Subcortical brain volumes and neurocognitive function in survivors of childhood acute lymphoblastic leukemia (ALL) treated with chemotherapy-only.

10517 Background: Brain deep grey nuclei and glucocorticoid receptor rich hippocampal subregions may be sensitive to neurotoxic effects of chemotherapy-only protocols for childhood ALL and associated with neurocognitive problems in long-term survivors. Methods: Brain MRIs and neurocognitive tests were obtained on 176 survivors (49% male, mean [range] age at diagnosis 6.8 [1-18] years, 14.5 [8-27] years at evaluation). MRI’s were also obtained on 82 healthy community controls (57% male, 13.8 [8-26] years at evaluation). General linear models were used to compare subcortical brain volumes between survivors and controls. Among survivors, gender stratified multivariable linear models were used to test associations between subcortical volumes, and serum concentration of dexamethasone (DEX) and high-dose methotrexate (HDMTX), adjusting for age at diagnosis, and intracranial volume (ICV). Volumes were also compared to neurocognitive tests. Results: Survivors had smaller volumes in bilateral thalami (p’s < 0.05) and hippocampal subregions (p’s < 0.001) compared to controls. After controlling for ICV, HDMTX exposure and younger age at diagnosis were associated with smaller bilateral thalami in male survivors (p’s < 0.05). DEX was associated with a smaller right thalamus in males (p = 0.04). Smaller hippocampi in both males and females were associated with younger age at diagnosis (p’s < 0.01). Smaller left thalamus was associated with worse verbal fluency scores in all survivors (p’s < 0.05). Smaller bilateral thalami and hippocampal subregions in girls were associated with worse processing speed, inhibition and cognitive flexibility; poor memory span correlated with smaller left CA1 and right thalamus volumes (all p’s < 0.05). Smaller bilateral thalami and right hippocampal subregions, in girls, correlated with slower processing speed (p’s < 0.05). In males, smaller left fimbria volume was correlated with poor attention (p = 0.03). Conclusions: ALL survivors have significantly smaller thalamic and hippocampal volumes compared to healthy community controls. In survivors, smaller volumes correlate with worse cognitive performance.

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Earlier Age of First Exposure to Competitive Fighting Has an Adverse Impact on Neuropsychiatric Symptoms and Brain Volume

Neurology ◽

10.1212/01.wnl.0000801920.99534.64 ◽

2021 ◽

Vol 98 (1 Supplement 1) ◽

pp. S20.1-S20

Author(s):

Barry Bryant ◽

Bharat Narapareddy ◽

Michael Johnathan Char Bray ◽

Lisa N. Richey ◽

Akshay D. Krieg ◽

...

Keyword(s):

Processing Speed ◽

Neuropsychiatric Symptoms ◽

Brain Mri ◽

Vital Signs ◽

Health Study ◽

Control Group ◽

Brain Health ◽

Brain Volumes ◽

Head Impacts ◽

Younger Age

ObjectiveThe objective of this study was to determine whether individuals who began fighting competitively at a younger age experienced adverse brain health outcomes compared to fighters who began competing at an older age.BackgroundEstablished literature has made clear that fighting sports such as boxing and mixed martial arts can lead to head injury. Prior work from this group on the Professional Fighters Brain Health Study (PFBHS) found that exposure to repetitive head impacts is associated with lower brain volumes and decreased processing speed in fighters.Design/MethodsAs part of the PFBHS, current and previously licensed professional fighters were recruited, divided into active and retired cohorts, and matched with a control group that had no prior experience in sports with likely head trauma. This present study examined the relationship between age of first exposure (AFE) to fighting sports and brain structure (MRI regional volume), cognitive performance (CNS Vital Signs, iComet C3), and clinical neuropsychiatric symptoms (PHQ-9, Barratt Impulsiveness Scale).ResultsBrain MRI data showed significant correlations between earlier AFE and smaller bilateral hippocampal and posterior corpus callosum volumes for both retired and active fighters. Earlier AFE in active fighters was correlated with decreased processing speed and decreased psychomotor speed. Retired fighters showed a correlation between earlier AFE and higher measures of depression and impulsivity.ConclusionsThe findings of this study help to inform clinicians, governing bodies, parents, and athletes of the risks associated with beginning to compete in fighting sports at a young age.

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Genetic correlations between subcortical brain volumes and psychiatric disorders

The British Journal of Psychiatry ◽

10.1192/bjp.2019.277 ◽

2020 ◽

Vol 216 (5) ◽

pp. 280-283

Author(s):

Kazutaka Ohi ◽

Takamitsu Shimada ◽

Yuzuru Kataoka ◽

Toshiki Yasuyama ◽

Yasuhiro Kawasaki ◽

...

