Epigenetic variation at the SLC6A4 gene promoter in mother-child pairs with major depressive disorder.

BACKGROUND: Genetic and epigenetic variations of the serotonin transporter gene (SLC6A4) have been related to the etiology of depression. The 5-HTTLPR polymorphism at the SLC6A4 promoter region has two variants, a short allele (S) and a long allele (L), in which the S allele results in lower gene transcription and has been associated with depression. The short S-allele of 5-HTTLPR polymorphism of this gene has been associated with depression. In addition to molecular mechanisms, exposure to early life risk factors such as maternal depression seems to affect the development of depression in postnatal life. The present study investigated the association of 5-HTTLPR polymorphism and CpG DNA methylation (5mC) levels of an AluJb repeat element at the SLC6A4 promoter region in mother-child pairs exposed to maternal depression. METHODS: We analyzed DNA samples from 60 subjects (30 mother-child pairs) split into three groups, with and without major depression disorder (DSM-IV) among children and mothers. The genotyping of 5-HTTLPR polymorphism and quantification of 5mC levels was performed by qualitative PCR and methylation-sensitive restriction enzyme digestion, and real-time quantitative PCR (MSRED-qPCR), respectively. RESULTS: The sample analyzed presented a higher frequency of S allele of 5-HTTLPR (67.5%). Despite the high frequency of this allele, we did not find statistically significant differences between individuals carrying at least one S allele between the depression and healthy control subjects, or among the mother-child pair groups with different patterns of occurrence of depression. In the group where the mother and child were both diagnosed with depression, we found a statistically significant decrease of the 5mC level at the SLC6A4 promoter region. LIMITATIONS: The limitations are the relatively small sample size and lack of gene expression data available for comparison with methylation data. CONCLUSION: In this study, we demonstrated a repeat element specific 5mC level reduction in mother-child pairs, concordant for the diagnosis of depression.

Burnout, anxiety, depression, and social skills in medical residents.

The medical residency is recognized as a risk period for the development of burnout and mental health problems, such as anxiety and depression, which have impact on the physician and clientele alike. There is a need for studies that address conditions of risk and protection for the development of such problems. This study aimed to verify the rates of burnout, anxiety, and depression presented by resident physicians, as well as the associations of these problems with social skills, as potential protective factors. The hypothesis was defined that the problems (burnout, anxiety, and depression) would be negatively associated with social skills. A total of 305 medical residents, of both genders, of different specialties, from clinical and surgical areas of a Brazilian university hospital were evaluated using the following standardized self-report instruments: Burnout Syndrome Inventory, Social Skills Inventory, and the Patient Health Questionnaire-4. High rates of burnout and mental health problems were verified and social skills were negatively associated with burnout dimensions such as emotional exhaustion, emotional detachment, and dehumanization, but positively associated with personal accomplishment. Furthermore, residents with indicators of problems presented significantly lower social skills means than those of residents without indicators of burnout, anxiety, or depression. More studies are needed, which include other types of instruments in addition to self-report ones and evaluate not only social skills but also social competence in the professional practice. These should adopt intervention and longitudinal designs that allow the continuity or overcoming of the problems to be verified. Since social skills can be learned, the results of the study highlight the importance of developing the interpersonal skills of the professionals during the training of resident physicians in order to improve their practice.

The response of social anxiety disorder patients to threat scenarios differs from that of healthy controls

The objective of the present study was to evaluate the response of social anxiety disorder (SAD) patients to threat scenarios. First-choice responses to 12 scenarios describing conspecific threatening situations and mean scores of defensive direction and defensive intensity dimensions were compared between 87 SAD patients free of medication and 87 matched healthy controls (HC). A significant gender difference in the first-choice responses was identified for seven scenarios among HCs but only for two scenarios among SAD patients. A significantly higher proportion of SAD patients chose "freezing" in response to "Bush" and "Noise" scenarios, whereas the most frequent response by HCs to these scenarios was "check out". SAD males chose "run away" and "yell" more often than healthy men in response to the scenarios "Park" and "Elevator", respectively. There was a positive correlation between the severity of symptoms and both defensive direction and defensive intensity dimensions. Factorial analysis confirmed the gradient of defensive reactions derived from animal studies. SAD patients chose more urgent defensive responses to threat scenarios, seeming to perceive them as more dangerous than HCs and tending to move away from the source of threat. This is consistent with the hypothesis that the physiopathology of anxiety disorders involves brain structures responsible for defensive behaviors.

The response of social anxiety disorder patients to threat scenarios differs from that of healthy controls.

