scholarly journals Prenatal stress and the developing brain: Risks for neurodevelopmental disorders

2018 ◽  
Vol 30 (3) ◽  
pp. 743-762 ◽  
Author(s):  
Bea R. H. Van den Bergh ◽  
Robert Dahnke ◽  
Maarten Mennes
Keyword(s):  
Brain Development ◽  
Psychiatric Disorders ◽  
Prenatal Stress ◽  
Imaging Techniques ◽  
Computational Simulation ◽  
Genetic Research ◽  
Brain Regions ◽  
Functional Changes ◽  
Temporal Lobes ◽  
Sensitivity Specificity

AbstractThe prenatal period is increasingly considered as a crucial target for the primary prevention of neurodevelopmental and psychiatric disorders. Understanding their pathophysiological mechanisms remains a great challenge. Our review reveals new insights from prenatal brain development research, involving (epi)genetic research, neuroscience, recent imaging techniques, physical modeling, and computational simulation studies. Studies examining the effect of prenatal exposure to maternal distress on offspring brain development, using brain imaging techniques, reveal effects at birth and up into adulthood. Structural and functional changes are observed in several brain regions including the prefrontal, parietal, and temporal lobes, as well as the cerebellum, hippocampus, and amygdala. Furthermore, alterations are seen in functional connectivity of amygdalar–thalamus networks and in intrinsic brain networks, including default mode and attentional networks. The observed changes underlie offspring behavioral, cognitive, emotional development, and susceptibility to neurodevelopmental and psychiatric disorders. It is concluded that used brain measures have not yet been validated with regard to sensitivity, specificity, accuracy, or robustness in predicting neurodevelopmental and psychiatric disorders. Therefore, more prospective long-term longitudinal follow-up studies starting early in pregnancy should be carried out, in order to examine brain developmental measures as mediators in mediating the link between prenatal stress and offspring behavioral, cognitive, and emotional problems and susceptibility for disorders.

scholarly journals Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders

2020 ◽  
Vol 13 (S11) ◽  
Author(s):  
Yulin Dai ◽  
Timothy D. O’Brien ◽  
Guangsheng Pei ◽  
Zhongming Zhao ◽  
Peilin Jia
Keyword(s):  
Brain Development ◽  
Psychiatric Disorders ◽  
Genome Wide Association Study ◽  
Developmental Stages ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Study Data ◽  
Spatiotemporal Regulation ◽  
Genome Wide ◽  
Active Expression

Abstract Background Psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BIP), major depressive disorder (MDD), attention deficit-hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) are often related to brain development. Both shared and unique biological and neurodevelopmental processes have been reported to be involved in these disorders. Methods In this work, we developed an integrative analysis framework to seek for the sensitive spatiotemporal point during brain development underlying each disorder. Specifically, we first identified spatiotemporal gene co-expression modules for four brain regions three developmental stages (prenatal, birth to 11 years old, and older than 13 years), totaling 12 spatiotemporal sites. By integrating GWAS summary statistics and the spatiotemporal co-expression modules, we characterized the risk genes and their co-expression partners for five disorders. Results We found that SCZ and BIP, ASD and ADHD tend to cluster with each other and keep a distance from other psychiatric disorders. At the gene level, we identified several genes that were shared among the most significant modules, such as CTNNB1 and LNX1, and a hub gene, ATF2, in multiple modules. Moreover, we pinpointed two spatiotemporal points in the prenatal stage with active expression activities and highlighted one postnatal point for BIP. Further functional analysis of the disorder-related module highlighted the apoptotic signaling pathway for ASD and the immune-related and cell-cell adhesion function for SCZ, respectively. Conclusion Our study demonstrated the dynamic changes of disorder-related genes at the network level, shedding light on the spatiotemporal regulation during brain development.

Is adult hippocampal neurogenesis really relevant for the treatment of psychiatric disorders?

