The effect of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on hippocampal and lateral ventricular volume in psychosis

2009 ◽  
Vol 39 (11) ◽  
pp. 1783-1797 ◽  
Author(s):  
A. Dutt ◽  
C. McDonald ◽  
E. Dempster ◽  
D. Prata ◽  
M. Shaikh ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Psychotic Disorders ◽  
Ventricular Volume ◽  
Hippocampal Volume ◽  
Epidemiological Studies ◽  
Brain Regions ◽  
Clinical Group ◽  
Linear Regression Models ◽  
Brain Volumes ◽  
Brain Morphometry

BackgroundMorphometric endophenotypes which have been proposed for psychotic disorders include lateral ventricular enlargement and hippocampal volume reductions. Genetic epidemiological studies support an overlap between schizophrenia and bipolar disorder, and COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes have been implicated in the aetiology of both these disorders. This study examined associations between these candidate genes and morphometric endophenotypes for psychosis.MethodA total of 383 subjects (128 patients with psychosis, 194 of their unaffected relatives and 61 healthy controls) from the Maudsley Family Psychosis Study underwent structural magnetic resonance imaging and genotyping. The effect of candidate genes on brain morphometry was examined using linear regression models adjusting for clinical group, age, sex and correlations between members of the same family.ResultsThe results showed no evidence of association between variation in COMT genotype and lateral ventricular, and left or right hippocampal volumes. Neither was there any effect of the BDNF, 5-HTTLPR, NRG1 and DTNBP1 genotypes on these regional brain volumes.ConclusionsAbnormal hippocampal and lateral ventricular volumes are among the most replicated endophenotypes for psychosis; however, the influences of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on these key brain regions must be very subtle if at all present.

scholarly journals Reported Hearing Loss in Alzheimer’s Disease Is Associated With Loss of Brainstem and Cerebellar Volume

2021 ◽  
Vol 15 ◽  
Author(s):  
Daniel A. Llano ◽  
Susanna S. Kwok ◽  
Viswanath Devanarayan ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hearing Loss ◽  
Normal Subjects ◽  
Neural Substrates ◽  
Epidemiological Studies ◽  
Brain Regions ◽  
Pathological State ◽  
Brain Volumes ◽  
The Relationship

Multiple epidemiological studies have revealed an association between presbycusis and Alzheimer’s Disease (AD). Unfortunately, the neurobiological underpinnings of this relationship are not clear. It is possible that the two disorders share a common, as yet unidentified, risk factor, or that hearing loss may independently accelerate AD pathology. Here, we examined the relationship between reported hearing loss and brain volumes in normal, mild cognitive impairment (MCI) and AD subjects using a publicly available database. We found that among subjects with AD, individuals that reported hearing loss had smaller brainstem and cerebellar volumes in both hemispheres than individuals without hearing loss. In addition, we found that these brain volumes diminish in size more rapidly among normal subjects with reported hearing loss and that there was a significant interaction between cognitive diagnosis and the relationship between reported hearing loss and these brain volumes. These data suggest that hearing loss is linked to brainstem and cerebellar pathology, but only in the context of the pathological state of AD. We hypothesize that the presence of AD-related pathology in both the brainstem and cerebellum creates vulnerabilities in these brain regions to auditory deafferentation-related atrophy. These data have implications for our understanding of the potential neural substrates for interactions between hearing loss and AD.

scholarly journals The Effect of Anxiety on Regional Brain Volumes in the National Alzheimer’s Coordinating Center Uniform Data Set

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 371-372
Author(s):  
Shanna Burke ◽  
Tan Li ◽  
Adrienne Grudzien ◽  
Christopher Barnes ◽  
Kevin Hanson ◽  
...  
Keyword(s):  
Parietal Lobe ◽  
Secondary Analysis ◽  
Occipital Lobe ◽  
Ventricular Volume ◽  
Brain Regions ◽  
Brain Morphology ◽  
Intracranial Volume ◽  
Data Set ◽  
Brain Volumes ◽  
Regional Brain

