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Background: Early-life stress is associated with alterations in telomere length, a marker of accumulated stress and aging, and a risk factor for psychiatric disorders. Nonhuman primate maternal variable foraging demand (VFD) is a validated early-life stress model, resulting in anxiety- and depressive-like symptoms in offspring. Previous studies reported increased plasma glucagon-like peptide 1 (pGLP-1) along with insulin resistance in this model. We investigated whether VFD rearing related to adult telomere length and to these neuroendocrine markers. Methods: Adult leukocyte telomere length was measured in VFD-reared (12 males, 13 females) and non-VFD–reared (9 males, 26 females) bonnet macaques. Associations between adult telomere length and adolescent fasting pGLP-1 or insulin resistance in VFD-reared versus non-VFD–reared groups were examined using regression modeling, controlling for sex, weight, and age. Results: VFD subjects had relatively longer telomeres than non-VFD subjects (p = .017), and females relatively longer than males (p = .0004). Telomere length was positively associated with pGLP-1 (p = .0009) and with reduced insulin sensitivity (p < .0001) in both sexes, but not as a function of rearing group. Conclusions: Unexpectedly, VFD was associated with longer adult telomere length. Insulin resistance may lead to higher pGLP-1 levels in adolescence, which could protect telomere length in VFD offspring as adults. Associations between adult telomere length and adolescent insulin resistance and high pGLP-1 may reflect an adaptive, compensatory response after early-life stress exposure.

Abstract The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

Abstract Cortical thinning occurs throughout the entire life and extends to late-life neurodegeneration, yet the neurobiological substrates are poorly understood. Here, we used a virtual-histology technique and gene expression data from the Allen Human Brain Atlas to compare the regional profiles of longitudinal cortical thinning through life (4004 magnetic resonance images [MRIs]) with those of gene expression for several neuronal and non-neuronal cell types. The results were replicated in three independent datasets. We found that inter-regional profiles of cortical thinning related to expression profiles for marker genes of CA1 pyramidal cells, astrocytes and, microglia during development and in aging. During the two stages of life, the relationships went in opposite directions: greater gene expression related to less thinning in development and vice versa in aging. The association between cortical thinning and cell-specific gene expression was also present in mild cognitive impairment and Alzheimer’s Disease. These findings suggest a role of astrocytes and microglia in promoting and supporting neuronal growth and dendritic structures through life that affects cortical thickness during development, aging, and neurodegeneration. Overall, the findings contribute to our understanding of the neurobiology underlying variations in MRI-derived estimates of cortical thinning through life and late-life disease.

Introduction Using proton magnetic resonance spectroscopy imaging, the effects of early life stress on nonhuman primate striatal neuronal integrity were examined as reflected by N -acetyl aspartate (NAA) concentrations. NAA measures were interrogated through examining their relationship to previously documented early life stress markers—cerebrospinal fluid corticotropin-releasing factor concentrations, hippocampal volume, body mass, and behavioral timidity. Rodent models of depression exhibit increases in neurotrophic effects in the nucleus accumbens. We hypothesized that rearing under conditions of early life stress (variable foraging demand, VFD) would produce persistent elevations of NAA concentrations (in absolute or ratio form) in ventral striatum/caudate nucleus (VS/CN) with altered correlation to early life stress markers. Methods Eleven bonnet macaque males reared under VFD conditions and seven age-matched control subjects underwent proton magnetic resonance spectroscopy imaging during young adulthood. Voxels were placed over VS/CN to capture nucleus accumbens. Cisternal cerebrospinal fluid corticotropin-releasing factor concentrations, hippocampal volume, body mass, and response to a human intruder had been previously determined. Results VFD-reared monkeys exhibited significantly increased NAA/creatine concentrations in right VS/CN in comparison to normally reared controls, controlling for multiple comparisons. In comparison to controls, VFD cerebrospinal fluid corticotropin-releasing factor concentrations were directly associated with right VS/CN absolute NAA. Left hippocampal volume was inversely associated with left VS/CN NAA/creatine in VFD reared but not in controls. Disruption of a normative inverse correlation between left VS/CN NAA and body mass was noted in VFD. Only non-VFD subjects exhibited a direct relationship between timidity response to an intruder and right VS/CN NAA. Conclusion Early life stress produced persistent increases in VS/CN NAA, which demonstrated specific patterns of association (or lack thereof) to early life stress markers in comparison to non-VFD subjects. The data are broadly consistent with a stable nonhuman primate phenotype of anxiety and mood disorder vulnerability whereby in vivo indicators of neuronal integrity, although reduced in hippocampus, are increased in striatum. The findings may provide a catalyst for further studies in humans and other species regarding a reciprocal hippocampal/nucleus accumbens relationship in affective disorders.