2020 ◽  
Vol 18 ◽  
Author(s):  
Marco Carli ◽  
Stefano Aringhieri ◽  
Shivakumar Kolachalam ◽  
Biancamaria Longoni ◽  
Giovanna Grenno ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Emotional Processing ◽  
Imaging Techniques ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Mood Stabilizers ◽  
Post Traumatic Stress ◽  
Newborn Neurons ◽  
Hippocampal Circuitry

: Adult neurogenesis consists in the generation of newborn neurons from neural stem cells taking place in the adult brain. In mammals, this process is limited to very few areas of the brain, and one of these neurogenic niches is the subgranular layer of the dentate gyrus (DG) of the hippocampus. Adult newborn neurons are generated from quiescent neural progenitors (QNPs), which differentiate through different steps into mature granule cells (GCs), to be finally integrated into the existing hippocampal circuitry. In animal models, adult hippocampal neurogenesis (AHN) is relevant for pattern discrimination, cognitive flexibility, emotional processing and resilience to stressful situations. Imaging techniques allow to visualize newborn neurons within the hippocampus through all their stages of development and differentiation. In humans, the evidence of AHN is more challenging, and, based on recent findings, it persists through the adulthood, even if it declines with age. Whether this process has an important role in human brain function and how it integrates into the existing hippocampal circuitry is still a matter of exciting debate. Importantly, AHN deficiency has been proposed to be relevant in many psychiatric disorders, including mood disorders, anxiety, post-traumatic stress disorder and schizophrenia. This review aims to investigate how AHN is altered in different psychiatric conditions and how pharmacological treatments can rescue this process. In fact, many psychoactive drugs, such as antidepressants, mood stabilizers and atypical antipsychotics (AAPs), can boost AHN with different results. In addition, some non-pharmacological approaches are discussed as well.

scholarly journals PET Scan Perfusion Imaging in the Prader–Willi Syndrome: New Insights into the Psychiatric and Social Disturbances

2010 ◽  
Vol 31 (1) ◽  
pp. 275-282 ◽  
Author(s):  
Carine Mantoulan ◽  
Pierre Payoux ◽  
Gwenaëlle Diene ◽  
Mélanie Glattard ◽  
Bernadette Rogé ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Severe Disabilities ◽  
Brain Regions ◽  
Pet Scan ◽  
Prader Willi Syndrome ◽  
Behavioral Skills ◽  
Positron Emission ◽  
Functional Consequences ◽  
Magnetic Resonance Imaging Mri ◽  
Pet Scans

The Prader–Willi syndrome (PWS), a rare multisystem genetic disease, leads to severe disabilities, such as morbid obesity, endocrine dysfunctions, psychiatric disorders, and social disturbances. We explored the whole brain of patients with PWS to detect abnormalities that might explain the behavioral and social disturbances, as well as the psychiatric disorders of these patients. Nine patients with PWS (six males, three females; mean age 16.4 years) underwent a positron emission tomography (PET) scan with H215O as a tracer to measure regional cerebral blood flow (rCBF). The images were compared with those acquired from nine controls (six males, three females; mean age 21.2 years). A morphologic magnetic resonance imaging (MRI) was also performed in PWS patients, and their cognitive and behavioral skills were assessed with Wechsler Intelligence Scale for Children III and the Child Behavior Check List (CBCL). The MRI images showed no evident anatomic abnormalities, whereas PET scans revealed hypoperfused brain regions in PWS patients compared with controls, particularly in the anterior cingulum and superior temporal regions. We observed a significant relationship ( P<0.05) between rCBF in the hypoperfused regions and CBCL scores. The functional consequences of these perfusion abnormalities in specific brain regions might explain the behavioral and social problems observed in these individuals.

