Impact of gonadectomy on maturational changes in brain volume in adolescent macaques.
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ABSTRACT:
SUBMITTER: Knickmeyer RC
PROVIDER: S-EPMC8121100 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ContextAdolescents are at high risk for menstrual dysfunction. The diagnosis of anovulatory disorders that may have long-term health consequences is too often delayed.Evidence acquisitionA review of the literature in English was conducted, and data were summarized and integrated from the author's perspective.Main findingsNormal adolescent anovulation causes only minor menstrual cycle irregularity: most cycles range from 21-45 days, even in the first postmenarcheal year, 90% by the fourth year. Approximately half of symptomatic menstrual irregularity is due to neuroendocrine immaturity, and half is associated with increased androgen levels. The former is manifest as aluteal or short/deficient luteal phase cycles and usually resolves spontaneously. The latter seems related to polycystic ovary syndrome because adolescent androgen levels are associated with adult androgens and ovulatory dysfunction, but data are sparse. Obesity causes hyperandrogenemia and, via unclear mechanisms, seems to suppress LH; it may mimic polycystic ovary syndrome. The role of pubertal insulin resistance in physiological adolescent anovulation is unclear. High-sensitivity gonadotropin and steroid assays, the latter by specialty laboratories, are necessary for accurate diagnosis of pubertal disorders. Polycystic ovaries are a normal ultrasonographic finding in young women and are associated with nearly 2-fold increased anti-Müllerian hormone levels. Oral contraceptives are generally the first-line treatment for ongoing menstrual dysfunction, and the effects of treatment are similar among preparations.ConclusionsMenstrual cycle duration persistently outside 21-45 days in adolescents is unusual, and persistence ≥ 1 year suggests that disordered hypothalamic-pituitary-gonadal function be considered. Research is needed on the mechanisms and prognosis of adolescent anovulation.
| S-EPMC3763969 | biostudies-literature
Project description:To investigate longitudinal changes in global and regional brain volume in patients 1 year after mild traumatic brain injury (MTBI) and to correlate such changes with clinical and neurocognitive metrics.This institutional review board-approved study was HIPAA compliant. Twenty-eight patients with MTBI (with 19 followed up at 1 year) with posttraumatic symptoms after injury and 22 matched control subjects (with 12 followed up at 1 year) were enrolled. Automated segmentation of brain regions to compute regional gray matter (GM) and white matter (WM) volumes was performed by using three-dimensional T1-weighted 3.0-T magnetic resonance imaging, and results were correlated with clinical metrics. Pearson and Spearman rank correlation coefficients were computed between longitudinal brain volume and neurocognitive scores, as well as clinical metrics, over the course of the follow-up period.One year after MTBI, there was measurable global brain atrophy, larger than that in control subjects. The anterior cingulate WM bilaterally and the left cingulate gyrus isthmus WM, as well as the right precuneal GM, showed significant decreases in regional volume in patients with MTBI over the 1st year after injury (corrected P < .05); this was confirmed by means of cross-sectional comparison with data in control subjects (corrected P < .05). Left and right rostral anterior cingulum WM volume loss correlated with changes in neurocognitive measures of memory (r = 0.65, P = .005) and attention (r = 0.60, P = .01). At 1-year follow-up, WM volume in the left cingulate gyrus isthmus correlated with clinical scores of anxiety (Spearman rank correlation r = -0.68, P = .007) and postconcussive symptoms (Spearman rank correlation r = -0.65, P = .01).These observations demonstrate structural changes to the brain 1 year after injury after a single concussive episode. Regional brain atrophy is not exclusive to moderate and severe traumatic brain injury but may be seen after mild injury. In particular, the anterior part of the cingulum and the cingulate gyrus isthmus, as well as the precuneal GM, may be distinctively vulnerable 1 year after MTBI.