Abstract Anxiety has been associated with greater risk of Alzheimer’s disease (AD) and existing research has identified structural differences in regional brain tissue in anxious compared to healthy samples, but results have been variable and somewhat inconsistent. We sought to determine the effect of anxiety on regional brain volumes by cognitive and apolipoprotein e (APOE) e4 status using data from a large, national dataset. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform (NACC) Data Set was conducted using complete MRI data from 1,371 participants (mean age: 70.5; SD: 11.7). Multiple linear regression was used to estimate the adjusted effect of anxiety (via the Neuropsychiatric Inventory Questionnaire) on regional brain volumes through measurement of 30 structural MRI biomarkers. Anxiety was associated with lower total brain and total cortical gray matter volumes and increased lateral ventricular volume (p<.05). Lower mean volumes were also observed in all hippocampal, frontal lobe, parietal lobe, temporal lobe, and right occipital lobe volumes among participants who reported anxiety. Conversely, greater ventricular volumes were also correlated with anxiety. Findings suggest that anxiety is associated with significant atrophy in multiple brain regions and ventricular enlargement, even after controlling for intracranial volume and demographic covariates. Anxiety-related changes to brain morphology may contribute to greater AD risk.

scholarly journals ASSOCIATION BETWEEN BRAIN VOLUMES AND PATTERNS OF COMMUNITY-DWELLING PHYSICAL ACTIVITY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S403-S403
Author(s):  
Amal A Wanigatunga ◽  
Yang An ◽  
Christos Davatzikos ◽  
Jacek K Urbanek ◽  
Adam P Spira ◽  
...  
Keyword(s):  
Physical Activity ◽  
White Matter ◽  
Structural Integrity ◽  
Community Dwelling ◽  
Aging Brain ◽  
Temporal Region ◽  
Intracranial Volume ◽  
Linear Regression Models ◽  
Brain Volumes ◽  
Brain Morphometry

Abstract With aging, brain structural integrity may influence patterns of physical activity (PA) performed in community-dwelling settings. In 281 cognitively-intact adults aged ≥65 years, linear regression models were fitted to examine whether MRI brain volumes (cc), assessed using an automated multi-atlas approach, were cross-sectionally associated with accelerometer-derived: 1) daily PA minutes and 2) activity fragmentation defined as the ratio of # of contiguous PA minutes over total PA minutes x 100. Higher white matter in the parietal and temporal lobes were associated with more daily active minutes (2.8 (SE=1.0) and 3.1 (0.9) min/day, respectively; p<0.005 for both) after adjusting for demographics, behavioral factors, medical conditions, and intracranial volume. Higher white matter in the temporal region was associated with lower fragmentation (-0.15 (0.05) %, p=0.004). Our results suggest sensorimotor-related brain morphometry is connected with both the amount and manner in which PA is performed throughout the day in well-functioning older adults.

The Effects of Mean of Visit-to-Visit Blood Pressure on Incident Brain Vascular Lesions and Functional-Cognitive Decline

2021 ◽  
pp. 1-12
Author(s):  
Bibek Gyanwali ◽  
Celestine Xue Ting Cai ◽  
Christopher Chen ◽  
Henri Vrooman ◽  
Chuen Seng Tan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cognitive Decline ◽  
Hippocampal Volume ◽  
Intracranial Stenosis ◽  
Vascular Lesions ◽  
Linear Regression Models ◽  
Volume Functional ◽  
Mri Scans ◽  
The Mean

Background: Cerebrovascular disease (CeVD) is an underlying cause of cognitive impairment and dementia. Hypertension is a known risk factor of CeVD, but the effects of mean of visit-to-visit blood pressure (BP) on incident CeVD and functional-cognitive decline remains unclear. Objective: To determine the association between mean of visit-to-visit BP with the incidence and progression of CeVD [white matter hyperintensities (WMH), infarcts (cortical infarcts and lacunes), cerebral microbleeds (CMBs), intracranial stenosis, and hippocampal volume] as well as functional-cognitive decline over 2 years of follow-up. Methods: 373 patients from a memory-clinic underwent BP measurements at baseline, year 1, and year 2. The mean of visit-to-visit systolic BP, diastolic BP, pulse pressure, and mean arterial pressure were calculated. Baseline and year 2 MRI scans were graded for WMH, infarcts, CMBs, intracranial stenosis, and hippocampal volume. Functional-cognitive decline was assessed using locally validated protocol. Logistic and linear regression models with odds ratios, mean difference, and 95%confidence interval were constructed to analyze associations of visit-to-visit BP on CeVD incidence and progression as well as functional-cognitive decline. Results: Higher mean of visit-to-visit diastolic BP was associated with WMH progression. Higher tertiles of diastolic BP was associated with WMH progression and incident CMBs. There was no association between mean of visit-to-visit BP measures with incident cerebral infarcts, intracranial stenosis, change in hippocampal volume, and functional-cognitive decline. Conclusion: These findings suggest the possibility of hypertension-related vascular brain damage. Careful monitoring and management of BP in elderly patients is essential to reduce the incidence and progression of CeVD.

