BackgroundThere is still little knowledge of objective suicide risk stratification.MethodsThis st... more BackgroundThere is still little knowledge of objective suicide risk stratification.MethodsThis study aims to develop models using machine-learning approaches to predict suicide attempt (1) among survey participants in a nationally representative sample and (2) among participants with lifetime major depressive episodes. We used a cohort called the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) that was conducted in two waves and included a nationally representative sample of the adult population in the United States. Wave 1 involved 43 093 respondents and wave 2 involved 34 653 completed face-to-face reinterviews with wave 1 participants. Predictor variables included clinical, stressful life events, and sociodemographic variables from wave 1; outcome included suicide attempt between wave 1 and wave 2.ResultsThe model built with elastic net regularization distinguished individuals who had attempted suicide from those who had not with an area under the ROC cur...
BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, ... more BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset.MethodsWe performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronologi...
Sodium valproate (VPA) has well-established neuroprotective effects and is recommended as treatme... more Sodium valproate (VPA) has well-established neuroprotective effects and is recommended as treatment in bipolar disorder patients. The neural effects of VPA in pediatric bipolar disorder (PBD) have yet to be established. This preliminary study explored the effects of VPA on brain structure in PBD. Fourteen PBD patients (10 males; mean = 13.43 ± 3.05 years old) underwent a structural MRI before and after a 6-week VPA treatment period. Bayesian linear mixed modeling explored seven brain region volumes as a function of dichotomous pre/post time. Results showed a decrease in amygdala volume over time. These findings need to be confirmed by large-scale, longitudinal studies.
Neuroimaging studies have been steadily explored in Bipolar Disorder (BD) in the last decades. Ne... more Neuroimaging studies have been steadily explored in Bipolar Disorder (BD) in the last decades. Neuroanatomical changes tend to be more pronounced in patients with repeated episodes. Although the role of such changes in cognition and memory is well established, daily-life functioning impairments bulge among the consequences of the proposed progression. The objective of this study was to analyze MRI volumetric modifications in BD and healthy controls (HC) as possible predictors of daily-life functioning through a machine learning approach. Ninety-four participants (35 DSM-IV BD type I and 59 HC) underwent clinical and functioning assessments, and structural MRI. Functioning was assessed using the Functioning Assessment Short Test (FAST). The machine learning analysis was used to identify possible candidates of regional brain volumes that could predict functioning status, through a support vector regression algorithm. Patients with BD and HC did not differ in age, education and marital...
Journal of neuroimaging : official journal of the American Society of Neuroimaging, Jan 20, 2018
As part of its technological sophistication, the International Space Station (ISS) Program operat... more As part of its technological sophistication, the International Space Station (ISS) Program operates a robust medical surveillance schedule for its rotating 6-person crew to control the known health risks and to address knowledge gaps related to human health in space flight environment. Recent evidence on visual impairment in a subset of ISS crew has renewed the interest in the effects of long-duration space flight on the central nervous system (CNS). Through retrospective analysis in a sample of 10 healthy astronauts, we demonstrate the utility of multimodal quantitative magnetic resonance imaging (qMRI) with diffusion tensor imaging (DTI)-based customized brain templates to examine the structural attributes of various CNS compartments in this occupational group. The study included 10 healthy astronauts (45-55 years). All subjects had previous space flights with the median duration of 110 days. Multimodal quantitative structural imaging modalities performed and used in analyses. A h...
Journal of applied physiology (Bethesda, Md. : 1985), Jan 16, 2017
In order to improve the pathophysiologic understanding of visual changes observed in astronauts, ... more In order to improve the pathophysiologic understanding of visual changes observed in astronauts, we aimed to use quantitative MRI to measure anatomic and physiologic responses during a ground-based spaceflight analogue (head down tilt, HDT) combined with increased ambient carbon dioxide (CO2). Six healthy, male subjects participated in the double-blinded, randomized cross-over design study with two conditions: 26.5 h of -12° HDT with ambient air and with 0.5% CO2, both followed by 2.5 h exposure to 3% CO2. Volume and mean diffusivity quantification of the lateral ventricle and phase-contrast flow sequences of the internal carotid arteries and cerebral aqueduct were acquired at 3T. Compared to supine baseline, HDT (ambient air) resulted in an increase in lateral ventricular volume (P=0.03). Cerebral blood flow, however, decreased with HDT in the presence of either ambient air or 0.5% CO2 (P=0.002 and P=0.01 respectively); this was partially reversed by acute 3% CO2 exposure. Followin...