Objective: Borderline personality disorder (BPD) is a devastating condition that causes intense disruption of patients' lives and relationships. Proper understanding of BPD neurobiology could help provide the basis for earlier and effective interventions. As neuroimaging studies of patients with BPD are still scarce, volumetric and geometric features of the cortical structure were assessed to ascertain whether structural cortical alterations are present in BPD patients. Methods: Twenty-five female outpatients with BPD underwent psychiatric evaluation (SCID-I and II) and a 1.5 T magnetic resonance imaging (MRI) brain scan. The control group comprised 25 healthy age-matched females. Images were processed with the FreeSurfer package, which allows analysis of cortical morphology with more detailed descriptions of volumetric and geometric features of cortical structure. Results: Compared with controls, BPD patients exhibited significant cortical abnormalities in the fronto-limbic and paralimbic regions of both hemispheres. Conclusion: Significant morphologic abnormalities were observed in patients with BPD on comparison with a healthy control group through a multimodal approach. This study highlights the involvement of regions associated with mood regulation, impulsivity, and social behavior in BPD patients and presents a new approach for further investigation through a method of structural analysis based on distinct and simultaneous volumetric and geometric parameters.

In the surgical management of skull base lesions and vascular diseases such as giant aneurysms, involvement of the internal carotid artery may require the resection or the occlusion of the vessel. The anastomosis of the external carotid artery and the middle cerebral artery with venous graft may be indicated to re-establish the blood flow. To determine the best suture site in the middle cerebral artery, an anatomical study was carried out. Fourteen cerebral hemispheres were analysed after the injection of red latex into the internal carotid artery. The superior and inferior trunk of the main division of the middle cerebral artery have more than 2 mm of diameter. They are superficial allowing an anastomosis using a venous graft. The superior trunk has a disadvantage, it gives rise to branches for the precentral and post-central giri. The anastomosis with the inferior trunk presents lower risk of neurological deficit even though the angular artery originates from it.No tratamento cirúrgico das lesões da base do crânio e patologias vasculares como aneurismas gigantes, a ressecção ou oclusão da artéria carótida interna pode ser necessária. A anastomose das artérias carótida externa e cerebral média com interposição de enxerto venoso pode ser utilizada para restabelecer o fluxo sangüíneo. Para determinar o melhor local de sutura na artéria cerebral média, realizou-se um estudo anatômico. Quatorze hemisférios cerebrais foram analisados depois da injeção de látex vermelho na artéria carótida interna. Os ramos superior e inferior da divisão principal da artéria cerebral média têm mais de 2 mm de diâmetro. Eles são superficiais e permitem uma anastomose utilizando um enxerto venoso. O tronco superior tem a desvantagem de dar origem aos ramos para os giros pré e pós-centrais. A anastomose com o tronca inferior apresenta menor risco de déficit neurológico, apesar da artéria angular ter origem desse vaso.

Abstract Recently, several studies have investigated the neurodevelopment of psychiatric disorders using brain data acquired via structural magnetic resonance imaging (sMRI). These analyses have shown the potential of sMRI data to provide a relatively precise characterization of brain structural biomarkers. Despite these advances, a relatively unexplored question is how reliable and consistent a model is when assessing subjects from other independent datasets. In this study, we investigate the performance and generalizability of the same model architecture trained from distinct datasets comprising youths in diverse stages of neurodevelopment and with different mental health conditions. We employed models with the same 3D convolutional neural network (CNN) architecture to assess autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), brain age, and a measure of dimensional psychopathology, the Child Behavior Checklist (CBCL) total score. The investigated datasets include the Autism Brain Imaging Data Exchange II (ABIDE-II, N = 580), Attention Deficit Hyperactivity Disorder (ADHD-200, N = 922), Brazilian High-Risk Cohort Study (BHRCS, N = 737), and Adolescent Brain Cognitive Development (ABCD, N = 11,031). Models’ performance and interpretability were assessed within each dataset (for diagnosis tasks) and inter-datasets (for age estimation). Despite the demographic and phenotypic differences of the subjects, all models presented significant estimations for age (p value

O trabalho apresenta revisão bibliográfica narrativa sobre música e funções executivas (FE), associadas ao córtex pré-frontal (CPF), em interação com o sistema límbico, ligado ao processamento das emoções, discutindo sua indissociabilidade. O artigo tem por objetivo examinar a literatura recente sobre CPF e FE, estudos correlacionais, longitudinais e experimentais sobre prática musical e desenvolvimento das habilidades relacionadas às funções executivas do cérebro. Conclui ressaltando a importância do uso de testes validados que captem subfunções das FE, emoções e habilidades musicais, de modo a verificar a eficácia de intervenções que usam o ensino da música como forma de beneficiar o desenvolvimento humano de populações em situação de risco.