Keyword(s):

Psychiatric Disorders ◽

Genetic Variants ◽

Large Scale ◽

Association Studies ◽

Genetic Correlations ◽

Intracranial Volume ◽

Genome Wide Association Studies ◽

Brain Volumes ◽

Subcortical Brain ◽

Genome Wide

SummaryPsychiatric disorders as well as subcortical brain volumes are highly heritable. Large-scale genome-wide association studies (GWASs) for these traits have been performed. We investigated the genetic correlations between five psychiatric disorders and the seven subcortical brain volumes and the intracranial volume from large-scale GWASs by linkage disequilibrium score regression. We revealed weak overlaps between the genetic variants associated with psychiatric disorders and subcortical brain and intracranial volumes, such as in schizophrenia and the hippocampus and bipolar disorder and the accumbens. We confirmed shared aetiology and polygenic architecture across the psychiatric disorders and the specific subcortical brain and intracranial volume.

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Cerebral ventricle dimensions as risk factors for schizophrenia and affective psychosis: an epidemiological approach to analysis

Psychological Medicine ◽

10.1017/s0033291700029081 ◽

1994 ◽

Vol 24 (4) ◽

pp. 995-1011 ◽

Cited By ~ 62

Author(s):

P. B. Jones ◽

I. Harvey ◽

S. W. Lewis ◽

B. K. Toone ◽

J. Van Os ◽

...

Keyword(s):

Third Ventricle ◽

Age At Onset ◽

Intracranial Volume ◽

Affective Psychosis ◽

Functional Psychosis ◽

Duration Of Illness ◽

History Of ◽

Community Controls ◽

Ventricle Size ◽

Healthy Community

SynopsisA case–control study was undertaken of volumetric computerized tomographic scan measures in 216 consecutive admissions for functional psychosis and 67 healthy community controls. Odds ratio analysis demonstrated significant linear trends in the association between increasing lateral and third ventricle volumes, and both RDC schizophrenia (N= 121) and schizoaffective disorder (N= 41); cases were consistently associated with larger volumes than controls. There was an association between larger third, but not lateral, ventricle size in affective psychoses (N= 54). These associations were statistically independent of intracranial volume, sex, social class and ethnicity, factors which were significantly associated with ventricular measures in the controls. There was no evidence of a threshold corresponding to the notion of normalversusenlarged ventricles.Within the schizophrenia group, there were no large or significant associations between ventricle dimensions and age at onset, duration of illness or pre-morbid social functioning. Neither obstetric complications nor a family history of schizophrenia or other psychiatric illness was associated with large ventricles in these cases.

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Development of subcortical volumes across adolescence in males and females: A multisample study of longitudinal changes

10.1101/171389 ◽

2017 ◽

Author(s):

Megan M. Herting ◽

Cory Johnson ◽

Kathryn L. Mills ◽

Nandita Vijayakumar ◽

Meg Dennison ◽

...

Keyword(s):

Sex Differences ◽

Linear Models ◽

Developmental Trajectories ◽

Generalized Additive Models ◽

Additive Models ◽

Brain Volumes ◽

University Of Pittsburgh ◽

Subcortical Brain ◽

Males And Females ◽

University Of Oslo

AbstractThe developmental patterns of subcortical brain volumes in males and females observed in previous studies have been inconsistent. To help resolve these discrepancies, we examined developmental trajectories using three independent longitudinal samples of participants in the age-span of 8-22 years (total 216 participants and 467 scans). These datasets, including Pittsburgh (PIT; University of Pittsburgh, USA), NeuroCognitive Development (NCD; University of Oslo, Norway), and Orygen Adolescent Development Study (OADS; The University of Melbourne, Australia), span three countries and were analyzed together and in parallel using mixed-effects modeling with both generalized additive models and general linear models. For all regions and across all samples, males were found to have significantly larger volumes as compared to females, and significant sex differences were seen in age trajectories over time. However, direct comparison of sample trajectories and sex differences identified within samples were not consistent. The trajectories for the amygdala, putamen, and nucleus accumbens were most consistent between the three samples. Our results suggest that even after using similar preprocessing and analytic techniques, additional factors, such as image acquisition or sample composition may contribute to some of the discrepancies in sex specific patterns in subcortical brain changes across adolescence, and highlight region-specific variations in congruency of developmental trajectories.

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Depression and Vegetarians: Association between Dietary Vitamin B6, B12 and Folate Intake and Global and Subcortical Brain Volumes

Nutrients ◽

10.3390/nu13061790 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1790

Author(s):

Samuel Berkins ◽

Helgi Birgir Schiöth ◽

Gull Rukh

Keyword(s):