The objective of the present study was to evaluate the response of social anxiety disorder (SAD) patients to threat scenarios. First-choice responses to 12 scenarios describing conspecific threatening situations and mean scores of defensive direction and defensive intensity dimensions were compared between 87 SAD patients free of medication and 87 matched healthy controls (HC). A significant gender difference in the first-choice responses was identified for seven scenarios among HCs but only for two scenarios among SAD patients. A significantly higher proportion of SAD patients chose "freezing" in response to "Bush" and "Noise" scenarios, whereas the most frequent response by HCs to these scenarios was "check out". SAD males chose "run away" and "yell" more often than healthy men in response to the scenarios "Park" and "Elevator", respectively. There was a positive correlation between the severity of symptoms and both defensive direction and defensive intensity dimensions. Factorial analysis confirmed the gradient of defensive reactions derived from animal studies. SAD patients chose more urgent defensive responses to threat scenarios, seeming to perceive them as more dangerous than HCs and tending to move away from the source of threat. This is consistent with the hypothesis that the physiopathology of anxiety disorders involves brain structures responsible for defensive behaviors.

Social anxiety disorder: what are we losing with the current diagnostic criteria?

OBJECTIVE: To assess the rate of comorbidities and the functional impairment associated with the social anxiety disorder (SAD), with an emphasis on the so-called subthreshold clinical signs and symptoms. METHOD: Psychiatric comorbidities and psychosocial functioning were evaluated in 355 volunteers (college students) who had been diagnosed as SAD (n = 141), Subthreshold SAD (n = 92) or Controls (n = 122). RESULTS: The rate of comorbidities was 71.6% in the SAD group and 50% in subjects with Subthreshold SAD, both significantly greater than Controls (28.7%). Concerning psychosocial functioning, the SAD group had higher impairment than the other two groups in all domains evaluated, and subjects with Subthreshold SAD presented intermediate values. CONCLUSION: The rates of psychiatric comorbidities and the impairment of psychosocial functioning increase progressively along the spectrum of social anxiety. The fact that Subthreshold SAD causes considerable disability and suffering in comparison with control subjects justifies a review of the validity of the diagnostic criteria.

Study of the psychometric qualities of the Brief Social Phobia Scale (BSPS) in Brazilian university students.

PURPOSE: To perform a psychometric analysis of the Brazilian version of the Brief Social Phobia Scale (BSPS). MATERIALS AND METHODS: Hundred and seventy-eight university students of both genders aged on average 21.2 years and identified as Social Anxiety Disorder (SAD) cases and non-cases was studied, with the structured clinical interview for DSM-IV being used as a parameter. The different instruments were applied in an individual manner in the presence of a rater and of an observer. RESULTS: The BSPS showed adequate internal consistency (0.48-0.88) and concurrent and divergent validity with the Beck Anxiety Inventory (BAI) (0.21-0.62), Social Phobia Inventory (0.24-0.82) and Self Statements During Public Speaking Scale (SSPS) (0.23-0.31). Discriminative validity revealed a sensitivity of 0.88-0.90 and a specificity of 0.81(0.83 for cut-off notes of 18/19. Factorial analysis demonstrated the presence of six factors that jointly explained 71.79% of data variance. Construct validity indicated some limits of the scale regarding the diagnosis of SAD. Inter-rater reliability was strong (0.86-1.00, p<0.001). CONCLUSIONS: The BSPS is adequate for use with university students, although further studies in different cultures, samples and contexts are still necessary.

Defensive responses to threat scenarios in Brazilians reproduce the pattern of Hawaiian Americans and non-human mammals.

A former study with scenarios conducted in Hawaii has suggested that humans share with non-human mammals the same basic defensive strategies - risk assessment, freezing, defensive threat, defensive attack, and flight. The selection of the most adaptive strategy is strongly influenced by features of the threat stimulus - magnitude, escapability, distance, ambiguity, and availability of a hiding place. Aiming at verifying if these strategies would be consistent in a different culture, 12 defensive scenarios were translated into Portuguese and adapted to the Brazilian culture. The sample consisted of male and female undergraduate students divided into two groups: 76 students, who evaluated the five dimensions of each scenario and 248 medical students, who chose the most likely response for each scenario. In agreement with the findings from studies of non-human mammal species, the scenarios were able to elicit different defensive behavioral responses, depending on features of the threat. "Flight" was chosen as the most likely response in scenarios evaluated as an unambiguous and intense threat, but with an available route of escape, whereas "attack" was chosen in an unambiguous, intense and close dangerous situation without an escape route. Less urgent behaviors, such as "check out", were chosen in scenarios evaluated as less intense, more distant and more ambiguous. Moreover, the results from the Brazilian sample were similar to the results obtained in the original study with Hawaiian students. These data suggest that a basic repertoire of defensive strategies is conserved along the mammalian evolution because they share similar functional benefits in maintaining fitness.

