Behavioral self-regulation in pediatric bipolar disorder and healthy offspring of bipolar patients

Objectives: This study investigated behavioral self-regulation problems using the Children's Hostility Inventory (CHI) in pediatric bipolar disorder (PBD), healthy offspring of bipolar disorder patients (HOBD), and healthy controls (HC) without previous history of psychiatric disorders. Methods: The CHI was administered to 41 consecutive children and adolescents diagnosed with PBD, to 16 HOBD, and to 22 HC. The inventory assessed irritability, expression, hostility, and aggression and was completed by the children with the help of their mothers. Adolescents and their respective parents were interviewed separately using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). Results: All subscales of the CHI presented statistically significant differences, except for the subscale assessing feelings of suspicion. Pairwise comparisons revealed consistently significant differences between the PBD group and controls, indicating more self-regulation difficulties in the PBD group, represented by high levels of hostility and aggressive behavior. There were no significant differences between the PBD and HOBD groups. Conclusions: Future studies should further investigate if such behavior is state-dependent or a trait of bipolar juvenile expression. Expression of hostility and irritability should be considered relevant targets in psychosocial approaches addressing this population.

Precision non-implantable neuromodulation therapies: a perspective for the depressed brain

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more "precision-oriented" practice.

Differences in total brain volume between sexes in a cognitively unimpaired elderly population

OBJECTIVES: Although a large number of studies have shown brain volumetric differences between men and women, only a few investigations have analyzed brain tissue volumes in representative samples of the general elderly population. We investigated differences in gray matter (GM) volumes, white matter (WM) volumes, and intracranial volumes (ICVs) between the sexes in individuals older than 66 years using structural magnetic resonance imaging (MRI). METHODS: Using FreeSurfer version 5.3, we obtained the ICVs and GM and WM volumes from the MRI datasets of 84 men and 92 women. To correct for interindividual variations in ICV, GM and WM volumes were adjusted with a method using the residuals of a least-square-derived linear regression between raw volumes and ICVs. We then performed an analysis of covariance comparing men and women, including age and years of schooling as confounding factors. RESULTS: Women had a lower socioeconomic status overall and fewer years of schooling than men. The comparison of unadjusted brain volumes showed larger GM and WM volumes in men. After the ICV correction, the adjusted volumes of GM and WM were larger in women. CONCLUSION: After the ICV correction and taking into account differences in socioeconomic status and years of schooling, our results confirm previous findings of proportionally larger GM in women, as well as larger WM volumes. These results in an elderly population indicate that brain volumetric differences between sexes persist throughout the aging process. Additional studies combining MRI and other biomarkers to identify the hormonal and molecular bases influencing such differences are warranted.

The validity and reliability of the CAMDEX-DS for assessing dementia in adults with Down syndrome in Brazil

Objective: Alzheimer's disease occurs at a higher prevalence and an earlier age in individuals with Down syndrome (DS) than typically developing individuals. However, diagnosing dementia in individuals with intellectual disability remains a challenge due to pre-existing cognitive deficits. The aim of this study was to investigate the validity and reliability of the Brazilian version of the Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS) for individuals with DS. Methods: Two psychiatrists, working independently, evaluated 92 adults with DS ≥ 30 years of age. The concurrent validity of the CAMDEX-DS was analyzed in relation to the gold standard of established international criteria. In a subgroup of 20 subjects, the concurrent validity of the CAMDEX-DS was analyzed in relation to an independent objective assessment of cognitive decline over three years. We analyzed the inter-rater reliability of cognitive assessment. Results: The diagnostic accuracy of the CAMDEX-DS compared to the gold standard was 96.7%. CAMDEX-DS-based diagnosis was considered consistent with cognitive decline. The probability of a participant with dementia having cognitive decline was 83%. Inter-rater reliability for the participant assessment was good, with a kappa of > 0.8 for 93% of the CAMDEX-DS items. Conclusion: The CAMDEX-DS can be considered the first valid and reliable instrument for evaluating dementia in adults with DS in Brazil. Its use in such individuals could improve clinical practice and research.