scholarly journals Neural Correlates of Feedback Processing in Toddlers

2014 ◽  
Vol 26 (7) ◽  
pp. 1519-1527 ◽  
Author(s):  
Marlene Meyer ◽  
Harold Bekkering ◽  
Denise J. C. Janssen ◽  
Ellen R. A. de Bruijn ◽  
Sabine Hunnius
Keyword(s):  
Early Childhood ◽  
Brain Development ◽  
Brain Activity ◽  
Feedback System ◽  
Brain Regions ◽  
Adaptive Performance ◽  
Feedback Processing ◽  
Essential Information ◽  
Electrophysiological Studies ◽  
Neural Feedback

External feedback provides essential information for successful learning. Feedback is especially important for learning in early childhood, as toddlers strongly rely on external signals to determine the consequences of their actions. In adults, many electrophysiological studies have elucidated feedback processes using a neural marker called the feedback-related negativity (FRN). The neural generator of the FRN is assumed to be the ACC, located in medial frontal cortex. As frontal brain regions are the latest to mature during brain development, it is unclear when in early childhood a functional feedback system develops. Is feedback differentiated on a neural level in toddlers and in how far is neural feedback processing related to children's behavioral adjustment? In an EEG experiment, we addressed these questions by measuring the brain activity and behavioral performance of 2.5-year-old toddlers while they played a feedback-guided game on a touchscreen. Electrophysiological results show differential brain activity for feedback with a more negative deflection for incorrect than correct outcomes, resembling the adult FRN. This provides the first neural evidence for feedback processing in toddlers. Notably, FRN amplitudes were predictive of adaptive behavior: the stronger the differential brain activity for feedback, the better the toddlers' adaptive performance during the game. Thus, already in early childhood toddlers' feedback-guided performance directly relates to the functionality of their neural feedback processing. Implications for early feedback-based learning as well as structural and functional brain development are discussed.

scholarly journals Maternal stress during pregnancy alters fetal cortico-cerebellar connectivity in utero and increases child sleep problems after birth

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marion I. van den Heuvel ◽  
Jasmine L. Hect ◽  
Benjamin L. Smarr ◽  
Tamara Qawasmeh ◽  
Lance J. Kriegsfeld ◽  
...  
Keyword(s):  
Prenatal Stress ◽  
Sleep Problems ◽  
Brain Connectivity ◽  
Fetal Brain ◽  
Brain Regions ◽  
In Utero ◽  
Resting State Functional Connectivity ◽  
Child Sleep ◽  
Maternal Prenatal Stress

AbstractChild sleep disorders are increasingly prevalent and understanding early predictors of sleep problems, starting in utero, may meaningfully guide future prevention efforts. Here, we investigated whether prenatal exposure to maternal psychological stress is associated with increased sleep problems in toddlers. We also examined whether fetal brain connectivity has direct or indirect influence on this putative association. Pregnant women underwent fetal resting-state functional connectivity MRI and completed questionnaires on stress, worry, and negative affect. At 3-year follow-up, 64 mothers reported on child sleep problems, and in the subset that have reached 5-year follow-up, actigraphy data (N = 25) has also been obtained. We observe that higher maternal prenatal stress is associated with increased toddler sleep concerns, with actigraphy sleep metrics, and with decreased fetal cerebellar-insular connectivity. Specific mediating effects were not identified for the fetal brain regions examined. The search for underlying mechanisms of the link between maternal prenatal stress and child sleep problems should be continued and extended to other brain areas.

scholarly journals Focal changes in brain energy and phospholipid metabolism in first-episode schizophrenia

2004 ◽  
Vol 184 (5) ◽  
pp. 409-415 ◽  
Author(s):  
J. Eric Jensen ◽  
Jodi Miller ◽  
Peter C. Williamson ◽  
Richard W J. Neufeld ◽  
Ravi S. Menon ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Imaging Techniques ◽  
High Energy ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
Membrane Breakdown ◽  
First Episode Schizophrenia

BackgroundMembrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy (31P-MRS) have been reported in patients with schizophrenia in several brain regions.AimsUsing improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T 31P-MRS.MethodBrain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm3 effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex.ResultsPeople with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group.ConclusionsThe increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.

