Pathophysiological mechanisms in subarachnoid haemorrhage. A study of the neuropharmacological, physiological and morphological changes that occur in a model of subarachnoid haemorrhage developed in the laboratory rat.

This thesis reviews current knowledge regarding the problems created by, possible causal factors, and present management of the disordered pathophysiology that may arise following subarachnoid haemorrhage (SAH) in man. Mechanisms responsible for the normal regulation of the cerebral vasculature are also reviewed. The present investigation explores how various neuropharmacological, physiological and morphological aspects of the major cerebral arteries are affected by such haemorrhage in a small animal model of experimental SAH developed in the laboratory rat. Preliminary immunohistochemical studies revealed that contrary to earlier reports, the extraparenchymal cerebral arteries do not receive a significant serotonergic innervation. Serotonin was only rarely present under normal circumstances in the neural plexus, and when found was invariably contained within nerves also identified as catecholaminergic in nature. Following SAH, major alterations in the neurotransmitter content of the cerebrovasculature occurred. The perivascular sympathetic nerves of major cerebral vessels rapidly accummulated serotonin, while a coincident depletion of neuropeptide Y took place. Using cortically implanted platinum-wire microelectrodes, with measurement of cerebral blood flow (CBF) by hydrogen-clearance, the timecourse of the global reduction in CBF that develops acutely in this model was documented. A 50% reduction in blood flow persisted for up to 3 hours posthaemorrhage, at 24 hours this was restored to 85% of normal, and recovered fully by 48 hours. The fall in CBF developed independently of concommitant changes in intracranial and cerebral perfusion pressure, and it would appear likely that early vasospasm secondary to released blood products, rather than pressure changes per-se, is responsible for the acute cerebral ischaemia that develops. Electron microscopic studies, demonstrated the delayed development of a mild cerebral vasculopathy, comprising focal areas of subintimal medial necrosis. Transformation of cells derived from the pia-arachnoid into macrophages, occurred on the second day post haemorrhage. These cells were then largely responsible for a rapid phagocytic removal of the subarachnoid blood clot. Previous findings obtained by workers using experimental models of SAH are reviewed, and suggestions as to the nature and aetiology of delayed cerebral ischaemia and vasospasm arising after SAH deduced

Crisis in neuroimaging: is neuroimaging failing 15 years after the decade of the brain?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Sao Paulo UNIFESP, Dept Psiquiatria, Lab Interdisciplinar Neurociencias Clin LiNC, Sao Paulo, SP, BrazilUniv Fed ABC, Ctr Matemat Comp & Cognicao, Santo Andre, SP, BrazilLaboratório Interdisciplinar de Neurociências Clínicas (LiNC), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP BrazilFAPESP: 2013/10498-6FAPESP: 2013/00506-1FAPESP: 2013/08531-5CNPq: 442026/2014-5CNPq: 312984/2014-6Web of Scienc

Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six latin american cities

Background Social and environmental factors such as poverty or violence, modulate the risk and course of schizophrenia, but how they affect the brain in patients with psychosis remains unclear. We here studied how they are related to brain structure in schizophrenia and healthy controls in Latin America, where these factors are large and unequally distributed. Methods This is an MRI multi-center study in patients with schizophrenia and healthy controls from six Latin American cities: Buenos Aires, Medellin, Mexico City, Santiago, Sao Paulo and Porto Alegre. Total and voxel-level gray matter volumes obtained from T1-weighted MRI images and their relationship with income and homicide rates were analyzed using a general linear model. Results 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total gray matter volume in the two groups (P=0.006). Controls showed a positive correlation between total gray matter volume and income (R=0.14, P=0.02). Surprisingly, this relationship was not present in schizophrenia (R=-0.076, P=0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure. Discussion Our results highlight the interplay between the environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as those from low and middle-income countries: potentially less brain vulnerability (less gray matter loss) is sufficient to become unwell in adverse (poor) environments. The development of algorithms exploring clinically-useful information from structural brain images in psychosis should include representative samples from low and middle-income countries.Fil: Crossley, Nicolas. Pontificia Universidad Católica de Chile; Chile.Fil: Zugman, Andre. Universidade Federal de São Paulo; Brasil.Fil: Reyes-Madrigal, Francisco. Instituto Nacional de Neurología y Neurocirugía; México.Fil: Czepielewski, Leticia. Universidade Federal do Rio Grande do Sul; Brasil.Fil: Castro, Mariana Nair. Fleni. Instituto de Neurociencias FLENI-CONICET; Argentina. Fleni. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina.Fil: Diaz-Zuluaga, Ana María. Universidad de Antioquía; Colombia.Fil: Pineda-Zapata, Julián. Instituto de Alta Tecnología Médica; Colombia.Fil: Reckziegel, Ramiro. Universidade Federal do Rio Grande do Sul; Brasil.Fil: Gadelha, Ary. Universidade Federal de São Paulo; Brasil.Fil: Jackowski, Andrea. Universidade Federal de São Paulo; Brasil.Fil: Noto, Cristiano. Universidade Federal de São Paulo; Brasil.Fil: Alliende Serra, Luz Maria. Pontificia Universidad Católica de Chile; Chile.Fil: Iruretagoyena, Bárbara. Pontificia Universidad Católica de Chile; Chile.Fil: Guinjoan, Salvador Martín. Fleni. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fleni. Servicio de Psiquiatría; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Psiquiatría y Salud Mental; Argentina.Fil: Ossandon, Tomas. Pontificia Universidad Católica de Chile; Chile.Fil: Ramirez-Mahaluf, Juan Pablo. Pontificia Universidad Católica de Chile; Chile.Fil: Castañeda, Carmen Paz. Instituto Psiquiátrico Dr. José Horwitz Barak; Chile.Fil: Gonzalez-Valderrama, Alfonso. Instituto Psiquiátrico Dr. José Horwitz Barak; Chile.Fil: Nachar, Rubén. Instituto Psiquiátrico Dr. José Horwitz Barak; Chile

ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

Shared and Distinct Alterations in Brain Structure of Youth With Internalizing or Externalizing Disorders: Findings From the Enigma Antisocial Behavior, ADHD, Mdd, and Anxiety Working Groups

BACKGROUND: Externalizing and internalizing disorders are common in youth but are often studied separately, preventing researchers from identifying shared (i.e., transdiagnostic) alterations in brain structure. Using data from the ENIGMA Consortium, we conducted a mega-analysis to identify shared and distinct cortical and subcortical brain alterations across internalizing (anxiety disorders and depression) and externalizing disorders (attention-deficit/hyperactivity disorder [ADHD] and conduct disorder [CD]) in youth. METHODS: 3D T1-weighted MRI data from youth (aged 4-21 years) with anxiety disorders (n=1,044), depression (n=504), ADHD (n=1,317), and CD (n=1,172), along with healthy controls (n=4,743) were analyzed. We assessed group differences in regional cortical thickness, surface area, and subcortical volume using linear models, adjusted for site, age, and sex, and total intracranial volume in the surface area and subcortical volume models. RESULTS: We observed transdiagnostic associations, with both internalizing and externalizing disorders characterized by lower surface area in the insula, entorhinal cortex, and middle temporal gyrus, and lower amygdala volume (Cohen\u27s ds=-0.07 to -0.24), as well as total surface area and intracranial volume (ds=-0.11 to -0.25). Externalizing-specific reductions in surface area were observed in fronto-parietal regions (ds=-0.08 to -0.13), but no internalizing-specific associations were identified. Disorder-specific alterations were identified for ADHD, CD, and anxiety disorders, but not depression. CONCLUSIONS: Both common and disorder-specific alterations were identified, with regions involved in salience attribution and emotion processing implicated across internalizing and externalizing disorders. These findings can guide future research targeting common biological processes across youth psychiatric disorders as well as features unique to individual disorders

Can neuroimaging be used to predict the onset of psychosis?

The onset of psychotic disorders is preceded by a high-risk phase characterised by attenuated or brief psychotic symptoms and a marked decline in functioning. About a third of individuals presenting with these features develop a psychotic disorder within 3 years. A fundamental challenge in the clinical management of this population is that it is not possible to predict whether an individual at high risk will go on to develop psychosis on the basis of their presenting features. Consequently, preventive interventions that might reduce the risk of progression to psychosis cannot be selectively offered to those patients for whom they would be most useful. However, neuroimaging investigation suggests that the structure, function, and chemistry of the brain in high-risk individuals who become psychotic differ from those in individuals who do not become psychotic. In this Personal View, we review these findings and discuss the main challenges for translating them into clinical practice. The development of techniques that allow clinicians to tailor interventions to the level of risk is a major translational goal for research in this field.</p