Support vector machine-based classification of neuroimages in Alzheimer's disease: direct comparison of FDG-PET, rCBF-SPECT and MRI data acquired from the same individuals

Objective: To conduct the first support vector machine (SVM)-based study comparing the diagnostic accuracy of T1-weighted magnetic resonance imaging (T1-MRI), F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and regional cerebral blood flow single-photon emission computed tomography (rCBF-SPECT) in Alzheimer's disease (AD). Method: Brain T1-MRI, FDG-PET and rCBF-SPECT scans were acquired from a sample of mild AD patients (n=20) and healthy elderly controls (n=18). SVM-based diagnostic accuracy indices were calculated using whole-brain information and leave-one-out cross-validation. Results: The accuracy obtained using PET and SPECT data were similar. PET accuracy was 68∼71% and area under curve (AUC) 0.77∼0.81; SPECT accuracy was 68∼74% and AUC 0.75∼0.79, and both had better performance than analysis with T1-MRI data (accuracy of 58%, AUC 0.67). The addition of PET or SPECT to MRI produced higher accuracy indices (68∼74%; AUC: 0.74∼0.82) than T1-MRI alone, but these were not clearly superior to the isolated neurofunctional modalities. Conclusion: In line with previous evidence, FDG-PET and rCBF-SPECT more accurately identified patients with AD than T1-MRI, and the addition of either PET or SPECT to T1-MRI data yielded increased accuracy. The comparable SPECT and PET performances, directly demonstrated for the first time in the present study, support the view that rCBF-SPECT still has a role to play in AD diagnosis.

High frequency of silent brain infarcts associated with cognitive deficits in an economically disadvantaged population

OBJECTIVE: Using magnetic resonance imaging, we aimed to assess the presence of silent brain vascular lesions in a sample of apparently healthy elderly individuals who were recruited from an economically disadvantaged urban region (São Paulo, Brazil). We also wished to investigate whether the findings were associated with worse cognitive performance. METHODS: A sample of 250 elderly subjects (66-75 years) without dementia or neuropsychiatric disorders were recruited from predefined census sectors of an economically disadvantaged area of Sao Paulo and received structural magnetic resonance imaging scans and cognitive testing. A high proportion of individuals had very low levels of education (4 years or less, n=185; 21 with no formal education). RESULTS: The prevalence of at least one silent vascular-related cortical or subcortical lesion was 22.8% (95% confidence interval, 17.7-28.5), and the basal ganglia was the most frequently affected site (63.14% of cases). The subgroup with brain infarcts presented significantly lower levels of education than the subgroup with no brain lesions as well as significantly worse current performance in cognitive test domains, including memory and attention (p<0.002). CONCLUSIONS: Silent brain infarcts were present at a substantially high frequency in our elderly sample from an economically disadvantaged urban region and were significantly more prevalent in subjects with lower levels of education. Covert cerebrovascular disease significantly contributes to cognitive deficits, and in the absence of magnetic resonance imaging data, this cognitive impairment may be considered simply related to ageing. Emphatic attention should be paid to potentially deleterious effects of vascular brain lesions in poorly educated elderly individuals from economically disadvantaged environments.

Neural correlates of hallucinations in bipolar disorder

Objective: Approximately one-half of all patients affected by bipolar disorder present with psychotic features on at least one occasion. Several studies have found that alterations in the activity of mesolimbic and prefrontal regions are related to aberrant salience in psychotic patients. The aim of the present study was to investigate the structural correlates of a history of hallucinations in a sample of euthymic patients with bipolar I disorder (BD-I). Methods: The sample consisted of 21 euthymic patients with BD-I and no comorbid axis I DSM-IV-TR disorders. Voxel based morphometry (VBM) was used to compare patients with and without a lifetime history of hallucinations. Preprocessing was performed using the Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra (DARTEL) algorithm for VBM in SPM8. Images were processed using optimized VBM. Results: The main finding of the present study was a reduction in gray matter volume in the right posterior insular cortex of patients with BD-I and a lifetime history of hallucinations, as compared to subjects with the same diagnosis but no history of hallucinations. Conclusions: This finding supports the presence of abnormalities in the salience network in BD patients with a lifetime history of hallucinations. These alterations may be associated with an aberrant assignment of salience to the elements of one’s own experience, which could result in psychotic symptoms.

Executive dysfunction and low academic attainment in adolescent substance abusers with a history of maltreatment / Disfunção executiva e baixo desempenho escolar em adolescentes usuários de drogas com história de maus-tratos

OBJECTIVE: Substance abuse and maltreatment are highly associated with Executive Cognitive Function impairments, but very little is known about how symptoms of a condition known as Dysexecutive Syndrome may impact on real-life activities, especially in adolescents. This study investigated the presence of Executive Cognitive Function deficits in maltreated substance-abusing adolescents relative to healthy control subjects and analyzed the association between executive performance and educational attainment. METHOD: The sample consisted of 15 maltreated adolescent substance abusers and 15 non-maltreated healthy adolescents (controls). They were assessed by the Frontal Assessment Battery, composed of six subtests: Conceptualization, Mental flexibility, Motor programming, Sensitivity to interference, Inhibitory control, and Environmental autonomy. RESULTS: Maltreated adolescents did not differ from controls in sociodemographic variables such as age, ethnicity, and handedness. However, they performed significantly and importantly below controls in almost all domains of Executive Cognitive Function, including abstract abilities, cognitive flexibility, motor planning, and sensitivity to interference. Maltreated adolescents also completed fewer years of formal education vs. controls. The Frontal Assessment Battery total score correlated with educational attainment throughout the sample (r = 0.511; p < 0.01). CONCLUSION: Substance-abusing adolescents with a history of maltreatment performed more poorly vs. controls on a variety of measurements of executive functioning, and the results of the Frontal Assessment Battery were associated with educational attainment. Our results evidence a negative impact of dysexecutive symptoms on educational attainment in adolescents. Strategies focusing on neuropsychological rehabilitation may be relevant to help substance-abusing and maltreated adolescents to perform better at school and perhaps in life.