Vitamin B12 ◽

Brain Structure ◽

Vitamin B6 ◽

Significant Interaction ◽

Longitudinal Design ◽

Folate Intake ◽

Dietary Vitamin ◽

Brain Volumes ◽

Subcortical Brain ◽

Depression Status

Deficiency of vitamin B6 and vitamin B12, mostly in vegetarians, is found to be associated with depression and adverse neurological function. We investigated whether vitamin B6, B12, and folate have an effect on brain structure, especially among depressed people who follow a specific diet. The study sample comprised 9426 participants from the UK Biobank cohort with a mean age of 62.4 years. A generalized linear model controlling for age, sex, body mass index, ethnicity, town send deprivation index, educational qualification, smoking, and alcohol intake was used to test the association between study groups and structural brain volumes. Depression was more prevalent, and intake of vitamin B6 and B12 was lower among vegetarians, while non-vegetarians had a lower intake of folate. Overall, no significant association was observed between vitamin B6, B12, and folate intakes and both global and subcortical brain volumes among participants with depression. However, vitamin B12 intake was positively associated with right pallidum among non-depressed participants, and a significant interaction between vitamin B12 intake and depression status on the right pallidum was observed. Also, a significant interaction between folate intake and depression status on grey matter (GM) volume and left thalamus was observed. Upon diet stratification, folate intake is associated with total brain volume and GM volume among vegetarians with depression. Furthermore, no significant associations were observed for subcortical regions. Our findings suggest that dietary intake of vitamin B6 and B12 might have an effect on brain structure. Vegetarians, particularly those who suffer from depression may benefit from supplementing their diets with vitamins B6, B12, and folate to ensure brain health. Further studies, especially with a larger sample size and longitudinal design, are needed to confirm these findings.

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The Longitudinal Association of Walking Efficiency With Brain Volumes in Community-Dwelling Older Adults

Innovation in Aging ◽

10.1093/geroni/igaa057.2834 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 783-783

Author(s):

Jennifer Schrack ◽

Fangyu Liu ◽

Amal Wanigatunga ◽

Yang An ◽

Christos Davatzikos ◽

...

Keyword(s):

Region Of Interest ◽

Cognitive Status ◽

Community Dwelling ◽

Intracranial Volume ◽

Brain Volumes ◽

Age Related ◽

Lower Baseline ◽

Longitudinal Association ◽

Mri Scans ◽

Walking Efficiency

Abstract Walking efficiency (WE) predicts mobility decline and is linked with higher fatigability. Fatigability is associated with cognitive decline and reduced brain volumes (BV), but the link between WE and BV is undefined. We examined associations between WE and BV in 860 participants of the BLSA (mean age 66.4(14.4) years, 54.5% women). WE was assessed during 2.5-minutes of usual-paced walking using indirect calorimetry and standardized per meter (ml/kg/m). BV measures were derived using MRI scans and an automated multi-atlas region-of-interest approach. In linear mixed models adjusted for demographics, education, BMI, intracranial volume, and cognitive status, lower baseline WE was associated with lower total, white, and gray matter, primarily in the frontal and temporal lobes (all p<0.05). Longitudinally, declining WE was associated with increasing ventricular and decreasing hippocampal volumes over follow-up (all p<0.01). Findings suggest rising age-related inefficiencies may reflect underlying brain atrophy and serve as a novel indicator for future interventions.

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

Molecular Psychiatry ◽

10.1038/s41380-021-01098-x ◽

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.

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POR polymorphisms are associated with 21 hydroxylase deficiency

Journal of Endocrinological Investigation ◽

10.1007/s40618-021-01527-2 ◽

2021 ◽

Author(s):

F. Pecori Giraldi ◽

S. Einaudi ◽

A. Sesta ◽

F. Verna ◽

M. Messina ◽

...

Keyword(s):

Clinical Features ◽

Modifier Genes ◽

Age At Diagnosis ◽

Adrenal Hyperplasia ◽

Phenotype Correlation ◽

Hydroxylase Deficiency ◽

Salt Wasting ◽

Control Subjects ◽

Younger Age ◽

21 Hydroxylase Deficiency

Abstract Purpose Genotype–phenotype correlation in congenital 21 hydroxylase deficiency is strong but by no means absolute. Indeed, clinical and hormonal features may vary among patients carrying similar CYP21A2 mutations, suggesting that modifier genes may contribute to the phenotype. Aim of the present study was to evaluate whether polymorphisms in the p450 oxidoreductase (POR) gene may affect clinical features in patients with 21 hydroxylase deficiency Methods Sequencing of the POR gene was performed in 96 patients with 21 hydroxylase deficiency (49 classic, 47 non-classic) and 43 control subjects. Results Prevalence of POR polymorphisms in patients with 21 hydroxylase was comparable to controls and known databases. The rs2228104 polymorphism was more frequently associated with non-classic vs classic 21 hydroxylase deficiency (allelic risk 7.09; 95% C.I. 1.4–29.5, p < 0.05). Classic 21 hydroxylase-deficient carriers of the minor allele in the rs2286822/rs2286823 haplotype presented more frequently the salt-wasting form (allelic risk 1.375; 95% C.I. 1.138–1.137), more severe Prader stage at birth (allelic risk 3.85; 95% C.I. 3.78–3.92), higher ACTH levels, and younger age at diagnosis. Conclusions Polymorphisms in the POR gene are associated with clinical features of 21 hydroxylase deficiency both as regards predisposition to classic vs non-classic forms and severity of classic adrenal hyperplasia.

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