Objective: Improved understanding of the time course of neural changes associated with adolescent PTSD would elucidate the development of the disorder and could inform approaches to treatment. We compared hippocampal volumes and resting state functional connectivity (RSFC) in adolescent girls with post-traumatic stress disorder (PTSD) secondary to sexual assault, within six months of onset and age- and gender-matched, non-trauma exposed healthy controls (HCs) in São Paulo, Brazil. We also examined the relationship between pre- and post-treatment PTSD symptoms and RSFC. Method: We collected brain structure, RSFC, and PTSD symptoms in 30 adolescents with PTSD (mean age: 15.7 ± 1.04 years) and 21 HCs (mean age: 16.2 ± 1.21 years) at baseline. We collected repeated measures in 21 participants with PTSD following treatment; 9 participants dropped out. Hippocampal volume and RSFC from hippocampal and default mode network (DMN) seeds were compared between participants with PTSD and HCs. We examined associations between within-subject changes in RSFC and PTSD symptoms following treatment. Results: No hippocampal volumetric differences between groups were found. Compared to HCs, adolescents with recent PTSD had reduced RSFC between hippocampus and the lateral parietal node of the DMN, encompassing the angular gyrus, peak coordinates: −38, −54, 16; 116 voxels; peak F1,47 = 31.76; FDR corrected p = 0.038. Improvements in PTSD symptoms were associated with increased RSFC between hippocampus and part of the lateral parietal node of the DMN, peak coordinates: −38, −84, 38; 316 voxels; peak F1,47 = 40.28; FDR corrected p < 0.001. Conclusion: Adolescents with recent PTSD had reduced hippocampal-DMN RSFC, while no group differences in hippocampal volume were found, suggesting that hippocampal function, but not structure, is altered early in the course of PSTD. Following treatment, hippocampal-DMN RSFC increased with symptom improvement and may indicate an important neural mechanism related to successful PTSD treatment.

Background: Thalamic volume measures have been linked to obsessive-compulsive disorder (OCD) in children and adolescents. However, it is unclear if alterations in thalamic volumes occur before or after symptom onset and if there is a relation to the presence of sub-clinical obsessive-compulsive symptoms (OCS). Here, we explore the relationship between OCS and the rate of thalamic volume change in a cohort of children and youth at high risk to develop a mental disorder. A secondary aim was to determine if there is a relationship between OCS and the individual's OCD polygenic risk score (OCD-PRS) and between the rate of thalamic volume change and the OCD-PRS.Methods: The sample included 378 children enrolled in the longitudinal Brazilian High-Risk Cohort for Mental Conditions. Participants were assessed for OCS and the symmetrized percent change (SPC) of thalamic volume across two time-points separated by 3 years, along with the OCD-PRS. Zero-altered negative binomial models were used to analyze the relationship between OCS and thalamic SPC. Multiple linear regressions were used to examine the relationship between thalamic SPC and OCD-PRS.Results: A significant relationship between OCS and the right thalamus SPC (p = 0.042) was found. There was no significant relationship between changes in thalamic volume SPC and OCD-PRS.Conclusions: The findings suggest that changes in the right thalamic volume over the course of 3 years in children may be associated to OCS. Future studies are needed to confirm these results and further characterize the specific nature of OCS symptoms associated with thalamic volumes.

Background: Ketamine is an effective antidepressant with a 65–70% response rate and a fast onset of action. Esketamine (S-ketamine) has been found to be twice as potent as R-ketamine, while inducing fewer adverse effects, such as sedation and cognitive impairment, than racemic ketamine. However, little is known about its heterogeneous effects in treating depression. The aim of this study was to evaluate heterogeneity in the trajectory of depression treated with subcutaneous esketamine. Methods: Seventy severely depressed patients were administered repeated subcutaneous esketamine injections, and four assessments on depressive symptoms were performed. A growth mixture model analysis of the sample was utilized to identify potential latent classes. Results: Our model revealed two distinct subgroups: responders (79.1%), those who showed a lower depression score at the first time point and a strong decline in symptoms; and non-responders (20.9%), those who showed a higher initial depression score and a limited decline in symptoms. Limitations: This study has an observational design, with possible confounders. We were unable to analyse class differences in baseline symptoms, probably due to sample size. The group behaviour observed here must be confirmed with different populations. There is currently no clear cutoff to predict group membership. Conclusion: These findings suggest a systematically heterogeneous amelioration of symptoms based on a person-centred analysis. Patients with lower depression scores 24 h after the first injection are more likely to be in the responder subgroup and to present better symptom relief. Further studies should focus on clinical aspects that might predict this heterogeneity.

Abstract Background Adaptive behavior can be impaired in different neurodevelopmental disorders and may be influenced by confounding factors, such as intelligence quotient (IQ) and socioeconomic classification. Our main objective was to verify whether adaptive behavior profiles differ in three conditions—Williams Beuren syndrome (WBS), Down syndrome (DS), and autism spectrum disorder (ASD), as compared with healthy controls (HC) and with each other. Although the literature points towards each disorder having a characteristic profile, no study has compared profiles to establish the specificity of each one. A secondary objective was to explore potential interactions between the conditions and socioeconomic status, and whether this had any effect on adaptive behavior profiles. Methods One hundred and five adolescents were included in the study. All adolescents underwent the following evaluations: the Vineland Adaptive Behavior Scale (VABS), the Wechsler Intelligence Scale for Children (WISC), and the Brazilian Economic Classification Criteria. Results Our results demonstrated that the WBS group performed better than the DS group in the communication domain, β = −15.08, t(3.45), p = .005, and better than the ASD group in the socialization domain, β = 8.92, t(−2.08), p = .013. The DS group also performed better than the ASD group in socialization, β = 16.98, t(−2.32), p = .024. IQ was an important confounding factor, and socioeconomic status had an important effect on the adaptive behavior of all groups. Conclusions There is a heterogeneity regarding adaptive behavior profiles in WBS, DS, and ASD. These data are important to better design specific strategies related to the health and social care of each particular group.

