Regional Gray Matter Volume Reductions Research Articles

Association of body mass index and its classifications with gray matter volume in individuals with a wide range of body mass index group: A whole-brain magnetic resonance imaging study.

AimTo examine the association of body mass index (BMI) [kg/m2] and its classifications (underweight [BMI < 18.5], normal [18.5 ≤ BMI < 25], overweight [25 ≤ BMI < 30], and obese [BMI ≥ 30]) with brain structure in individuals with a wide range of BMI group.Materials and methodsThe participants included 382 right-handed individuals (mean age: 46.9 ± 14.3 years, 142 men and 240 women). The intelligence quotient was assessed using the Japanese Adult Reading Test. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to analyze the association of BMI and its classifications with gray and white matter structures, respectively.ResultsAccording to VBM, BMI was significantly and negatively correlated with the bilateral cerebellum exterior volumes. In group comparisons, the right cerebellum exterior volume was significantly lower in the overweight or obese group than in the underweight or normal group, while the bilateral cuneus and calcarine cortex, left cuneus, and left precuneus volume was significantly lower in the underweight group than in the non-underweight group. Sex-related stratification analyses for VBM revealed that BMI was significantly and negatively correlated with the bilateral cerebellum exterior volumes only in women. In group comparisons, the left cerebellum exterior volume was significantly lower in obese women than in non-obese women. The left thalamus proper and the right cerebellum exterior volumes were significantly lower in overweight or obese group than in underweight or normal group in men and women, respectively. The bilateral cuneus and calcarine cortex, left cuneus and carcarine cortex, and bilateral cuneus volume was significantly lower in underweight men than in non-underweight men. In contrast, there were no notable findings on DTI.ConclusionOur results suggest association of continuous BMI, being overweight or obese, and being underweight with decreased gray matter volume in individuals with a wide range of BMI group. Furthermore, sex-related differences are seen in the association of BMI and its classifications with regional gray matter volume reductions. Abnormally high or low BMIs may have a negative influence on regional gray matter volumes.

Immune-Related Genetic Overlap Between Regional Gray Matter Reductions and Psychiatric Symptoms in Adolescents, and Gene-Set Validation in a Translational Model.

Adolescence is a period of vulnerability for the maturation of gray matter (GM) and also for the onset of psychiatric disorders such as major depressive disorder (MDD), bipolar disorder and schizophrenia. Chronic neuroinflammation is considered to play a role in the etiology of these illnesses. However, the involvement of neuroinflammation in the observed link between regional GM volume reductions and psychiatric symptoms is not established yet. Here, we investigated a possible common immune-related genetic link between these two phenomena in european adolescents recruited from the community. Hippocampal and medial prefrontal cortex (mPFC) were defined a priori as regions of interest (ROIs). Their GM volumes were extracted in 1,563 14-year-olds from the IMAGEN database. We found a set of 26 SNPs that correlated with the hippocampal volumes and 29 with the mPFC volumes at age 14. We formed two ROI-Related Immune-gene scores (RRI) with the inflammation SNPs that correlated to hippocampal GM volume and to mPFC GM volume. The predictive ability of both RRIs with regards to the presence of psychiatric symptoms at age 18 was investigated by correlating the RRIs with psychometric questionnaires obtained at age 18. The RRIs (but not control scores constructed with random SNPs) correlated with the presence of depressive symptoms, positive psychotic symptoms, and externalizing symptoms in later adolescence. In addition, the effect of childhood maltreatment, one of the major environmental risk factors for depression and other mental disorders, interacted with the RRI effect. We next sought to validate this finding by investigating our set of inflammatory genes in a translational animal model of early life adversity. Mice were subjected to a protocol of maternal separation at an early post-natal age. We evaluated depressive behaviors in separated and non-separated mice at adolescence and their correlations with the concomitant expression of our genes in whole blood samples. We show that in mice, early life adversity affected the expression of our set of genes in peripheral blood, and that levels of expression correlated with symptoms of negative affect in adolescence. Overall, our translational findings in adolescent mice and humans provide a novel validated gene-set of immune-related genes for further research in the early stages of mood disorders.