Journal of neuroimaging : official journal of the American Society of Neuroimaging, May 7, 2016
Cerebrospinal fluid (CSF) in the brain can be compartmentalized into two main divisions: ventricu... more Cerebrospinal fluid (CSF) in the brain can be compartmentalized into two main divisions: ventricular CSF and subarachnoid space (sulcal CSF). Changes in CSF volumetry are seen in many neurological conditions including multiple sclerosis (MS) and found to correlate with clinical outcomes. We aimed to test the relation between the volumetry of sulcal and ventricular CSF and cognitive impairment (CI) based on the minimal assessment of cognitive function in MS (MACFIMS) in patients with MS. Forty-six patients with MS underwent the MACFIMS battery and classified as nonimpaired (MSNI) (n = 10) and cognitively impaired (MSCI) (n = 30) and borderline (MSBD) MS patients (n = 6). Volumes of sulcal and ventricular CSF along with global gray and white matter volumes and cortical thickness were obtained by diffusion tensor imaging (DTI) and T1-weighted (T1w)-based segmentation. These measures were statistically analyzed for associations with CI after adjusting for the age, education in years, le...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, Aug 18, 2016
Unhealthy eating behaviors often develop in the setting of inadequate inhibitory control, a funct... more Unhealthy eating behaviors often develop in the setting of inadequate inhibitory control, a function broadly ascribed to the prefrontal cortex (PFC). Regulation of inhibitory control by the PFC and its anatomical components and their contribution to increasing body mass index (BMI) are poorly understood. To study the role of PFC in the regulation of inhibitory control and body weight, we examined measures of cortical thickness in PFC sub-regions, inhibitory control (color-word interference task (CWIT)), and BMI in 91 healthy volunteers. We tested the predictive effect of PFC sub-regional cortical thickness on BMI and mediation by inhibitory control measured with CWIT. Measures of depression (BDI-II), anxiety (STAI-T) and trauma-related symptoms (TSC-40) were collected; the disinhibition scale of the three-factor eating questionnaire (TFEQ) was used to assess disinhibited eating. We then tested the relationship between BD-II, STAI-T, TSC-40, TFEQ, CWIT, and BMI with correlation analy...
www.thelancet.com/psychiatry Vol 3 January 2016 13 defi cit). These fi ndings, like those highlig... more www.thelancet.com/psychiatry Vol 3 January 2016 13 defi cit). These fi ndings, like those highlighted above, have drawn into serious question the usefulness of symptom-based diagnostic constructs if they fail to provide information or insight about the underlying psycho patholgical mechanisms. Another long-standing challenge has been the limited contact between neuroimaging and other areas of psychiatric neuroscience, especially genetic and molecular investigations. This too has seen progress in 2015, in part related to larger neuroimaging sample sizes that can allow such interfaces. Findings from a large twin study of white matter structure in schizophrenia showed a strong association between white matter integrity and genetic risk for schizophrenia, suggesting a potential common causal genetic mechanism. Another study of amygdala volume and emotion recognition task performance in a very large sample (n=858) showed a common relationship of both to a polymorphism in the PDE5 gene using a genome-wide quantitative trait locus analysis. Particularly exciting is that this association suggests potential pharmacological treatment insights for many neuropsychiatric disorders in which emotion recognition is impaired, as drugs that target PDE5 (a phosphodiesterase) already exist. Finally, even the organising theme of anatomically distributed, large-scale connectivity networks, which has been central to many neuroimaging studies during the past decade, has made contact with genomics. Specifi cally, using a post-mortem gene expression dataset drawn from many regions across the human brain, a relationship has been found between spatial patterns of functional connectivity and gene expression . Perhaps the biggest obstacle to the clinical utility of neuroimaging, however, has been the dependence on group-level analyses, which generally preclude insights about individual patients. This too has seen striking progress, both with respect to methods that can readily parcellate functional regions within individual brains, and demonstrations that functional connectivity-based analyses are powerful and specifi c enough to reliably identify an individual from a group. Thus, looking forward to 2016, it would seem that a greater focus on individuals will be a crucial area of progress that can fi nally bring neuroimaging into the clinical sphere in psychiatry. We must therefore also demand more of study design so that it can be relevant to individuals, such as use of control arms when studying interventions, which still remains rare in neuroimaging.
