Hippocampal Volume In Children Research Articles

Polygenic risk for depression and anterior and posterior hippocampal volume in children and adolescents

BackgroundDepression has frequently been associated with smaller hippocampal volume. The hippocampus varies in function along its anterior-posterior axis, with the anterior hippocampus more strongly associated with stress and emotion processing. The goals of this study were to examine the associations among parental history of anxiety/depression, polygenic risk scores for depression (PGS-DEP), and anterior and posterior hippocampal volumes in children and adolescents. To examine specificity to PGS-DEP, we examined associations of educational attainment polygenic scores (PGS-EA) with anterior and posterior hippocampal volume. MethodsParticipants were 350 3- to 21-year-olds (46 % female). PGS-DEP and PGS-EA were computed based on recent, large-scale genome-wide association studies. High-resolution, T1-weighted magnetic resonance imaging (MRI) data were acquired, and a semi-automated approach was used to segment the hippocampus into anterior and posterior subregions. ResultsChildren and adolescents with higher polygenic risk for depression were more likely to have a parent with a history of anxiety/depression. Higher polygenic risk for depression was significantly associated with smaller anterior but not posterior hippocampal volume. PGS-EA was not associated with anterior or posterior hippocampal volumes. LimitationsParticipants in these analyses were all of European ancestry. ConclusionsPolygenic risk for depression may lead to smaller anterior but not posterior hippocampal volume in children and adolescents, and there may be specificity of these effects to PGS-DEP rather than PGS-EA. These findings may inform the earlier identification of those in need of support and the design of more effective, personalized treatment strategies.Declarations of interest: none. Declarations of interestNone.

Hippocampal Volume in Children with Attention Deficit Hyperactivity Disorder and Speech and Language Delay.

Hippocampus is a complex brain structure located deep in the temporal lobes of the brain. The structure has been implicated in several disorders related to cognition. Reports are emerging of its involvement in attention deficit hyperactivity disorder (ADHD). The current study was planned to assess the volume of the hippocampus in children with ADHD and speech and language delay with normal birth history using magnetic resonance imaging (MRI) of the brain. MRI brain of 12 children (age range = 3-6 years) and 22 controls with clinical diagnosis of ADHD as per Diagnostic and Statistical Manual-5 were obtained in oblique coronal sequence (T1 weighted). The entire hippocampus formation was outlined manually using Image-J software available freely from www.freesurfer.com. Results were expressed as volume cubic millimeters ± SD. Volumes of the hippocampi of children with ADHD were 2450.2 ± 667 mm3 (R) and 2505.8 ± 878.5 mm3 (L), respectively. The mean volume (bilateral) of the cases was 2478 ± 772.75 mm3. The right hippocampal volume of the controls was 3255.8 ± 1374.3 mm3 (R) and that of the left side was 3159.3 ± 1451 (L) mm3, respectively. Current study reported a substantial shrinkage (23%) of the left and right hippocampus in children with ADHD compared to controls.

Epilepsy Outcomes and Hippocampal Volumes in Children with Multiple Parenchymal Neurocysticercoses.

ABSTRACTBackground:We aimed to study the radiological and epilepsy outcomes of children with multiple neurocysticercosis (NCC) and the relationship with hippocampus volume.Study Design:Observational study.Materials and Methods:Children between 5 and 18 years of age with NCC lesions and completed more than 2-year follow-up were enrolled. Magnetic resonance imaging (MRI) brain with a predefined protocol was done as per clinical indication, and bilateral hippocampi volume was measured with a region of interest-based manual method. Proportion of children who had radiological resolution of lesions, proportion of children who were seizure-free for at least 3 months after antiepileptic drugs withdrawal, and mean hippocampi volume were calculated.Results:During the study period, 229 children followed up in pediatric NCC clinic were enrolled, the mean age was 10.5 ± 3 years, and 129 (56%) were boys. A total of 159 (65%) children had single-lesion NCC, and 79 (35%) had multiple lesion (> 2) NCC. Resolution of lesions was seen in 8% children with multiple NCC, significantly less as compared to the single NCC group (8% vs. 27%, P = 0.006). Multiple-lesion NCC group had a higher rate of calcification as compared to children with a single lesion (66% vs. 47%, P = 0.008). Twenty-nine (37%) children with multiple-lesion NCC were seizure free for at least 3 months after antiepileptic drug withdrawal. Mean combined hippocampal volume in children with single-lesion NCC was 2.96 (0.62) mL and multiple-lesion NCC was 2.88(0.43) mL.Conclusion:Children with multiple-lesion NCC have lower resolution, and higher calcification during follow-up in comparison to single-lesion NCC. Frequency of children who remained seizure-free 3-month post AED withdrawal was similar in single- and multiple-lesion groups.