Functional brain hubs are key integrative regions in brain networks. Recently, brain hubs identified through resting-state fMRI have emerged as interesting targets to increase understanding of the relationships between large-scale functional networks and psychopathology. However, few studies have directly addressed the replicability and consistency of the hub regions identified and their association with symptoms. Here, we used the eigenvector centrality (EVC) measure obtained from graph analysis of two large, independent population-based samples of children and adolescents (7–15 years old; total N = 652; 341 subjects for site 1 and 311 for site 2) to evaluate the replicability of hub identification. Subsequently, we tested the association between replicable hub regions and psychiatric symptoms. We identified a set of hubs consisting of the anterior medial prefrontal cortex and inferior parietal lobule/intraparietal sulcus (IPL/IPS). Moreover, lower EVC values in the right IPS were associated with psychiatric symptoms in both samples. Thus, low centrality of the IPS was a replicable sign of potential vulnerability to mental disorders in children. The identification of critical and replicable hubs in functional cortical networks in children and adolescents can foster understanding of the mechanisms underlying mental disorders.

Background The anterior cingulate gyrus is involved in the extinction of conditioned fear responses and is implicated in the pathophysiology of posttraumatic stress disorder. The expression of N-acetylaspartate and choline may be altered in the anterior cingulate gyri of children and adolescents with posttraumatic stress disorder. Methods We conducted a proton magnetic resonance spectroscopy study, longitudinally investigating N-acetylaspartate/creatine and choline/creatine ratios in the anterior cingulate gyri of children and adolescents, aged from 8 to 12 years, who had been exposed to various forms of violence or were non-trauma control. Based on baseline posttraumatic stress symptoms (“sub-clinical”), participants were divided into two groups: posttraumatic stress (n = 19) and control (n = 19). Proton magnetic resonance spectroscopy scans were repeated a year later in trauma exposed participants. Trauma assessments included the Childhood Trauma Questionnaire. Results Exploratory analyses revealed a significant negative correlation between follow-up anterior cingulate gyrus N-acetylaspartate/creatine and Childhood Trauma Questionnaire scores in posttraumatic stress (r = −0.62, p = 0.01) but not control group (r = 0.16, p = 0.66). However, we found no significant differences in anterior cingulate gyrus N-acetylaspartate/creatine or choline/creatine between posttraumatic stress and control. In addition, there were no significant effects of time, group, or time-by-group interactions. Conclusions In this pediatric population, anterior cingulate gyrus N-acetylaspartate/creatine and choline/creatine were not affected by posttraumatic stress and on average these metabolites remained stable over time. However, the study provided intriguing preliminary evidence revealing that participants suffering from posttraumatic stress at baseline have shown, a year later, reduced anterior cingulate gyrus N-acetylaspartate/creatine among those with high trauma severity. This pilot evidence warrants replication in future studies to confirm these findings and to determine the longitudinal effects and interactions between childhood posttraumatic stress and trauma.

OBJECTIVE: To establish whether alterations of brain structures in Alzheimer's disease are associated with executive dysfunction. METHODS: Nineteen patients with Alzheimer's disease and 22 older control subjects underwent a comprehensive evaluation. The clock drawing test, digit span test, executive motor function test, Behavioral Assessment of the Dysexecutive Syndrome battery (Rule Shift Cards test), and Stroop test were used to evaluate executive dysfunction. A multiparametric approach using the FreeSurfer image analysis suite provided a description of volumetric and geometric features of the gray matter structures. RESULTS: The cortical thickness maps showed a negative correlation between the Behavioral Assessment of the Dysexecutive Syndrome battery (Rule Shift Cards test) and the right middle frontal gyrus; a positive correlation between the executive motor function test and the left superior parietal gyrus, left middle temporal gyrus, bilateral supramarginal gyri, right middle frontal gyrus, and right precuneus; a negative correlation between the Stroop test (part III) and the right superior parietal gyrus; and a negative correlation between the Stroop test (part III) and the right middle temporal gyrus. CONCLUSION: Executive dysfunction in Alzheimer's disease is correlated with alterations not only in the frontal areas but also within many temporal and parietal regions.