Defensive responses to threat scenarios in Brazilians reproduce the pattern of Hawaiian Americans and non-human mammals

A former study with scenarios conducted in Hawaii has suggested that humans share with non-human mammals the same basic defensive strategies - risk assessment, freezing, defensive threat, defensive attack, and flight. The selection of the most adaptive strategy is strongly influenced by features of the threat stimulus - magnitude, escapability, distance, ambiguity, and availability of a hiding place. Aiming at verifying if these strategies would be consistent in a different culture, 12 defensive scenarios were translated into Portuguese and adapted to the Brazilian culture. The sample consisted of male and female undergraduate students divided into two groups: 76 students, who evaluated the five dimensions of each scenario and 248 medical students, who chose the most likely response for each scenario. In agreement with the findings from studies of non-human mammal species, the scenarios were able to elicit different defensive behavioral responses, depending on features of the threat. "Flight" was chosen as the most likely response in scenarios evaluated as an unambiguous and intense threat, but with an available route of escape, whereas "attack" was chosen in an unambiguous, intense and close dangerous situation without an escape route. Less urgent behaviors, such as "check out", were chosen in scenarios evaluated as less intense, more distant and more ambiguous. Moreover, the results from the Brazilian sample were similar to the results obtained in the original study with Hawaiian students. These data suggest that a basic repertoire of defensive strategies is conserved along the mammalian evolution because they share similar functional benefits in maintaining fitness.

Reliability and validity of a Portuguese version of the Young Mania Rating Scale.

The reliability and validity of a Portuguese version of the Young Mania Rating Scale were evaluated. The original scale was translated into and adapted to Portuguese by the authors. Definitions of clinical manifestations, a semi-structured anchored interview and more explicit rating criteria were added to the scale. Fifty-five adult subjects, aged 18 to 60 years, with a diagnosis of Current Manic Episode according to DSM-III-R criteria were assessed using the Young Mania Rating Scale as well as the Brief Psychiatric Rating Scale in two sessions held at intervals from 7 to 10 days. Good reliability ratings were obtained, with intra-class correlation coefficient of 0.97 for total scores, and levels of agreement above 0.80 (P < 0.001) for all individual items. Internal consistency analysis resulted in an alpha = 0.67 for the scale as a whole, and an alpha = 0.72 for each standardized item (P < 0.001). For the concurrent validity, a correlation of 0.78 was obtained by the Pearson coefficient between the total scores of the Young Mania Rating Scale and Brief Psychiatric Rating Scale. The results are similar to those reported for the English version, indicating that the Portuguese version of the scale constitutes a reliable and valid instrument for the assessment of manic patients.

Reliability and validity of a Portuguese version of the Young Mania Rating Scale

The reliability and validity of a Portuguese version of the Young Mania Rating Scale were evaluated. The original scale was translated into and adapted to Portuguese by the authors. Definitions of clinical manifestations, a semi-structured anchored interview and more explicit rating criteria were added to the scale. Fifty-five adult subjects, aged 18 to 60 years, with a diagnosis of Current Manic Episode according to DSM-III-R criteria were assessed using the Young Mania Rating Scale as well as the Brief Psychiatric Rating Scale in two sessions held at intervals from 7 to 10 days. Good reliability ratings were obtained, with intra-class correlation coefficient of 0.97 for total scores, and levels of agreement above 0.80 (P < 0.001) for all individual items. Internal consistency analysis resulted in an alpha = 0.67 for the scale as a whole, and an alpha = 0.72 for each standardized item (P < 0.001). For the concurrent validity, a correlation of 0.78 was obtained by the Pearson coefficient between the total scores of the Young Mania Rating Scale and Brief Psychiatric Rating Scale. The results are similar to those reported for the English version, indicating that the Portuguese version of the scale constitutes a reliable and valid instrument for the assessment of manic patients.

Factor structure of Bech's version of the Brief Psychiatric Rating Scale in Brazilian patients.

The objective of the present study was to evaluate the factor structure of Bech's version of the Brief Psychiatric Rating Scale (BPRS), translated into Portuguese. The BPRS was administered to a heterogeneous group of psychiatric inpatients (N = 98) and outpatients (N = 62) in a University Hospital. Each patient was evaluated from one to eight times. The interval between consecutive interviews was one week for the inpatients and one month for the outpatients. The results were submitted to factorial analysis. The internal consistency of the total scale and of each factor was also estimated. Factorial analysis followed by normalized orthogonal rotation (Varimax) yielded four factors: Withdrawal-Retardation, Thinking Disorder, Anxious-Depression and Activation. Internal consistency measured by Cronbach's alpha coefficient ranged from 0.766 to 0.879. The data show that the factor structure of the present instrument is similar to that of the American version of the BPRS which contains 18 items, except for the absence of the fifth factor of the latter scale, Hostile-Suspiciousness.