A Preliminary Investigation of the Effects of a Western Diet on Hippocampal Volume in Children.

Introduction: Over the course of the 20th century, there has been a sharp increase in the consumption of saturated fat and refined sugars. This so-called “western diet” (WD) has been extensively linked to biological alterations and associated functional deficits in the hippocampus of animals. However, the effects of a WD on the human hippocampus are less well-characterized. This preliminary study aimed to extend prior animal work by investigating the effects of a WD on hippocampal volume in children.Methods: Twenty-one healthy children (ages 5–9) completed a structural T1-weighted magnetic resonance imaging scan. Bilateral hippocampal volumes (as regions-of-interest) and bilateral amygdala volumes (as medial temporal lobe control regions-of-interest) were calculated. WD variables were derived from the parent-completed Youth/Adolescent Food Frequency Questionnaire. Specifically, variables were calculated as percent of daily calories consumed from sugars, fats, or a combination of these (WD).Results: While the relationships between overall WD consumption and bilateral hippocampal volumes were not significant, increased fat consumption was significantly related to decreased left hippocampal volume. Sugar consumption was not related to hippocampal size. Control region volumes were not related to any diet variables.Discussion: This study is the first to directly link diet—specifically fat consumption—to decreased left hippocampal volume in children. This extends previous work showing smaller left hippocampal volume related to obesity in pediatric samples. Though preliminary, findings represent an important step toward understanding the impact of diet on child brain development.

Sex differences in the association between prenatal exposure to maternal obesity and hippocampal volume in children.

IntroductionAnimal studies have shown that male but not female offspring exposed to maternal obesity have abnormal hippocampal development. Similar sex differences were observed in animal models of developmental programming by prenatal stress or maternal diabetes. We aimed to translate this work into humans by examining sex‐specific effects of exposure to maternal obesity on hippocampal volume in children.MethodsEighty‐eight children (37 boys and 51 girls) aged 7–11 years completed the study. Maternal prepregnancy body mass index (BMI) was obtained from electronic medical records. A high‐resolution anatomical scan was performed using a 3‐Tesla magnetic resonance imaging (MRI) scanner. Total hippocampal volume and hippocampal subfield volumes were analyzed using FreeSurfer 6.0. Linear regression was used to investigate sex differences in relationships between maternal prepregnancy BMI and child hippocampal volume.ResultsMaternal prepregnancy BMI ranged from 19.0 to 50.4 kg/m2. We observed a significant interaction between maternal prepregnancy BMI and sex on total hippocampal volume (p < .001) such that boys (r = −.39, p = .018) but not girls (r = .11, p = .45) had a significant negative relationship between maternal prepregnancy BMI and total hippocampal volume. This relationship in boys remained significant after adjusting for child and maternal covariates (β = −126.98, p = .012). The sex interactions with prepregnancy BMI were consistently observed in hippocampal subfields CA1 (p = .008), CA2/3 (p = .016), CA4 (p = .002), dentate gyrus (p < .001), and subiculum (p < .001).ConclusionsOur results support findings in animal models and suggest that boys may be more vulnerable to the adverse effects of exposure to maternal obesity on hippocampal development than girls.

