In a study analyzing whole-brain images from nearly 16,000 people, researchers at the Stanford University School of Medicine identified a common pattern across a spectrum of psychiatric disorders that are widely perceived to be quite distinct.
The meta-analysis of 193 peer-reviewed papers, published Feb. 4 in JAMA Psychiatry, reports a loss of gray matter in three brain structures that, although physically separate, participate in a network associated with high-level functions, including planning and decision-making.
The findings call into question a longstanding tendency to distinguish psychiatric disorders chiefly by their symptoms rather than their underlying brain pathology.
To address that question, he and his colleagues pooled data from 193 separate studies containing, in all, magnetic-resonance images of the brains of 7,381 patients falling into six diagnostic categories: schizophrenia, bipolar disorder, major depression, addiction, obsessive-compulsive disorder and a cluster of related anxiety disorders. Comparing the images with those from 8,511 healthy control subjects, the research team identified three separate brain structures, several centimeters apart from one another, with a diminished volume of gray matter, the brain tissue that serves to process information. These structures -- the left and right anterior insula and the dorsal anterior cingulate -- are known to be parts of a larger network in the brain whose component parts tend to fire in synchrony. This network is associated with higher-level executive functions such as concentrating in the face of distractions, multitasking or task-switching, planning and decision-making, and inhibition of counterproductive impulses.
Gray matter loss in the three brain structures was similar across patients with different psychiatric conditions, the researchers found.
Showing posts with label pathology. Show all posts
Showing posts with label pathology. Show all posts
Unexpected signaling role for foul-smelling hydrogen sulfide in cell response to protein misfolding
hydrogen sulfide (H2S) – the flammable, highly toxic gas that smells of rotten eggs – plays an important role in the regulation of thge endoplasmic reticulum stress signaling pathway ( the unfolded protein response ) implicated in biological malfunctions linked to Alzheimer's and Parkinson's diseases, among others.
RIKEN | Press Release | 2011 | New study uncovers how brain cells degrade dangerous protein aggregates
Researchers at the RIKEN Brain Science Institute (BSI) have discovered a key mechanism responsible for selectively degrading aggregates of ubiquitinated proteins from the cell. Their findings indicate that the capture and removal of such aggregates is mediated by the phosphorylation of a protein called p62, opening the door to new avenues for treating neurodegenerative diseases such as Huntington's disease and Alzheimer's disease.
Salmonella-induced mucosal lectin RegIIIβ kills competing gut microbiota.
A clever ruse by a Salmonella pathogen: The host killer lectin is one factor designed to help kill pathogens, but Salmonella itself is resistant,and the result is destruction of beneficial or harmless commensals.
Discovery offers molecular insights into link between Parkinson's and pesticides
Rotenone and paraquat, as well as MPTP inhibit various components of the mitochondrial respiratory chain, enough in itself to severely compromise substantia nigra neurones. The oxidative stress that ensues also oxidises Parkin, the product of a gene implicated in Parkinson's disease , producing Parkin aggregation and malfunction.
