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

Continuing lack of evidence for the psychotic subtyping of PTSD

Universidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilWeb of Scienc

Brain-based classification of youth with anxiety disorders: transdiagnostic examinations within the ENIGMA-Anxiety database using machine learning

Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size, and have limited clinical relevance. These concerns have prompted a paradigm shift towards highly powered (i.e., big data) individual-level inferences, which are data-driven, transdiagnostic, and neurobiologically informed. Hence, we uniquely built/validated supervised neuroanatomical machine learning (ML) models for individual-level inferences, using the largest up to date neuroimaging database on youth anxiety disorders: ENIGMA Anxiety Consortium (N=3,343; Age: 10-25 years; Global Sites: 32). Modest, yet robust, brain-based classifications were achieved for specific anxiety disorders (Panic Disorder), but also transdiagnostically for all anxiety disorders when patients were subgrouped according to their sex, medication status, and symptom severity (AUC’s 0.59-0.63). Classifications were driven by neuroanatomical features (cortical thickness/surface area, subcortical volumes) in fronto-striato-limbic and temporo-parietal regions. This benchmark study provides estimates on individual-level classification performances that can be realistically achieved with ML using neuroanatomical data, within a large, heterogenous, and multi-site sample of youth with anxiety disorders

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

Speech Illusions in People at Clinical High Risk for Psychosis Linked to Clinical Outcome

BACKGROUND AND HYPOTHESIS: Around 20% of people at clinical high risk (CHR) for psychosis later develop a psychotic disorder, but it is difficult to predict who this will be. We assessed the incidence of hearing speech (termed speech illusions [SIs]) in noise in CHR participants and examined whether this was associated with adverse clinical outcomes. STUDY DESIGN: At baseline, 344 CHR participants and 67 healthy controls were presented with a computerized white noise task and asked whether they heard speech, and whether speech was neutral, affective, or whether they were uncertain about its valence. After 2 years, we assessed whether participants transitioned to psychosis, or remitted from the CHR state, and their functioning. STUDY RESULTS: CHR participants had a lower sensitivity to the task. Logistic regression revealed that a bias towards hearing targets in stimuli was associated with remission status (OR = 0.21, P = 042). Conversely, hearing SIs with uncertain valence at baseline was associated with reduced likelihood of remission (OR = 7.72. P = .007). When we assessed only participants who did not take antipsychotic medication at baseline, the association between hearing SIs with uncertain valence at baseline and remission likelihood remained (OR = 7.61, P = .043) and this variable was additionally associated with a greater likelihood of transition to psychosis (OR = 5.34, P = .029). CONCLUSIONS: In CHR individuals, a tendency to hear speech in noise, and uncertainty about the affective valence of this speech, is associated with adverse outcomes. This task could be used in a battery of cognitive markers to stratify CHR participants according to subsequent outcomes

Do desenvolvimento normal à psicopatologia: o desafio da replicação em neuroimagem

