In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group.

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

Using structural MRI to identify bipolar disorders - 13 site machine learning study in 3020 individuals from the ENIGMA Bipolar Disorders Working Group.

Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47-67.00, ROC-AUC = 71.49%, 95% CI = 69.39-73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70-60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen's Kappa = 0.83, 95% CI = 0.829-0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data.

Cognitive reserve attenuates age-related cognitive decline in the context of putatively accelerated brain ageing in schizophrenia-spectrum disorders.

BACKGROUND: In schizophrenia, relative stability in the magnitude of cognitive deficits across age and illness duration is inconsistent with the evidence of accelerated deterioration in brain regions known to support these functions. These discrepant brain-cognition outcomes may be explained by variability in cognitive reserve (CR), which in neurological disorders has been shown to buffer against brain pathology and minimize its impact on cognitive or clinical indicators of illness. METHODS: Age-related change in fluid reasoning, working memory and frontal brain volume, area and thickness were mapped using regression analysis in 214 individuals with schizophrenia or schizoaffective disorder and 168 healthy controls. In patients, these changes were modelled as a function of CR. RESULTS: Patients showed exaggerated age-related decline in brain structure, but not fluid reasoning compared to controls. In the patient group, no moderation of age-related brain structural change by CR was evident. However, age-related cognitive change was moderated by CR, such that only patients with low CR showed evidence of exaggerated fluid reasoning decline that paralleled the exaggerated age-related deterioration of underpinning brain structures seen in all patients. CONCLUSIONS: In schizophrenia-spectrum illness, CR may negate ageing effects on fluid reasoning by buffering against pathologically exaggerated structural brain deterioration through some form of compensation. CR may represent an important modifier that could explain inconsistencies in brain structure - cognition outcomes in the extant literature.

ParentWorks: Evaluation of an Online, Father-Inclusive, Universal Parenting Intervention to Reduce Child Conduct Problems.

Evidence-based parenting interventions are effective in reducing conduct problems, yet these interventions have limited reach, and few involve the participation of fathers. This paper describes the outcomes of an open trial of ParentWorks, a universal, online, father-inclusive parenting intervention aiming to decrease childhood behavioural problems and promote positive parenting in mothers and fathers. A total of 388 families (456 individual parents; 36.6% fathers) were included in the study. Mixed model analyses showed significant decreases in child emotional/behavioural problems, dysfunctional parenting, interparental conflict, and parental mental health problems. The baseline severity of child behavioural problems significantly moderated the effects on child outcomes so that children with higher levels of problems benefitted more from the program. Participation of both caregivers in two-parent families, as well as parent sex, did not significantly affect the program outcomes. Results provide initial empirical support for the universal, self-directed, online parenting intervention, in addressing both child behavioural problems and parenting outcomes. Trial registration: ACTRN12616001223426, registered 05/09/2016.

Spatial dynamics within and between brain functional domains: A hierarchical approach to study time-varying brain function.

The analysis of time-varying activity and connectivity patterns (i.e., the chronnectome) using resting-state magnetic resonance imaging has become an important part of ongoing neuroscience discussions. The majority of previous work has focused on variations of temporal coupling among fixed spatial nodes or transition of the dominant activity/connectivity pattern over time. Here, we introduce an approach to capture spatial dynamics within functional domains (FDs), as well as temporal dynamics within and between FDs. The approach models the brain as a hierarchical functional architecture with different levels of granularity, where lower levels have higher functional homogeneity and less dynamic behavior and higher levels have less homogeneity and more dynamic behavior. First, a high-order spatial independent component analysis is used to approximate functional units. A functional unit is a pattern of regions with very similar functional activity over time. Next, functional units are used to construct FDs. Finally, functional modules (FMs) are calculated from FDs, providing an overall view of brain dynamics. Results highlight the spatial fluidity within FDs, including a broad spectrum of changes in regional associations, from strong coupling to complete decoupling. Moreover, FMs capture the dynamic interplay between FDs. Patients with schizophrenia show transient reductions in functional activity and state connectivity across several FDs, particularly the subcortical domain. Activity and connectivity differences convey unique information in many cases (e.g., the default mode) highlighting their complementarity information. The proposed hierarchical model to capture FD spatiotemporal variations provides new insight into the macroscale chronnectome and identifies changes hidden from existing approaches.

Keeping Parents Involved: Predicting Attrition in a Self-Directed, Online Program for Childhood Conduct Problems.

