respect to total brain volume. Conclusions Our results show amygdalar and hippocampal volume alterations in social anxiety, possibly associated with symptom severity. The time course of such alterations and the cellular and molecular bases of limbic plasticity in social anxiety should be further investigated.

BACKGROUND: Recreational drugs are generally used to intentionally alter conscious experience. Long-lasting cannabis users frequently seek this effect as a means to relieve negative affect states. As with conventional anxiolytic drugs, however, changes in subjective feelings may be associated with memory impairment. We have tested whether the use of cannabis, as a psychoactive compound, is associated with alterations in spontaneous activity in brain networks relevant to self-awareness, and whether such potential changes are related to perceived anxiety and memory performance. METHODS: Functional connectivity was assessed in the Default and Insula networks during resting state using fMRI in 28 heavy cannabis users and 29 control subjects. Imaging assessments were conducted during cannabis use in the unintoxicated state and repeated after one month of controlled abstinence. RESULTS: Cannabis users showed increased functional connectivity in the core of the Default and Insula networks and selective enhancement of functional anticorrelation between both. Reduced functional connectivity was observed in areas overlapping with other brain networks. Observed alterations were associated with behavioral measurements in a direction suggesting anxiety score reduction and interference with memory performance. Alterations were also related to the amount of cannabis used and partially persisted after one month of abstinence. CONCLUSIONS: Chronic cannabis use was associated with significant effects on the tuning and coupling of brain networks relevant to self-awareness, which in turn are integrated into brain systems supporting the storage of personal experience and motivated behavior. The results suggest potential mechanisms for recreational drugs to interfere with higher-order network interactions generating conscious experience.

There a lack of consistent neuroimaging data on specific phobia (SP) and a need to assess volumetric and metabolic differences in structures implicated in this condition. The aim of this study is investigate possible metabolic (via 1H MRS) and cortical thickness abnormalities in spider-phobic patients compared to healthy volunteers. Participants were recruited via public advertisement and underwent clinical evaluations and MRI scans. The study started in 2010 and the investigators involved were not blind in respect to patient groupings. The study was conducted at the Ribeirao Preto Medical School University Hospital of the University of Sao Paulo, Brazil. Patients with spider phobia (n=19) were matched to 17 healthy volunteers with respect to age, education and socio-economic status. The spider SP group fulfilled the diagnostic criteria for spider phobia according to the Structured Clinical Interview for DSM-IV. None of the participants had a history of neurological, psychiatric or other relevant organic diseases, use of prescribed psychotropic medication or substance abuse. All imaging and spectroscopy data were collected with a 3 T MRI scanner equipped with 25 mT gradient coils in 30-minute scans. The Freesurfer image analysis package and LC Model software were used to analyze data. The hypothesis being tested was formulated before the data collection (neural correlates of SP would include the amygdala, insula, anterior cingulate gyrus and others). The results indicated the absence of metabolic alterations, but thinning of the right anterior cingulate cortex (ACC) in the SP group when compared to the healthy control group (mean cortical thickness±SD: SP=2.11±0.45 mm; HC=2.16±0.42 mm; t (34)=3.19, p=0.001 [−35.45, 71.00, −23.82]). In spectroscopy, the ratios between N-acetylaspartate and creatine and choline levels were measured. No significant effect or correlation was found between MRS metabolites and scores in the Spider Phobia Questionnaire and Beck Anxiety Inventory (p>0.05). The ACC is known to be related to the cognitive processing of fear and anxiety and to be linked with the conditioning circuit. The MRS findings are preliminary and need more studies. The finding of reduced ACC thickness in SP is in agreement with evidence from previous functional neuroimaging studies and highlights the importance of this brain area in the pathophysiology of SP.

Objective: To present the most relevant findings regarding the Brazilian Medical Associationguidelines for the diagnosis and differential diagnosis of panic disorder.Methods: We used the methodology proposed by the Brazilian Medical Association for the DiretrizesProject. The MEDLINE (PubMed), Scopus, Web of Science, and LILACS online databases werequeried for articles published from 1980 to 2012. Searchable questions were structured using thePICO format (acronym for ‘‘patient’’ [or population], ‘‘intervention’’ [or exposure], ‘‘comparison’’ [orcontrol], and ‘‘outcome’’).Results: We present data on clinical manifestations and implications of panic disorder and itsassociation with depression, drug abuse, dependence and anxiety disorders. In addition, discussionswere held on the main psychiatric and clinical differential diagnoses.Conclusions: The guidelines are proposed to serve as a reference for the general practitioner andspecialist to assist in and facilitate the diagnosis of panic disorder.Keywords: Panic disorder; anxiety; guidelines; diagnosis; differential diagnosis

OBJECTIVES To characterize a motivational profile of reasons for smoking among teenagers. To investigate the influence of clinical and social elements on observed scores. METHODS High school students who smoked in the past month (n = 226; age, 16.4 ± 10 years; 46.5% male) answered a questionnaire during school time. The instrument included the University of Sao Paulo Reasons for Smoking Scale (USP-RSS), the Fagerstrom Test for Nicotine Dependence, and clinical and social information. The USP-RSS scores from 307 healthy adult smokers (67.5% male; age, 37.9 ± 11.2 years) were also used for comparisons. RESULTS Most of the adolescents (90.2%) exhibited low or very low levels of nicotine addiction (median Fagerstrom Test for Nicotine Dependence score 0, range 0 to 8). The mean scores of the USP-RSS subscales were as follows: Addiction, 1.9 ± 1.1; Pleasure From Smoking, 3.0 ± 1.3; Tension Reduction, 2.4 ± 1.3; Stimulation, 1.9 ± 0.9; Automatism, 1.3 ± 0.6; Handling, 2.3 ± 1.1; Social Smoking, 1.9 ± 1.0; Weight Control, 1.4 ± 1.0; and Affiliative Attachment, 1.6 ± 0.9. In comparison with adults, teenagers exhibited lower scores for Addiction, Pleasure From Smoking, Tension Reduction, Automatism, Weight Control, and Affiliative Attachment and higher scores for Social Smoking (P < 0.05). Older age, past school failure, illicit drugs use, alcohol abuse, high levels of perceived stress, and the death of at least one parent were associated with high scores for all subscales. CONCLUSIONS The USP-RSS subscales Addiction, Pleasure From Smoking, and Social Smoking were important factors for adolescent smoking. Comparisons with adult smokers stressed the importance of the component of Social Smoking. The identification of distinctive factors that drive teenagers to smoke might help in making decisions dealing with interventions aimed at smoking cessation and control.

