Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.Significance StatementLeft-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

Schizophrenia is associated with widespread alterations in subcortical brain structure.While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed moreconcave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.

Around 400 BC, Hippocrates wrote: "Melancholics ordinarily become epileptics, and epileptics, melancholics; what determines the preference is the direction the malady takes; if it bears upon the body, epilepsy, if upon the intelligence, melancholy".The relationship between depression and epilepsy has been known since ancient times, however, to date, it is not fully understood.The prevalence of psychiatric disorders (PD) in persons with epilepsy is high compared to general population. Mood disorders occur in 11 to 62%, psychosis in 7 to 10% and personality disorders in 5 to 33% [1][2][3][4][5][6][7][8] . Depression is the most frequent PD in persons with epilepsy [9][10][11] . It is assumed that the rate of depression ranges from 20 to 55% in patients with refractory epilepsy, especially considering those with temporal lobe epilepsy caused by mesial temporal sclerosis (TLE-MTS). Furthermore, people with epilepsy have a lifetime prevalence of any type of mood disorder higher than that observed in general population or people with other chronic medical disorders. Despite its high prevalence, depression remains underdiagnosed and undertreated in persons with epilepsy, with relevant personal and social costs. The impact of depression in morbidity can be ABSTRACTThe relationship between depression and epilepsy has been known since ancient times, however, to date, it is not fully understood. The prevalence of psychiatric disorders in persons with epilepsy is high compared to general population. It is assumed that the rate of depression ranges from 20 to 55% in patients with refractory epilepsy, especially considering those with temporal lobe epilepsy caused by mesial temporal sclerosis. Temporal lobe epilepsy is a good biological model to understand the common structural basis between depression and epilepsy. Interestingly, mesial temporal lobe epilepsy and depression share a similar neurocircuitry involving: temporal lobes with hippocampus, amygdala and entorhinal and neocortical cortex; the frontal lobes with cingulate gyrus; subcortical structures, such as basal ganglia and thalamus; and the connecting pathways. We provide clinical and brain structural evidences that depression and epilepsy represent an epiphenomenon sharing similar neural networks.Key words: epilepsy, depression, neuroimaging, temporal lobe. RESUMOA relação entre depressão e epilepsia é conhecida desde a antiguidade; entretanto, até o momento, não é completamente compreendida. A prevalência de transtornos psiquiátricos nas pessoas com epilepsia é elevada quando comparada à população em geral. A taxa de depressão varia de 20 a 55% nos pacientes com epilepsia refratária, especialmente considerando-se aqueles com epilepsia do lobo temporal causada por esclerose mesial temporal. A epilepsia do lobo temporal é um bom modelo biológico para compreender as bases estruturais comuns entre a epilepsia e a depressão. É relevante ressaltar que a epilepsia do lobo mesial e a depressão apresentam circuitos similares envolvendo: os lobos temporais com o hipocampo...

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Importance: Owing to its anti-inflammatory properties and antiviral ''in vitro'' effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cannabidiol (CBD) has been proposed as a potential treatment for coronavirus disease 2019 . Objective: To investigate the safety and efficacy of CBD for treating patients with mild to moderate COVID-19. Design: Randomized, parallel-group, double-blind, placebo-controlled clinical trial conducted between July 7 and October 16, 2020, in two sites in Brazil. Setting: Patients were recruited in an emergency room. Participants: Block randomized patients (1:1 allocation ratio-by a researcher not directly involved in data collection) with mild and moderate COVID-19 living in Ribeira ˜o Preto, Brazil, seeking medical consultation, and those who voluntarily agreed to participate in the study. Interventions: Patients received 300 mg of CBD or placebo added to standard symptomatic care during 14 days. Main Outcome and Measure: The primary outcome was reduction or prevention of the deterioration in clinical status from mild/moderate to severe/critical measured with the COVID-19 Scale or the natural course of the resolution of typical clinical symptoms. Primary study outcome was assessed on days 14, 21, and 28 after enrollment. Results: A total of 321 patients were recruited and assessed for eligibility, and 105 were randomly allocated either in CBD (n = 49) or in placebo (n = 42) group. Ninety-one participants were included in the analysis of efficacy. There were no baseline between-group differences regarding disease severity (v 2 = 0.025, p = 0.988) and median time to symptom resolution (12 days [95% confidence interval, CI, 6.

Objective:To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (11C-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer’s disease (AD), and explore possible group differences in 11C-PIB binding to white matter.Methods: 11C-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM).Results:Cerebellar normalization showed higher 11C-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased 11C-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule.Conclusion:The present case-control voxelwise 11C-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased 11C-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.

ResumoContexto: A esquizofrenia é uma das mais intrigantes doenças psiquiátricas e, talvez por isso, a mais pesquisada, com grandes avanços sobre sua fisiopatologia no último século. Objetivo: Revisar os principais avanços na compreensão fisiopatológica da esquizofrenia. Método: Revisão da literatura para cada tópico proposto a partir de artigos levantados no Medline e/ou considerados importantes a partir da experiência dos autores. Resultados: A hipótese dopaminér-gica representa uma das primeiras teorias etiológicas e permanece até os dias atuais como uma das que apresenta evidências mais consistentes. No entanto, essa teoria falha em explicar a história natural, os prejuízos cognitivos e as alterações estruturais encontradas na esquizofrenia. A demonstração de estudos epidemiológicos de fatores de risco genéticos e ambientais, somados aos estudos neuropatológicos e de neuroimagem, sugerem um modelo interativo em que inúmeros fatores atuam conjuntamente para alterações mais globais do desenvolvimento cerebral. Conclusão: A compreensão fisiopatológica da esquizofrenia avançou bastante no último século, evoluindo de teorias etiológicas unicausais para modelos mais complexos que consideram a interação de inúmeros fatores genéticos e ambientais.Araripe Neto, A.G.A. et al. / Rev. Psiq. Clín. 34, supl 2; 198-203, 2007 Palavras-chave: Esquizofrenia, fisiopatologia, hipótese dopaminérgica, hipótese glutamatérgica, neurodesenvolvimento. AbstractBackground: schizophrenia is one of the most intriguing and studied psychiatric diseases and its physiopathology has advanced a lot in the last century. Objective: To review the most important advances in the physiopathology of schizophrenia. Method: Review of the literature of each proposed topic by articles searched in Medline and/or chosen accordingly the authors' experience. Results: The dopaminergic hypothesis was one of the first ethiological theories and until today is among the ones that presents the most consistent evidences. However, it fails to explain important features found in schizophrenia, such as the natural history, the cognitive impairments and the structural abnormalities. Evidences provided by epidemiological studies of genetic and environmental risk factors, associated with the findings of neuropathological and neuroimaging studies, suggest an interactive model with several factors acting together to create a global alteration of the brain development. Conclusion: The physiophatology of schizophrenia has advanced a lot in the last century, evolving from unicausal theories towards more complex models that consider the interaction among several genetic and environmental factors.