scholarly journals Association between body mass index and subcortical brain volumes in bipolar disorders–ENIGMA study in 2735 individuals

2021 ◽  
Author(s):  
Sean R. McWhinney ◽  
◽  
Christoph Abé ◽  
Martin Alda ◽  
Francesco Benedetti ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Bipolar Disorders ◽  
Ventricular Volume ◽  
Group Differences ◽  
Intracranial Volume ◽  
Brain Volumes ◽  
Lateral Ventricles ◽  
Mixed Effects Modeling ◽  
Subcortical Volumes

AbstractIndividuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles  and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.

scholarly journals Cannabinoids, reward processing, and psychosis

2021 ◽  
Author(s):  
Brandon Gunasekera ◽  
Kelly Diederen ◽  
Sagnik Bhattacharyya
Keyword(s):  
Psychotic Disorders ◽  
Neural Substrates ◽  
Brain Regions ◽  
Reward Processing ◽  
Anterior Cingulate ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Future Research ◽  
Drug Challenge ◽  
Psychotomimetic Effects

Abstract Background Evidence suggests that an overlap exists between the neurobiology of psychotic disorders and the effects of cannabinoids on neurocognitive and neurochemical substrates involved in reward processing. Aims We investigate whether the psychotomimetic effects of delta-9-tetrahydrocannabinol (THC) and the antipsychotic potential of cannabidiol (CBD) are underpinned by their effects on the reward system and dopamine. Methods This narrative review focuses on the overlap between altered dopamine signalling and reward processing induced by cannabinoids, pre-clinically and in humans. A systematic search was conducted of acute cannabinoid drug-challenge studies using neuroimaging in healthy subjects and those with psychosis Results There is evidence of increased striatal presynaptic dopamine synthesis and release in psychosis, as well as abnormal engagement of the striatum during reward processing. Although, acute THC challenges have elicited a modest effect on striatal dopamine, cannabis users generally indicate impaired presynaptic dopaminergic function. Functional MRI studies have identified that a single dose of THC may modulate regions involved in reward and salience processing such as the striatum, midbrain, insular, and anterior cingulate, with some effects correlating with the severity of THC-induced psychotic symptoms. CBD may modulate brain regions involved in reward/salience processing in an opposite direction to that of THC. Conclusions There is evidence to suggest modulation of reward processing and its neural substrates by THC and CBD. Whether such effects underlie the psychotomimetic/antipsychotic effects of these cannabinoids remains unclear. Future research should address these unanswered questions to understand the relationship between endocannabinoid dysfunction, reward processing abnormalities, and psychosis.

Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. II. Behavioral and Neurodevelopment Effects

2005 ◽  
Vol 24 (6) ◽  
pp. 451-467 ◽  
Author(s):  
Raymond G. York ◽  
John Barnett ◽  
Michael F. Girard ◽  
David R. Mattie ◽  
Marni V. K. Bekkedal ◽  
...  
Keyword(s):  
Drinking Water ◽  
Ammonium Perchlorate ◽  
Brain Regions ◽  
Male Rats ◽  
Male Rat ◽  
Sprague Dawley ◽  
Continuous Access ◽  
Brain Morphometry ◽  
The Central Nervous System ◽  
The Right

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.

scholarly journals Population-specific brain [18F]-FDG PET templates of Chinese subjects for statistical parametric mapping

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Hongkai Wang ◽  
Yang Tian ◽  
Yang Liu ◽  
Zhaofeng Chen ◽  
Haoyu Zhai ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Statistical Parametric Mapping ◽  
Brain Regions ◽  
Brain Images ◽  
Parametric Mapping ◽  
Brain Morphometry ◽  
Brain Pet ◽  
Positron Emission ◽  
The Family ◽  
Function Impairment