After a hundred-years of its publication, the Karl Jaspers' book, General Psychopathology, is still an indispensable book to psychiatrists and for all those who study psychopathology. It's a clear delineation of the phenomenological method for describing the symptoms of mental disorders that remains unmatched until nowadays. The book focuses on the relevance of phenomenological and hermeneutical methods in psychopathology. Although this work is grounded in the clinical thought and practices of the late nineteenth and early twentieth centuries, Jaspers' delineation of psychiatric methods in this work is still evaluated as unmatched to this day, a work that is indispensable to contemporary psychiatry. Jaspers also contributed with important articles and book reviews to psychiatric periodicals during the first two decades of the twentieth century. Após cem anos de sua publicação, o livro de Karl Jaspers, Psicopatologia Geral, continua sendo uma obra indispensável para psiquiatras e para todos que se dedicam ao estudo de psicopatologia. Seu claro delineamento do método fenomenológico para a descrição dos sintomas dos transtornos mentais permanece intocável até hoje. O livro foca a relevância dos métodos fenomenológico e hermenêutico em psicopatologia. Apesar do trabalho ter sido baseado no pensamento e na prática clínica do final do século XIX e do início do século XX, a delineação dos métodos em psiquiatria de Jaspers é avaliado como ímpar até hoje, um trabalho indispensável para a psiquiatria atual. Jaspers também contribuiu com importantes artigos e revisões de livros para revistas psiquiátricas durante as primeiras duas décadas do século XX.

Importance The treatment of schizophrenia remains a challenge, and the currently available antipsychotic drugs are slow acting and produce a number of adverse effects. Objective To examine the effectiveness and safety of a single intravenous administration of sodium nitroprusside (0.5 μg/kg/min for 4 hours) on the positive, negative, anxiety, and depressive symptoms in patients with schizophrenia. Design Single-center, randomized, double-blind, placebo-controlled trial performed from March 9, 2007, to March 12, 2009. Setting University teaching hospital in Sao Paulo, Brazil. Participants Twenty inpatients aged 19 to 40 years with a diagnosis of schizophrenia who were in the first 5 years of the disease who are taking antipsychotics. Intervention Sodium nitroprusside administration. Main Outcome Measures The 18-item Brief Psychiatric Rating Scale and the negative subscale of the Positive and Negative Syndrome Scale. Results After the infusion of sodium nitroprusside, a rapid (within 4 hours) improvement of symptoms was observed. The placebo and experimental groups had significant differences in the 18-item Brief Psychiatric Rating Scale total score and subscale scores, which persisted for 4 weeks after infusion. Conclusions The results clearly show a therapeutic effect of sodium nitroprusside. If this drug is approved for routine clinical use in patients with schizophrenia, this discovery will be an important advance in the pharmacologic treatment of this devastating disorder. Trial Registration clinicaltrials.gov Identifier:NCT01548612

This study aims to translate and validate Early Trauma Inventory Self Report -Short Form (ETISR-SF) to Brazilian Portuguese. 253 adult subjects answered the ETISR-SF, Beck Anxiety Inventory (BAI), Fagerström Test for Nicotine Dependence (FTND), Patient Health Questionnaire (PHQ-9) and Fast Alcohol Screening Test (FAST). The instrument showed good internal consistency (0.83). Correlations with the PHQ-9 and BAI were moderate (r=0.26-0.47) and showed the expected associations with psychiatric constructs. No associations were found for FTND and FAST. Confirmatory Factor Analysis revealed that a correlated four-factor model as well as a second order model subsuming four lower order components presented the best model fit. Test-retest reliability was also excellent (ICC=0.78-0.90). ETISR-SF is suitable for assessing traumatic experiences in a Brazilian community sample. Given the importance of trauma as a public health problem, tools such as ETISR-SF may help clinicians/ researchers to better evaluate and measure such events and further advance clinical care of trauma victims.

We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson’s and Alzheimer’s, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats. We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.

It has been shown that GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei (DMH and VMH, respectively) induces elaborated defensive behavioural responses accompanied by antinociception, which has been utilized as an experimental model of panic attack. Furthermore, the prelimbic (PL) division of the medial prefrontal cortex (MPFC) has been related to emotional reactions and the processing of nociceptive information. The aim of the present study was to investigate the possible involvement of the PL cortex and the participation of local cannabinoid CB1 receptors in the elaboration of panic-like reactions and in innate fear-induced antinociception. Elaborated fear-induced responses were analysed during a 10-min period in an open-field test arena. Microinjection of the GABAA receptor antagonist bicuculline into the DMH/VMH evoked panic-like behaviour and fear-induced antinociception, which was decreased by microinjection of the non-selective synaptic contact blocker cobalt chloride in the PL cortex. Moreover, microinjection of AM251 (25, 100 or 400 pmol), an endocannabinoid CB1 receptor antagonist, into the PL cortex also attenuated the defensive behavioural responses and the antinociception that follows innate fear behaviour elaborated by DMH/VMH. These data suggest that the PL cortex plays an important role in the organization of elaborated forward escape behaviour and that this cortical area is also involved in the elaboration of innate fear-induced antinociception. Additionally, CB1 receptors in the PL cortex modulate both panic-like behaviours and fear-induced antinociception elicited by disinhibition of the DMH/VMH through microinjection of bicuculline.

Background: The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. Methods: Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. Results: One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure. Limitations: However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings. Conclusion: Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives.

Until the beginning of the 19th century, psychiatric patients did not receive specialized treatment. The problem that was posed by the presence of psychiatric patients in the Santas Casas de Misericórdia and the social pressure from this issue culminated in a Decree of the Brazilian Emperor, D. Pedro II, on July 18, 1841. The “Lunatic Palace” was the first institution in Latin America exclusively designed for mental patients. It was built between 1842 and 1852 and is an example of neoclassical architecture in Brazil, located at Saudade Beach in the city of Rio de Janeiro. In the 1930s and 1940s, the D. Pedro II Hospital was overcrowded, and patients were gradually transferred to other hospitals. By September of 1944, all the patients had been transferred and the hospital was deactivated. Key words: psychiatry, history, madness. Até o início do século 19, os pacientes psiquiátricos não recebiam nenhum tipo de tratamento específico. A pressão social da época decorrente do problema representado pela presença dos pacientes psiquiátricos nas Santas Casas de Misericórdia culminou no Decreto do Imperador brasileiro, D. Pedro II, em 18 de julho de 1841. O “Palácio dos Loucos” foi a primeira instituição na América Latina voltada exclusivamente para a assistência aos doentes mentais. Foi construído entre 1842 e 1852, na Praia da Saudade na cidade do Rio de Janeiro, e é um dos expoentes da arquitetura neoclássica do Brasil. Nas décadas de 1930 e 1940, o então Hospital D. Pedro II estava superlotado, tendo sido os pacientes gradualmente transferidos para outros hospitais. Em setembro de 1944, concluiu-se a tranferência de todos os pacientes e o hospital foi desativado.