| S-EPMC3662902 | biostudies-other
Project description:The neurobiological underpinnings of anorexia nervosa (AN) are poorly understood. In this study, we tested whether brain gray matter (GM) and white matter (WM) in adolescents with AN would show alterations comparable to those in adults.We used magnetic resonance imaging to study GM and WM volume, and diffusion tensor imaging to assess fractional anisotropy for WM integrity in 19 adolescents with AN and 22 controls.Individuals with AN showed greater left orbitofrontal, right insular, and bilateral temporal cortex GM, as well as temporal lobe WM volumes compared to controls. WM integrity in adolescents with AN was lower (lower fractional anisotropy) in fornix, posterior frontal, and parietal areas, but higher in anterior frontal, orbitofrontal, and temporal lobes. In individuals with AN, orbitofrontal GM volume correlated negatively with sweet taste pleasantness. An additional comparison of this study cohort with adult individuals with AN and healthy controls supported greater orbitofrontal cortex and insula volumes in AN across age groups.This study indicates larger orbitofrontal and insular GM volumes, as well as lower fornix WM integrity in adolescents with AN, similar to adults. The pattern of larger anteroventral GM and WM volume as well as WM integrity, but lower WM integrity in posterior frontal and parietal regions may indicate that developmental factors such as GM pruning and WM growth could contribute to brain alterations in AN. The negative correlation between taste pleasantness and orbitofrontal cortex volume in individuals with AN could contribute to food avoidance in this disorder.
| S-EPMC4082770 | biostudies-other
Project description:ObjectiveChildren of parents with depression are two to three times more likely to develop major depressive disorder than children without parental history; however, subcortical brain volume abnormalities characterizing major depressive disorder risk remain unclear. The Adolescent Brain and Cognitive Development (ABCD) Study provides an opportunity to identify subcortical differences associated with parental depressive history.MethodStructural magnetic resonance data were acquired from 9- and 10-year-old children (N = 11,876; release 1.1, n = 4,521; release 2.0.1, n = 7,355). Approximately one-third of the children had a parental depressive history, providing sufficient power to test differences in subcortical brain volume between low- and high-risk youths. Children from release 1.1 were examined as a discovery sample, and we sought to replicate effects in release 2.0.1. Secondary analyses tested group differences in the prevalence of depressive disorders and clarified whether subcortical brain differences were present in youths with a lifetime depressive disorder history.ResultsParental depressive history was related to smaller right putamen volume in the discovery (release 1.1; d = -0.10) and replication (release 2.0.1; d = -0.10) samples. However, in release 1.1, this effect was driven by maternal depressive history (d = -0.14), whereas in release 2.0.1, paternal depressive history showed a stronger relationship with putamen volume (d = -0.09). Furthermore, high-risk children exhibited a near twofold greater occurrence of depressive disorders relative to low-risk youths (maternal history odds ratio =1.99; paternal history odds ratio = 1.45), but youths with a lifetime depressive history did not exhibit significant subcortical abnormalities.ConclusionA parental depressive history was associated with smaller putamen volume, which may affect reward learning processes that confer increased risk for major depressive disorder.
| S-EPMC7165045 | biostudies-literature
Project description:The pathophysiology of migraine is complex. Neuroimaging studies reveal functional and structural changes in the brains of migraine patients. We sought to explore regional volume differences in intracranial structures in patients with episodic and chronic migraine. Sixteen episodic migraine patients, 16 chronic migraine patients, and 24 normal controls were recruited and underwent 3.0 T MRI scanning. The volumes of 142 brain regions were calculated by an automatic volumetric algorithm and compared with clinical variables. Results demonstrated that the volumes of specific regions in the frontal and occipital lobes, and the right putamen, were increased and the volume of the fourth ventricle was decreased in the episodic migraine patients compared with controls. The volumes of the left basal forebrain, optic chiasm, and, the fourth ventricle were decreased in the chronic migraine patients, while the occipital cortex and the right putamen were larger. Compared to episodic migraine patiants, chronic migraine patients displayed larger left thalamus and smaller frontal regions. Correlation analysis showed that headache frequency was negatively correlated with the volume of the right frontal pole, right lateral orbital gyrus, and medial frontal lobes and positively correlated with the volume of the left thalamus. The sleep disturbance score was negatively correlated with the volume of the left basal forebrain. This suggests that migraine patients have structural changes in regions associated with pain processing and modulation, affective and cognitive processing, and visual perception. The remodeling of selective intracranial structures may be involved in migraine attacks. This study was approved by the Ethics Committee of Chinese PLA General Hospital (approval No. S2018-027-02) on May 31, 2018.