OBJETIVO: Abuso de substâncias e maus-tratos têm sido altamente associados com déficits nas funções executivas, porém pouco se conhece sobre o impacto da disfunção executiva nas atividades da vida real, especialmente em adolescentes. O objetivo deste estudo foi investigar a presença de déficits nas funções executivas em adolescentes abusadores de substâncias com histórico de maus-tratos, comparando-os com um grupo de jovens controles saudáveis, assim como analisar a associação entre o desempenho executivo e o nível de escolaridade dos participantes. MÉTODO: A amostra foi composta por 15 adolescentes abusadores de substâncias, vítimas de maus tratos e 15 adolescentes saudáveis, sem história de maus-tratos. Todos os participantes foram avaliados pela Bateria de Avaliação Frontal, composto por seis subtestes: Conceituação, Flexibilidade mental, Programação motora, Sensibilidade à interferência, Controle inibitório e Autonomia Ambiental RESULTADOS: Os adolescentes abusadores não diferiram dos controles saudáveis em variáveis sócio-demográficas, tais como idade, etnia e lateralidade. No entanto, apresentaram desempenho significativamente abaixo dos controles em quase todos os domínios das funções executivas, incluindo capacidade de abstração, flexibilidade cognitiva, planejamento motor e sensibilidade à interferência. Os adolescentes vítimas de maus tratos concluíram menos anos de educação formal do que os controles. A pontuação total da Bateria de Avaliação Frontal correlacionou com o nível de escolaridade, na amostra total (r = 0.511; p < 0.01). CONCLUSÃO: Os adolescentes abusadores de substâncias com histórico de maus-tratos apresentam prejuízos em várias medidas de Funções Executivas. Os resultados da Bateria de Avaliação Frontal associam-se com os anos completados de escolaridade. Nossos resultados evidenciam o impacto negativo da disfunção executiva no aproveitamento escolar em adolescentes. Estratégias com foco em reabilitação neuropsicológica podem ser relevantes para ajudar adolescentes abusadores de substâncias e vítimas de maus tratos a atingirem melhor aproveitamento na escola e, talvez, na vida como um todo.

The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

Objective: To review functional neuroimaging studies about the relationship between cardiovascular risk factors (CVRFs), Alzheimer's disease (AD), and mild cognitive impairment (MCI). Methods: We performed a comprehensive literature search to identify articles in the neuroimaging field addressing CVRF in AD and MCI. We included studies that used positron emission tomography (PET), single photon emission computerized tomography (SPECT), or functional magnetic resonance imaging (fMRI). Results: CVRFs have been considered risk factors for cognitive decline, MCI, and AD. Patterns of AD-like changes in brain function have been found in association with several CVRFs (both regarding individual risk factors and also composite CVRF measures). In vivo assessment of AD-related pathology with amyloid imaging techniques provided further evidence linking CVRFs and AD, but there is still limited information resulting from this new technology. Conclusion: There is a large body of evidence from functional neuroimaging studies supporting the hypothesis that CVRFs may play a causal role in the pathophysiology of AD. A major limitation of most studies is their cross-sectional design; future longitudinal studies using multiple imaging modalities are expected to better document changes in CVRF-related brain function patterns and provide a clearer picture of the complex relationship between aging, CVRFs, and AD. .

Effects of affective valence on a mixed Spatial Correspondence Task: a reply to Proctor (2013)

The present study investigated the influence of emotional valence on the spatial stimulus-key location correspondence effect in three experiments using the Affective Spatial Correspondence task (AffSCt). We initially reanalyzed the results of Conde et al. (2011) according to the model proposed by Proctor (2013). In that study, compatible and incompatible responses were chosen according to the participants' team preference. In one block, the volunteers had to press a key on the same side for the Favorite team and on the opposite side for the Rival team. In another block, a reverse code was used. We found that responses were faster for the Favorite-compatible/Rival-incompatible condition (614 ms) compared with the Favorite-incompatible/Rival-compatible condition (691 ms). The same experimental arrangement was replicated in another Brazilian city, and similar results were found. Additionally, we employed non-affective "fake" soccer teams as a control condition, and no mapping-rule effect was observed. Finally, a final experiment that used the same design but different non-affective stimuli (yellow and blue bars) was performed to provide further evidence that the valence effect in the present experimental paradigm only occurs with affective stimuli. As expected, non-affective stimuli did not produce an overall advantage for any mapping rules, corroborating earlier findings with similar mixed designs. The results confirmed the previous findings and validity of the AffSCt as a methodology to investigate the effects of emotional valence on stimulus-response correspondence. However, we are unable to provide a conclusive explanation to support the several hypotheses proposed previously in our paper and by Proctor (2013)...

