The designed environment and how it affects brain morphology and mental health

Background The environment is inextricably related to mental health. Recent research replicates findings of a significant, linear correlation between a childhood exposure to the urban environment and psychosis. Related studies also correlate the urban environment and aberrant brain morphologies. These findings challenge common beliefs that the mind and brain remain neutral in the face of worldly experience. Aim There is a signature within these neurological findings that suggests that specific features of design cause and trigger mental illness. The objective in this article is to work backward from the molecular dynamics to identify features of the designed environment that may either trigger mental illness or protect against it. Method This review analyzes the discrete functions putatively assigned to the affected brain areas and a neurotransmitter called dopamine, which is the primary target of most antipsychotic medications. The intention is to establish what the correlations mean in functional terms, and more specifically, how this relates to the phenomenology of urban experience. In doing so, environmental mental illness risk factors are identified. Conclusions Having established these relationships, the review makes practical recommendations for those in public health who wish to use the environment itself as a tool to improve the mental health of a community through design.

Polymorphisms in genes involved in neurodevelopment may be associated with altered brain morphology in schizophrenia: Preliminary evidence

An abnormality in neurodevelopment is one of the most robust etiologic hypotheses in schizophrenia (SZ). There is also strong evidence that genetic factors may influence abnormal neurodevelopment in the disease. The present study evaluated in SZ patients, whose brain structural data had been obtained with magnetic resonance imaging (MRI), the possible association between structural brain measures, and 32 DNA polymorphisms,located in 30 genes related to neurogenesis and brain development. DNA was extracted from peripheral blood cells of 25 patients with schizophrenia, genotyping was performed using diverse procedures, and putative associations were evaluated by standard statistical methods (using the software Statistical Package for Social Sciences - SPSS) with a modified Bonferroni adjustment. For reelin (RELN), a protease that guides neurons in the developing brain and underlies neurotransmission and synaptic plasticity in adults, an association was found for a non-synonymous polymorphism (Va1997Leu) with left and right ventricular enlargement. A putative association was also found between protocadherin 12 (PCDH12), a cell adhesion molecule involved in axonal guidance and synaptic specificity, and cortical folding (asymmetry coefficient of gyrification index). Although our results are preliminary, due to the small number of individuals analyzed, such an approach could reveal new candidate genes implicated in anomalous neurodevelopment in schizophrenia. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Brain morphology in large pelagic fishes: A comparison between sharks and teleosts

A quantitative comparison was made of both relative brain size (encephalization) and the relative development of five brain area of pelagic sharks and teleosts. Two integration areas (the telencephalon and the corpus cerebellum) and three sensory brain areas (the olfactory bulbs, optic tectum and octavolateralis area, which receive primary projections from the olfactory epithelium, eye and octavolateralis senses, respectively), in four species of pelagic shark and six species of pelagic teleost were investigated. The relative proportions of the three sensory brain areas were assessed as a proportion of the total 'sensory brain', while the two integration areas were assessed relative to the sensory brain. The allometric analysis of relative brain size revealed that pelagic sharks had larger brains than pelagic teleosts. The volume of the telencephalon was significantly larger in the sharks, while the corpus cerebellum was also larger and more heavily foliated in these animals. There were also significant differences in the relative development of the sensory brain areas between the two groups, with the sharks having larger olfactory bulbs and octavolateralis areas, whilst the teleosts had larger optic tecta. Cluster analysis performed on the sensory brain areas data confirmed the differences in the composition of the sensory brain in sharks and teleosts and indicated that these two groups of pelagic fishes had evolved different sensory strategies to cope with the demands of life in the open ocean.

MRI of postmortem specimens of endangered species for comparative brain anatomy

Many of the 5,500 threatened species of vertebrates found worldwide are highly protected and generally unavailable for scientific investigation. Here we describe a noninvasive protocol to visualize the structure and size of brain in postmortem specimens. We demonstrate its utility by examining four endangered species of kiwi (Apteryx spp.). Frozen specimens are thawed and imaged using MRI, revealing internal details of brain structure. External brain morphology and an estimate of brain volume can be reliably obtained by creating 3D models. This method has facilitated a comparison of brain structure in the different kiwi species, one of which is on the brink of extinction. This new approach has the potential to extend our knowledge of brain structure to species that have until now been outside the reach of anatomical investigation.