Positive parenting programs have a strong evidence base for improving parent-child relationships, strengthening families, and reducing childhood behavior disturbances. Their reach is less than optimal however, with only a minority of families in need of help participating. Father involvement is particularly low. Online, self-directed programs have the potential to improve participation rates. This article examines risk factors for dropout/attrition from a free, evidence-based, self-directed, father-inclusive parenting program, Parentworks, which was made available across Australia. Parents (N = 2,967) enrolled in the program and completed preintervention questionnaires. There was a steady and consistent loss of participants through the sequence of core program modules, until a final sample of 218 completed the postintervention questionnaire. A range of demographic and parent and child variables were tested as predictors of 3 subgroups: nonstarters, partial completers, and full completers. Nonstarters (n = 1,625) tended to have older children with fewer behavioral problems and report higher psychopathology and dysfunctional parenting than those who partially (n = 1,124) or fully completed. Contrary to findings from face-to-face research, single parents had the highest completion rates. Coparticipation of partners and interparental conflict had no impact on completion rates. Fathers participated at relatively high levels. Results show that parents with the greatest need tend to engage with online programs, and online programs may be particularly useful for fathers, single parents, and those in conflicted relationships. Directions for future program design and research are discussed.

Evaluation of 'The Father Effect' Media Campaign to Increase Awareness of, and Participation in, an Online Father-Inclusive Parenting Program.

There is substantial evidence that parenting programs are effective in improving parenting and child mental health outcomes. While there is increasing focus on delivering parenting interventions online to increase their reach and dissemination, fathers are underrepresented in all formats of parenting programs. However, research suggests that father participation is important for intervention effectiveness. This study evaluated the effectiveness of a media campaign for increasing awareness of, and participation in, an online father-inclusive parenting program called 'ParentWorks'. An 8-week campaign was conducted in Australia via social media channels, digital display advertising, digital television, and radio. To assess the impact of the campaign, data were obtained from caregivers registering for ParentWorks during the campaign period (n = 848) and an 8-week comparison period that occurred 3 months later (n = 254). Additionally, a nationally representative sample of 2021 caregivers of children aged 2-16 years completed an online survey. Survey questions asked about exposure to the campaign, registration for participation in ParentWorks, and knowledge of the importance of father participation in parenting programs. Three times as many caregivers registered during the 8-week media campaign compared to the comparison period, and a significantly greater proportion of male caregivers registered in the campaign versus the comparison period. The online survey found that 11% of caregivers reported exposure to the campaign, and significantly more fathers than mothers reported exposure. Results showed that those who were exposed to the campaign were significantly more likely to endorse the importance of father participation in parenting programs, than those not exposed to the campaign. The findings indicate that media campaigns appear to be an effective method of increasing awareness of online parenting programs and enhancing rates of father involvement.

Optimising child outcomes from parenting interventions: fathers' experiences, preferences and barriers to participation.

BACKGROUND: Early childhood interventions can have both immediate and long-term positive effects on cognitive, behavioural, health and education outcomes. Fathers are underrepresented in interventions focusing on the well-being of children. However, father participation may be critical for intervention effectiveness, especially for parenting interventions for child externalising problems. To date, there has been very little research conducted to understand the low rates of father participation and to facilitate the development of interventions to meet the needs of fathers. This study examined fathers' experiences of, and preferences for, parenting interventions as well as perceptions of barriers to participation. It also examined how these factors were associated with child externalising behaviour problems, and explored the predictors of participation in parenting interventions. METHODS: A community sample of 1001 fathers of children aged 2-16 years completed an online survey about experiences with parenting interventions, perceived barriers to participation, the importance of different factors in their decision to attend, and preferred content and delivery methods. They also completed ratings of their child's behaviour using the Strengths and Difficulties Questionnaire. RESULTS: Overall, 15% of fathers had participated in a parenting intervention or treatment for child behaviour, with significantly higher rates of participation for fathers of children with high versus low levels of externalising problems. Fathers rated understanding what is involved in the program and knowing that the facilitator is trained as the two most important factors in their decision to participate. There were several barriers to participation that fathers of children with high-level externalising problems were more likely to endorse, across practical barriers and help-seeking attitudes, compared to fathers of children with low-level externalising problems. Almost two-thirds of fathers of children with high-level externalising behaviour had not participated in a parenting intervention or treatment. The only significant predictors of intervention participation were severity of child externalising behaviour problems and child age. CONCLUSIONS: The findings have important implications for services seeking to increase father engagement and highlight a number of strategies to enhance the promotion and delivery of parenting interventions to fathers. These strategies include more public health messaging about parenting programs and the importance of father participation.