| S-EPMC7437590 | biostudies-literature
Project description:In the last few years, a significant amount of work has aimed to characterize maturational trajectories of cortical development. The role of pericortical microstructure putatively characterized as the gray-white matter contrast (GWC) at the pericortical gray-white matter boundary and its relationship to more traditional morphological measures of cortical morphometry has emerged as a means to examine finer grained neuroanatomical underpinnings of cortical changes. In this work, we characterize the GWC developmental trajectories in a representative sample (n = 394) of children and adolescents (~4 to ~22 years of age), with repeated scans (1-3 scans per subject, total scans n = 819). We tested whether linear, quadratic, or cubic trajectories of contrast development best described changes in GWC. A best-fit model was identified vertex-wise across the whole cortex via the Akaike Information Criterion (AIC). GWC across nearly the whole brain was found to significantly change with age. Cubic trajectories were likeliest for 63% of vertices, quadratic trajectories were likeliest for 20% of vertices, and linear trajectories were likeliest for 16% of vertices. A main effect of sex was observed in some regions, where males had a higher GWC than females. However, no sex by age interactions were found on GWC. In summary, our results suggest a progressive decrease in GWC at the pericortical boundary throughout childhood and adolescence. This work contributes to efforts seeking to characterize typical, healthy brain development and, by extension, can help elucidate aberrant developmental trajectories.
| S-EPMC8278832 | biostudies-literature
Project description:Nonhuman primates (NHPs) in research institutions may be housed in a variety of social settings, such as group housing, pair housing or single housing based on the needs of studies. Furthermore, housing may change over the course of studies. The effects of housing and changes in housing on cell activation and vaccine mediated immune responses are not well documented. We hypothesized that animals moved indoors from group to single housing (GH-SH) would experience more stress than those separated from groups into pair housing (GH-PH), or those placed briefly into pair housing and separated 5 weeks later into single housing (GH-PH-SH). We also compared the effects of separation from group to pair housing with the separation from pair to single housing. Eighteen male rhesus macaques were followed over the course of changes in housing condition over 10-14 weeks, as well as prior to and after primary vaccination with a commercially available measles vaccine. We identified two phenotypic biomarkers, namely total CD8 population and proliferating B cells, that differed significantly across treatment groups over time. At 10 weeks post-separation, levels of proliferating B cells were higher in GH-SH subjects compared to GH-PH subjects, and in the latter, levels were lower at 10 weeks than prior to removal from group housing. At 2 weeks post-separation from group to single housing, the frequency of CD8+ T cells was higher in GH-SH subjects compared to one week post separation from pair into single housing in the GH-PH-SH subjects. Comparing the same elapsed time since the most recent separation activated CD20 populations were persistently higher in the GH-SH animals than the GH-PH-SH animals. Housing configuration did not influence vaccine-mediated responses. Overall, our study found benefits of pair housing over single housing, suggesting that perturbations in immune function will be more severe following separation from group to single housing than from pair to single housing, and supporting the use of short-duration pair housing even when animals must subsequently be separated. These findings are useful for planning the housing configurations of research NHPs used for vaccine studies and other studies where immune response is being assessed.