A tensor-based morphometry study of genetic influences on brain structure using a new fluid registration method

We incorporated a new Riemannian fluid registration algorithm into a general MRI analysis method called tensor-based morphometry to map the heritability of brain morphology in MR images from 23 monozygotic and 23 dizygotic twin pairs. All 92 3D scans were fluidly registered to a common template. Voxelwise Jacobian determinants were computed from the deformation fields to assess local volumetric differences across subjects. Heritability maps were computed from the intraclass correlations and their significance was assessed using voxelwise permutation tests. Lobar volume heritability was also studied using the ACE genetic model. The performance of this Riemannian algorithm was compared to a more standard fluid registration algorithm: 3D maps from both registration techniques displayed similar heritability patterns throughout the brain. Power improvements were quantified by comparing the cumulative distribution functions of the p-values generated from both competing methods. The Riemannian algorithm outperformed the standard fluid registration.

Alzheimer's disease risk gene, GAB2, is associated with regional brain volume differences in 755 young healthy twins

The development of late-onset Alzheimer's disease (LOAD) is under strong genetic control and there is great interest in the genetic variants that confer increased risk. The Alzheimer's disease risk gene, growth factor receptor bound protein 2-associated protein (GAB2), has been shown to provide a 1.27- 1.51 increased odds of developing LOAD for rs7101429 major allele carriers, in case-control analysis. GAB2 is expressed across the brain throughout life, and its role in LOAD pathology is well understood. Recent studies have begun to examine the effect of genetic variation in the GAB2 gene on differences in the brain. However, the effect of GAB2 on the young adult brain has yet to be considered. Here we found a significant association between the GAB2 gene and morphological brain differences in 755 young adult twins (469 females) (M = 23.1, SD = 3.1 years), using a gene-based test with principal components regression (PCReg). Detectable differences in brain morphology are therefore associated with variation in the GAB2 gene, even in young adults, long before the typical age of onset of Alzheimer's disease.

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen’s d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen’s d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen’s d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen’s d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen’s d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Organotypic slice cultures from rat brain tissue: a new approach for Naegleria fowleri CNS infection in vitro

The free-living amoeba Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis (PAM), a disease leading to death in the vast majority of cases. In patients suffering from PAM, and in corresponding animal models, the brain undergoes a massive inflammatory response, followed by haemorrhage and severe tissue necrosis. Both, in vivo and in vitro models are currently being used to study PAM infection. However, animal models may pose ethical issues, are dependent upon availability of specific infrastructural facilities, and are time-consuming and costly. Conversely, cell cultures lack the complex organ-specific morphology found in vivo, and thus, findings obtained in vitro do not necessarily reflect the situation in vivo. The present study reports infection of organotypic slice cultures from rat brain with N. fowleri and compares the findings in this culture system with in vivo infection in a rat model of PAM, that proved complementary to that of mice. We found that brain morphology, as present in vivo, is well retained in organotypic slice cultures, and that infection time-course including tissue damage parallels the observations in vivo in the rat. Therefore, organotypic slice cultures from rat brain offer a new in vitro approach to study N. fowleri infection in the context of PAM.

