scholarly journals The Speed of Development of Adolescent Brain Age Depends on Sex and Is Genetically Determined

2020 ◽  
Author(s):  
Rachel M Brouwer ◽  
Jelle Schutte ◽  
Ronald Janssen ◽  
Dorret I Boomsma ◽  
Hilleke E Hulshoff Pol ◽  
...  

Abstract Children and adolescents show high variability in brain development. Brain age—the estimated biological age of an individual brain—can be used to index developmental stage. In a longitudinal sample of adolescents (age 9–23 years), including monozygotic and dizygotic twins and their siblings, structural magnetic resonance imaging scans (N = 673) at 3 time points were acquired. Using brain morphology data of different types and at different spatial scales, brain age predictors were trained and validated. Differences in brain age between males and females were assessed and the heritability of individual variation in brain age gaps was calculated. On average, females were ahead of males by at most 1 year, but similar aging patterns were found for both sexes. The difference between brain age and chronological age was heritable, as was the change in brain age gap over time. In conclusion, females and males show similar developmental (“aging”) patterns but, on average, females pass through this development earlier. Reliable brain age predictors may be used to detect (extreme) deviations in developmental state of the brain early, possibly indicating aberrant development as a sign of risk of neurodevelopmental disorders.

Author(s):  
Ellyn R. Butler ◽  
Andrew Chen ◽  
Rabie Ramadan ◽  
Trang T. Le ◽  
Kosha Ruparel ◽  
...  

AbstractOver the past decade, there has been an abundance of research on the difference between age and age predicted using brain features, which is commonly referred to as the “brain age gap”. Researchers have identified that the brain age gap, as a linear transformation of an out-of-sample residual, is dependent on age. As such, any group differences on the brain age gap could simply be due to group differences on age. To mitigate the brain age gap’s dependence on age, it has been proposed that age be regressed out of the brain age gap. If this modified brain age gap (MBAG) is treated as a corrected deviation from age, model accuracy statistics such as R2 will be artificially inflated. Given the limitations of proposed brain age analyses, further theoretical work is warranted to determine the best way to quantify deviation from normality.HighlightsThe brain age gap is an out-of-sample residual, and as such varies as a function of age.A recently proposed modification of the brain age gap, designed to mitigate the dependence on age, results in inflated model accuracy statistics if used incorrectly.Given these limitations, we suggest that new methods should be developed to quantify deviation from normal developmental and aging trajectories.


2020 ◽  
Author(s):  
Vanessa L. Cropley ◽  
Ye Tian ◽  
Kavisha Fernando ◽  
L. Sina Mansour ◽  
Christos Pantelis ◽  
...  

AbstractBackgroundThis study aims to investigate whether dimensional constructs of psychopathology relate to advanced, attenuated or normal patterns of brain development, and to determine whether these constructs share common neurodevelopmental profiles.MethodsPsychiatric symptom ratings from 9312 youths (8-21 years) were parsed into 7 independent dimensions of clinical psychopathology representing conduct, anxiety, obsessive-compulsive, attention, depression, bipolar, and psychosis symptoms. Using a subset of this cohort with structural MRI (n=1313), a normative model of brain morphology was established and the model was then applied to predict the age of youth with clinical symptoms. We investigated whether the deviation of brain-predicted age from true chronological age, called the brain age gap, explained individual variation in each psychopathology dimension.ResultsIndividual variation in the brain age gap significantly associated with clinical dimensions representing psychosis (t=3.16, p=0.0016), obsessive-compulsive symptoms (t=2.5, p=0.01), and general psychopathology (t=4.08, p<0.0001). Greater symptom severity along these dimensions was associated with brain morphology that appeared older than expected for typically developing youth of the same age. Psychopathology dimensions clustered into two modules based on shared brain loci where putative accelerated neurodevelopment was most prominent. Patterns of morphological development were accelerated in frontal cortices for depression, psychosis and conduct symptoms (Module I), whereas acceleration was most evident in subcortex and insula for the remaining dimensions (Module II).ConclusionsOur findings suggest that advanced brain development, particularly in frontal cortex and subcortical nuclei, underpins clinical psychosis and obsessive-compulsive symptoms in youth. Psychopathology dimensions share common neural substrates, despite representing clinically independent symptom profiles.


2017 ◽  
Vol 45 (1) ◽  
pp. 190-198 ◽  
Author(s):  
Tomas Hajek ◽  
Katja Franke ◽  
Marian Kolenic ◽  
Jana Capkova ◽  
Martin Matejka ◽  
...  