Cannabidiol (CBD) is one of the main components of Cannabis sativa and has a wide spectrum of action, including effects in the sleep-wake cycle. Objective: The objective of this paper is to assess the effects on sleep of acute systemic administration of CBD. Method: Adult male Wistar rats were randomly distributed into four groups that received intraperitoneal injections of CBD 2.5 mg/kg, CBD 10 mg/kg, CBD 40 mg/kg or vehicle ( n=seven animals/group). Sleep recordings were made during light and dark periods for four days: two days of baseline recording, one day of drug administration (test), and one day after drug (post-test). Results: During the light period of the test day, the total percentage of sleep significantly increased in the groups treated with 10 and 40 mg/kg of CBD compared to placebo. REM sleep latency increased in the group injected with CBD 40 mg/kg and was significantly decreased with the dose of 10 mg/kg on the post-test day. There was an increase in the time of SWS in the group treated with CBD 40 mg/kg, although this result did not reach statistical significance. Conclusion: The systemic acute administration of CBD appears to increase total sleep time, in addition to increasing sleep latency in the light period of the day of administration.

The study aims to conduct a psychometric study of the Fagerström Test for Nicotine Dependence (FTND) and to assess the prevalence, sociodemographic profile, and psychiatric comorbidities of smokers in a general hospital.Two hundred sixty-four inpatients were elegible for inclusion in the study and assessed with Structured Clinical Interview for the DSM-IV (Module E), Patient Health Questionnaire, Fast Alcohol Screening Test, and FTND.The cut-off note two of the FTND is the most adequate to identify tobacco abuse/dependence (sensibility: 0.59-0.76). The reliability was estimated to be 0.68-0.96. A 44% rate of tobacco abuser/dependent patients was detected, with a 28% rate of psychiatric comorbidity.Detection of the smoking habits at the time of hospitalization can be opportune, favoring the planning and the beginning of treatment.

Recent debate and cases involving elite athletes raised the question whether or not Cannabis sativa (cannabis) should be considered doping in sports. Results from a 2010 report in the United States (Substance Abuse and Mental Health Services Administration, 2011) showed that cannabis is the most used illicit drug, with 17.4 million users smoking cannabis and 6.9 million users smoking cannabis on a daily or near daily basis. The World Anti-Doping Agency (WADA) included cannabis in its Prohibited List in 2004, claiming that cannabis may improve performance in some sports and is an illegal drug in most countries (Huestis et al., 2011); however, the inclusion of a substance in the Code (World Anti-Doping Agency, 2009) is complex, requiring intense debate among delegates and the fulfillment of specific criteria. For instance, Section 4 of the Code establishes that a substance be considered for inclusion in the Prohibited List if it is a masking agent or meets two of the three following criteria: (i) potential to enhance performance in sports – smoked cannabis affects cognition and performance, causes memory loss, executive function, and motor impairment, among other undesirable effect (Saugy et al., 2006). Cannabis smoking can be helpful for some activities such as extreme sports, as it improves muscle relaxation, reduces anxiety, and extincts fear memories (e.g., negative experiences) leading to enhanced performance. It is also worthwhile to note that cannabis smoking improves sleep time and recovery, which may favor performance when an athlete is facing multiple competitions in a short period of time. In light of these positive effects, one can assume cannabis is a doping substance that relaxes the mind and improves recovery (Huestis et al., 2011); (ii) potential or actual health risk – cannabis’ cognitive effects in chronic users are still unclear, but it may downregulate CB1 receptors, affect executive functions, and cause motor impairment, reversed only after weeks of abstinence (Hirvonen et al., 2012). It seems unlikely that athletes are chronic cannabis smokers due to the detrimental effects of chronic use including inconsistent performance, concentration, and motivation. Cyclists who smoked cannabis had a 1-min decrease in maximal exercise performance at 10 min after smoking (Renaud and Cormier, 1986). These negative effects on cognition and performance can impair critical skills (e.g., decision making, vigilance, alertness) required in high-risk sports to avoid accidents and/or injuries; or (iii) violation of the spirit of sport – doping is essentially contrary to the spirit of sport, which is the principle of Olympism, characterized by several values, such as ethics, fair play and honesty, health, respect for rules and laws, and respect for self and other participants (World Anti-Doping Agency, 2009). Over 60 cannabinoids are present in cannabis, with Δ9-tetrahydrocannabinol (THC) the main psychoactive constituent and responsible for the observed toxic effects after smoking, while other cannabinoids are responsible for minor effects, such as cannabinol (CBN), which is 10% as psychoactive as THC (Huestis, 2005). THC is lipophilic and stores in several organs, especially in adipose tissue; this extensive body burden explains the prolonged cannabinoid detection rate in blood and urine for at least 4 weeks in chronic daily cannabis smokers (Lowe et al., 2009; Bergamaschi et al., 2013). The WADA (World Anti-Doping Agency, 2013) establishes a 15 ng/mL urinary 11-nor-9-carboxy-THC (THCCOOH) threshold; urine analyses involves THCCOOH-glucuronide conjugates cleavage, which significantly increases free THCCOOH concentrations and detection time. Urinary THCCOOH concentrations above the 15 ng/mL threshold are considered Adverse Analytical Findings and may be interpreted as a violation of anti-doping rules (World Anti-Doping Agency, 2009). Studies showed that even occasional and single cannabis smoking might yield a THCCOOH positive result (≥15 ng/mL) for up to 5 days (Huestis et al., 1996). Thus, consuming cannabis even weeks before a match may imply a considerable risk of being detected in a doping test. In light of this considerable risk, some users started using a new preparation of herbal smoking blends named “Spice.” Such substances are highly potent cannabinoid analogs, with unknown and potentially harmful toxicological properties that may cause prolonged intoxication. These substances mimic or worsen cannabis’ toxic effects provoking cognitive and motor impairment (UNODC, 2011). The non-psychoactive cannabidiol (CBD) is anxiolytic in humans following a single dose (Zuardi et al., 1993; Bergamaschi et al., 2011); decreased anxiety and fear memories extinction after oral CBD intake may enhance sports performance with no “violation” of the Code, as no THCCOOH is detected in urine. One way to protect athletes’ health and to promote health, fairness, and equality in sports is to include any illicit drugs, their constituents and analogs in the anti-doping program. The sports may assist to create educational program for youth and athletes as an alternative to keep them away from drugs and to preserve the intrinsic value about the “spirit of sport.”

Functional impairment scales are important to assess Social Anxiety Disorder (SAD) patients. The present study aims to evaluate the reliability, internal consistency, validity and factorial structure of the Disability Profile/Clinician-Rate (DP) scale, as well as to present an interview-guide to support its application by clinicians. University students (n = 173) of both genders participated in the study (SAD = 84 and Non-SAD = 89), with ages ranging between 17 and 35 years, systematically diagnosed. The SAD group presented more difficulties when compared to the Non-SAD group. The DP presented, for the SAD group, internal consistency of 0.68 (lifetime) and 0.67 (last two weeks). Inter-rater reliability varied from 0.75 to 0.93. Two factors were extracted and the correlation among such factors and the Social Phobia Inventory subscales presented association between fear and avoidance symptoms and the functional impairments. The scale presents good psychometric properties and can contribute to the assessment of functional impairments.