BackgroundThere is still little knowledge of objective suicide risk stratification.MethodsThis st... more BackgroundThere is still little knowledge of objective suicide risk stratification.MethodsThis study aims to develop models using machine-learning approaches to predict suicide attempt (1) among survey participants in a nationally representative sample and (2) among participants with lifetime major depressive episodes. We used a cohort called the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) that was conducted in two waves and included a nationally representative sample of the adult population in the United States. Wave 1 involved 43 093 respondents and wave 2 involved 34 653 completed face-to-face reinterviews with wave 1 participants. Predictor variables included clinical, stressful life events, and sociodemographic variables from wave 1; outcome included suicide attempt between wave 1 and wave 2.ResultsThe model built with elastic net regularization distinguished individuals who had attempted suicide from those who had not with an area under the ROC cur...
BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, ... more BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset.MethodsWe performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronologi...
Sodium valproate (VPA) has well-established neuroprotective effects and is recommended as treatme... more Sodium valproate (VPA) has well-established neuroprotective effects and is recommended as treatment in bipolar disorder patients. The neural effects of VPA in pediatric bipolar disorder (PBD) have yet to be established. This preliminary study explored the effects of VPA on brain structure in PBD. Fourteen PBD patients (10 males; mean = 13.43 ± 3.05 years old) underwent a structural MRI before and after a 6-week VPA treatment period. Bayesian linear mixed modeling explored seven brain region volumes as a function of dichotomous pre/post time. Results showed a decrease in amygdala volume over time. These findings need to be confirmed by large-scale, longitudinal studies.
Neuroimaging studies have been steadily explored in Bipolar Disorder (BD) in the last decades. Ne... more Neuroimaging studies have been steadily explored in Bipolar Disorder (BD) in the last decades. Neuroanatomical changes tend to be more pronounced in patients with repeated episodes. Although the role of such changes in cognition and memory is well established, daily-life functioning impairments bulge among the consequences of the proposed progression. The objective of this study was to analyze MRI volumetric modifications in BD and healthy controls (HC) as possible predictors of daily-life functioning through a machine learning approach. Ninety-four participants (35 DSM-IV BD type I and 59 HC) underwent clinical and functioning assessments, and structural MRI. Functioning was assessed using the Functioning Assessment Short Test (FAST). The machine learning analysis was used to identify possible candidates of regional brain volumes that could predict functioning status, through a support vector regression algorithm. Patients with BD and HC did not differ in age, education and marital...
Journal of neuroimaging : official journal of the American Society of Neuroimaging, Jan 20, 2018
As part of its technological sophistication, the International Space Station (ISS) Program operat... more As part of its technological sophistication, the International Space Station (ISS) Program operates a robust medical surveillance schedule for its rotating 6-person crew to control the known health risks and to address knowledge gaps related to human health in space flight environment. Recent evidence on visual impairment in a subset of ISS crew has renewed the interest in the effects of long-duration space flight on the central nervous system (CNS). Through retrospective analysis in a sample of 10 healthy astronauts, we demonstrate the utility of multimodal quantitative magnetic resonance imaging (qMRI) with diffusion tensor imaging (DTI)-based customized brain templates to examine the structural attributes of various CNS compartments in this occupational group. The study included 10 healthy astronauts (45-55 years). All subjects had previous space flights with the median duration of 110 days. Multimodal quantitative structural imaging modalities performed and used in analyses. A h...
Journal of applied physiology (Bethesda, Md. : 1985), Jan 16, 2017
In order to improve the pathophysiologic understanding of visual changes observed in astronauts, ... more In order to improve the pathophysiologic understanding of visual changes observed in astronauts, we aimed to use quantitative MRI to measure anatomic and physiologic responses during a ground-based spaceflight analogue (head down tilt, HDT) combined with increased ambient carbon dioxide (CO2). Six healthy, male subjects participated in the double-blinded, randomized cross-over design study with two conditions: 26.5 h of -12° HDT with ambient air and with 0.5% CO2, both followed by 2.5 h exposure to 3% CO2. Volume and mean diffusivity quantification of the lateral ventricle and phase-contrast flow sequences of the internal carotid arteries and cerebral aqueduct were acquired at 3T. Compared to supine baseline, HDT (ambient air) resulted in an increase in lateral ventricular volume (P=0.03). Cerebral blood flow, however, decreased with HDT in the presence of either ambient air or 0.5% CO2 (P=0.002 and P=0.01 respectively); this was partially reversed by acute 3% CO2 exposure. Followin...