Factor structure of Bech's version of the Brief Psychiatric Rating Scale in Brazilian patients

The objective of the present study was to evaluate the factor structure of Bech's version of the Brief Psychiatric Rating Scale (BPRS), translated into Portuguese. The BPRS was administered to a heterogeneous group of psychiatric inpatients (N = 98) and outpatients (N = 62) in a University Hospital. Each patient was evaluated from one to eight times. The interval between consecutive interviews was one week for the inpatients and one month for the outpatients. The results were submitted to factorial analysis. The internal consistency of the total scale and of each factor was also estimated. Factorial analysis followed by normalized orthogonal rotation (Varimax) yielded four factors: Withdrawal-Retardation, Thinking Disorder, Anxious-Depression and Activation. Internal consistency measured by Cronbach's alpha coefficient ranged from 0.766 to 0.879. The data show that the factor structure of the present instrument is similar to that of the American version of the BPRS which contains 18 items, except for the absence of the fifth factor of the latter scale, Hostile-Suspiciousness

A structured interview guide increases Brief Psychiatric Rating Scale reliability in raters with low clinical experience.

OBJECTIVE: To assess the beneficial impact of a structured interview on the reliability of BPRS ratings in raters with low clinical experience. METHOD: Each patient was rated once a week in two separate interviews, conducted on the same day. The first interview was conducted by a rater with low clinical experience (recruited from a group of five residents in psychiatry and one clinical psychologist in training). All second interviews were conducted by the same highly experienced psychiatrist. RESULTS: The number of items with full agreement between observers increased with the use of SIG. The value of intraclass correlation coefficients for individual items and the total score also increased, approaching reported studies with experienced raters. CONCLUSION: These results suggest that the use of SIG reduces variability of information gathering in reliability testing of BPRS with less experienced raters.

Reliability, validity and factorial dimensions of the Interactive Observation Scale for Psychiatric Inpatients.

The Interactive Observation Scale for Psychiatric Inpatients (IOSPI) is characterized by the necessity of interaction between the rater and the patient during the evaluation process. The reliability, validity and factor structure of the IOSPI were evaluated by using a total of 186 sets of ratings accomplished by 2 nursing aides on 34 adult psychiatric inpatients submitted to weekly evaluations during the 3 first weeks of hospitalization. The patients were observed by the 2 nursing aides simultaneously during the morning shift (5 h). In the afternoon of the same day, they were interviewed by two psychiatrists who filled in separately the Brief Psychiatric Rating Scale (BPRS). Factor analysis of the 16 IOSPI items revealed 5 distinct clusters of items, which represented higher-order constructs of social interest, psychomotor agitation, psychoticism, neatness and irritability. It was found that the IOSPI has significant interrater reliability, estimated by an intraclass correlation coefficient of total score and factor score. The total scores of the IOSPI showed a significant correlation with the total scores of the BPRS, meeting the criteria of concurrent validity. The criteria of predictive validity were also met, since the patients who could be discharged presented IOSPI scores significantly lower than the patients who could not be discharged. In conclusion, the IOSPI met the requirements of an evaluation scale and can stimulate therapeutic attitudes of the nursing staff by its characteristics of interactive observation.

Um estudo multidisciplinar do sindrome da disfuncao cerebral minima (DCM). / A multidisciplinary study of minimal brain dysfunction

Analisamos 15 criancas com o sindrome DCM, sendo 12 do sexo masculino, com idade media de 8 anos e 1 mes e 3 do sexo feminino, com idade media de 7 anos e 7 meses.Cada paciente foi submetido a entrevista estruturada, a historia contada pelos pais, e ainda avaliada do ponto de vista psiquiatrico, neurologico e psicometrico.Os resultados foram quantificados em forma de frequencia de ocorrencia e confrontados com os do grupo de criancas controle constituido de 13 sujeitos, sendo 8 do sexo masculino, com idade media de 7 anos. A comparacao entre os resultados dos dois grupos indicou as seguintes diferencas: a frequencia de ocorrencia dos sintomas e sinais e maior nas criancas DCM e que as diferencas da sintomatologia entre os dois grupos sao de ordem quantitativa. A analise dos nossos dados mostrou que o estudo interdisciplinar se mostrou efetivo para se diferenciar a crianca DCM da normal

Estudo comparativo das populacoes de pacientes psiquiatricos de dois ambulatorios que funcionam anexos a um hospital geral e a um hospital psiquiatrico. / Comparative study of psychiatric patients of two ambulatory services joined to a general hospital and a psychiatric hospital

O objetivo deste trabalho e descrever e analisar as diferencas entre servicos ambulatoriais de psiquiatria em uma mesma cidade. Dois servicos foram selecionados em uma cidade brasileira: Ribeirao Preto, Estado de Sao Paulo, sendo, respectivamente de um hospital psiquiatrico publico e de um hospital universitario