Abstract Background The greater presence of neurodevelopmental antecedants may differentiate schizophrenia from bipolar disorders (BD). Machine learning/pattern recognition allows us to estimate the biological age of the brain from structural magnetic resonance imaging scans (MRI). The discrepancy between brain and chronological age could contribute to early detection and differentiation of BD and schizophrenia. Methods We estimated brain age in 2 studies focusing on early stages of schizophrenia or BD. In the first study, we recruited 43 participants with first episode of schizophrenia-spectrum disorders (FES) and 43 controls. In the second study, we included 96 offspring of bipolar parents (48 unaffected, 48 affected) and 60 controls. We used relevance vector regression trained on an independent sample of 504 controls to estimate the brain age of study participants from structural MRI. We calculated the brain-age gap estimate (BrainAGE) score by subtracting the chronological age from the brain age. Results Participants with FES had higher BrainAGE scores than controls (F(1, 83) = 8.79, corrected P = .008, Cohen’s d = 0.64). Their brain age was on average 2.64 ± 4.15 years greater than their chronological age (matched t(42) = 4.36, P &lt; .001). In contrast, participants at risk or in the early stages of BD showed comparable BrainAGE scores to controls (F(2,149) = 1.04, corrected P = .70, η2 = 0.01) and comparable brain and chronological age. Conclusions Early stages of schizophrenia, but not early stages of BD, were associated with advanced BrainAGE scores. Participants with FES showed neurostructural alterations, which made their brains appear 2.64 years older than their chronological age. BrainAGE scores could aid in early differential diagnosis between BD and schizophrenia.


Author(s):  
F. Riva ◽  
T. Fracasso ◽  
A. Guerra ◽  
P. Genet

AbstractIn shooting crimes, ballistics tests are often recommended in order to reproduce the wound characteristics of the involved persons. For this purpose, several “simulants” can be used. However, despite the efforts in the research of “surrogates” in the field of forensic ballistic, the development of synthetic models needs still to be improved through a validation process based on specific real caseworks. This study has been triggered by the findings observed during the autopsy performed on two victims killed in the same shooting incident, with similar wounding characteristics; namely two retained head shots with ricochet against the interior wall of the skull; both projectiles have been recovered during the autopsies after migration in the brain parenchyma. The thickness of the different tissues and structures along the bullets trajectories as well as the incident angles between the bullets paths and the skull walls have been measured and reproduced during the assemblage of the synthetic head models. Two different types of models (“open shape” and “spherical”) have been assembled using leather, polyurethane and gelatine to simulate respectively skin, bone and soft tissues. Six shots have been performed in total. The results of the models have been compared to the findings of post-mortem computed tomography (PMCT) and the autopsy findings.Out of the six shots, two perforated the models and four were retained. When the projectile was retained, the use of both models allowed reproducing the wounds characteristics observed on both victims in terms of penetration and ricochet behaviour. However, the projectiles recovered from the models showed less deformation than the bullets collected during the autopsies. The “open shape” model allowed a better controlling on the shooting parameters than the “spherical” model. Finally, the difference in bullet deformation could be caused by the choice of the bone simulant, which might under-represent either the strength or the density of the human bone. In our opinion, it would be worth to develop a new, more representative material for ballistic which simulates the human bone.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1754-1754
Author(s):  
Giselle Greisman ◽  
June Kloubec ◽  
Alexandra Kazaks ◽  
Kelly Morrow ◽  
Cristen Harris