Objective: Functional neuroimaging techniques represent fundamental tools in the context of translational research integrating neurobiology, psychopathology, neuropsychology, and therapeutics. In addition, cognitive-behavioral therapy (CBT) has proven its efficacy in the treatment of anxiety disorders and may be useful in phobias. The literature has shown that feelings and behaviors are mediated by specific brain circuits, and changes in patterns of interaction should be associated with cerebral alterations. Based on these concepts, a systematic review was conducted aiming to evaluate the impact of CBT on phobic disorders measured by functional neuroimaging techniques. Methods: A systematic review of the literature was conducted including studies published between January 1980 and April 2012. Studies written in English, Spanish or Portuguese evaluating changes in the pattern of functional neuroimaging before and after CBT in patients with phobic disorders were included. Results: The initial search strategy retrieved 45 studies. Six of these studies met all inclusion criteria. Significant deactivations in the amygdala, insula, thalamus and hippocampus, as well as activation of the medial orbitofrontal cortex, were observed after CBT in phobic patients when compared with controls. Conclusion: In spite of their technical limitations, neuroimaging techniques provide neurobiological support for the efficacy of CBT in the treatment of phobic disorders. Further studies are needed to confirm this conclusion.

OBJECTIVE: To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB) and hippocampal volume (HV) as predictors of conversion from mild cognitive impairment (MCI) to dementia. METHODS: Twenty-eight individuals (9 normal and 19 with MCI) were classified according to their CDR sum of boxes scores into 3 groups. RESULTS: The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. CONCLUSION: We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.

OBJECTIVE: To report structural and functional neuroimaging studies exploring the potential role of the orbitofrontal cortex (OFC) in the pathophysiology of the most prevalent psychiatric disorders (PD). METHOD: A non-systematic literature review was conducted by means of MEDLINE using the following terms as parameters: "orbitofrontal cortex", "schizophrenia", "bipolar disorder", "major depression", "anxiety disorders", "personality disorders" and "drug addiction". The electronic search was done up to July 2011. DISCUSSION: Structural and functional OFC abnormalities have been reported in many PD, namely schizophrenia, mood disorders, anxiety disorders, personality disorders and drug addiction. Structural magnetic resonance imaging studies have reported reduced OFC volume in patients with schizophrenia, mood disorders, PTSD, panic disorder, cluster B personality disorders and drug addiction. Furthermore, functional magnetic resonance imaging studies using cognitive paradigms have shown impaired OFC activity in all PD listed above. CONCLUSION: Neuroimaging studies have observed an important OFC involvement in a number of PD. However, future studies are clearly needed to characterize the specific role of OFC on each PD as well as understanding its role in both normal and pathological behavior, mood regulation and cognitive functioning.OBJETIVO: Relatar estudos de neuroimagens estruturais e funcionais explorando o papel potencial do córtex orbitofrontal (COF) na fisiopatologia dos transtornos psiquiátricos (TP) mais prevalentes. MÉTODO: Foi realizada uma revisão não sistemática da literatura no MEDLINE, usando como parâmetros os seguintes termos: "córtex orbitofrontal", "esquizofrenia", "transtorno bipolar", "depressão maior", "transtornos ansiosos", "transtornos de personalidade" e "dependência a drogas". A pesquisa eletrônica foi feita até julho de 2011. DISCUSSÃO: Foram relatadas anormalidades estruturais e funcionais do COF em muitos TP, particularmente esquizofrenia, transtornos afetivos, transtornos ansiosos, transtornos de personalidade e dependência a drogas. Estudos de aquisição de imagens estruturais por ressonância magnética relataram a redução do volume do COF em pacientes portadores de esquizofrenia, transtornos afetivos, TEPT, transtorno do pânico, transtornos de personalidade do grupo B e dependência a drogas. Além disso, estudos de aquisição de imagens funcionais por ressonância magnética empregando paradigmas cognitivos demonstraram alterações na atividade do COF em todos os TP anteriormente relacionados. CONCLUSÃO: Estudos de neuroimagens observaram um envolvimento importante do COF em vários TP. Entretanto, estudos futuros são claramente necessários para caracterizar o papel específico do COF em cada TP, assim como para a compreensão de seu papel tanto no comportamento normal como no patológico, na regulação do humor e no funcionamento cognitivo.