Learning and memory and its relationship with the lateralization of epileptic focus in subjects with temporal lobe epilepsy / Aprendizagem e memória e sua relação com a lateralização do foco epileptogênico em sujeitos com epilepsia do lobo temporal

Background: In medial temporal lobe epilepsy (MTLE), previous studies addressing the hemispheric laterality of epileptogenic focus and its relationship with learning and memory processes have reported controversial findings. Objective: To compare the performance of MTLE patients according to the location of the epileptogenic focus on the left (MTLEL) or right temporal lobe (MTLER) on tasks of episodic learning and memory for verbal and visual content. Methods: One hundred patients with MTLEL and one hundred patients with MTLER were tested with the following tasks: the Rey Auditory Verbal Learning Test (RAVLT) and the Logical Memory-WMS-R to evaluate verbal learning and memory; and the Rey Visual Design Learning Test (RVDLT) and the Visual Reproduction-WMS-R to evaluate visual learning and memory. Results: The MTLEL sample showed significantly worse performance on the RAVLT (p < 0.005) and on the Logical Memory tests (p < 0.01) than MTLER subjects. However, there were no significant between-group differences in regard to the visual memory tests. Discussion: Our findings suggest that verbal learning and memory abilities are dependent on the structural and functional integrity of the left temporal lobe, while visual abilities are less dependent on the right temporal lobe...

Contexto: Estudos anteriores abordando a lateralidade hemisférica de foco epiléptico na epilepsia do lobo temporal mesial (ELTM) e sua relação com os processos de aprendizagem e memória têm relatado resultados controversos. Objetivo: Comparar o desempenho de pacientes com ELTM de acordo com a localização do foco epiléptico à esquerda (ELTME) ou à direita (ELTMD) em tarefas de aprendizagem e memória episódica para conteúdo verbal e visual. Métodos: Cem pacientes com ELTME e cem pacientes com ELTMD foram avaliados com os seguintes testes: Teste de Aprendizagem Auditiva Verbal de Rey (RAVLT) e Memória Lógica – WMS-R para avaliar aprendizagem e memória verbal e o Teste de Aprendizagem Visual para Desenhos de Rey (RVDLT) e Reprodução Visual – WMS-R para avaliar a aprendizagem e memória visual. Resultados: A amostra com ELTME mostrou desempenho significativamente pior no RAVLT (p < 0,005) e na Memória Lógica (p < 0,01) em comparação aos indivíduos ELTMD. No entanto, não houve diferenças significativas entre os grupos no que diz respeito aos testes de aprendizagem e memória visual. Conclusão: Nossos resultados sugerem que a aprendizagem e a memória verbais são dependentes da integridade estrutural e funcional do lobo temporal esquerdo, enquanto as capacidades de aprendizagem e memória visual são menos dependentes do lobo temporal direito...

Neuroimaging in Alzheimer's disease: current role in clinical practice and potential future applications

'Alzheimer's disease is the most common cause of dementia and its prevalence is expected to increase in the coming years. Therefore, accurate diagnosis is crucial for patients, clinicians and researchers. Neuroimaging techniques have provided invaluable information about Alzheimer's disease and, owing to recent advances, these methods will have an increasingly important role in research and clinical practice. The purpose of this article is to review recent neuroimaging studies of Alzheimer's disease that provide relevant information to clinical practice, including a new modality: in vivo amyloid imaging. Magnetic resonance imaging, single photon emission computed tomography and 18F-fluorodeoxyglucose-positron emission tomography are currently available for clinical use. Patients with suspected Alzheimer's disease are commonly investigated with magnetic resonance imaging because it provides detailed images of brain structure and allows the identification of supportive features for the diagnosis. Neurofunctional techniques such as single photon emission computed tomography and 18F-fluorodeoxyglucose-positron emission tomography can also be used to complement the diagnostic investigation in cases of uncertainty. Amyloid imaging is a non-invasive technique that uses positron emission tomography technology to investigate the accumulation of the β-amyloid peptide in the brain, which is a hallmark of Alzheimer's disease. This is a promising test but currently its use is restricted to very few specialized research centers in the world. Technological innovations will probably increase its availability and reliability, which are the necessary steps to achieve robust clinical applicability. Thus, in the future it is likely that amyloid imaging techniques will be used in the clinical evaluation of patients with Alzheimer's disease.