A doença de Parkinson é universal, sendo a segunda doença neurodegenerativa mais comum em idosos e tem alta prevalência, afetando entre 0,5 e 1% da população com idade entre 65 e 69 anos. A adesão à terapia medicamentosa é considerada o principal determinante para a efetividade do tratamento, porém apenas recentemente vem sendo estudado em pacientes com doença de Parkinson. Trata-se de estudo transversal e descritivo que avaliou a adesão à terapia com levodopa em 112 pacientes com doença de Parkinson que frequentavam regularmente o ambulatório de distúrbios do movimento do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo utilizando o teste Morisky e Green e o instrumento que avalia atitudes frente à tomada dos remédios (IAAFTR). Dos pacientes entrevistados, 53% não apresentaram adesão ao tratamento e 52% não tomam a medicação no horário correto. Os pacientes devem ser orientados sobre a importância de ingerir sua medicação no horário correto, entendendo os benefícios que a adesão pode proporcionar estando cientes de que doses não tomadas, tomadas em excesso, ou em horários diferentes dos prescritos podem diminuir sua resposta ao tratamento, afetando negativamente sua evolução clínica e qualidade de vida, gerando maiores custos à saúde pública do país. Parkinson's disease is universal and the second most prevalent neurodegenerative disease among the elderly affecting between 0.5 and 1% of the population between 65 and 69 years of age. Adherence to medication is considered the main determinant for the effectiveness of treatment, but only recently has it been studied in patients with Parkinson's disease. This cross-sectional and descriptive study assessed adherence to medication in 112 patients with Parkinson's disease who regularly attended the movement disorder outpatient unit at the Hospital das Clinicas of the School of Medicine of Ribeirao Preto, University of São Paulo, using the Morisky and Green test and an instrument that assesses attitudes of medicine intake (IAAFTR). Of the patients interviewed, 53% failed to adhere to treatment and 52% did not take the medication at the correct time. Patients should receive guidance about the importance of taking their medication at the correct time, understanding the benefits that adherence to medication can provide. They should also be aware that doses not taken, taken in excess or not taken at the prescribed times can reduce their response to treatment, having a negative effect on the clinical outcome and quality of life, thereby generating higher costs to public health in the country.

BackgroundCannabis can induce transient psychotic symptoms, but not all users experience these adverse effects. We compared the neural response to Δ9-tetrahydrocannabinol (THC) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms.MethodIn a double-blind, placebo-controlled, pseudorandomized design, 21 healthy men with minimal experience of cannabis were given either 10 mg THC or placebo, orally. Behavioural and functional magnetic resonance imaging measures were then recorded whilst they performed a go/no-go task.ResultsThe sample was subdivided on the basis of the Positive and Negative Syndrome Scale positive score following administration of THC into transiently psychotic (TP; n = 11) and non-psychotic (NP; n = 10) groups. During the THC condition, TP subjects made more frequent inhibition errors than the NP group and showed differential activation relative to the NP group in the left parahippocampal gyrus, the left and right middle temporal gyri and in the right cerebellum. In these regions, THC had opposite effects on activation relative to placebo in the two groups. The TP group also showed less activation than the NP group in the right middle temporal gyrus and cerebellum, independent of the effects of THC.ConclusionsIn this first demonstration of inter-subject variability in sensitivity to the psychotogenic effects of THC, we found that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum, suggesting that these regions mediate the effects of the drug on psychotic symptoms.

The use of antipsychotic drugs represents an important approach for the treatment of schizophrenia. However, their efficacy is limited to certain symptoms of this disorder, and they induce serious side effects. As a result, there is a strong demand for the development of new drugs, which depends on reliable animal models for pharmacological characterization. The present review discusses the face, construct, and predictive validity of classical animal models for studying the efficacy and side effects of compounds for the treatment of schizophrenia. These models are based on the properties of antipsychotics to impair the conditioned avoidance response and reverse certain behavioral changes induced by psychotomimetic drugs, such as stereotypies, hyperlocomotion, and deficit in prepulse inhibition of the startle response. Other tests, which are not specific to schizophrenia, may predict drug effects on negative and cognitive symptoms, such as deficits in social interaction and memory impairment. Regarding motor side effects, the catalepsy test predicts the liability of a drug to induce Parkinson-like syndrome, whereas vacuous chewing movements predict the liability to induce dyskinesia after chronic treatment. Despite certain limitations, these models may contribute to the development of more safe and efficacious antipsychotic drugs.

Social Anxiety Disorder (SAD) is prevalent and rarely diagnosed due to the difficulty in recognizing its symptoms as belonging to a disorder. Therefore, the evaluation/screening scales are of great importance for its detection, with the most used being the Liebowitz Social Anxiety Scale (LSAS). Thus, this study proposed to evaluate the psychometric properties of internal consistency and convergent validity, as well as the confirmatory factorial analysis and reliability of the self-reported version of the LSAS (LSAS-SR), translated into Brazilian Portuguese, in a sample of the general population (N = 413) and in a SAD clinical sample (N = 252). The convergent validity with specific scales for the evaluation of SAD and a general anxiety scale presented correlations ranging from 0.21 to 0.84. The confirmatory factorial analysis did not replicate the previously indicated findings of the literature, with the difficulty being in obtaining a consensus factorial structure common to the diverse cultures in which the instrument was studied. The LSAS-SR presented excellent internal consistency (α = 0.90–0.96) and test-retest reliability (Intraclass Correlation Coefficient = 0.81; Pearson’s = 0.82). The present findings support those of international studies that attest to the excellent psychometric properties of the LSAS-SR, endorsing its status as the gold standard.

The epidemiological dimension of mental health problems in childhood and its impact warrant new studies. Knowledge about the predictors of mental health in children is scant in developing countries. The present study estimated the prevalence of psychiatric disorders in Brazilian school-age children based on a community sample from primary health care services, with the aim of verifying the predictive value of biological, social, and familial risk factors in children's mental health. The study was performed with 120 children of both genders identified through their mothers. The children's mental health was evaluated by sociodemographic factors and a diagnostic interview conducted with parents. Biological, social, and familial risk factors were evaluated by the Supplemental Questionnaire and Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Of the 120 children, 45.8 % were diagnosed with at least one mental health disorder. Children with diagnoses of depressive disorder and generalized anxiety disorder presented evidence of greater exposure to risk factors compared with children without these psychiatric diagnoses. Children with more risk factors throughout their lifetime had greater comorbidities compared with children with a lower number of risk factors. The identification of groups exposed to interconnected risk factors represents a priority when planning mental health practices. The strong role of chronic familial risk factors needs to be emphasized because they are a possible target for the prevention of depressive and anxiety disorders.

Great progress has been observed in the literature over the last decade regarding the validation of instruments for the assessment of Social Anxiety Disorder in the Brazilian context. Particularly outstanding in this respect is the production of a group of Brazilian investigators regarding the psychometric study of the following instruments: Liebowitz Social Anxiety Scale, Social Phobia Inventory, Brief Social Phobia Scale, Disability Profile, Liebowitz Self-Rated Disability Scale, Social Phobia Safety Behaviors Scale and Self-Statements During Public Speaking Scale, which have proved to be appropriate and valid for use in the adult Brazilian population, representing resources for the assessment of social anxiety in clinical and experimental situations.