scholarly journals Study of Osteocyte Behavior by High-Resolution Intravital Imaging Following Photo-Induced Ischemia

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2874
Author(s):  
Hengfeng Yuan ◽  
Wen Jiang ◽  
Yuanxin Chen ◽  
Betty Kim
Keyword(s):  
Imaging Techniques ◽  
Avascular Osteonecrosis ◽  
Functional Changes ◽  
Cellular Processes ◽  
Non Invasive ◽  
Behavioral Dynamics ◽  
Bony Anatomy ◽  
Magnetic Resonance Imaging Mri

Ischemic injuries and local hypoxia can result in osteocytes dysfunction and play a key role in the pathogenesis of avascular osteonecrosis. Conventional imaging techniques including magnetic resonance imaging (MRI) and computed tomography (CT) can reveal structural and functional changes within bony anatomy; however, characterization of osteocyte behavioral dynamics in the setting of osteonecrosis at the single cell resolution is limited. Here, we demonstrate an optical approach to study real-time osteocyte functions in vivo. Using nicotinamide adenine dinucleotide (NADH) as a biomarker for metabolic dynamics in osteocytes, we showed that NADH level within osteocytes transiently increase significantly after local ischemia through non-invasive photo-induced thrombosis of afferent arterioles followed by a steady decline. Our study presents a non-invasive optical approach to study osteocyte behavior through the modulation of local environmental conditions. Thus it provides a powerful toolkit to study cellular processes involved in bone pathologies in vivo.

scholarly journals Birth delivery mode alters perinatal cell death in the mouse brain

2018 ◽  
Vol 115 (46) ◽  
pp. 11826-11831 ◽  
Author(s):  
Alexandra Castillo-Ruiz ◽  
Morgan Mosley ◽  
Andrew J. Jacobs ◽  
Yarely C. Hoffiz ◽  
Nancy G. Forger
Keyword(s):  
Cell Death ◽  
Brain Development ◽  
Vaginal Delivery ◽  
Maternal Separation ◽  
Developmental Process ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Brain Regions ◽  
Delivery Mode ◽  
Gestation Length

Labor and a vaginal delivery trigger changes in peripheral organs that prepare the mammalian fetus to survive ex utero. Surprisingly little attention has been given to whether birth also influences the brain, and to how alterations in birth mode affect neonatal brain development. These are important questions, given the high rates of cesarean section (C-section) delivery worldwide, many of which are elective. We examined the effect of birth mode on neuronal cell death, a widespread developmental process that occurs primarily during the first postnatal week in mice. Timed-pregnant dams were randomly assigned to C-section deliveries that were yoked to vaginal births to carefully match gestation length and circadian time of parturition. Compared with rates of cell death just before birth, vaginally-born offspring had an abrupt, transient decrease in cell death in many brain regions, suggesting that a vaginal delivery is neuroprotective. In contrast, cell death was either unchanged or increased in C-section–born mice. Effects of delivery mode on cell death were greatest for the paraventricular nucleus of the hypothalamus (PVN), which is central to the stress response and brain–immune interactions. The greater cell death in the PVN of C-section–delivered newborns was associated with a reduction in the number of PVN neurons expressing vasopressin at weaning. C-section–delivered mice also showed altered vocalizations in a maternal separation test and greater body mass at weaning. Our results suggest that vaginal birth acutely impacts brain development, and that alterations in birth mode may have lasting consequences.

scholarly journals Multidimensional brain-age prediction reveals altered brain developmental trajectory in psychiatric disorders

2020 ◽  
Author(s):  
Xin Niu ◽  
Alexei Taylor ◽  
Russell T. Shinohara ◽  
John Kounios ◽  
Fengqing Zhang
Keyword(s):  
Psychiatric Disorders ◽  
Robust Regression ◽  
Developmental Trajectories ◽  
Brain Structures ◽  
Brain Regions ◽  
Developmental Trajectory ◽  
Imaging Features ◽  
Neuroimaging Data ◽  
Brain Age ◽  
Age Prediction