Lower regional gray matter volume in the absence of higher cortical amyloid burden in late-life depression

Late-life depression (LLD) is associated with a risk of developing Alzheimer’s disease (AD). However, the role of AD-pathophysiology in LLD, and its association with clinical symptoms and cognitive function are elusive. In this study, one hundred subjects underwent amyloid positron emission tomography (PET) imaging with [18F]-flutemetamol and structural MRI: 48 severely depressed elderly subjects (age 74.1 ± 7.5 years, 33 female) and 52 age-/gender-matched healthy controls (72.4 ± 6.4 years, 37 female). The Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess the severity of depressive symptoms and episodic memory function respectively. Amyloid deposition was quantified using the standardized uptake value ratio. Whole-brain voxel-wise comparisons of amyloid deposition and gray matter volume (GMV) between LLD and controls were performed. Multivariate analysis of covariance was conducted to investigate the association of regional differences in amyloid deposition and GMV with clinical factors, including GDS and RAVLT. As a result, there were no significant group differences in amyloid deposition. In contrast, LLD showed significant lower GMV in the left temporal and parietal region. GMV reduction in the left temporal region was associated with episodic memory dysfunction, but not with depression severity. Regional GMV reduction was not associated with amyloid deposition. LLD is associated with lower GMV in regions that overlap with AD-pathophysiology, and which are associated with episodic memory function. The lack of corresponding associations with amyloid suggests that lower GMV driven by non-amyloid pathology may play a central role in the neurobiology of LLD presenting as a psychiatric disorder.Trial registration: European Union Drug Regulating Authorities Clinical Trials identifier: EudraCT 2009-018064-95.

Different Patterns of Gray Matter Volume Reduction in Early-onset and Late-onset Alzheimer Disease.

Individuals with early-onset Alzheimer disease (EOAD) differ from those with late-onset Alzheimer disease (LOAD) not only in genetics and age at onset but also in their clinical symptoms. To differentiate the neuropathological and neurocognitive features of EOAD and LOAD by comparing the pattern of regional gray matter volume (GMV) reduction and its symptomatic correlates. Three-dimensional T1-weighted MRIs and Mini-Mental State Examination (MMSE) scores were obtained from 12 individuals with EOAD, 65 with LOAD, and 49 healthy controls (HC). Regional GMV reduction between the three groups was assessed using voxel-based morphometry. Multiple regression analyses were conducted with MMSE total score as an independent variable. Compared to the HC, both AD groups showed a significant GMV reduction in the bilateral hippocampus and the left temporoparietal junction; in addition, the LOAD group showed one in the bilateral anterior temporal lobes. Multiple regression analyses revealed a positive correlation between MMSE total score and GMV in the left anterior temporal lobe in both AD groups; that is, lower scores were associated with reduced GMV. Interestingly, a positive correlation in hippocampal GMV was revealed only in the LOAD group. MMSE total score is associated with the anterior temporal lobe volume in individuals with AD. Hippocampal volume and its relationship with MMSE total score are associated with LOAD pathophysiology but not EOAD pathophysiology. The hippocampal volume reduction and low MMSE scores are hallmarks of LOAD but are less specific to EOAD, which may cause a delay in diagnosis.

Frontolimbic brain volume abnormalities in bipolar disorder with suicide attempts

Over 2.3 million people in the United States live with bipolar disorder. Sixty percent of those with a bipolar disorder diagnosis attempt suicide at least once in their lifetime and up to 19% die by suicide. However, the neurobiology of suicide attempts in bipolar disorder remains unclear. We studied the gray matter volume (GMV) of 81 participants with a bipolar-I diagnosis (age-range: 14-34 years old) and 40 healthy participants (age-range 14.7-32 years old) to compare their neuroanatomy and histories of suicide attempt. In the bipolar group, 42 were manic with ages ranging from 14-30.6 years, and 39 were depressed with ages ranging from 14-34.3 years). Twenty three bipolar participants had a suicide attempt history, and 58 had no suicide attempt history. All participants completed behavioral/diagnostic assessments and MRI. We focused on a predefined frontolimbic circuitry in bipolar disorder versus controls to first identify diagnostic GMV correlates and to specifically identify GMV correlates for suicide attempt history. We found reduced GMV in bipolar diagnosis versus controls in the subgenual cingulate and dorsolateral prefrontal cortices. Our observed regional GMV reductions were associated with histories of suicide attempts and measures of individual variations in current suicidal ideation at the time of scanning.

No regional gray matter volume reduction observed in young Japanese people at ultra-high risk for psychosis: A voxel-based morphometry study.