Maternal Obesity Is Associated with Reduced Hippocampal Volume in Children

Offspring exposed to maternal obesity in utero are at increased risk for the development of metabolic disorders. Recent evidence also links exposure to maternal obesity with impaired cognition during childhood. While the underlying mechanisms are unclear, studies in animals have shown that fetal exposure to maternal obesity causes decreased neurogenesis in the dentate gyrus and impaired hippocampal learning. The hippocampus is important for memory, and its development is sensitive to the in utero metabolic environment. We tested the hypothesis that in utero exposure to maternal obesity would be associated with reduced hippocampal volume in children. Sixty-seven children (41 girls, 26 boys) ages 7 to 11 years participated in the study. Children were born at Kaiser Permanente Southern California. Maternal pre-pregnancy BMI was obtained from electronic medical records. Children’s height and weight were measured, and a high-resolution anatomical scan was performed using a 3 Tesla MRI. Total hippocampus volume and hippocampus subfield volumes were analyzed using FreeSurfer 6.0. Linear regression was used to investigate relationships between maternal pre-pregnancy BMI and child hippocampus volume. Maternal pre-pregnancy BMIs ranged from 19.0 to 50.4 kg/m2. Children’s BMI z-scores ranged from -1.8 to 2.6. Maternal pre-pregnancy BMI was negatively correlated with total hippocampus volume, adjusting for child age, sex, BMI-z score, intracranial volume (P=0.05). Results remained after further adjusting for maternal diabetes exposure (P=0.04). A 5-unit increase in maternal pre-pregnancy BMI was associated with 78 mm3 (95% CI:3.3-152.8 mm3) reductions in total hippocampus volume. The inverse correlation was also observed in CA3 (P=.04), CA4 (P=.03), dentate gyrus (P=.03) and subiculum (P=.01) subfields, adjusting for the same covariates. Our results suggest that exposure to maternal obesity adversely impacts hippocampus volume in children, and this impact is uniform across subfields. Disclosure K.A. Page: None. S. Luo: None. X. Wang: None. J. Alves: None. M.P. Martinez: None. A. Xiang: None.

Socioeconomic status and hippocampal volume in children and young adults.

An individual's socioeconomic status (SES) is often viewed as a proxy for a host of environmental influences. SES disparities have been linked to variance in brain structures particularly the hippocampus, a neural substrate of learning and memory. However, it is unclear whether the association between SES and hippocampal volume is similar in children and adults. We investigated the relationship between hippocampal volume and SES in a group of children (n = 31, age 8-12years) and a group of young adults (n = 32, age 18-25years). SES was assessed with four indicators that loaded on a single factor, therefore a composite SES scores was used in the main analyses. Hippocampal volume was measured using manual demarcation on high resolution structural images. SES was associated with hippocampal volume in the children, but not in adults, suggesting that in childhood, but not adulthood, SES-related environmental factors influence hippocampal volume. In addition, hippocampal volume, but not SES, was associated with scores on a memory task, suggesting that net effects of postnatal environmental factors, captured by SES, are more distal determinants of memory performance than hippocampal volume. Longitudinal investigation of the association between SES, hippocampal volume and cognitive functioning may further our understanding of the putative neural mechanisms underlying SES-related environmental effects on cognitive development.

Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder.

Pediatric bipolar disorder (PBD) is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF) is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder). We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm3, respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.

Neuroplastic effects of music lessons on hippocampal volume in children with congenital hypothyroidism

Children with congenital hypothyroidism (CH) who experience a neonatal thyroid hormone deficiency have reduced hippocampal volumes compared with healthy controls. Interestingly, evidence suggests that musical training can contribute to structural plasticity in a number of brain areas, including the hippocampus. Therefore, we investigated whether taking music lessons could ameliorate the volumetric reductions of the hippocampus in children with CH. Left and right hippocampal volumes were measured in four groups of children: children with CH with and without music lessons, and healthy controls with and without music lessons. We found that the volume of the right hippocampus was comparable between children with CH who had taken music lessons and the healthy controls. Children with CH who had not taken music lessons had reduced hippocampal volumes compared with the other three groups. These results suggest that music lessons may induce structural neuroplasticity in children with atypical hippocampal development because of early thyroid hormone deficiencies.