Cognitive control associated with irritability induction: an autobiographical recall fMRI study / Controle cognitivo associado à indução de irritabilidade: um estudo de RMf usando recordações autobiográficas

OBJECTIVE: Despite the relevance of irritability emotions to the treatment, prognosis and classification of psychiatric disorders, the neurobiological basis of this emotional state has been rarely investigated to date. We assessed the brain circuitry underlying personal script-driven irritability in healthy subjects (n = 11) using functional magnetic resonance imaging. METHOD: Blood oxygen level-dependent signal changes were recorded during auditory presentation of personal scripts of irritability in contrast to scripts of happiness or neutral emotional content. Self-rated emotional measurements and skin conductance recordings were also obtained. Images were acquired using a 1,5T magnetic resonance scanner. Brain activation maps were constructed from individual images, and between-condition differences in the mean power of experimental response were identified by using cluster-wise nonparametric tests. RESULTS: Compared to neutral scripts, increased blood oxygen level-dependent signal during irritability scripts was detected in the left subgenual anterior cingulate cortex, and in the left medial, anterolateral and posterolateral dorsal prefrontal cortex (cluster-wise p-value < 0.05). While the involvement of the subgenual cingulate and dorsal anterolateral prefrontal cortices was unique to the irritability state, increased blood oxygen level-dependent signal in dorsomedial and dorsal posterolateral prefrontal regions were also present during happiness induction. CONCLUSION: Irritability induction is associated with functional changes in a limited set of brain regions previously implicated in the mediation of emotional states. Changes in prefrontal and cingulate areas may be related to effortful cognitive control aspects that gain salience during the emergence of irritability.

OBJETIVO: Apesar da relevância de emoções de irritabilidade para o tratamento, prognóstico e classificação dos transtornos psiquiátricos, as bases neurobiológicas deste tipo de estado emocional foram raramente investigadas até hoje. Este estudo avaliou os circuitos cerebrais subjacentes à irritabilidade induzida por scripts pessoais em voluntários saudáveis (n = 11) usando ressonância magnética funcional. MÉTODO: Mudanças no sinal dependente do nível de oxigenação sanguínea (blood-oxygen level dependent signal) foram registradas durante a apresentação por via auditiva de scripts pessoais de irritabilidade em contraste com scripts de felicidade ou de conteúdo emocional neutro. Escores em escalas de autoavaliação emocional e medidas de condutância da pele também foram obtidos. A aquisição de imagens foi realizada em aparelho de ressonância magnética de 1,5 T. Os mapas de ativação cerebral foram construídos a partir das imagens individuais, e as diferenças entre as condições experimentais foram investigadas utilizando testes não-paramétricos baseados em permutações. RESULTADOS: Em comparação com scripts neutros, a apresentação de scripts de irritabilidade levou a aumentos de sinal dependente do nível de oxigenação sanguínea na porção subgenual do giro do cíngulo anterior esquerdo e nas porções medial, ântero-lateral e póstero-lateral do córtex pré-frontal dorsal (cluster-wise p-valor < 0,05). Enquanto o envolvimento do cíngulo anterior subgenual e do córtex pré-frontal dorsal antero-lateral surgiu apenas em associação com o estado de irritabilidade, aumentos do sinal dependente do nível de oxigenação sanguínea nas porções dorso-medial e dorsal póstero-lateral do córtex pré-frontal também estiveram presentes durante indução de felicidade. CONCLUSÃO: Indução de irritabilidade está associada a mudanças de atividade funcional num conjunto restrito de regiões cerebrais previamente implicadas na mediação de estados emocionais. Mudanças na atividade...

The drug-naïve OCD patients imaging genetics, cognitive and treatment response study: methods and sample description / Estudo de genética, imagem, cognição e resposta a tratamento em pacientes com TOC virgens de tratamento: métodos e descrição da amostra