Structural brain magnetic resonance imaging studies of individuals at ultra-high risk (UHR) for psychosis have shown subtle but widespread reductions in baseline gray matter volume (GMV) in the frontal, temporal, and limbic regions compared with healthy controls (HC). These regions coincide with regions of reduced GMV in patients with established psychosis and have led to the consideration of structural changes in UHR as a potential biomarker for future transition to psychosis. However, most studies have been from Europe, North America, and Australia, with few reports from other regions, and two recent studies from Asian countries have failed to detect regional GMV reduction in UHR, suggesting the need for further analysis of an Asian sample. In this study, we investigated GMV reduction in Japanese UHR subjects. The study used voxel-based morphometry to compare magnetic resonance imaging brain scans between 45 UHR individuals recruited by a specialist and 33 HCs. This showed no significant GMV reduction in the UHR group compared with the healthy control group. This negative result may be attributable to characteristics of Asian samples, such as a low prevalence of illicit drug use, or to the heterogeneous nature of UHR subjects.

Shared Genetic Risk of Schizophrenia and Gray Matter Reduction in 6p22.1.

Genetic factors are known to influence both risk for schizophrenia (SZ) and variation in brain structure. A pressing question is whether the genetic underpinnings of brain phenotype and the disorder overlap. Using multivariate analytic methods and focusing on 1,402 common single-nucleotide polymorphisms (SNPs) mapped from the Psychiatric Genomics Consortium (PGC) 108 regions, in 777 discovery samples, we identified 39 SNPs to be significantly associated with SZ-discriminating gray matter volume (GMV) reduction in inferior parietal and superior temporal regions. The findings were replicated in 609 independent samples. These 39 SNPs in chr6:28308034-28684183 (6p22.1), the most significant SZ-risk region reported by PGC, showed regulatory effects on both DNA methylation and gene expression of postmortem brain tissue and saliva. Furthermore, the regulated methylation site and gene showed significantly different levels of methylation and expression in the prefrontal cortex between cases and controls. In addition, for one regulated methylation site we observed a significant in vivo methylation-GMV association in saliva, suggesting a potential SNP-methylation-GMV pathway. Notably, the risk alleles inferred for GMV reduction from in vivo imaging are all consistent with the risk alleles for SZ inferred from postmortem data. Collectively, we provide evidence for shared genetic risk of SZ and regional GMV reduction in 6p22.1 and demonstrate potential molecular mechanisms that may drive the observed in vivo associations. This study motivates dissecting SZ-risk variants to better understand their associations with focal brain phenotypes and the complex pathophysiology of the illness.

Regional Gray Matter Volume Reduction Associated with Major Depressive Disorder: A Voxel-Based Morphometry

Background and Purpose: The association between the low emotional regulation and the brain structural change of major depressive disorder (MDD) has been proposed, but the voxel-based morphometry (VBM) studies on female MDD are rare. The purpose of the present study was to show the regional volume ch...

Reduced amygdala and hippocampal volumes in patients with methamphetamine psychosis

The similarity between psychotic symptoms in patients with schizophrenia such as hallucinations and delusions and those caused by administration of methamphetamine has been accepted. While the etiology of schizophrenia remains unclear, methamphetamine induced psychosis, which is obviously occurred by methamphetamine administration, had been widely considered as a human pharmaceutical model of exogenous psychosis. Although volume reductions in medial temporal lobe structure in patients with schizophrenia have repeatedly been reported, those in patients with methamphetamine psychosis have not yet been clarified. Magnetic resonance images (MRI) were obtained from 20 patients with methamphetamine psychosis and 20 age, sex, parental socio-economic background, and IQ matched healthy controls. A reliable manual tracing methodology was employed to measure the gray matter volume of the amygdala and the hippocampus from MRIs. Significant gray matter volume reductions of both the amygdala and hippocampus were found bilaterally in the subjects with methamphetamine psychosis compared with the controls. The degree of volume reduction was significantly greater in the amygdala than in hippocampus. While the total gray, white matter and intracranial volumes were also significantly smaller-than-normal in the patients; the regional gray matter volume reductions in these medial temporal structures remained statistically significant even after these global brain volumes being controlled. The prominent volume reduction in amygdala rather than that in hippocampus could be relatively specific characteristics of methamphetamine psychosis, since previous studies have shown significant volume reductions less frequently in amygdala than in hippocampus of the other psychosis such as schizophrenia.

