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. Objectives selfregulation self regulation Childrens Children s (CHI , (PBD) (HOBD) HC (HC disorders Methods 4 1 2 expression mothers SchoolAge School Age ChildrenPresent Present KSADSPL. KSADSPL K SADS PL . (K-SADS-PL) Results suspicion groups Conclusions statedependent state dependent population (PBD (HOBD (K-SADS-PL

ABSTRACT Recent studies suggested that cannabis use influences on the emergence of psychosis by disrupting neurodevelopmental processes that occur during adolescence and early adulthood and which are reflected on brain anatomical changes detectable with MRI. However, no MRI studies have investigated whether intrauterine neurodevelopmental abnormalities also interact with later cannabis use to influence on psychosis risk. We investigated differences between first-episode psychosis (FEP) patients with history of cannabis use (FEPC+, n=28), FEP subjects without cannabis use (FEPC-, n=78) and healthy controls (n=80) in regard to the frequency of absent or short Adhesio Interthalamica (AI), a well-established marker of intrauterine neurodevelopment. The FEPC+ subgroup had a significantly lower prevalence of absent AI than FEPC- subjects, as well as a lack of a significantly shorter AI length compared to controls (as found in FEPC- subjects). These preliminary results show that psychosis subjects with cannabis use present a low rather than high frequency of absent AI, suggesting that fixed intrauterine neurodevelopmental abnormalities may not be associated with cannabis use later in life to influence on the emergence of psychosis. This is consistent with a view that multiple different etiological processes may lead to similar clinical presentations in patients with FEP.

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.

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.

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.

Abstract Background With the growth of the elderly population in Brazil and the increasing impact of depression and anxiety, the importance of preventing these disorders has been highlighted. Studies have shown an inverse relationship between rates of depression/anxiety and physical activity, pointing out its role as a possible protective factor. Objectives To conduct a randomized study with elderly adults in the community, who present with subsyndromal depression and anxiety, that will evaluate the effectiveness of physical activity with a collaborative stepped-care strategy; and to compare the effectiveness of physical activity in preventing subsyndromal depression and anxiety, with regard to the usual care group. Methods The article contains the methodological description of an arm of a large study entitled “Prevention and Treatment of Depression in Elderly”, in which 2,566 Brazilian older adults were screened to identify clinically significant depressive and anxiety symptoms. Those with clinically significant depressive or anxiety symptoms, not meeting criteria for depressive or anxiety disorder, will be invited to participate in a randomized clinical trial with 2 intervention groups: a step-by-step preventive care programme using physical activity, and usual care. The effectiveness of physical activity in the prevention of depressive and anxiety disorders will be evaluated. Discussion New health policies could be implemented, aiming to reduce the number of elderly people with depression and anxiety in primary care. In addition, training may be implemented for family health teams so that screening tools could be used to make an early identification of individuals with (or at risk of developing) mental disorders.

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.

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.

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.

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.

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.

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.

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).

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.

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.

RESUMO OBJETIVO O Transtorno de déficit de atenção e hiperatividade (TDAH) é um transtorno do neurodesenvolvimento que causa importantes prejuízos em várias áreas do funcionamento humano, resultando em pior qualidade de vida (QoL). Entretanto, são escassos os estudos que se utilizam de escalas válidas para documentar, objetivamente, os prejuízos na QoL de adultos com TDAH nunca tratados. O presente estudo teve por objetivos avaliar QoL numa amostra clínica de adultos com TDAH virgens de tratamento comparando com grupo controle saudável (GC) e investigar a relação entre QoL e gravidade de sintomas. MÉTODO Foram utilizadas para classificação de gravidade de sintomas a escala Auto-relato de sintomas TDAH em adultos, ASRS e como medida de QoL a WHOQOL-BREF em uma amostra de 46 adultos com TDAH com média de idade de 29,3 anos, que nunca receberam tratamento; estes foram comparados com 28 voluntários saudáveis - GC, com média de idade de 28,7 anos). RESULTADOS Observou-se QoL significativamente pior no grupo TDAH comparado ao GC (p<0,001). A gravidade de sintomas de hiperatividade (mas não os de desatenção) correlacionou negativamente com escores da escala de QoL (p<0,05). CONCLUSÃO O uso de um instrumento genérico de QoL como a WHOQOL-BREF, permite a detecção de baixa QoL em adultos com TDAH comparado ao GC e destaca a importância que deve ser atribuída a prejuízos na QoL durante o planejamento e monitoramento de estratégias de tratamento para esta população.

OBJECTIVE Attention-Deficit and Hyperactivity Disorder is a neurodevelopmental condition that causes substantial deficits in several aspects of human function, resulting in a poor quality of life. However, studies using valid reports to objectively document Quality of Life impairment in never-treated adults with Hyperactivity Disorder Self-Report Scale have, to date, been scarce. The aim of this study was to assess Quality of Life in a clinical sample of treatment-naïve adults with Attention-Deficit and Hyperactivity Disorder in comparison to a healthy control group, and to investigate the relationship between Quality of Life and symptom severity ratings. METHOD Symptom severity ratings (assessed using the Attention-Deficit and Hyperactivity Disorder Self-Report Scale) and quality of life measurements using the World Health Organization Quality of Life scale (through WHOQOL-BREF) were obtained from a sample of 46 treatment-naïve adults with Attention-Deficit and Hyperactivity Disorder (mean age=29.3 years) and a group of 28 healthy controls (mean age=28.7 years). RESULTS Quality of Life was significantly worse in the Attention-deficit and Hyperactivity Disorder group compared to the healthy controls. The severity of symptoms of hyperactivity (but not of inattention) was negatively correlated with quality of life. CONCLUSION The use of a generic Quality of Life tool such as the WHOQOL-BREF allows the detection of lower Quality of Life, vs. healthy controls, in adult Attention-Deficit and Hyperactivity Disorder patients, and highlights the relevance of Quality of Life impairment when planning and monitoring treatment strategies for such a population.