OBJECTIVE: The aim of this study was to examine the cerebellar volume of subjects at different stages of Alzheimer's disease and to investigate whether volume reductions in this structure are related to cognitive decline. METHOD: Ninety-six subjects from an epidemiological study were submitted to a magnetic resonance imaging scan and evaluated using the Mini-Mental State Examination and the Functional Activities Questionnaire. Subjects were divided into five groups according to the Clinical Dementia Rating scale. Twenty-six subjects from the original group who had no dementia diagnosis at baseline were re-evaluated for the onset of dementia after two years. RESULTS: The volumes of the cerebellar hemispheres, posterior cerebellar lobe, vermis and temporal lobe were found to be reduced as a function of the severity of the disease. There were significant positive correlations between the volume of the temporal lobe and cerebellum and the language, attention, and total scores in the Mini-Mental State Examination and the Functional Activities Questionnaire. A logistic regression analysis demonstrated that reduced temporal lobe, posterior cerebellar lobe and vermal volume at baseline is a risk factor for the onset of dementia. CONCLUSION: This is the first study demonstrating that reduced cerebellar volume is already apparent at the predementia stage. The results of this study support the involvement of the cerebellum in the progression of dementia. Whereas the cerebellum might not be directly associated with the origin of Alzheimer's disease, it may provide useful information related to its prognosis.OBJETIVO: O objetivo deste estudo foi examinar o volume cerebelar em indivíduos em diferentes fases da doença de Alzheimer e investigar se sua redução estaria relacionada com o declínio cognitivo. MÉTODO: Noventa e seis indivíduos de um estudo epidemiológico foram submetidos à ressonância magnética e avaliados por meio do Mini Exame do Estado Mental e do Questionário de Atividades Funcionais. Os sujeitos foram divididos em cinco grupos de acordo com a Escala de Gravidade da Demência. Vinte e seis indivíduos do grupo original que não tinham o diagnóstico de demência no início do estudo foram reavaliados após dois anos para detectar o desenvolvimento da doença. RESULTADOS: Os volumes dos hemisférios cerebelares, lobo cerebelar posterior, vermis e lobo temporal estavam diminuídos proporcionalmente à gravidade da doença. Houve correlações positivas e significativas entre o Questionário de Atividades Funcionais, Mini Exame do Estado Mental e seus respectivos subtestes para linguagem e atenção com os volumes dos lobos temporal e cerebelar. A análise de regressão logística demonstrou que o volume reduzido do lobo temporal, lobo cerebelar posterior e vermis pode ser um fator de risco para o futuro desenvolvimento de demência. CONCLUSÃO: Este é o primeiro estudo que demonstrou que o volume do cerebelo pode estar reduzido na fase pré-demência e reforça o papel dessa estrutura na progressão da doença de Alzheimer. Considerando que o cerebelo pode não estar diretamente associado com a origem da doença de Alzheimer, este achado tem valor para o prognóstico.

OBJECTIVE: To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior. METHOD: One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or haloperidol alone. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage. RESULTS: All medications produced a calming effect within one hour of administration, but only olanzapine and haloperidol reduced agitation by less than 10 points, and only olanzapine reduced aggression by less than four points in the first hour. After twelve hours, only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects. Ziprasidone, olanzapine and haloperidol alone had more stable results for agitation control, while ziprasidone, haloperidol plus promethazine and olanzapine had stable results for aggression control. CONCLUSION: Olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours. Although all the drugs had advantages and disadvantages, haloperidol plus midazolam was associated with the worst results in all the observed parameters.OBJETIVO: Comparar a eficácia da olanzapina, ziprasidona, haloperidol associado ao midazolam, haloperidol associado à prometazina e haloperidol isoladamente por via intramuscular como primeira escolha no tratamento de pacientes em agitação e agressividade. MÉTODO: Cento e cinquenta pacientes com agitação psicomotora por transtorno psicótico ou transtorno bipolar foram recrutados para estudo duplo-cego e receberam olanzapina, ziprasidona, haloperidol associado a midazolam, haloperidol associado a prometazina ou haloperidol isoladamente. Foram aplicadas as escalas Overt Agitation Severity Scale, Overt Aggression Scale e Ramsay Sedation Scale no período de 12 horas após a primeira aplicação. RESULTADOS: Todas as medicações foram capazes de acalmar os pacientes após uma hora da administração. Apenas a olanzapina e o haloperidol reduziram a agitação para menos de 10 pontos e apenas a olanzapina reduziu a agressividade para menos de quatro pontos nesse período. Doze horas depois, apenas o haloperidol com midazolam apresentou valores altos para a agitação e agressividade, e também esteve relacionado com maior proporção de efeitos colaterais. A ziprasidona, a olanzapina e o haloperidol apresentaram resultados mais estáveis para o controle da agitação e a ziprasidona, haloperidol associado a prometazina e olanzapina para o controle da agressividade. CONCLUSÃO: A olanzapina, a ziprasidona, o haloperidol associado a prometazina, o haloperidol associado ao midazolam e o haloperidol isoladamente foram efetivos no controle da agitação e da agressividade secundária a transtornos mentais dentro de 12 horas. Todas as drogas apresentaram vantagens e desvantagens, exceto pela associação haloperidol e midazolam que demonstrou os piores resultados em todos os parâmetros.

INTRODUCTION: The role of structural brain changes and their correlations with neuropsychiatric symptoms and disability in Alzheimer's disease are still poorly understood. OBJECTIVE: To establish whether structural changes in grey matter volume in patients with mild Alzheimer's disease are associated with neuropsychiatric symptoms and disability METHODS: Nineteen Alzheimer's disease patients (9 females; total mean age =75.2 y old +4.7; total mean education level =8.5 y +4.9) underwent a magnetic resonance imaging (MRI) examination and voxel-based morphometry analysis. T1-weighted images were spatially normalized and segmented. Grey matter images were smoothed and analyzed using a multiple regression design. The results were corrected for multiple comparisons. The Neuropsychiatric Inventory was used to evaluate the neuropsychiatric symptoms, and the Functional Activities Questionnaire and Disability Assessment for Dementia were used for functional evaluation RESULTS: A significant negative correlation was found between the bilateral middle frontal gyri, left inferior temporal gyrus, right orbitofrontal gyrus, and Neuropsychiatric Inventory scores. A negative correlation was found between bilateral middle temporal gyri, left hippocampus, bilateral fusiform gyri, and the Functional Activities Questionnaire. There was a positive correlation between the right amygdala, bilateral fusiform gyri, right anterior insula, left inferior and middle temporal gyri, right superior temporal gyrus, and Disability Assessment for Dementia scores CONCLUSIONS: The results suggest that the neuropsychiatric symptoms observed in Alzheimer's disease patients could be mainly due to frontal structural abnormalities, whereas disability could be associated with reductions in temporal structures.