The dynamic role of genetics on cortical patterning during childhood and adolescence.

Longitudinal imaging and quantitative genetic studies have both provided important insights into the nature of human brain development. In the present study we combine these modalities to obtain dynamic anatomical maps of the genetic contributions to cortical thickness through childhood and adolescence. A total of 1,748 anatomic MRI scans from 792 healthy twins and siblings were studied with up to eight time points per subject. Using genetically informative latent growth curve modeling of 81,924 measures of cortical thickness, changes in the genetic contributions to cortical development could be visualized across the age range at high resolution. There was highly statistically significant (P < 0.0001) genetic variance throughout the majority of the cerebral cortex, with the regions of highest heritability including the most evolutionarily novel regions of the brain. Dynamic modeling of changes in heritability over time demonstrated that the heritability of cortical thickness increases gradually throughout late childhood and adolescence, with sequential emergence of three large regions of high heritability in the temporal poles, the inferior parietal lobes, and the superior and dorsolateral frontal cortices.

Hospital admission for infection during early childhood influences developmental vulnerabilities at age 5 years.

AIM: Childhood infectious diseases can be associated with later physical and psychological ill health, and the effects of this association may be evident during early childhood development. This study aimed to examine the effects of hospitalisation for early life infection on early childhood development. METHODS: Hospital admission data for infection were obtained from the New South Wales Ministry of Health Admitted Patient Data Collection for 87 026 children, for whom the Australian Early Development Census (AEDC) was completed in their first year of formal schooling (age approximately 5 years). The AEDC provides estimates of each child's level of functioning on five domains of development spanning social and emotional skills, communication skills, numeracy and literacy and physical health. Multinomial logistic regressions were used to determine the relationship between exposure to hospital admissions for infectious disease prior to age 4 years and vulnerability on the AEDC. Models were adjusted for the effects of potential confounding factors related to the perinatal period, exposure to maltreatment and family characteristics. RESULTS: Single and multiple hospitalisation(s) for infections were consistently associated with increased likelihood of being developmentally vulnerable on all AEDC domains, with odds ratios ranging from 1.02 to 1.28, after adjustment for confounding factors. CONCLUSIONS: This study demonstrates a pervasive effect of early life infections that require hospital admission on multiple aspects of early child development, even after adjustment for potential confounding factors. Relatively, severe infection during early childhood constitutes a risk factor for developmental vulnerability by the time of entry to school.

Trauma exposure and disclosure in Hispanic youth at clinical high risk for psychosis: A retrospective review study.

AIM: This exploratory study aimed to examine differences in rates of self and clinician-reports of trauma in youth at clinical high risk for psychosis (CHR) and whether rates of reporting differed by ethnicity. METHODS: Self-reported history of trauma was collected at intake amongst youth at CHR enrolled in Coordinated Specialty Care (CSC) services (N = 52). A structured chart review was conducted for the same sample to identify clinician-reported history of trauma throughout treatment in CSC. RESULTS: For all patients, frequency of self-reported trauma at intake to CSC (56%) was lower compared to clinician-reports of trauma throughout treatment (85%). Hispanic patients self-reported trauma at intake (35%) less frequently than non-Hispanics (69%) (p = .02). No differences were found in clinician reported exposure to trauma by ethnicity throughout treatment. CONCLUSION: Whilst further research is needed, these findings suggest the need for formalised, repeated, and culturally appropriate assessments of trauma within CSC.

Distinct cortical correlates of autistic versus antisocial traits in a longitudinal sample of typically developing youth.

In humans, behaviors associated with autism and antisociality, disorders characterized by distinct social impairments, can be viewed as quantitative traits that range from frank impairment to normal variation, as found in the general population. Neuroimaging investigations of autism and antisociality demonstrate diagnostically specific aberrant cortical brain structure. However, little is known about structural brain correlates of social behavior in nonclinical populations. Therefore, we sought to determine whether autistic and antisocial traits exhibit dissociable cortical correlates and whether these associations are stable across development among typically developing youth. Three hundred twenty-three typically developing youth (age at first scan: mean = 10.63, SD = 3.71 years) underwent anatomic magnetic resonance imaging (1-6 scans each; total = 742 scans), and provided ratings of autistic and antisocial traits. Higher autistic trait ratings were associated with thinner cortex most prominently in right superior temporal sulcus while higher antisocial trait ratings were associated with thinner cortex in primarily bilateral anterior prefrontal cortices. There was no interaction with age, indicating that these brain-behavior associations were stable across development. Using assessments of both subclinical autistic and subclinical antisocial traits within a large longitudinal sample of typically developing youth, we demonstrate dissociable neuroanatomic correlations that parallel those found in the frank clinical disorders of autism (e.g., superior temporal cortex) and antisociality (e.g., anterior prefrontal cortex). Moreover, these correlations appear to be established in early childhood and remain fixed into early adulthood. These results support the dimensional view of psychopathology and provide neural signatures that can serve as informative endophenotypes for future genetic studies.

Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group.

BACKGROUND: Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD. METHODS: Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables. RESULTS: Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18

Annual Research Review: Developmental considerations of gene by environment interactions.

Biological development is driven by a complex dance between nurture and nature, determined not only by the specific features of the interacting genetic and environmental influences but also by the timing of their rendezvous. The initiation of large-scale longitudinal studies, ever-expanding knowledge of genetics, and increasing availability of neuroimaging data to provide endophenotypic bridges between molecules and behavior are beginning to provide some insight into interactions of developmental stage, genes, and the environment, although daunting challenges remain. Prominent amongst these challenges are difficulties in identifying and quantifying relevant environmental factors, discerning the relative contributions to multiply determined outcomes, and the likelihood that brain development is a non-linear dynamic process in which small initial differences may yield large later effects. Age-sensitive mechanisms include developmental changes in gene expression, epigenetic modifications, synaptic arborization/pruning, and maturational improvements in our capacity to seek out environments of our choosing. Greater understanding of how genetic and environmental factors interact differently across ages is an important step toward elucidating the mechanisms by which phenotypes are created - and how they may differ in health and disease. This knowledge may also provide clues to guide the type and timing of interventions to maximize outcomes.

Executive function in young males with Klinefelter (XXY) syndrome with and without comorbid attention-deficit/hyperactivity disorder.

Deficits in executive function (EF) are reported to occur in individuals with Klinefelter syndrome (XXY). The degree of impairment, if any, is variable and the nature of these deficits has not been clearly elucidated in young males. In this report, we (a) examine EF skills using multiple tasks in a non-clinic referred group of youth with XXY, (b) describe the extent of EF weaknesses in XXY when this group is compared with typical males of a similar SES or typical males with similar verbal abilities, and (c) evaluate the contribution of comorbid attention-deficit/hyperactivity disorder (ADHD) to EF skills. The sample included 27 males with XXY (ages 9-25), 27 typically developing age- and vocabulary-matched males, and 22 age- and socioeconomic status-matched males. EF tasks included Verbal Fluency, the Trail Making Test, and the CANTAB Spatial Working Memory and Stockings of Cambridge tasks. Mixed model analysis of variance was used to compare the groups on EF tasks and revealed a main effect of group but no group by task interaction. Overall, the XXY group performed less well than both control groups, but performance did not differ significantly as a function of task. ADHD comorbidity in males with XXY was related to poorer EF skills.

Characteristics of Hispanics Referred to Coordinated Specialty Care for First-Episode Psychosis and Factors Associated With Enrollment.

OBJECTIVE: The primary objectives of this study were to examine referral sources and demographic, clinical, and socioenvironmental characteristics of Hispanics referred to and enrolled in a program of coordinated specialty care (Early CSC program) for first-episode psychosis, to compare them with characteristics of other referred and enrolled racial-ethnic groups, and to identify factors associated with enrollment in the program. METHODS: A retrospective review was conducted for all individuals referred to and enrolled in the Early CSC program over a 2-year period. Extracted data included referral sources and demographic and clinical characteristics. Zip code-level data from publicly available sources were cross-referenced with individual records. Nonparametric tests and appropriate secondary analysis were used to determine significant differences across racial-ethnic groups referred to (N=180) or enrolled in (N=75) the Early CSC program. A random forest model was used to determine which factors or interacting factors were associated with enrollment among the eligible referrals (N=114). RESULTS: Hispanic individuals were more likely to be referred from inpatient or outpatient mental health providers and not from other community sources. Among eligible Hispanic referrals, those who lived in areas with a lower percentage of Spanish speaking in the home were more likely to enroll in services, compared with those who lived in areas with a higher percentage of Spanish speaking. CONCLUSIONS: Continued exploration of factors associated with referral and enrollment in CSC programs for the growing Hispanic ethnic group in the United States can help determine best steps for developing these programs.

Cortical mediation of relationships between dopamine receptor D2 and cognition is absent in youth at risk of bipolar disorder.