BackgroundNeurodevelopmental alterations have been described inconsistently in psychosis probably because of lack of standardization among studies. The aim of this study was to conduct the first longitudinal and population-based magnetic resonance imaging (MRI) evaluation of the presence and size of the cavum septum pellucidum (CSP) and adhesio interthalamica (AI) in a large sample of patients with first-episode psychosis (FEP).MethodFEP patients (n=122) were subdivided into schizophrenia (n=62), mood disorders (n=46) and other psychosis (n=14) groups and compared to 94 healthy next-door neighbour controls. After 13 months, 80 FEP patients and 52 controls underwent a second MRI examination.ResultsWe found significant reductions in the AI length in schizophrenia FEP in comparison with the mood disorders and control subgroups (longer length) at the baseline assessment, and no differences in any measure of the CSP. By contrast, there was a diagnosis×time interaction for the CSP length, with a more prominent increase for this measure in the psychosis group. There was an involution of the AI length over time for all groups but no diagnosis×time interaction.ConclusionsOur findings suggest that the CSP per se may not be linked to the neurobiology of emerging psychotic disorders, although it might be related to the progression of the disease. However, the fact that the AI length was shown to be shorter at the onset of the disorder supports the neurodevelopmental model of schizophrenia and indicates that an alteration in this grey matter junction may be a risk factor for developing psychosis.

INTRODUCTION: There is substantial evidence regarding the impact of negative life events during childhood on the aetiology of psychiatric disorders. We examined the association between negative early life events and social anxiety in a sample of 571 Spanish University students. METHODS: In a cross-sectional survey conducted in 2007, we collected data through a semistructured questionnaire of sociodemographic variables, personal and family psychiatric history, and substance abuse. We assessed the five early negative life events: (i) the loss of someone close, (ii) emotional abuse, (iii) physical abuse, (iv) family violence, and (v) sexual abuse. All participants completed the Liebowitz Social Anxiety Scale. RESULTS: Mean (SD) age was 21 (4.5), 75% female, LSAS score was 40 (DP = 22), 14.2% had a psychiatric family history and 50.6% had negative life events during childhood. Linear regression analyses, after controlling for age, gender, and family psychiatric history, showed a positive association between family violence and social score (p = 0.03). None of the remaining stressors produced a significant increase in LSAS score (p > 0.05). CONCLUSION: University students with high levels of social anxiety presented higher prevalence of negative early life events. Thus, childhood family violence could be a risk factor for social anxiety in such a population. INTRODUÇÃO: Existem evidências substanciais sobre o impacto de eventos negativos da vida durante a infância na etiologia dos transtornos psiquiátricos. Examinamos a associação entre os eventos negativos ocorridos na infância e a ansiedade social em uma amostra de 571 estudantes universitários espanhóis. MÉTODOS: Em um estudo transversal realizado em 2007, foram coletados os dados de variáveis sociodemográficas, história psiquiátrica pessoal e familiar e abuso de substâncias por meio de um questionário semiestruturado e avaliamos cinco eventos negativos ocorridos na infância: (i) a perda de alguém próximo, (ii) abuso emocional, (iii) abuso físico, (iv) violência familiar e (v) abuso sexual. Todos os participantes preencheram a escala de Liebowitz para ansiedade social. RESULTADOS: A média (DP) de idade foi de 21 anos (4,5); 75% eram do sexo feminino; o escore na LSAS foi 40 (DP = 22); 14,2% tinham história psiquiátrica familiar e 50,6% tiveram eventos negativos durante a infância. A análise de regressão linear, após o controle para idade, sexo e história psiquiátrica familiar, mostraram associação positiva entre violência familiar e escore de ansiedade social (p = 0,03). Nenhum dos fatores estressores restantes produziu aumento significativo no escore da LSAS (p > 0,05). CONCLUSÃO: Os estudantes universitários com altos níveis de ansiedade social apresentaram prevalência maior de eventos negativos precoces. Portanto, a violência familiar na infância pode ser um fator de risco para ansiedade social em tal população.

Objective: To investigate the effects of cannabidiol (CBD) on mitochondrial complex and creatinekinase (CK) activity in the rat brain using spectrophotometry.Method: Male adult Wistar rats were given intraperitoneal injections of vehicle or CBD (15, 30, or 60mg/kg) in an acute (single dose) or chronic (once daily for 14 consecutive days) regimen. Theactivities of mitochondrial complexes and CK were measured in the hippocampus, striatum, andprefrontal cortex.Results: Both acute and chronic injection of CBD increased the activity of the mitochondrialcomplexes (I, II, II-III, and IV) and CK in the rat brain.Conclusions: Considering that metabolism impairment is certainly involved in the pathophysiology ofmood disorders, the modulation of energy metabolism (e.g., by increased mitochondrial complex andCK activity) by CBD could be an important mechanism implicated in the action of CBD.Keywords: Cannabidiol; mitochondrial respiratory chain; creatine kinase

Objective: Depression is a highly prevalent condition and is considered a major public health issue. The aim of the present study was to estimate the prevalence of depressive symptoms in the Brazilian population and establish their sociodemographic correlates. Method: A cross-sectional study was conducted between November 2005 and April 2006. Data were collected in face-to-face interviews using a standardized questionnaire. The sample consisted of 3,007 interviews with individuals aged 14 years and older and followed a probabilistic design covering the Brazilian national territory. Depressive symptoms were assessed according to the Center for Epidemiologic Studies Depression Scale. Results: The observed prevalence of depressive symptoms was 28.3% (13% mild/moderate; 15.3% major/severe; p < 0.01). Increased depressive symptom rates were associated with being a female, being 45 years of age and older, having lower educational attainment, being single, having family income of up to 2.5 times minimum wage, and living in the northern region of Brazil (p < 0.05). Conclusions: The prevalence of depressive symptoms in Brazil is high, with major depressive symptoms being the most frequent form of this symptomatology. Considering the biopsychosocial model of mental disorders, this survey points to the involvement of psychosocial factors in the prevalence of depressive symptoms in Brazil.