Abstract Objectives The nitrates found in beetroot juice (BR) are known to be a precursor of nitric oxide (NO). NO is a known vasodilator which allows more oxygen to travel in the blood and may improve muscle efficiency. This study aims to measure the effect of BR supplementation on performance on 500-meter row time for trained CrossFit athletes. Many past studies have analyzed the effect of BR on male athletes, this study aimed to include both males and females. Methods This study used a randomized, cross-over, double-blind, placebo-controlled design to measure 500-meter row time. Thirty athletes age 18–60 consumed either a 2.7 oz shot of BR (6.5 mmol nitrate) or a placebo nitrate-free beetroot juice (PL). Two hours later, they rowed 500 meters. After at least a seven-day washout period, athletes repeated the 500-meter row with either BR or PL for comparison. This study was performed from July 2019 – January 2020 and was conducted in Mercer Island, Washington. Results Ten males age 18.0 to 60.3 (median 47.7) and twenty females age 26.7 to 58.3 (median 43.8), participated in this study. Row times for the 500-meter row ranged from 88.2 seconds to 150.7 seconds. Data indicate that although 60% of all participants rowed faster with BR (mean 112.83 seconds), compared to PL (mean 113.40 seconds), the difference in the means of row times (−0.563) was not significant overall (P = 0.29). However, for the 10 males, row times were significantly faster (1.02 second difference, P = 0.04) on average with BR compared to PL. For the 20 females, the difference in mean row time (−0.335 seconds) was not significant (P = 0.66). Competitive rowers were defined as those who rowed under 110 seconds (N = 15). For competitive rowers (10 males, 5 females), row times were significantly faster with BR compared to PL (difference in means −0.94, P = 0.009). However, for those rowers, the P-value of drink * group was 0.015. Conclusions Dietary nitrate improved indoor rowing performance in males but not in females. In addition, competitive rowers were also significantly faster with BR, however, there may be an order bias, since there was significant interaction between beverage type and testing order. Food based nitrate supplements may increase rowing performance with male rowers. Funding Sources Supported by Bastyr Faculty Student Research Grant.


2008 ◽  
Vol 10 (2) ◽  
pp. 96-108 ◽  
Author(s):  
Fred A. Baughman

All physicians attend medical school and learn of (a) all things physically normal; anatomy, physiology, and chemistry, (b) all things physically abnormal; pathology, disease, and (c) how to tell the difference. Diagnosis is the first obligation of every physician to every patient, and must precede treatment. Diagnosis first asks, “Is there a physical abnormality (physical abnormality = disorder = disease), yes or no?” Patients with no abnormality (no physical abnormality = no disorder = no disease = normal) are referred to as having “no evidence or disease” (NED) or “no organic disease” (NOD). Their problems may be psychological or psychiatric, but they are not medical or surgical. In patients found to have an abnormality, diagnosis now asks, “Which disease?” Psychiatrists are the only physicians who do not perform physical diagnosis. The absence of disease is determined for them by other physicians, usually referring physicians. In 1948 the previously conjoint specialty of neuropsychiatry was divided into neurology—responsible for the diagnosis and treatment or physical/organic disease of the nervous system—and psychiatry—responsible for the treatment of emotional and psychological problems, none of them due to organic diseases. Nor did psychiatry object to this scientific division of labor at the time. However, in the 1950s, with the advent of psychotropic drugs, psychiatry, increasingly in league with the pharmaceutical industry, began referring to psychological diagnoses as disorders/diseases/chemical imbalances of the brain, albeit with no proof or science. In a congressional hearing in 1970, psychiatrists and federal officials, including the Food and Drug Administration and the Department of Health, Education, and Welfare, represented hyperkinetic disorder (HKD) to be a disorder/disease of the brain leading to the appropriation of millions of dollars for research, diagnosis and treatment into the drug treatment of school children said to have the new disease HKD. HKD became ADD, then ADHD, a disorder/disease/chemical imbalance always in need of a “chemical balancer”—a pill. Without proof of an abnormality/disorder/disease, the ADHD epidemic grew from 150,000 in 1970 to 6 million to 7 million today, the most common childhood diagnosis in the United States, a multi-billion dollar industry, and a model for all 374 DSM–IV psychological/psychiatric diagnoses—none of them actual diseases. As such, psychiatry is not a legitimate branch of medicine deserving scientific-fiscal parity; rather, collectively, it is the greatest health care fraud in history. Every time a so-called chemical imbalance is diagnosed, a patient’s right to informed consent has been abrogated. Every time a medically normal person is treated with a psychotropic chemical balancer—a pill—their first and only abnormality is the iatrogenic intoxication: poisoning.


1984 ◽  
Vol 44 (2) ◽  
pp. 219-224 ◽  
Author(s):  
Ursula Mittwoch ◽  
Shantha Mahadevaiah ◽  
Leslie A. Setterfield

SUMMARYTwo male-sterile chromosome anomalies, the insertion Is(7; 1)40H and the tertiary trisomy, Ts(512)31H, were found to be associated with reduced ovarian volumes in immature females. Together with the reciprocal translocation, T(11; 19)42H, in which this effect was described previously, reduced ovaries have been found in all three male-sterile chromosome anomalies investigated so far, suggesting that ovarian involvement is likely to be common in these conditions. Assuming that the smaller ovarian size reflects a reduction in the number of oocytes, it is suggested that male-sterile chromosome anomalies may exert basically similar deleterious effects on meiotic germ cells in males and females, the difference in outcome being due to cell-physiological differences between spermatocytes and oocytes and to the small number of surviving oocytes required for fertility in females.