Journal of neuroimaging : official journal of the American Society of Neuroimaging, May 7, 2016
Cerebrospinal fluid (CSF) in the brain can be compartmentalized into two main divisions: ventricu... more Cerebrospinal fluid (CSF) in the brain can be compartmentalized into two main divisions: ventricular CSF and subarachnoid space (sulcal CSF). Changes in CSF volumetry are seen in many neurological conditions including multiple sclerosis (MS) and found to correlate with clinical outcomes. We aimed to test the relation between the volumetry of sulcal and ventricular CSF and cognitive impairment (CI) based on the minimal assessment of cognitive function in MS (MACFIMS) in patients with MS. Forty-six patients with MS underwent the MACFIMS battery and classified as nonimpaired (MSNI) (n = 10) and cognitively impaired (MSCI) (n = 30) and borderline (MSBD) MS patients (n = 6). Volumes of sulcal and ventricular CSF along with global gray and white matter volumes and cortical thickness were obtained by diffusion tensor imaging (DTI) and T1-weighted (T1w)-based segmentation. These measures were statistically analyzed for associations with CI after adjusting for the age, education in years, le...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, Aug 18, 2016
Unhealthy eating behaviors often develop in the setting of inadequate inhibitory control, a funct... more Unhealthy eating behaviors often develop in the setting of inadequate inhibitory control, a function broadly ascribed to the prefrontal cortex (PFC). Regulation of inhibitory control by the PFC and its anatomical components and their contribution to increasing body mass index (BMI) are poorly understood. To study the role of PFC in the regulation of inhibitory control and body weight, we examined measures of cortical thickness in PFC sub-regions, inhibitory control (color-word interference task (CWIT)), and BMI in 91 healthy volunteers. We tested the predictive effect of PFC sub-regional cortical thickness on BMI and mediation by inhibitory control measured with CWIT. Measures of depression (BDI-II), anxiety (STAI-T) and trauma-related symptoms (TSC-40) were collected; the disinhibition scale of the three-factor eating questionnaire (TFEQ) was used to assess disinhibited eating. We then tested the relationship between BD-II, STAI-T, TSC-40, TFEQ, CWIT, and BMI with correlation analy...
www.thelancet.com/psychiatry Vol 3 January 2016 13 defi cit). These fi ndings, like those highlig... more www.thelancet.com/psychiatry Vol 3 January 2016 13 defi cit). These fi ndings, like those highlighted above, have drawn into serious question the usefulness of symptom-based diagnostic constructs if they fail to provide information or insight about the underlying psycho patholgical mechanisms. Another long-standing challenge has been the limited contact between neuroimaging and other areas of psychiatric neuroscience, especially genetic and molecular investigations. This too has seen progress in 2015, in part related to larger neuroimaging sample sizes that can allow such interfaces. Findings from a large twin study of white matter structure in schizophrenia showed a strong association between white matter integrity and genetic risk for schizophrenia, suggesting a potential common causal genetic mechanism. Another study of amygdala volume and emotion recognition task performance in a very large sample (n=858) showed a common relationship of both to a polymorphism in the PDE5 gene using a genome-wide quantitative trait locus analysis. Particularly exciting is that this association suggests potential pharmacological treatment insights for many neuropsychiatric disorders in which emotion recognition is impaired, as drugs that target PDE5 (a phosphodiesterase) already exist. Finally, even the organising theme of anatomically distributed, large-scale connectivity networks, which has been central to many neuroimaging studies during the past decade, has made contact with genomics. Specifi cally, using a post-mortem gene expression dataset drawn from many regions across the human brain, a relationship has been found between spatial patterns of functional connectivity and gene expression . Perhaps the biggest obstacle to the clinical utility of neuroimaging, however, has been the dependence on group-level analyses, which generally preclude insights about individual patients. This too has seen striking progress, both with respect to methods that can readily parcellate functional regions within individual brains, and demonstrations that functional connectivity-based analyses are powerful and specifi c enough to reliably identify an individual from a group. Thus, looking forward to 2016, it would seem that a greater focus on individuals will be a crucial area of progress that can fi nally bring neuroimaging into the clinical sphere in psychiatry. We must therefore also demand more of study design so that it can be relevant to individuals, such as use of control arms when studying interventions, which still remains rare in neuroimaging.
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