Dear Editor, The use of antipsychotics in patients with anxiety in recent years has increased, with a recent study showing that over a 12-year period, antipsychotic prescriptions in visits for anxiety disorders increased from 10.6 to 21.3 %, with the biggest increase among panic disorder (PD) patients (from 8 to 21.3 %) (Comer et al. 2011). Reasons for this remain unclear, but possible explanations include changes in patient characteristics, including increasing severity of illnesses among outpatient clients; greater prevalence or recognition of comorbidities (Comer et al. 2011); greater physician emphasis on symptom reduction, with increased acceptance of off-label antipsychotic prescriptions; a possible extrapolation to anxiety subjects by psychiatrists from their clinical experience of treating depressed patients with antipsychotics (Berman et al. 2009); and the availability of new antipsychotics with better side effect profiles, leading to a trend of changing from typical to atypical antipsychotics (Crystal et al. 2009). Also, contributing to this scenario could have been the fact that even with well-established treatment options, nearly 20 % of PD patients will remain substantially ill despite the use of the usual antipanic medication (Holt and Lydiard 2007). Furthermore, there is increasing evidence for the role of dopamine in fear and anxiety, through its modulation as a cortical brake that themedial prefrontal cortex exerts on the anxiogenic output of the amygdala, influencing the trafficking of impulses between the basolateral and central nuclei of the amygdala (de la Mora et al. 2010). Sulpiride is an antipsychotic of the benzamide type, structurally similar to amisulpride, and is used to treat schizophrenia, as well as depressive symptoms (Ruther et al. 1999). Also, anxiolytic-like effects of this drug have been reported in the elevated plus-maze test (Rodgers et al. 1994) and stress-induced freezing behavior in rats (Cavazzuti et al. 1999), in punished drinking behavior (Pich and Samanin 1986), and the mouse hyperdefensiveness test (PuglisiAllegra and Cabib 1988), suggesting a probable role in treatment of anxiety disorders, even as monotherapy. It is an antagonist of D2/D3 receptors, with almost no affinity for other receptors (Miyamoto et al. 2005), representing a good option in studies targeting effects on dopaminergic transmission. The aim of this study was to investigate the effects of 8 weeks of treatment with sulpiride on anxiety symptoms in a population with refractory PD. An open label challenge with sulpiride was conducted with 19 subjects (8 males and 11 females), aged 22 to 58 (mean age, 37.4 years). All patients were recruited from the outpatient clinic of Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro, in its Panic and Respiration Laboratory after a structured clinical interview (The Mini International Neuropsychiatric Interview) (Sheehan et al. 1998) and meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for PD with agoraphobia. The subjects had no other E. A. Nunes (*) : J. A. S. Crippa : J. E. C. Hallak Department of Neuroscience and Behavior, Ribeirao Preto Medical School, University of Sao Paulo, National Institute for Translational Medicine (INCT-TM), Av. Bandeirantes, 3900, Monte Alegre S/N, Hospital das Clinicas 3o andar, Ribeirao Preto, SP, Brazil 14048-900 e-mail: emerson_arcoverde@yahoo.com.br

The survival of any organism, animal or human, relies on the ability to accurately process, sense or tell time. Emerging evidence shows that timing is a crucial element in most, if not all, cognitive functioning and motor behaviour. Advances made by timing researchers provide valuable information on the neural substrates of interval timing, which indicate the involvement of certain brain areas and networks, most of which have not only been implicated in conditions such as schizophrenia, but are also abundant with cannabinoid receptors. A distorted sense of time is one of the most common effects of cannabis reported by users. In this paper, we present a critical review of the existing research on the topic. The findings are inconclusive, mainly due to methodological variations and the paucity of research. Even though 70% of time estimation studies report over-estimation, the findings of time production and time reproduction studies remain inconclusive. More research with robust methods is required to reach conclusions about the precise effect of cannabis and its active compounds on time perception. Such studies may also lead towards a better understanding of the mechanisms involved in brain functioning.

Δ(9)-tetrahydrocannabinol (Δ(9)-THC) is the main compound of the Cannabis Sativa responsible for most of the effects of the plant. Another major constituent is cannabidiol (CBD), formerly regarded to be devoid of pharmacological activity. However, laboratory rodents and human studies have shown that this cannabinoid is able to prevent psychotic-like symptoms induced by high doses of Δ(9)- THC. Subsequent studies have demonstrated that CBD has antipsychotic effects as observed using animal models and in healthy volunteers. Thus, this article provides a critical review of the research evaluating antipsychotic potential of this cannabinoid. CBD appears to have pharmacological profile similar to that of atypical antipsychotic drugs as seem using behavioral and neurochemical techniques in animal models. Additionally, CBD prevented human experimental psychosis and was effective in open case reports and clinical trials in patients with schizophrenia with a remarkable safety profile. Moreover, fMRI results strongly suggest that the antipsychotic effects of CBD in relation to the psychotomimetic effects of Δ(9)-THC involve the striatum and temporal cortex that have been traditionally associated with psychosis. Although the mechanisms of the antipsychotic properties are still not fully understood, we propose a hypothesis that could have a heuristic value to inspire new studies. These results support the idea that CBD may be a future therapeutic option in psychosis, in general and in schizophrenia, in particular.

Objective: Specific phobia (SP) is characterized by irrational fear associated with avoidance of specific stimuli. In recent years, neuroimaging techniques have been used in an attempt to better understand the neurobiology of anxiety disorders. The objective of this study was to perform a systematic review of articles that used neuroimaging techniques to study SP. Method: A literature search was conducted through electronic databases, using the keywords: imaging, neuroimaging, PET, spectroscopy, functional magnetic resonance, structural magnetic resonance, SPECT, MRI, DTI, and tractography, combined with simple phobia and specific phobia. One-hundred fifteen articles were found, of which 38 were selected for the present review. From these, 24 used fMRI, 11 used PET, 1 used SPECT, 2 used structural MRI, and none used spectroscopy. Result: The search showed that studies in this area were published recently and that the neuroanatomic substrate of SP has not yet been consolidated. Conclusion: In spite of methodological differences among studies, results converge to a greater activation in the insula, anterior cingulate cortex, amygdala, and prefrontal and orbitofrontal cortex of patients exposed to phobia-related situations compared to controls. These findings support the hypotheses of the hyperactivation of a neuroanatomic structural network involved in SP. ©2012 Elsevier Editora Ltda. All rights reserved.

Body stability is controlled by the postural system and can be affected by fear and anxiety. Few studies have addressed freezing posture in psychiatric disorders. The purpose of the present study was to assess posturographic behavior in 30 patients with social anxiety disorder (SAD) and 35 without SAD during presentation of blocks of pictures with different valences. Neutral images consisted of objects taken from a catalog of pictures, negative images were mutilation pictures and anxiogenic images were related to situations regarding SAD fears. While participants were standing on a force platform, similar to a balance, displacement of the center of pressure in the mediolateral and anteroposterior directions was measured. We found that the SAD group exhibited a lower sway area and a lower velocity of sway throughout the experiment independent of the visual stimuli, in which the phobic pictures, a stimulus associated with a defense response, were unable to evoke a significantly more rigid posture than the others. We hypothesize that patients with SAD when entering in a situation of exposure, from the moment the pictures are presented, tend to move less than controls, remaining this way until the experiment ends. This discrete body manifestation can provide additional data to the characterization of SAD and its differentiation from other anxiety disorders, especially in situations regarding facing fear.