Voxel-based morphometric study of brain volume changes in patients with Alzheimer’s disease assessed according to the Clinical Dementia Rating score

We evaluated the volume reduction of gray matter (GM) and white matter (WM) in patients with an Alzheimer’s disease (AD) assessment based on the Clinical Dementia Rating (CDR) score. Patients with AD ( n = 61), with no subcortical WM ischemia, and healthy control patients ( n = 33) underwent T1-weighted spoiled gradient echo sequences, which were analyzed using voxel-based morphometry. Global GM volume reduction was observed in patients with a CDR score of 1 or a CDR score of 2, and WM volume reduction was observed in patients with a CDR score of 2. Regional GM volume reduction was found in the right inferior frontal gyrus, bilateral dorso-lateral and medial temporal lobes; WM volume reduction was found in the bilateral temporal subcortex (family-wise error, p < 0.01). A CDR score of 0.5 was associated with volume reduction in the left olfactory gyrus. The peak z-score and spatial extent of volume reduction increased with increasing CDR score and were higher on the left side. GM volume reduction increased with increasing CDR scores and suggests a possible pathomechanism of AD.

Central Nervous System Changes in Pediatric Heart Failure: A Volumetric Study

Autonomic dysfunction, mood disturbances, and memory deficits appear in pediatric and adult heart failure (HF). Brain areas controlling these functions show injury in adult HF patients, many of whom have comorbid cerebrovascular disease. We examined whether similar brain pathology develops in pediatric subjects without such comorbidities. In this study, high-resolution T1 brain magnetic resonance images were collected from seven severe HF subjects age (age 8–18 years [mean 13]; left ventricular shortening 9 to 19% [median 14%]) and seven age-matched healthy controls (age 8–18 years [mean 13]). After segmentation into gray matter (GM), white matter, and cerebrospinal fluid (CSF), regional volume loss between groups was determined by voxel-based morphometry. GM volume loss appeared on all HF scans, but ischemic changes and infarcts were absent. HF subjects showed greater CSF volume than controls (mean ± SD 0.30 ± 0.04 vs. 0.25 ± 0.04 l, P = 0.03), but total intracranial volume was identical (1.39 ± 0.11 vs. 1.39 ± 0.09 l, P = NS). Regional GM volume reduction appeared in the right and left posterior hippocampus, bilateral mid-insulae, and the superior medial frontal gyrus and mid-cingulate cortex of HF subjects (threshold P < 0.001). No volume-loss sites appeared in control brains. We conclude that pediatric HF patients show brain GM loss in areas similar to those of adult HF subjects. Substantial changes emerged in sites that regulate autonomic function as well as mood, personality and short-term memory. In the absence of thromboembolic disease and many comorbid conditions found in adult HF patients, pediatric HF patients show significant, focal GM volume loss, which may coincide with the multiple neurologic and psychological changes observed in patients with HF.

Decreased Regional Brain Volume and Cognitive Impairment in Preterm Children at Low Risk

To investigate whether preterm children with low risk for neurodevelopmental deficits show long-term changes in gray matter (GM) and white matter (WM) volumes compared with term children and to relate these changes to cognitive outcome. MRI was used to evaluate 20 preterm children who were determined to be at low risk for neurodevelopmental deficits and were born between 30 and 34 weeks' gestational age without major neonatal morbidity or cerebral pathology in the neonatal period and 22 matched, term control subjects. Volumetric images were analyzed by means of voxel-based morphometry to identify regional cerebral alterations. Children also underwent cognitive and behavioral/emotional assessments. Preterm children showed global and regional GM volume reductions in several brain areas, including temporal and parietal lobes and concomitant WM volume reductions in the same areas, although only the left temporal regions achieved statistical significance. Global intellectual performance in the preterm group was significantly decreased compared with control subjects. Neither behavioral nor emotional problems were found in the preterm group. In the whole sample, we found a positive correlation between GM volume bilaterally in the middle temporal and in the postcentral gyri with IQ. Positive correlations were observed between GM and gestational age at birth in parietal and temporal cerebral regions and with WM in parietal regions. Preterm birth has an important impact on the neurodevelopmental and cognitive outcome of children at 9 years of age, being a risk factor for decreased regional cortical GM and WM even in preterm children with low risk for neurodevelopmental deficits.