Hippocampal volume in children with temporal lobe epilepsy compared to healthy children : A magnetic resonance imaging study

There are currently few published studies that compare hippocampal volume (HCV) in children with temporal lobe epilepsy (TLE). Aims : T0 o compare HCVs in children with TLE and in relation to normal controls (NC), and to analyze HCV change in the acute phase in pediatric subjects using magnetic resonance imaging (MRI). Setting and Design : T0 he case group (n=24) was matched in gender and age range with NC subjects (n=24). Subjects were divided into three groups according to age: 2-5.9 years, 6-8.9 years and 9-13 years. M0 anual measurements were used to obtain HCVs on oblique coronary MRI images obtained by three-dimensional magnetization-prepared rapid gradient-echo (3D-MPRAGE) sequence. Statistical Analyses : T0 he HCV was calculated and normalized. Paired t-tests were used to compare the right and left HCVs within each study group. Analysis of covariance (ANCOVA) was used to consider the impact of age and gender on HCVs. T0 wenty-two patients were diagnosed with definite/probable TLE, and two were non-syndromic focal epilepsy which was distributed in the 2-5.9 years group. The range of left to right mean HCVs of the case and NC group aged 2-13 years was 2014.14 ± 54.32 mm 3 to 2165.31 ± 80.99 mm 3 and 2015.46 ± 26.97 mm 3 to 2100.93 ± 57.33 mm 3 respectively. There were age-related differences in left and right HCV, but no effect of gender. Relative to NC subjects, cases group aged 2-5.9 years had significantly different HCVs, while no significant difference was found in the other two groups. There was significant difference in the right to left HCVs in the case subjects aged 2-5.9 years, but not in the other age groups. T0 he heterogeneity in the 2-5.9 years age cohort may relate to the increased HCVs. The HCV data from NC subjects may be used as a reference to assess hippocampal abnormalities in clinical practice.

Hippocampal MR Volumetric Studies in Paediatric Patients with Epilepsy and Normal Controls

The aim of this study was to determine and compare the hippocampal volume in children with epilepsy and in children in a control group and to compare the mean of right and left hippocampal volume in control subjects. This study was carried out at University Sains Malaysia (USM) from January 2008 to June 2009. This is a cross sectional study of 40 children with epilepsy and 40 children in a control volunteer group. Serial MRI of brain and temporal lobe were performed using a Signa Horizon LX 1.0 Tesla system. Oblique coronal sections perpendicular to the axis of temporal lobe were done with 4 mm slice thickness and 1 mm gap. T1, T2, FLAIR and SPGR series were done. The whole hippocampal volume was measured. Volumetry was done manually by using Osirix workstation (v 3.5.1-64 bit). All slices were measured three times and the average volume was taken. Data were analyzed by paired t test and independent t test for univariate data. The mean hippocampal volume in the control group was 2.81 cm(3) (SD=0.38) and 2.65 cm(3) (SD=0.41) for right and left hippocampus respectively. The mean hippocampal volume in epilepsy patients was 2.47 cm(3) (SD=0.52) and 2.39 cm(3) (SD=0.44) for right and left respectively. The hippocampal volume in epileptic children was significantly smaller than normal control children in average volume (p=0.001) and both right (p=0.002) and left (p=0.007) individually. In the control group, the right hippocampus volume was much greater than the left (p<0.001). The data of this study provide a useful reference for the study of hippocampal volume in the Malay paediatric population. It is useful in doubtful cases to determine which side is affected and also serves as part of the study to establish the whole age-related hippocampal growth.

Hippocampal and amygdala volumes in children and adults with childhood maltreatment‐related posttraumatic stress disorder: A meta‐analysis

Little work has directly examined the course of hippocampal volume in children and adults with childhood maltreatment-related posttraumatic stress disorder (PTSD). Data from adults suggest that hippocampal volume deficits are associated with PTSD, whereas findings from children with PTSD generally show no hippocampal volume deficits in PTSD. Additionally, the role of the amygdala in emotional response makes it a possible region for investigation in children and adults with childhood maltreatment-related PTSD. The objectives of this study were 2-fold: (1) to meta-analytically determine whether hippocampal and amygdala volumes in children and adults with PTSD from childhood maltreatment differ from those in healthy controls, and (2) to use cross-sectional findings performed with meta-analyses as a proxy for longitudinal studies to estimate the course of hippocampal and amygdala volumes in child and adult subjects with PTSD from childhood maltreatment. Using electronic databases, we identified articles containing hippocampal and amygdala data for children with PTSD and adults with PTSD from childhood maltreatment. Data were extracted and effect sizes were calculated using Comprehensive Meta-Analysis Version 2.0. Reduced bilateral hippocampal volume was found in adults with childhood maltreatment-related PTSD compared with healthy controls, but this deficit was not seen in children with maltreatment-related PTSD, suggesting hippocampal volume deficits from childhood maltreatment may not be apparent until adulthood. Greater left than right hippocampal volume was found in the adult healthy control group but not in the PTSD group. Amygdala volume in children with maltreatment-related PTSD did not differ from that in healthy controls. Hippocampal volume is normal in children with maltreatment-related PTSD but not in adults with PTSD from childhood maltreatment, suggesting an initially volumetrically normal hippocampus with subsequent abnormal volumetric development occurring after trauma exposure. However, longitudinal studies are needed to support these preliminary findings.