The present study evaluated mitochondrial respiratory chain and creatine kinase activities after administration of harmine (5, 10, and 15 mg/kg) and imipramine (10, 20, and 30 mg/kg) in rat brain. After acute treatment occurred an increase of creatine kinase in the prefrontal with imipramine (20 and 30 mg/kg) and harmine in all doses, in the striatum with imipramine (20 and 30 mg/kg) and harmine (5 and 10 mg/kg); harmine (15 mg/kg) decreased creatine kinase. In the chronic treatment occurred an increase of creatine kinase with imipramine (20 mg/kg), harmine (5 mg/kg) in the prefrontal with imipramine (20 and 30 mg/kg) and harmine (5 and 10 mg/kg) in the striatum. In the acute treatment, the complex I increased in the prefrontal with harmine (15 mg/kg) and in the striatum with harmine (10 mg/kg); the complex II decreased with imipramine (20 and 30 mg/kg) in the striatum; the complex IV increased with imipramine (30 mg/kg) in the striatum. In the chronic treatment, the complex I increased with harmine (5 mg/kg) in the prefrontal; the complex II increased with imipramine (20 mg/kg) in the prefrontal; the complex IV increased with harmine (5 mg/kg) in the striatum. Finally, these findings further support the hypothesis that harmine and imipramine could be involved in mitochondrial function.

Neuropsychiatric sequelae are the predominant long-term disability after traumatic brain injury (TBI). This study reports a case of late-onset social anxiety disorder (SAD) following TBI.A patient that was spontaneous and extroverted up to 18-years-old started to exhibit significant social anxiety symptoms. These symptoms became progressively worse and he sought treatment at age 21. He had a previous history of traumatic brain injury (TBI) at age 17. Neuroimaging investigations (CT, SPECT and MRI) showed a bony protuberance on the left frontal bone, with mass effect on the left frontal lobe. He had no neurological signs or symptoms. The patient underwent neurosurgery with gross total resection of the lesion and the pathological examination was compatible with intradiploic haematoma.Psychiatric symptoms may be the only findings in the initial manifestation of slowly growing extra-axial space-occupying lesions that compress the frontal lobe from the outside. Focal neurological symptoms may occur only when the lesion becomes large. This case report underscores the need for careful exclusion of general medical conditions and TBI history in cases of late-onset SAD and may also contribute to the elucidation of the neurobiology of this disorder.

The objective was to conduct a retrospective and comparative study of the requests for consultation-liaison (RCLs), during a period of six years, sent to the Occupational Therapy (OT) team that acts as the Consultation-liaison Service in Mental Health. During the studied period 709 RCLs were made and 633 patients received OT consultations. The comparison group was extended to 1 129 consecutive referrals to the psychiatric CL service, within the same period and that were also retrospectively reviewed. Regarding to RCLs to the OT team, most of the subjects were women with incomplete elementary schooling, with a mean age of 39.2 years, and were self-employed or retired. Internal Medicine was responsible for most of the RCLs. The mean length of hospitalization was 51 days and the mean rate of referral was 0.5%, with the most frequent reason for the request being related to the emotional aspects and the most frequent psychiatric diagnosis was mood disorder. It is concluded that there is a clear demand for the development of consultation-liaison in OT, particularly with regard to the promotion of mental health in general hospitals.

Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4days after the induction of LPS-induced acute lung injury. Additionally, adenosine A2A receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (a highly selective antagonist of adenosine A2A receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A2A receptor.

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

Background Despite the fact that public speaking is a common academic activity and that social phobia has been associated with lower educational achievement and impaired academic performance, little research has examined the prevalence of social phobia in college students. The aim of this study was to evaluate the prevalence of social phobia in a large sample of Brazilian college students and to examine the academic impact of this disorder. Methods The Social Phobia Inventory (SPIN) and the MINI-SPIN, used as the indicator of social phobia in the screening phase, were applied to 2319 randomly selected students from two Brazilian universities. For the second phase (diagnostic confirmation), four psychiatrists and one clinical psychologist administered the SCID-IV to subjects with MINI-SPIN scores of 6 or higher. Results The prevalence of social phobia among the university students was 11.6%. Women with social phobia had significantly lower grades than those without the disorder. Fear of public speaking was the most common social fear. Only two of the 237 students with social phobia (0.8%) had previously received a diagnosis of social phobia and were under treatment. Limitations Social phobia comorbidities were not evaluated in this study. The methods of assessment employed by the universities (written exams) may mask the presence of social phobia. This was not a population-based study, and thus the results are not generalizable to the entire population with social phobia. Conclusion Preventive strategies are recommended to reduce the under-recognition and the adverse impact of social phobia on academic performance and overall quality of life of university students.

Rationale: Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately. Objective: To evaluate and compare the acute pharmacological effects of both THC and CBD in the same human volunteers. Methods: A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Oral THC 10 mg or CBD 600 mg or placebo was administered in three consecutive sessions, at one-month interval. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration. The area under the curve (AUC) between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition (THC or CBD or placebo) as the factor. Results: Relative to both placebo and CBD, administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication (AUC and effect at 2 hours: p

This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.

To analyze the psychometric properties of the Brazilian Portuguese version of the Beck Anxiety Inventory (BAI) in terms of its internal consistency, scores distribution, concurrent and discriminant validity, and factorial analysis in a sample of university students and social anxiety disorder (SAD) cases and non-cases.A sample of Brazilian university students from the general population (N = 2314) and a sample of university students identified as cases (N = 88) and non-cases (N = 90) of SAD were assessed, using as a parameter the Structured Clinical Interview for the DSM-IV. The different instruments were completed individually in the presence of an experienced rater.The BAI showed adequate internal consistency (0.88-0.92) and discriminant validity, with 0.74 sensitivity and 0.71 specificity for a cut-off score of 10. The factorial analysis suggested a three-factor solution to be the most adequate.The version of the BAI studied is quite adequate to be used in the context of Brazilian university students, identifying the presence of anxiety indicators. However, its usefulness to screen for SAD seems limited.

Parkinson's disease is universal and the second most prevalent neurodegenerative disease among the elderly affecting between 0.5 and 1% of the population between 65 and 69 years of age. Adherence to medication is considered the main determinant for the effectiveness of treatment, but only recently has it been studied in patients with Parkinson's disease. This cross-sectional and descriptive study assessed adherence to medication in 112 patients with Parkinson's disease who regularly attended the movement disorder outpatient unit at the Hospital das Clinicas of the School of Medicine of Ribeirao Preto, University of São Paulo, using the Morisky and Green test and an instrument that assesses attitudes of medicine intake (IAAFTR). Of the patients interviewed, 53% failed to adhere to treatment and 52% did not take the medication at the correct time. Patients should receive guidance about the importance of taking their medication at the correct time, understanding the benefits that adherence to medication can provide. They should also be aware that doses not taken, taken in excess or not taken at the prescribed times can reduce their response to treatment, having a negative effect on the clinical outcome and quality of life, thereby generating higher costs to public health in the country.