OBJECTIVE: To describe a protocol that was based on an integrative neurobiological model of scientific investigation to better understand the pathophysiology of obsessive-compulsive disorder and to present the clinical and demographic characteristics of the sample. METHOD: A standardized research protocol that combines different methods of investigation (genetics, neuropsychology, morphometric magnetic resonance imaging and molecular neuroimaging of the dopamine transporter) obtained before and after treatment of drug-naïve adult obsessive-compulsive disorder patients submitted to a sequentially allocated 12-week clinical trial with a selective serotonin reuptake inhibitor (fluoxetine) and group cognitive-behavioral therapy. RESULTS: Fifty-two treatment-naïve obsessive-compulsive disorder patients entered the clinical trial (27 received fluoxetine and 25 received group cognitive-behavioral therapy). At baseline, 47 blood samples for genetic studies, 50 neuropsychological evaluations, 50 morphometrical magnetic resonance images and 48 TRODAT-1 single-photon emission computed tomography (SPECT) exams were obtained. After 12 weeks, 38 patients completed the protocol (fluoxetine = 20 and GCBT = 18). Thirty-eight neuropsychological evaluations, 31 morphometrical magnetic resonance images and 34 TRODAT-1 SPECT exams were obtained post-treatment. Forty-one healthy controls matched for age, gender, socioeconomic status, level of education and laterality were submitted to the same research procedures at baseline. CONCLUSION: The comprehensive treatment response protocol applied in this project allowing integration on genetic, neuropsychological, morphometrical and molecular imaging of the dopamine transporter data in drug-naïve patients has the potential to generate important original information on the neurobiology of obsessive-compulsive disorder, and at the same time be clinically meaningful.

OBJETIVO: Descrever um protocolo integrativo de investigação neurobiológica para melhor compreender as bases patofisiológicas do transtorno obsessivo-compulsivo e apresentar as características clínicas e demográficas da amostra. MÉTODO: Protocolo padronizado que combina diferentes modalidades de investigação (genética, neuropsicologia, ressonância magnética cerebral e imagem molecular do transportador de dopamina) obtidas antes e depois do tratamento em pacientes com transtorno obsessivo-compulsivo nunca expostos à medicação submetidos a um ensaio clínico comparando um inibidor seletivo da recaptação de serotonina (fluoxetina) e terapia cognitivo-comportamental em grupo. RESULTADOS: Cinquenta e dois pacientes com transtorno obsessivo-compulsivo entraram no ensaio clínico (27 no grupo fluoxetina e 25 no grupo de terapia). No início, foram realizadas 47 coletas de sangue para genética, 50 avaliações neuropsicológicas, 50 ressonâncias magnéticas cerebrais e 48 exames de tomografia computadorizada por emissão de fóton único (SPECT) com TRODAT-1. Depois de 12 semanas, 38 pacientes terminaram o protocolo (20 no grupo de fluoxetina e 18 no grupo de terapia). Trinta e oito reavaliações neuropsicológicas, 31 ressonâncias magnéticas de crânio e 34 exames de SPECT foram obtidos após o tratamento. Quarenta e um controles pareados foram submetidos ao mesmo protocolo inicial. CONCLUSÃO: Os dados genéticos, neuropsicológicos, volumétricos e moleculares do transportador de dopamina aliados à resposta a tratamento podem tanto gerar informações importantes a respeito da neurobiologia do transtorno obsessivo-compulsivo quanto ter uma aplicação clínica.

Structural magnetic ressonance imaging in anxiety disorders: an update of research findings: [review] / Ressonância magnética estrutural em transtornos de ansiedade: atualização dos achados de pesquisa: [revisão]

OBJECTIVE: The aim of the present report is to present a systematic and critical review of the more recent literature data about structural abnormalities detected by magnetic ressonance in anxiety disorders. METHOD: A review of the literature in the last five years was conducted by a search of the Medline, Lilacs and SciELO indexing services using the following key words: "anxiety", "panic", "agoraphobia", "social anxiety", "posttraumatic" and "obsessive-compulsive", crossed one by one with "magnetic resonance", "voxel-based", "ROI" and "morphometry". RESULTS: We selected 134 articles and 41 of them were included in our review. Recent studies have shown significant morphological abnormalities in various brain regions of patients with anxiety disorders and healthy controls. Despite some apparently contradictory findings, perhaps reflecting the variability and limitations of the methodologies used, certain brain regions appear to be altered in a consistent and relatively specific manner in some anxiety disorders. These include the hippocampus and the anterior cingulate cortex in posttraumatic stress disorder and the orbitofrontal cortex in obsessive-compulsive disorder. CONCLUSIONS: The present review indicates that structural neuroimaging has contributed to a better understanding of the neurobiology of anxiety disorders. Further development of neuroimaging techniques, better sample standardization and the integration of data across neuroimaging modalities may extend progress in this area.