Stressing About Posttraumatic Stress Disorder

To the Editor .— We are writing to you about a recent article that appeared in Pediatrics .1 The authors of this very interesting article claimed that posttraumatic stress disorder (PTSD) “symptoms and cortisol levels at baseline are associated with changes in hippocampal volume over an ensuing 12- to 18-month interval” after a stressful life event. However, we believe that this strong claim is not supported by the data the authors presented. The first problem is that the methods the authors used to measure hippocampal volume are of low precision. In all studies that use MRI to measure brain volume, experimental variance can be introduced during data acquisition (eg, patient motion, changes in scanner hardware or software, scanner field variation) and during data analysis (eg, partial-volume problems, voxel misclassification, manual delineation error).2 Among the 15 children who they evaluated, the authors acknowledged (in line 3 of “Results”) that there was 1 child who showed an increase in right hippocampal volume that amounted to a full SD, or ∼15%. This child was excluded from additional evaluation. However, the existence of 1 outlier this extreme suggests that the method of measuring hippocampal volume was relatively imprecise. This inference is consistent with the fact that the authors measured interrater reliability but did not report the results. If we hypothesize that the volume-measurement methods used were imprecise and that hippocampal volume of these subjects did not actually change over the time interval studied, what results would have been obtained? We would expect that hippocampal volume change scores would have fluctuated randomly and would not have been significantly different from 0. This is precisely the outcome shown in Table 1, in …

Hippocampal volume in childhood complex partial seizures

Purpose This study compared hippocampal volume in children with cryptogenic epilepsy, all of whom had complex partial seizures (CPS), and age and gender matched normal children controlling for between group differences in IQ and demographic variables (e.g., age, gender, ethnicity, socioeconomic status). It also examined the relationship between hippocampal volumes and seizure variables in the patients. Methods Using quantitative magnetic resonance imaging (MRI), we compared the hippocampal volumes of 19 medically treated children with CPS, aged 6–14 years, to 21 age and gender matched normal children. Results The children with CPS had significantly smaller total hippocampal volumes than the normal children. This finding was accounted for primarily by significantly smaller anterior hippocampal volumes. Within the CPS group, smaller total and posterior hippocampus volumes were significantly associated with longer duration of illness. Anterior hippocampal volumes, however, were unrelated to seizure variables. Conclusions These findings imply impaired development of the hippocampus, particularly the anterior hippocampus, and a differential effect of the underlying illness and on-going seizures on hippocampal development in medically controlled pediatric CPS.

Segmented Hippocampal Volume in Children and Adolescents with Posttraumatic Stress Disorder

Although many studies of adults with posttraumatic stress disorder (PTSD) have reported smaller hippocampal volume compared with control subjects, comparable studies of children and adolescents have failed to replicate these findings or have noted opposite trends suggesting a larger hippocampus. We therefore performed a secondary analysis combining data from prior studies to examine the hypothesis that hippocampus would be larger in pediatric subjects with PTSD compared with non-maltreated control subjects. We also hypothesized that differences in PTSD subjects would be observed between boys and girls. Sixty-one subjects (31 boys, 30 girls) with maltreatment-related PTSD and 122 control subjects matched on age and gender underwent magnetic resonance imaging. As hypothesized, we observed a significantly larger hippocampus controlling for cerebral volume in PTSD subjects compared with control subjects. Segmented hippocampal white-matter volume was greater in PTSD subjects but not gray-matter volume. Hippocampal volume was positively related to age of trauma onset and level of psychopathology, particularly externalizing behavior. No interactions with group were observed for age or gender. Future longitudinal studies with trauma control subjects and neuropsychological measures are indicated to further elucidate the relationship between hippocampus and behavioral abnormalities in young PTSD subjects.