OBJECTIVE: The objective of this update article is to report structural and functional neuroimaging studies exploring the potential role of cerebellum in the pathophysiology of psychiatric disorders. METHOD: A non-systematic literature review was conducted by means of Medline using the following terms as a parameter: "cerebellum", "cerebellar vermis", "schizophrenia", "bipolar disorder", "depression", "anxiety disorders", "dementia" and "attention deficit hyperactivity disorder". The electronic search was done up to April 2008. DISCUSSION: Structural and functional cerebellar abnormalities have been reported in many psychiatric disorders, namely schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, dementia and attention deficit hyperactivity disorder. Structural magnetic resonance imaging studies have reported smaller total cerebellar and vermal volumes in schizophrenia, mood disorders and attention deficit hyperactivity disorder. Functional magnetic resonance imaging studies using cognitive paradigms have shown alterations in cerebellar activity in schizophrenia, anxiety disorders and attention deficit hyperactivity disorder. In dementia, the cerebellum is affected in later stages of the disease. CONCLUSION: Contrasting with early theories, cerebellum appears to play a major role in different brain functions other than balance and motor control, including emotional regulation and cognition. Future studies are clearly needed to further elucidate the role of cerebellum in both normal and pathological behavior, mood regulation, and cognitive functioning.OBJETIVO: Este artigo de atualização tem como objetivo avaliar estudos em neuroimagem estrutural e funcional a fim de explorar o papel do cerebelo na patofisiologia dos transtornos psiquiátricos. MÉTODO: Uma revisão não sistemática foi realizada através do Medline utilizando-se como parâmetro os seguintes termos: "cerebellum", "cerebellar vermis", "schizophrenia", "bipolar disorder", "depression", "anxiety disorders", "dementia" e "attention deficit hyperactivity disorder". A busca eletrônica foi feita até abril de 2008. DISCUSSÃO: Anormalidades cerebelares estruturais e funcionais têm sido relatadas em muitos transtornos psiquiátricos, entre eles a esquizofrenia, transtorno bipolar, transtorno depressivo, transtornos ansiosos, demências e transtorno de déficit de atenção e hiperatividade. Estudos utilizando imagem por ressonância magnética estrutural relataram a diminuição do volume total do cerebelo e do vermis cerebelar na esquizofrenia, transtornos do humor e transtorno de falta de atenção com hiperatividade. Estudos utilizando ressonância magnética funcional e paradigmas cognitivos têm demonstrado alterações na atividade cerebelar na esquizofrenia, transtornos ansiosos e transtorno de falta de atenção com hiperatividade. Nas demências, o cerebelo é afetado nos estágios mais avançados dessas doenças. CONCLUSÃO: Contrastando com as primeiras teorias, o cerebelo parece apresentar um papel mais importante em diferentes funções cerebrais além do controle motor e do equilíbrio, incluindo a regulação emocional e cognição. Futuros estudos são necessários para melhor elucidar o papel do cerebelo em ambos os comportamentos, normal e patológico, na regulação do humor e nas funções cognitivas.

Introduction/Objective. Evidence suggests that the prefrontal cortex has been implicated in the pathophysiology of bipolar disorder (BD), but few neurochemical studies have evaluated this region in bipolar patients and there is no information from BD suicide attempters using Proton Magnetic Resonance Spectroscopy (H+MRS). The objective was to evaluate the metabolic function of the medial orbital frontal cortex in euthymic BD type I suicide and nonsuicide attempters compared to healthy subjects by H+MRS. Methods. 40 euthymic bipolar I outpatients, 19 without and 21 with history of suicide attempt, and 22 healthy subjects were interviewed using the Structured Clinical Interview with the DSM-IV axis I, the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Barratt Impulsiveness Scale-11 and underwent H+MRS. Results. We did not find any metabolic abnormality in medial orbital frontal regions of suicide and nonsuicide BD patients and BD patients as a group compared to healthy subjects. Conclusions. The combined chronic use of psychotropic drugs with neuroprotective or neurotrophic effects leading to a euthymic state for longer periods of time may improve neurometabolic function, at least measured by H+MRS, even in suicide attempters. Besides, these results may implicate mood dependent alterations in brain metabolic activity. However, more studies with larger sample sizes of this heterogeneous disorder are warranted to clarify these data.