OBJETIVO: Apresentar uma revisão sistemática e crítica dos achados mais recentes da literatura em relação a alterações estruturais avaliados por ressonância magnética nos transtornos de ansiedade. MÉTODO: Uma revisão da literatura dos últimos cinco anos foi realizada utilizando uma busca nos indexadores Medline, Lilacs e SciELO utilizando as seguintes palavras-chave: "anxiety", "panic", "agoraphobia", "social anxiety", "posttraumatic" e "obsessive-compulsive" cruzadas uma a uma com "magnetic ressonance", "voxel-based", "ROI" e "morphometry". RESULTADOS: Foram selecionados 134 artigos, sendo 41 foram incluídos nesta revisão. Estudos recentes mostram alterações morfológicas significativas entre os pacientes com transtorno de ansiedade e os controles saudáveis em várias regiões cerebrais. Apesar de achados contraditórios, sobretudo devido à variabilidade e às limitações nas metodologias utilizadas, algumas estruturas aparecem alteradas de forma mais consistente e relativamente específica em alguns transtornos de ansiedade, como o hipocampo e o córtex cingulado anterior no transtorno de estresse pós-traumático e o córtex orbitofrontal no transtorno obsessivo-compulsivo. CONCLUSÕES: A presente revisão aponta que a neuroimagem estrutural pode ser utilizada na busca de uma maior compreensão da neurobiologia dos transtornos de ansiedade. É possível que o rápido avanço das técnicas de neuroimagem, uma maior padronização das amostras e a associação de dados de diferentes modalidades permitam um maior entendimento deste cenário.

Gender differences in aggressiveness in children and adolescents at risk for schizophrenia / Comportamentos agressivos em crianças e adolescentes com risco para esquizofrenia: diferenças entre gêneros

OBJECTIVE: This study aimed to investigate whether differences in aggression-related behavioral problems occur between boys and girls at high risk for schizophrenia living in the city of São Paulo, Brazil. METHOD: Using the Child Behavior Checklist, we compared the prevalence of behavioral problems between genders for the offspring (6-18 years) of mothers with diagnosis of schizophrenia and a comparison group of children born to women with no severe mental disorders recruited at the gynecology outpatient clinic of the same hospital. The Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition was applied for the evaluation of diagnostic status of mothers. RESULTS: Male children of women with schizophrenia had a lower prevalence of aggressive behavior compared to females (4 percent vs. 36 percent; p = 0.005), whereas no gender differences regarding aggression were detected in the comparison group (24 percent vs. 32 percent; p = 0.53). Logistic regression analyses showed that male gender and being a child of women with schizophrenia interacted so as to favor lower prevalence of aggressive behavior (p = 0.03). CONCLUSION: These findings reinforce the notion that behavioral gender differences related to schizophrenia are already detectable in childhood.

OBJETIVO: Investigar diferenças da ocorrência de comportamentos agressivos entre crianças e adolescentes do sexo masculino e feminino com risco genético para desenvolver esquizofrenia. MÉTODO: A prevalência de comportamentos agressivos foi medida utilizando o inventário de comportamentos para crianças e adolescentes, Child Behavior Checklist, e comparada entre os gêneros para o grupo de crianças filhas de mulheres com esquizofrenia e para um grupo de crianças filhas de mulheres atendidas no serviço de ginecologia do mesmo hospital. A entrevista clínica estruturada para DSM-IV (The Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition) foi utilizada para confirmar o diagnóstico materno. RESULTADOS: Os filhos de mulheres com esquizofrenia do sexo masculino apresentaram prevalência menor de comportamentos agressivos quando comparados às meninas (4 por cento x 36 por cento; p = 0,005), o que não ocorreu para o grupo comparativo (24 por cento x 32 por cento; p = 0,53). A análise de regressão logística mostrou que pertencer ao sexo masculino e ser filho de mulher com esquizofrenia interagiram de forma a favorecer menor prevalência de comportamentos agressivos (p = 0,03). CONCLUSÃO: Esses achados corroboram para a noção que as diferenças comportamentais entre os gêneros na esquizofrenia podem ser detectadas precocemente durante a infância.

Reliability of the Brazilian version of the Camberwell Assessment of Needs (CAN) in first-episode psychosis cases in São Paulo, Brazil

OBJECTIVE: To translate and adapt the Brazilian version of the Camberwell Assessment of Needs schedule for research, and to assess its inter-rater reliability in a sample of first-episode psychosis cases in São Paulo, Brazil. METHOD: A sub-sample of participants included in a study of first-episode psychosis in São Paulo was assessed utilizing the 22 domains of the Brazilian version of the Camberwell Assessment of Needs. The Camberwell Assessment of Needs was applied, tape-recorded and rated by research assistants. An independent rater gave scores to the same participants, based on the recorded interviews. The kappa coefficient and the intraclass correlation coefficient were used to assess inter-rater reliability. RESULTS: Fifty-two subjects were included. For seven domains the inter-rater reliability was almost perfect to total (range: 0.81 to 1.0). The domains with the lowest agreement were transport and benefits. The inter-rater reliability for the total number of needs was excellent (ICC = 0.95). CONCLUSIONS: The inter-rater reliability of the Camberwell Assessment of Needs was similar to what has been found in previous studies. The Camberwell Assessment of Needs showed to be easy to use and reliable with first-episode psychosis individuals. The use of standardized instruments to assess needs of care in Brazil will contribute to the assessment of the effectiveness of treatment and to the planning of individualized care for individuals with mental illnesses.