Neurosurgery ◽  
2003 ◽  
Vol 53 (2) ◽  
pp. 387-392 ◽  
Author(s):  
Michael B. Horowitz ◽  
Kamal Ramzipoor ◽  
Ajit Nair ◽  
Susan Miller ◽  
George Rappard ◽  
...  

Abstract OBJECTIVE Endoscopic third ventriculostomy has developed into a therapeutic alternative to shunting for the management of carefully selected patients with primarily noncommunicating hydrocephalus. This procedure, however, requires a general anesthetic and necessitates violation of the brain parenchyma and manipulation near vital neural structures to access the floor of the third ventricle. Using two cadavers and off-the-shelf angiographic catheters, we sought to determine whether it was possible to navigate a catheter, angioplasty balloon, and stent percutaneously through the subarachnoid space from the thecal sac into the third ventricle so as to perform a third ventriculostomy from below. METHODS Using biplane angiography and off-the-shelf angiographic catheters along with angioplasty balloons and stents, we were able to pass a stent coaxially from the thecal sac to and across the floor of the third ventricle so as to achieve a third ventriculostomy from below. RESULTS Coaxial catheter techniques allowed for the percutaneous insertion of a stent across the floor of the third ventricle. Ventriculostomy was confirmed by injecting contrast medium into the lateral ventricle and seeing it pass through the stent and into the chiasmatic cistern. CONCLUSION We describe the performance of third ventriculostomies in two cadavers by use of the new concept of percutaneous intradural neuronavigation. This procedure may obviate the need for general anesthetic and minimize the potential for brain and vascular injury, especially if ultimately combined with magnetic resonance fluoroscopy.


2009 ◽  
Vol 106 (17) ◽  
pp. 7203-7208 ◽  
Author(s):  
Pei-Yu Wang ◽  
Anna Protheroe ◽  
Andrew N. Clarkson ◽  
Floriane Imhoff ◽  
Kyoko Koishi ◽  
...  

Many behavioral traits and most brain disorders are common to males and females but are more evident in one sex than the other. The control of these subtle sex-linked biases is largely unstudied and has been presumed to mirror that of the highly dimorphic reproductive nuclei. Sexual dimorphism in the reproductive tract is a product of Müllerian inhibiting substance (MIS), as well as the sex steroids. Males with a genetic deficiency in MIS signaling are sexually males, leading to the presumption that MIS is not a neural regulator. We challenge this presumption by reporting that most immature neurons in mice express the MIS-specific receptor (MISRII) and that male Mis−/− and Misrii−/− mice exhibit subtle feminization of their spinal motor neurons and of their exploratory behavior. Consequently, MIS may be a broad regulator of the subtle sex-linked biases in the nervous system.


Genetics ◽  
1994 ◽  
Vol 138 (4) ◽  
pp. 1163-1170 ◽  
Author(s):  
E Wojcik ◽  
A M Murphy ◽  
H Fares ◽  
K Dang-Vu ◽  
S I Tsubota

Abstract A hybrid dysgenesis-induced mutation, enhancer of rudimentaryp1 (e(r)p1), is a recessive enhancer of a weak rudimentary mutant phenotype in Drosophila melanogaster. The e(r) gene was cloned using P element tagging and localized to region 8B on the X chromosome. It encodes a 1.0-kb and a 1.2-kb transcript. The 1.0-kb transcript is present in both adult males and females, while the 1.2-kb transcript is predominantly found in females. The difference in the lengths of the two e(r) transcripts is caused by two different polyadenylation sites spaced 228 bp apart. The amounts of both of these transcripts are drastically reduced in the e(r)p1 mutant. The P element in e(r)p1 is inserted in the 5'-untranslated leader region near the start of transcription. It may be producing its effect by suppressing transcription and/or by providing transcription termination and polyadenylation signals. The putative e(r) protein is 104 amino acids in length and bears no striking resemblance to protein sequences in GenBank or PIR. While its biochemical function is unknown at this time, sequence analysis indicates that the e(r) protein is highly conserved and, presumably, functionally very important. The amino acid sequences of the D. melanogaster and the Drosophila virilis proteins are 95% identical.


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