Bipolar disorder is associated with cognitive deficits and cortical changes for which the developmental dynamics are not well understood. The dopamine D2 receptor (DRD2) gene has been associated with both psychiatric disorders and cognitive variability. Here we examined the mediating role of brain structure in the relationship between DRD2 genomic variation and cognitive performance, with target cortical regions selected based on evidence of association with DRD2, bipolar disorder and/or cognition from prior literature. Participants (n = 143) were aged 12-30 years and comprised 62 first-degree relatives of bipolar patients (deemed 'at-risk'), 55 controls, and 26 patients with established bipolar disorder; all were unrelated Caucasian individuals with complete data across the three required modalities (structural magnetic resonance imaging, neuropsychological and genetic data). A DRD2 haplotype was derived from three functional polymorphisms (rs1800497, rs1076560, rs2283265) associated with alternative splicing (i.e., D2-short/-long isoforms). Moderated mediation analyses explored group differences in relationships between this DRD2 haplotype, three structural brain networks which subsume the identified cortical regions of interest (frontoparietal, dorsal-attention, and ventral-attention), and three cognitive indices (intelligence, attention, and immediate memory). Controls who were homozygous for the DRD2 major haplotype demonstrated greater cognitive performance as a result of dorsal-attention network mediation. However, this association was absent in the 'at-risk' group. This study provides the first evidence of a functional DRD2-brain-cognition pathway. The absence of typical brain-cognition relationships in young 'at-risk' individuals may reflect biological differences that precede illness onset. Further insight into early pathogenic processes may facilitate targeted early interventions.

Cerebellum development during childhood and adolescence: a longitudinal morphometric MRI study.

In addition to its well-established role in balance, coordination, and other motor skills, the cerebellum is increasingly recognized as a prominent contributor to a wide array of cognitive and emotional functions. Many of these capacities undergo dramatic changes during childhood and adolescence. However, accurate characterization of co-occurring anatomical changes has been hindered by lack of longitudinal data and methodologic challenges in quantifying subdivisions of the cerebellum. In this study we apply an innovative image analysis technique to quantify total cerebellar volume and 11 subdivisions (i.e. anterior, superior posterior, and inferior posterior lobes, corpus medullare, and three vermal regions) from anatomic brain MRI scans from 25 healthy females and 25 healthy males aged 5-24 years, each of whom was scanned at least three times at approximately 2-year intervals. Total cerebellum volume followed an inverted U shaped developmental trajectory peaking at age 11.8 years in females and 15.6 years in males. Cerebellar volume was 10% to 13% larger in males depending on the age of comparison and the sexual dimorphism remained significant after covarying for total brain volume. Subdivisions of the cerebellum had distinctive developmental trajectories with more phylogenetically recent regions maturing particularly late. The cerebellum's unique protracted developmental trajectories, sexual dimorphism, preferential vulnerability to environmental influences, and frequent implication in childhood onset disorders such as autism and ADHD make it a prime target for pediatric neuroimaging investigations.

Anatomic magnetic resonance imaging of the developing child and adolescent brain and effects of genetic variation.

Magnetic resonance imaging studies have begun to map effects of genetic variation on trajectories of brain development. Longitudinal studies of children and adolescents demonstrate a general pattern of childhood peaks of gray matter followed by adolescent declines, functional and structural increases in connectivity and integrative processing, and a changing balance between limbic/subcortical and frontal lobe functions, which extends well into young adulthood. Twin studies have demonstrated that genetic factors are responsible for a significant amount of variation in pediatric brain morphometry. Longitudinal studies have shown specific genetic polymorphisms affect rates of cortical changes associated with maturation. Although over-interpretation and premature application of neuroimaging findings for diagnostic purposes remains a risk, converging data from multiple imaging modalities is beginning to elucidate the influences of genetic factors on brain development and implications of maturational changes for cognition, emotion, and behavior.

A twin study of intracerebral volumetric relationships.

Using high resolution magnetic resonance imaging data, we examined the interrelationships between eight cerebral lobar volumetric measures via both exploratory and confirmatory factor analyses in a large sample (N = 484) of pediatric twins and singletons. These analyses suggest the presence of strong genetic correlations between cerebral structures, particularly between regions of like tissue type or in spatial proximity. Structural modeling estimated that most of the variance in all structures is associated with highly correlated lobar latent factors, with differences in genetic covariance and heritability driven by a common genetic factor that influenced gray and white matter differently. Reanalysis including total brain volume as a covariate dramatically reduced the total residual variance and disproportionately influenced the additive genetic variance in all regions of interest.