OBJETIVO: Traduzir e adaptar a versão para pesquisa da escala Camberwell de Avaliação de Necessidades e avaliar sua confiabilidade entre avaliadores em uma amostra de casos incidentes de psicoses funcionais em São Paulo, Brasil. MÉTODO: Uma amostra de participantes incluídos em um estudo de casos incidentes de psicoses funcionais em São Paulo foi avaliada utilizando-se os 22 domínios da versão brasileira da escala Camberwell de Avaliação de Necessidades. A escala Camberwell de Avaliação de Necessidades foi aplicada, gravada e pontuada por assistentes de pesquisa. Um avaliador independente pontuou os mesmos participantes, baseando-se nas gravações das entrevistas. O coeficiente kappa e o coeficiente de correlação intraclasse foram utilizados para avaliar a confiabilidade entre avaliadores. RESULTADOS: Cinqüenta e dois indivíduos foram incluídos. Para sete domínios, a confiabilidade entre avaliadores foi de quase perfeita a total (k = 0,81 a 1,00). Os domínios com a menor concordância entre avaliadores foram transporte e benefícios. O coeficiente de correlação intraclasse para o total de necessidades foi excelente (ICC = 0,95). CONCLUSÕES: A confiabilidade entre avaliadores da escala Camberwell de Avaliação de Necessidades foi similar aos resultados de estudos anteriores. A escala Camberwell de Avaliação de Necessidades mostrou-se confiável e fácil de aplicar em indivíduos com psicoses incidentes. O uso de instrumentos padronizados para a avaliação de necessidades de cuidado no Brasil contribuirá para a avaliação da efetividade de tratamentos e para o planejamento de cuidados personalizados para indivíduos com transtornos mentais.

Voxel-based investigations of regional cerebral blood flow abnormalities in Alzheimer's disease using a single-detector SPECT system

PURPOSE: To evaluate the feasibility of using the Statistical Parametric Mapping (SPM) program for an automated, voxel-by-voxel assessment of regional cerebral blood flow (rCBF) deficits in Alzheimer's disease (AD) subjects relative to age-matched controls studied with a conventional, single-detector SPECT system. METHODS: We used a databank of 99mTc-HMPAO images of 19 patients with a diagnosis of probable AD and 15 elderly healthy volunteers; data were acquired using an Orbiter-Siemens single-detector SPECT system. Using SPM, images were transformed spatially, smoothed (12mm), and the data were compared on a voxel-by-voxel basis with t-tests. RESULTS: There were significant rCBF reductions in AD patients relative to controls involving regions predicted a priori to be affected in AD, namely the left temporal and parietal neocortices, and the right posterior cingulate gyrus (p<0.05, corrected for multiple comparisons). DISCUSSION: The location of rCBF reductions in AD subjects in our study is consistent with the deficits detected in previous functional imaging studies of AD using higher-resolution devices. This suggests the potential usefulness of using SPM for the analysis of data acquired with single-detector SPECT systems, despite the limited sensitivity and spatial resolution of such equipment.

OBJETIVO: Avaliar a viabilidade de emprego do programa Statistical Parametric Mapping (SPM) para investigar de forma automatizada, voxel-a-voxel, a presença de déficits de fluxo sanguíneo cerebral regional (FSCr) em pacientes com doença de Alzheimer (DA) comparados a sujeitos-controle pareados para idade, usando imagens de SPECT adquiridas com um equipamento convencional de detector único. MÉTODOS: Foi utilizado um banco de imagens adquiridas após injeção de 99mTc-HMPAO em 19 pacientes com diagnóstico provável de DA e 15 voluntários idosos saudáveis, usando um equipamento de SPECT Orbiter-Siemens de detector único. Empregando o programa SPM, as imagens foram transformadas espacialmente, suavizadas (12mm FWHM), e comparadas estatisticamente voxel-a-voxel entre os dois grupos, usando o teste de T. RESULTADOS: Foram identificadas reduções significativas de FSCr nos pacientes com DA comparados aos controles em regiões previstas a priori como afetadas por esta forma de demência, quais sejam os neocórtices temporal e parietal em hemisfério esquerdo e o cíngulo posterior direito (p<0,05, corrigido para comparações múltiplas). DISCUSSÃO: A localização dos focos de redução de FSCr em pacientes com DA no nosso estudo é, de forma geral, consistente com os achados de déficits cerebrais detectados em estudos anteriores de neuroimagem funcional na DA realizados com equipamentos de resolução espacial mais alta. Isto sugere o potencial de utilidade do programa SPM para a análise de dados de SPECT adquiridos com equipamentos de detector único, apesar da sensibilidade e resolução espacial limitadas de tais aparelhos.