Schizophrenia is a neurodevelopmental disorder with high heritability. Several lines of evidence indicate that the PRODH gene may be related to the disorder. Therefore, our study investigates the effects of 12 polymorphisms of PRODH on schizophrenia and its phenotypes. To further evaluate the roles of the associated variants in the disorder, we have conducted magnetic resonance imaging (MRI) scans to assess cortical volumes and thicknesses. A total of 192 patients were evaluated using the Structured Clinical Interview for DSM-IV (SCID), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) instruments. The study included 179 controls paired by age and gender. The samples were genotyped using the real-time polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-PCR and Sanger sequencing methods. A sample of 138 patients and 34 healthy controls underwent MRI scans. One polymorphism was associated with schizophrenia (rs2904552), with the G-allele more frequent in patients than in controls. This polymorphism is likely functional, as predicted by PolyPhen and SIFT, but it was not associated with brain morphology in our study. In summary, we report a functional PRODH variant associated with schizophrenia that may have a neurochemical impact, altering brain function, but is not responsible for the cortical reductions found in the disorder.

BACKGROUND: Early life social adversity can influence stress response mechanisms and is associated with anxious behaviour and reductions in callosal area later in life. OBJECTIVE: To evaluate the association between perceptions of parental bonding in childhood/adolescence, hypothalamic-pituitary-adrenal (HPA) axis response, and callosal structural integrity in adult victims of severe urban violence with and without PTSD. METHODS: Seventy-one individuals with PTSD and 62 without the disorder were assessed with the Parental Bonding Instrument (PBI). The prednisolone suppression test was administered to assess cortisol levels, and magnetic resonance imaging was used to assess the total area of the corpus callosum (CC), as well as the areas of callosal subregions. RESULTS: The PBI items related to the perception of 'not having a controlling mother' (OR 4.84; 95%CI [2.26-10.3]; p=0.01), 'having a caring father' (OR 2.46; 95'%CI [1.18-5.12]; p=0.02), and 'not having controlling parents' (OR 2.70; 95%CI [1.10-6.63]; p=0.04) were associated with a lower risk of PTSD. The PTSD group showed a blunted response to the prednisolone suppression test, with lower salivary cortisol levels upon waking up (p=0.03). Individuals with PTSD had smaller total CC area than those without the disorder, but these differences were not statistically significant (e-value =0.34). CONCLUSIONS: Healthy parental bonding, characterized by the perception of low parental control and high affection, were associated with a lower risk of PTSD in adulthood, suggesting that emotional enrichment and the encouragement of autonomy are protective against PTSD in adulthood.

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

Tinnitus is characterized by the perception of sound in the absence of an external auditory stimulus. The network connectivity of auditory and non-auditory brain structures associated with emotion, memory and attention are functionally altered in debilitating tinnitus. Current studies suggest that tinnitus results from neuroplastic changes in the frontal and limbic temporal regions. The objective of this study was to use Single-Photon Emission Computed Tomography (SPECT) to evaluate changes in the cerebral blood flow in tinnitus patients with normal hearing compared with healthy controls.Twenty tinnitus patients with normal hearing and 17 healthy controls, matched for sex, age and years of education, were subjected to Single Photon Emission Computed Tomography using the radiotracer ethylenedicysteine diethyl ester, labeled with Technetium 99 m (99 mTc-ECD SPECT). The severity of tinnitus was assessed using the "Tinnitus Handicap Inventory" (THI). The images were processed and analyzed using "Statistical Parametric Mapping" (SPM8).A significant increase in cerebral perfusion in the left parahippocampal gyrus (pFWE

ABSTRACT. New evidence suggests that the cerebellum has structural and functional abnormalities in psychiatric disorders. Objective: In this research, the goal was to measure the volume of the cerebellum and its subregions in individuals with psychiatric disorders and to relate these findings to their symptoms. Methods: Patients with different degrees of cognitive impairment (Epidemiology of the Elderly - UNIFESP) and patients with post-traumatic stress disorder (PTSD) from population studies were analyzed. Also, patients with bipolar disorder from an outpatient clinic (Center for the Study of Mood and Anxiety Disorders, Universidade Federal da Bahia) were recruited for this study. All subjects underwent a 1.5T structural magnetic resonance scan. Volumetric measures and symptom measurements, by psychometric scales, were performed and compared between patients and controls. Results: The cerebellum volume was reduced in patients with cognitive impairment without dementia and with dementia, in patients with PTSD, and in patients with bipolar disorder compared to controls. In dementia and PTSD, the left cerebellar hemisphere and vermis volume were reduced. In bipolar disorder, volumes of both hemispheres and the vermis were reduced. In the first two studies, these cerebellar volumetric reductions correlated with symptoms of the disease. Conclusion: The exact nature of cerebellar involvement in mental processes is still not fully understood. However, abnormalities in cerebellar structure and its functions have been reported in some of these diseases. Future studies with larger samples are needed to clarify these findings and investigate whether they are important for treatment and prognosis.