AbstractStatistical Parametric Mapping (SPM) is a computational approach for analysing functional brain images like Positron Emission Tomography (PET). When performing SPM analysis for different patient populations, brain PET template images representing population-specific brain morphometry and metabolism features are helpful. However, most currently available brain PET templates were constructed using the Caucasian data. To enrich the family of publicly available brain PET templates, we created Chinese-specific template images based on 116 [18F]-fluorodeoxyglucose ([18F]-FDG) PET images of normal participants. These images were warped into a common averaged space, in which the mean and standard deviation templates were both computed. We also developed the SPM analysis programmes to facilitate easy use of the templates. Our templates were validated through the SPM analysis of Alzheimer’s and Parkinson’s patient images. The resultant SPM t-maps accurately depicted the disease-related brain regions with abnormal [18F]-FDG uptake, proving the templates’ effectiveness in brain function impairment analysis.

scholarly journals AMPed-up adolescents: the role of age in the abuse of amphetamines and its consequences on cognition and prefrontal cortex development

2020 ◽  
Author(s):  
Sara Ruth Westbrook ◽  
Lauren Carrica ◽  
Asia Banks ◽  
Joshua Michael Gulley
Keyword(s):  
Prefrontal Cortex ◽  
Animal Studies ◽  
Drug Effects ◽  
Epidemiological Studies ◽  
Brain Regions ◽  
Vulnerability Factors ◽  
Brain And Behavior ◽  
And Behavior ◽  
Detrimental Impact

Adolescent use of amphetamine and its closely related, methylated version methamphetamine, is alarmingly high in those who use drugs for nonmedical purposes. This raises serious concerns about the potential for this drug use to have a long-lasting, detrimental impact on the normal development of the brain and behavior that is ongoing during adolescence. In this review, we explore recent findings from both human and laboratory animal studies that investigate the consequences of amphetamine and methamphetamine exposure during this stage of life. We highlight studies that assess sex differences in adolescence, as well as those that are designed specifically to address the potential unique effects of adolescent exposure by including groups at other life stages (typically young adulthood). We consider epidemiological studies on age and sex as vulnerability factors for developing problems with the use of amphetamines, as well as human and animal laboratory studies that tap into age differences in use, its short-term effects on behavior, and the long-lasting consequences of this exposure on cognition. We also focus on studies of drug effects in the prefrontal cortex, which is known to be critically important for cognition and is among the later maturing brain regions. Finally, we discuss important issues that should be addressed in future studies so that the field can further our understanding of the mechanisms underlying adolescent use of amphetamines and its outcomes on the developing brain and behavior.

scholarly journals Neuropsychiatric copy number variants exert shared effects on human brain structure

2020 ◽  
Author(s):  
Claudia Modenato ◽  
Kuldeep Kumar ◽  
Clara Moreau ◽  
Sandra Martin-Brevet ◽  
Guillaume Huguet ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Brain Anatomy ◽  
Brain Volumes ◽  
Brain Morphometry ◽  
Main Gene ◽  
Psychiatric Conditions ◽  
Mirror Effects ◽  
The Uk ◽  
Meta Analyses

AbstractBackgroundCopy Number Variants (CNVs) associated with autism and schizophrenia have large effects on brain anatomy. Yet, neuroimaging studies have been conducted one mutation at a time. We hypothesize that neuropsychiatric CNVs may exert general effects on brain morphometry because they confer risk for overlapping psychiatric conditions.MethodsWe analyzed T1-weighted MRIs and characterized shared patterns on brain anatomy across 8 neuropsychiatric CNVs. Clinically ascertained samples included 1q21.1 (n=48), 16p11.2 (n=156), or 22q11.2 (n=96) and 331 non-carriers. Non-clinically ascertained samples from the UK Biobank included 1q21.1 (n=19), 16p11.2 (n=8), 22q11.2 (n=9), 15q11.2 (n=148) and 965 non-carriers. Canonical correlation analysis (CCA) and univariate models were used to interrogate brain morphometry changes across 8 CNVs.ResultsEight CNVs affect regional brain volumes along two main gene-morphometry dimensions identified by CCA. While fronto-temporal regions contributed to dimension 1, dimension 2 was driven by subcortical, parietal and occipital regions. Consistently, voxel-wise whole-brain analyses identified the same regions involved in patterns of alteration present across the 4 deletions and duplications. These neuroanatomical patterns are similar to those observed in cross-psychiatric disorder meta-analyses. Deletions and duplications at all 4 loci show mirror effects at either the global and/or the regional level.ConclusionNeuropsychiatric CNVs share neuroanatomical signatures characterized by a parsimonious set of brain dimensions. The latter may underlie the risk conferred by CNVs for a similar spectrum of neuropsychiatric conditions.

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