Atlas-free Brain Tissue Segmentation Using a Single T1-weighted MRI Acquisition

Many studies investigating the aging brain or disease-induced brain alterations rely on accurate and reproducible brain tissue segmentation. Being a preliminary processing step prior to the segmentation, reliableskull-stripping the removal ofnon-brain tissue is also crucial for all later image assessment. Typically, segmentation algorithms rely on an atlas i.e. pre-segmented template data. Brain morphology, however, differs considerably depending on age, sex and race. In addition, diseased brains may deviate significantly from the atlas information typically gained from healthy volunteers. The imposed prior atlas information can thus lead to degradation of segmentation results. The recently introduced MP2RAGE sequence provides a bias-free T1 contrast with heavily reduced T2*- and PD-weighting compared to the standard MP-RAGE [1]. To this end, it acquires two image volumes at different inversion times in one acquisition, combining them to a uniform, i.e. homogenous image. In this work, we exploit the advantageous contrast properties of the MP2RAGE and combine it with a Dixon (i.e. fat-water separation) approach. The information gained by the additional fat image of the head considerably improves the skull-stripping outcome [2]. In conjunction with the pure T1 contrast of the MP2RAGE uniform image, we achieve robust skull-stripping and brain tissue segmentation without the use of an atlas

Excitatory versus inhibitory GABA as a divergence point in steroid-mediated sexual differentiation of the brain

Whereas adult sex differences in brain morphology and behavior result from developmental exposure to steroid hormones, the mechanism by which steroids differentiate the brain is unknown. Studies to date have described subtle sex differences in levels of proteins and neurotransmitters during brain development, but these have lacked explanatory power for the profound sex differences induced by steroids. We report here a major divergence in the response to injection of the γ-aminobutyric acid type A (GABAA) agonist, muscimol, in newborn male and female rats. In females, muscimol treatment primarily decreased the phosphorylation of cAMP response element binding protein (CREB) within the hypothalamus and the CA1 region of the hippocampus. In contrast, muscimol increased the phosphorylation of CREB in males within these same brain regions. Within the arcuate nucleus, muscimol treatment increased the phosphorylation of CREB in both females and males. Thus, the response to GABA can be excitatory or inhibitory on signal-transduction pathways that alter CREB phosphorylation depending on the sex and the region in developing brain. This divergence in response to GABA allows for a previously unknown form of steroid-mediated neuronal plasticity and may be an initial step in establishing sexually dimorphic signal-transduction pathways in developing brain.

Post-mortem CT and MR brain imaging of putrefied corpses

INTRODUCTION Putrefaction of the brain is a challenge to a forensic pathologist because it may lead to considerable organ alterations and restrict documenting reliable autopsy findings. OBJECTIVES This study aims to present a new and systematic evaluation of possible benefits of post-mortem MR Neuroimaging (1.5 Tesla, sequences: T1w, T2w) in putrefied corpses in comparison to PMCT and autopsy. METHODS A post-mortem MRI brain examination was conducted on 35 adult, putrefied corpses after performing a whole body CT scan prior to a forensic autopsy. Imaging data and autopsy findings were compared with regard to brain symmetry, gray and white matter junction, ventricular system, basal ganglia, cerebellum, brain stem, and possible pathological findings. RESULTS At autopsy, a reliable assessment of the anatomical brain structures was often restricted. MR imaging offered an assessment of the anatomical brain structures, even at advanced stages of putrefaction. In two cases, MR imaging revealed pathological findings that were detectable neither by CT scans nor at autopsy. CONCLUSIONS Post-mortem MR imaging of putrefied brains offers the possibility to assess brain morphology, even if the brain is liquefied. Post-mortem MR imaging of the brain should be considered if the assessment of a putrefied brain is crucial to the evaluation of a forensic autopsy case.

Vitamin D3 and brain development

Evidence for the presence of the vitamin D receptor in brain implies this vitamin may have some function in this organ. This study investigates whether vitamin D-3 acts during brain development. We demonstrate that rats born to vitamin D-3-deficient mothers had profound alterations in the brain at birth. The cortex was longer but not wider, the lateral ventricles were enlarged, the cortex was proportionally thinner and there was more cell proliferation throughout the brain. There were reductions in brain content of nerve growth factor and glial cell line-derived neurotrophic factor and reduced expression of p75(NTR), the low-affinity neurotrophin receptor. Our findings would suggest that low maternal vitamin D3 has important ramifications for the developing brain. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.