Introduction: It is critical to understanding the typical trajectory of brain development and how changes in brain measures during development are related to psychopathology and mental disorders. The replication of findings is being discussed intensely in the scientific literature in recent years. This study has the main objective of exploring neuroimaging findings related to age, sex and behavior and also check the reproducibility of these findings. We will explore the main objective in two specific studies: a) validate the findings of the sex and age effect on cortical thickness and cortical surface area. b) validation of brain-behavioral correlation, as assessed by CBCL (child behavior checklist) and cortical thickness. Method: 781 children were enrolled in the neuroimaging phase of the High Risk Cohort (HRC) study in two different cities. Of these 749 completed the examination of structural MRI. The images were processed using the FreeSurfer 5.1 software and statistical analyzes conducted in MATLAB software as appropriate for each specific objective. Results: The results described here suggest that there is a high potential for replicability for sex and age measures, while behavioral measures by CBCL changes seem more difficult to replicate. It is noteworthy that one of our analysis indicated a rate of 48% false positives, even with statistical methods of correction for multiple comparisons. Conclusion: The results described in this thesis indicate that the validation of findings in the sample is an effective way to control for false positives. We believe that the differences in the replicability between the findings relating to age, sex and behavioral changes is due to the nature of the measures. While age and sex are objective characteristics, the characteristics assessed by CBCL are subjective. Future neuroimaging studies should take into account not only the finding of location but also effect size measures, and include in its design a sample for confirmatory analyses.Introdução: É fundamental entender a trajetória típica do neurodesenvolvimento e como alterações de medidas cerebrais durante o desenvolvimento estão relacionados a psicopatologia e aos transtornos mentais. A replicação de achados vem sendo discutida de maneira intensa na literatura cientifica nos últimos anos. Este estudo tem como objetivos principal explorar a achados de neuroimagem relacionados a idade, sexo e comportamento e também verificar a replicabilidade destes achados. Abordaremos o objetivo principal em dois estudos específicos: a) A validação dos achados do efeito de sexo e idade sobre a espessura cortical e área de superfície cortical. b) validação da relação entre a medida de alteração de comportamento (CBCL ? child behavior check-list) e espessura cortical. Método: Ao todo 781 crianças foram convocadas para participar da fase de neuroimagem do estudo High Risk Cohort (HRC) em duas cidades diferentes. Destas 749 completaram o exame de ressonância magnética estrutural. As imagens foram processadas utilizando o software freesurfer 5.1 e as análises estatísticas conduzidas no software MATLAB conforme adequado para cada objetivo especifico. Resultados: Os resultados aqui descritos sugerem que há um alto potencial de replicabilidade para medidas de sexo e idade, enquanto que alterações comportamentais medidas pela CBCL parecem mais difíceis de serem replicadas. Vale ressaltar que uma de nossas análises indicou um potencial de 48% de falsos positivos, mesmo com métodos de correção estatístico para múltiplas comparações. Conclusão: Os resultados descritos nos dois estudos nessa tese indicam que a validação dos achados em parte da amostra é uma maneira eficaz de controle para falsos positivos. Acreditamos que a diferença de replicabilidade entre os achados referentes a idade, sexo e alterações do comportamento se deve a natureza das medidas. Enquanto idade e sexo são características objetivas, as características avaliadas pela CBCL são subjetivas. Estudos futuros de neuroimagem devem levar em consideração não apenas o achado de localização, mas também medidas de tamanho de efeito, e incluir em seu desenho uma amostra para a confirmação dos achados.Dados abertos - Sucupira - Teses e dissertações (2013 a 2016

Is adenosine associated with sudden death in schizophrenia?:A new framework linking the adenosine pathway to risk of sudden death

Schizophrenia is associated with an increased mortality from cardiovascular disease. Relatively few studies have assessed the putative association of schizophrenia pathophysiology with sudden death. Low adenosine levels have been associated with schizophrenia. In cardiology, increased mortality among patients with congestive heart failure has been associated with genetic polymorphisms that potentially lead to lower adenosine levels. Thus, we hypothesize that adenosine could link schizophrenia and cardiovascular mortality, with decreased adenosine levels leading to increased vulnerability to hyperexcitability following hypoxic insults, increasing the odds of fatal arrhythmias. Low adenosine levels might also lead to a small increase in overall mortality rates and a major increase in the sudden death rate. This hypothesis paves the way for further investigation of the increased cardiac mortality associated with schizophrenia. Potentially, a better characterization of adenosine related mechanisms of sudden death in schizophrenia could lead to new evidence of factors leading to sudden death in the general population.Univ Fed Sao Paulo, Dept Psiquiatria, LINC, Rua Pedro Toledo,669 Vila Clementino, BR-04039032 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psiquiatria, Programa Esquizofrenia, PROESQ, Rua Machado Bittencourt 222, BR-04044000 Sao Paulo, BrazilUniv Sao Paulo, Heart Inst InCor, Med Sch, Av Dr Endas Carvaiho Aguiar 44, BR-05403900 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Neurol Neurocirurgia, Disciplina Neurociencia, Rua Pedro Toledo,669 Vila Clementino, BR-04039032 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psiquiatria, LINC, Rua Pedro Toledo,669 Vila Clementino, BR-04039032 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psiquiatria, Programa Esquizofrenia, PROESQ, Rua Machado Bittencourt 222, BR-04044000 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Neurol Neurocirurgia, Disciplina Neurociencia, Rua Pedro Toledo,669 Vila Clementino, BR-04039032 Sao Paulo, SP, BrazilWeb of Scienc