AbstractBrain regions change in different ways and at different rates. This staggered developmental unfolding is determined by genetics and postnatal experience and is implicated in the progression of psychiatric and neurological disorders. Neuroimaging-based brain-age prediction has emerged as an important new approach for studying brain development. However, the unidimensional brain-age estimates provided by previous methods do not capture the divergent developmental trajectories of various brain structures. Here we propose and illustrate an analytic pipeline to compute an index of multidimensional brain-age that provides regional age predictions. First, using a database of 556 subjects that includes psychiatric and neurological patients as well as healthy controls we conducted robust regression to characterize the developmental trajectory of each MRI-based brain-imaging feature. We then utilized cluster analysis to identify subgroups of imaging features with a similar developmental trajectory. For each identified cluster, we obtained a brain-age prediction by applying machine-learning models with imaging features belonging to each cluster. Brain-age predictions from multiple clusters form a multidimensional brain-age index (MBAI). The MBAI is more sensitive to alterations in brain structures and captured distinct regional change patterns. In particular, the MBAI provided a more flexible analysis of brain age across brain regions that revealed changes in specific structures in psychiatric disorders that would otherwise have been combined in a unidimensional brain age prediction. More generally, brain-age prediction using a subset of homogeneous features circumvents the curse of dimensionality in neuroimaging data.

scholarly journals Neuronal and synaptic plasticity in the visual thalamus in mouse models of glaucoma

2020 ◽  
Author(s):  
Matthew J. Van Hook ◽  
Corrine Monaco ◽  
Jennie C. Smith
Keyword(s):  
Mouse Models ◽  
Ganglion Cells ◽  
Brain Regions ◽  
Synaptic Function ◽  
Homeostatic Plasticity ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Intrinsic Excitability ◽  
Dependent Manner ◽  
Functional Changes ◽  
Genetic Mouse Model

AbstractHomeostatic plasticity plays important roles in regulating synaptic and intrinsic neuronal function to stabilize output following perturbations to circuit activity. In glaucoma, a neurodegenerative disease of the visual system commonly associated with elevated intraocular pressure (IOP), early disease is associated with altered synaptic inputs to retinal ganglion cells (RGCs), changes in RGC intrinsic excitability, and deficits in optic nerve transport and energy metabolism. These early functional changes can precede RGC degeneration and are likely to alter RGC outputs to their target structures in the brain and thereby trigger homeostatic changes in synaptic and neuronal properties in those brain regions. In this study, we sought to determine whether and how neuronal and synaptic function is altered in the dorsal lateral geniculate nucleus (dLGN), an important RGC projection target in the thalamus, and how functional changes relate to IOP. We accomplished this using patch-clamp recordings from thalamocortical (TC) relay neurons in the dLGN in two established mouse models of glaucoma – the DBA/2J (D2) genetic mouse model and an inducible glaucoma model with intracameral microbead injections to elevate IOP. We found that the intrinsic excitability of TC neurons was enhanced in D2 mice and these functional changes were mirrored in recordings of TC neurons from microbead-injected mice. Notably, many neuronal properties were correlated with IOP in older D2 mice, but not younger D2 mice or microbead-injected mice. The frequency of miniature excitatory synaptic currents (mEPSCs) was reduced in both ages of D2 mice, and vGlut2 staining of RGC synaptic terminals was reduced in an IOP-dependent manner in older D2 mice. Among D2 mice, functional changes observed in younger mice without elevated IOP were distinct from those observed in older mice with elevated IOP and RGC degeneration, suggesting that glaucoma-associated changes to neurons in the dLGN might represent a combination of stabilizing/homeostatic plasticity at earlier stages and pathological dysfunction at later stages.

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