1.1 Social anxiety disorder Social anxiety disorder (SAD) is considered to be the third most prevalent psychiatric disorder (Brunello, 2000; Moutier & Stein, 1999). The condition was officially recognized as a diagnostic category in the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), in 1980 (American Psychiatric Association [APA], 1980), and currently, in the fourth edition of the manual (DSM-IV, APA, 1994), it is classified among anxiety disorders. SAD is characterized by the fear and/or avoidance of public exposure and performance, in an attempt to avoid possible humiliation, shame or embarrassment, associated with significant subjective anxiety accompanied mainly by autonomic symptoms such as tachycardia, tremors, and sweating, with substantial psychic suffering and functional impairment (APA, 1994). The most frequently feared and avoided situations include speaking, eating, drinking, and writing in public, interacting with strangers, people of the opposite sex, and authorities, and being the center of attention and/or the target of criticism (APA, 1994; Crippa et al., 2007). According to the situations avoided, SAD may be clinically classified as generalized (fear/avoidance of several performance situations and social interaction) or circumscribed (fear/avoidance of specific situations and events, the most frequent of which is public speaking) (APA, 1994; Raj & Sheehan, 2001). The onset of SAD usually occurs in early adolescence (Crippa et al., 2007; Kessler et al., 1998). Although it is not considered a disabling condition, SAD causes severe impairment in such different areas of life as work, academic activities, family and loving relationships, and social and economic life (Furmark, 2000; Schneier et al., 1992; Stein et al., 2005). The level of comorbidity associated with SAD is significant – around 70% and the most commonly associated conditions are depression, substance abuse (alcohol and drugs), dysthymia, suicidal ideation, and other anxiety disorders (Filho et al., 2010; Mohammadi et al., 2006; Raj S Wittchen & Fehm, 2003). Despite its high prevalence rates (5-14%), the recognition of SAD as a pathological condition by patients and even by health professionals is low, around 3% (Davidson et al., 1993; Martin-Santos & Crippa, 2003). In a Brazilian study by Baptista (2006), only 0.8% out of 237

SummaryWe investigated whether there is an association between anxiety disorders and mitral valve prolapse. We compared mitral valve prolapse prevalence in individuals with panic disorder (n = 41), social anxiety disorder (n = 89) and in healthy controls (n = 102) in an attempt to overcome the biases of previous studies. Our results show no associations between panic disorder or social anxiety disorder and mitral valve prolapse, regardless of the diagnostic criteria employed, and that the relationship between these conditions seems not to be clinically relevant.

INTRODUÇÃO: O transtorno de ansiedade social (TAS) é o transtorno de ansiedade mais comum, freqüentemente sem remissões, sendo comumente associado com importante prejuízo funcional e psicossocial. A Associação Médica Brasileira (AMB), através do "Projeto Diretrizes", busca desenvolver consensos de diagnóstico e tratamento para as doenças mais comuns. O objetivo deste trabalho é apresentar os achados mais relevantes das diretrizes relativas ao tratamento do TAS, servindo de referência para o médico generalista e especialista. MÉTODO: O método utilizado foi o proposto pela AMB. A busca foi realizada nas bases de dados do MEDLINE (PubMed), Scopus, Web of Science e Lilacs, entre 1980 e 2010. A estratégia utilizada baseou-se em perguntas estruturadas na forma P.I.C.O (acrônimo das iniciais "paciente ou população"; "intervenção, indicador ou exposição"; "controle ou comparação" e; "outcome ou desfecho"). RESULTADOS: Estudos evidenciam que o tratamento farmacológico de primeira linha para adultos e crianças são os inibidores seletivos de recaptação de serotonina e os inibidores de recaptação de serotonina e noradrenalina, enquanto que a terapia cognitivo-comportamental é apontada como melhor tratamento psicoterápico. Além disso, algumas comorbidades psiquiátricas foram associadas a uma pior evolução do TAS. CONCLUSÕES: Apesar da alta prevalência, o TAS acaba por não receber a devida atenção e tratamento. A melhor escolha para o tratamento de adultos é a associação psicoterapia cognitivo-comportamental com inibidores seletivos de recaptação de serotonina e os inibidores de recaptação de serotonina e noradrenalina. Outras opções como benzodiazepínicos ou inibidores da monoamino-oxidase devem ser usados como segunda e terceira opção respectivamente. INTRODUCTION: Social anxiety disorder (SAD) is the most common anxiety disorder, usually with no remission, and is commonly associated with significant functional and psychosocial impairment. The Brazilian Medical Association (BMA), with the project named Diretrizes (Guidelines, in English), seeks to develop consensus for the diagnosis and treatment of common diseases. The aim of this article is to present the most important findings of the guidelines on the treatment of SAD, serving as a reference for the general practitioner and specialist. METHOD: The method used was proposed by the BMA. The search was conducted in the databases of MEDLINE (PubMed), Scopus, Web of Science and LILACS, between 1980 and 2010. The strategy used was based on structured questions as PICO (acronym formed by the initials of "patient or population", "intervention, display or exhibition", "control or comparison" and "outcome"). RESULTS: Studies show that the first-line pharmacological treatment for adults and children are serotonin selective reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, whereas cognitive-behavioral therapy is considered the best psychotherapeutic treatment. Moreover, some psychiatric comorbidities were associated with a worse outcome of SAD. CONCLUSIONS: Despite its high prevalence, SAD does not receive adequate attention and treatment. The best choice for the treatment of adults is a combination of cognitive-behavioral psychotherapy with serotonin selective reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors. Other options as benzodiazepines or monoamine oxidase inhibitors must be used as second and third choices, respectively.

Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", "cannabidiol" and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.

Generalized Social Anxiety Disorder (SAD) is one of the most common anxiety conditions with impairment in social life. Cannabidiol (CBD), one major non-psychotomimetic compound of the cannabis sativa plant, has shown anxiolytic effects both in humans and in animals. This preliminary study aimed to compare the effects of a simulation public speaking test (SPST) on healthy control (HC) patients and treatment-naive SAD patients who received a single dose of CBD or placebo. A total of 24 never-treated patients with SAD were allocated to receive either CBD (600 mg; n=12) or placebo (placebo; n=12) in a double-blind randomized design 1 h and a half before the test. The same number of HC (n=12) performed the SPST without receiving any medication. Each volunteer participated in only one experimental session in a double-blind procedure. Subjective ratings on the Visual Analogue Mood Scale (VAMS) and Negative Self-Statement scale (SSPS-N) and physiological measures (blood pressure, heart rate, and skin conductance) were measured at six different time points during the SPST. The results were submitted to a repeated-measures analysis of variance. Pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in their speech performance, and significantly decreased alert in their anticipatory speech. The placebo group presented higher anxiety, cognitive impairment, discomfort, and alert levels when compared with the control group as assessed with the VAMS. The SSPS-N scores evidenced significant increases during the testing of placebo group that was almost abolished in the CBD group. No significant differences were observed between CBD and HC in SSPS-N scores or in the cognitive impairment, discomfort, and alert factors of VAMS. The increase in anxiety induced by the SPST on subjects with SAD was reduced with the use of CBD, resulting in a similar response as the HC.