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Biomedical subjects

Rhoshel Lenroot

Publications and source records attributed to Rhoshel Lenroot.

5 recordsLinked to original sources

A multivariate analysis of neuroanatomic relationships in a genetically informative pediatric sample.

An important component of brain mapping is an understanding of the relationships between neuroanatomic structures, as well as the nature of shared causal factors. Prior twin studies have demonstrated that much of individual differences in human anatomy are caused by genetic differences, but information is limited on whether different structures share common genetic factors. We performed a multivariate statistical genetic analysis on volumetric MRI measures (cerebrum, cerebellum, lateral ventricles, corpus callosum, thalamus, and basal ganglia) from a pediatric sample of 326 twins and 158 singletons. Our results suggest that the great majority of variability in cerebrum, cerebellum, thalamus and basal ganglia is determined by a single genetic factor. Though most (75%) of the variability in corpus callosum was explained by additive genetic effects these were largely independent of other structures. We also observed relatively small but significant environmental effects common to multiple neuroanatomic regions, particularly between thalamus, basal ganglia, and lateral ventricles. These findings are concordant with prior volumetric twin studies and support radial models of brain evolution.

Adolescent↗

Puberty-related influences on brain development.

Puberty is a time of striking changes in cognition and behavior. To indirectly assess the effects of puberty-related influences on the underlying neuroanatomy of these behavioral changes we will review and synthesize neuroimaging data from typically developing children and adolescents and from those with anomalous hormone or sex chromosome profiles. The trajectories (size by age) of brain morphometry differ between boys and girls, with girls generally reaching peak gray matter thickness 1-2 years earlier than boys. Both boys and girls with congenital adrenal hyperplasia (characterized by high levels of intrauterine testosterone), have smaller amygdala volume but the brain morphometry of girls with CAH did not otherwise significantly differ from controls. Subjects with XXY have gray matter reductions in the insula, temporal gyri, amygdala, hippocampus, and cingulate-areas consistent with the language-based learning difficulties common in this group.

Adolescent↗

A pediatric twin study of brain morphometry.

BACKGROUND: Longitudinal pediatric neuroimaging studies have demonstrated increasing volumes of white matter and regionally-specific inverted U shaped developmental trajectories of gray matter volumes during childhood and adolescence. Studies of monozygotic and dyzygotic twins during this developmental period allow exploration of genetic and non-genetic influences on these developmental trajectories. METHOD: Magnetic resonance imaging brain scans were acquired on a pediatric sample of 90 monozygotic twin pairs, 38 same-sex dyzygotic twin pairs, and 158 unrelated typically developing singletons. Structural equation modeling was used to estimate the additive genetic, common environment, and unique environment effects, as well as age by heritability interactions, on measures of brain volumes from these images. RESULTS: Consistent with previous adult studies, additive genetic effects accounted for a substantial portion of variability in nearly all brain regions with the notable exception of the cerebellum. Significant age by heritability interactions were observed with gray matter volumes showing a reduction in heritability with increasing age, while white matter volume heritability increased with greater age. CONCLUSION: Understanding the relative contributions of genetic and nongenetic factors on developmental brain trajectories may have implications for better understanding brain-based disorders and typical cognitive development.

Adolescent↗

Effects of ketamine on anterior cingulate glutamate metabolism in healthy humans: a 4-T proton MRS study.

OBJECTIVE: The authors' goal was to test in humans the hypothesis that N-methyl-d-aspartate receptor (NMDAR) antagonism results in increased cortical glutamate activity, as proposed by the NMDAR hypofunction model of schizophrenia. METHOD: 4-T 1H proton magnetic resonance spectroscopy (1H-MRS) was used to acquire in vivo spectra from the bilateral anterior cingulate of 10 healthy subjects while they received a subanesthetic dose of either placebo or ketamine, an NMDAR antagonist. Assessments given before and after ketamine or placebo administration included the Brief Rating Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, the Clinician-Administered Dissociative States Scale, and the Stroop task. RESULTS: As predicted, there was a significant increase in anterior cingulate glutamine, a putative marker of glutamate neurotransmitter release, with ketamine administration. This increase was not related to schizophrenia-like positive or negative symptoms but was marginally related to Stroop performance. CONCLUSIONS: In humans as in animals, an acute hypofunctional NMDAR state is associated with increased glutamatergic activity in the anterior cingulate.

Adult↗

Maximizing the synergy between pharmacotherapy and psychosocial therapies for schizophrenia.

Although the traditional antipsychotic medications were a major advancement in schizophrenia therapeutics and made possible the era of deinstitutionalization, just maintaining a patient out of the hospital no longer can be viewed as the final goal of treatment. Most patients are able to maintain outpatient status despite persistent psychotic symptoms, pervasive negative symptoms and poor social competence. It is hoped that the availability of the atypical antipsychotic drugs will improve significantly compliance, treatment of symptoms, and possibly relapse rates and overall outcome. It should be the norm and not the exception for patients to be treated with these new medications as early as possible in their illness. The clinician should not be complacent and quick to accept persistent psychosis, and patients with various forms of treatment resistance should be tried early in the course of illness with clozapine (or other medications as they become available if they show superiority for treatment-resistant patients). Pharmacologic interventions aimed at deficit symptoms may become available in the future. Psychosocial interventions have a place in the modern therapeutic armamentarium. Relatively simple sustained family interventions and more comprehensive ACT programs are effective for relapse prevention and reduction of the "revolving door syndrome," whereas patients with psychosis nonresponsive to medication may benefit from new modalities of CBT. For patients with persistent negative symptoms and limited social competence, SST is indicated where available, and even in places where staff may be limited and social skills and other programs difficult to implement, family psychoeducational interventions can be carried out to good effect.

Antipsychotic Agents↗