| S-EPMC7593645 | biostudies-literature
Project description:Hearing impairment in older adults is independently associated in longitudinal studies with accelerated cognitive decline and incident dementia, and in cross-sectional studies, with reduced volumes in the auditory cortex. Whether peripheral hearing impairment is associated with accelerated rates of brain atrophy is unclear. We analyzed brain volume measurements from magnetic resonance brain scans of individuals with normal hearing versus hearing impairment (speech-frequency pure tone average>25 dB) followed in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging for a mean of 6.4 years after the baseline scan (n=126, age 56-86 years). Brain volume measurements were performed with semi-automated region-of-interest (ROI) algorithms, and brain volume trajectories were analyzed with mixed-effect regression models adjusted for demographic and cardiovascular factors. We found that individuals with hearing impairment (n=51) compared to those with normal hearing (n=75) had accelerated volume declines in whole brain and regional volumes in the right temporal lobe (superior, middle, and inferior temporal gyri, parahippocampus, p<.05). These results were robust to adjustment for multiple confounders and were consistent with voxel-based analyses, which also implicated right greater than left temporal regions. These findings demonstrate that peripheral hearing impairment is independently associated with accelerated brain atrophy in whole brain and regional volumes concentrated in the right temporal lobe. Further studies investigating the mechanistic basis of the observed associations are needed.
| S-EPMC3951583 | biostudies-literature
Project description:ObjectivesWe used simian immunodeficiency virus (SIV)-infected nonhuman primates to investigate longitudinal changes of brain volume caused by SIV and the effect of combined antiretroviral therapy (cART). In addition, the relation between viral load, immune status, and brain volume were explored.DesignA longitudinal study of two healthy controls, five SIVmac239-infected macaques received cART (SIV+cART+) at 40 days postinnoculation, and five SIVmac239-infected macaques received no therapy (SIV+cART-).MethodsStructural T1-weighted MRI, blood and cerebrospinal fluid testing were acquired at multiple time points for 48 weeks postinfection (wpi). Brain volume was estimated using region of interest (ROI)-based analysis. Volume differences were compared among three groups. Linear regression models tested the associations between brain volumes and biomarkers (viral load, CD4+ T-cell count, CD4+/CD8+ ratio).ResultsIn our model, brain volume alteration in SIV-infected macaques can be detected at 12 wpi in several brain regions. As the infection progresses, the SIV+cART- macaques displayed generalized gray matter atrophy at the endpoint. Though initiate cART right after acute infection, SIV+cART+ macaques still displayed brain atrophy but showed signs of reversibility. Plasma viral load is mainly associated with subcortical nucleus volume whereas CD4+ T-cell count and CD4+/CD8+ ratio in plasma were associated with widespread cortical volume.ConclusionThe SIVmac239-infected Chinese origin macaque is a valid model for neuroHIV. Brain atrophy caused by SIV infection can be relieved, even reversed, by cART. Our model also provides new insights into understanding the pathogenesis of brain injury in people with HIV (PWH).
| S-EPMC8631166 | biostudies-literature
Project description:ObjectiveDetermining the sequence in which Huntington's disease biomarkers become abnormal can provide important insights into the disease progression and a quantitative tool for patient stratification. Here, we construct and present a uniquely fine-grained model of temporal progression of Huntington's disease from premanifest through to manifest stages.MethodsWe employ a probabilistic event-based model to determine the sequence of appearance of atrophy in brain volumes, learned from structural MRI in the Track-HD study, as well as to estimate the uncertainty in the ordering. We use longitudinal and phenotypic data to demonstrate the utility of the patient staging system that the resulting model provides.ResultsThe model recovers the following order of detectable changes in brain region volumes: putamen, caudate, pallidum, insula white matter, nonventricular cerebrospinal fluid, amygdala, optic chiasm, third ventricle, posterior insula, and basal forebrain. This ordering is mostly preserved even under cross-validation of the uncertainty in the event sequence. Longitudinal analysis performed using 6 years of follow-up data from baseline confirms efficacy of the model, as subjects consistently move to later stages with time, and significant correlations are observed between the estimated stages and nonimaging phenotypic markers.InterpretationWe used a data-driven method to provide new insight into Huntington's disease progression as well as new power to stage and predict conversion. Our results highlight the potential of disease progression models, such as the event-based model, to provide new insight into Huntington's disease progression and to support fine-grained patient stratification for future precision medicine in Huntington's disease.
| S-EPMC5945962 | biostudies-literature