Parkinson's disease genes risk factors and pathways
Parkinson's disease genes risk factors and pathways
Human Ecstasy Use is Associated with Increased Cortical Excitability: An fMRI Study
The neurotoxic effects of ecstacy (MDMA) in animals have long been known. This human study confirms such effects
Alzheimer’s disease plaques and tangles: Cemeteries of a Pyrrhic immune victory against herpes simplex infection at the cost of neuronal destruction
Neurochem.Int (in press)
Plaques and tangles are highly and significantly enriched in herpes simplex (HSV-1) binding proteins (by 11 and 15-fold respectively (P = 4.47E-39) and 132/341 (39%) of the known HSV-1 binding partners or associates are present in these structures. The classes involved include the majority (63-100%) of the known HSV-1 host protein carriers and receptors, 85-91% of the viral associated proteins involved in endocytosis, intracellular transport and exocytosis and 71% of the host proteins associated with the HSV-1 virion. The viral associated proteins found in plaques or tangles trace out a complete itinerary of the virus from entry to exocytosis and the virus also binds to plaque or tangle components involved in apoptosis, DNA transcription, translation initiation, protein chaperoning, the ubiquitin/proteasome system and the immune network. Along this route, the virus deletes mitochondrial DNA, as seen in Alzheimer’s disease, sequesters the neuroprotective peptide, ADNP, and interferes with key proteins related to amyloid precursor protein processing and signalling as well as beta-amyloid processing, microtubule stability and tau phosphorylation, the core pathologies of Alzheimer’s disease. Amyloid-containing plaques or neurofibrillary tangles also contain a large number of complement, acute phase and immune-related proteins, and the presence of these pathogen defence related classes along with HSV-1 binding proteins suggests that amyloid plaques and tangles represent cemeteries for a battle between the virus and the host’s defence network. The presence of the complement membrane attack complex in Alzheimer’s disease neurones suggests that complement mediated neuronal lysis may be a consequence of this struggle. HSV-1 infection is known to increase beta-amyloid deposition and tau phosphorylation and also results in cortical and hippocampal neuronal loss, cerebral shrinkage and memory deficits in mice. This survey supports the contention that herpes simplex viral infection contributes to Alzheimer’s disease, in genetically predisposed individuals. Genetic conditioning effects are likely to be important, as all of the major risk promoting genes in Alzheimer’s disease, (Apolipoprotein E, clusterin, complement receptor 1 and the phosphatidylinositol binding clathrin assembly protein PICALM), and many lesser susceptibility genes, are related to the herpes simplex life cycle Ref. 33 susceptibility genes are related to the immune system. Vaccination or antiviral agents and immune suppressants should therefore perhaps be considered as viable therapeutic options, prior to, or in the early stages of Alzheimer’s disease.
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Plaques and tangles are highly and significantly enriched in herpes simplex (HSV-1) binding proteins (by 11 and 15-fold respectively (P = 4.47E-39) and 132/341 (39%) of the known HSV-1 binding partners or associates are present in these structures. The classes involved include the majority (63-100%) of the known HSV-1 host protein carriers and receptors, 85-91% of the viral associated proteins involved in endocytosis, intracellular transport and exocytosis and 71% of the host proteins associated with the HSV-1 virion. The viral associated proteins found in plaques or tangles trace out a complete itinerary of the virus from entry to exocytosis and the virus also binds to plaque or tangle components involved in apoptosis, DNA transcription, translation initiation, protein chaperoning, the ubiquitin/proteasome system and the immune network. Along this route, the virus deletes mitochondrial DNA, as seen in Alzheimer’s disease, sequesters the neuroprotective peptide, ADNP, and interferes with key proteins related to amyloid precursor protein processing and signalling as well as beta-amyloid processing, microtubule stability and tau phosphorylation, the core pathologies of Alzheimer’s disease. Amyloid-containing plaques or neurofibrillary tangles also contain a large number of complement, acute phase and immune-related proteins, and the presence of these pathogen defence related classes along with HSV-1 binding proteins suggests that amyloid plaques and tangles represent cemeteries for a battle between the virus and the host’s defence network. The presence of the complement membrane attack complex in Alzheimer’s disease neurones suggests that complement mediated neuronal lysis may be a consequence of this struggle. HSV-1 infection is known to increase beta-amyloid deposition and tau phosphorylation and also results in cortical and hippocampal neuronal loss, cerebral shrinkage and memory deficits in mice. This survey supports the contention that herpes simplex viral infection contributes to Alzheimer’s disease, in genetically predisposed individuals. Genetic conditioning effects are likely to be important, as all of the major risk promoting genes in Alzheimer’s disease, (Apolipoprotein E, clusterin, complement receptor 1 and the phosphatidylinositol binding clathrin assembly protein PICALM), and many lesser susceptibility genes, are related to the herpes simplex life cycle Ref. 33 susceptibility genes are related to the immune system. Vaccination or antiviral agents and immune suppressants should therefore perhaps be considered as viable therapeutic options, prior to, or in the early stages of Alzheimer’s disease.
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Hippocampal Interneurons in Bipolar Disorder. [Arch Gen Psychiatry. 2010] - PubMed result
Image via WikipediaBipolar brain pathology is perhaps less well characterised than in schizophrenia. This study showed a number of hippocampal changes including reduced volume of the nonpyramidal cell layers, reduced cell body volume in CA2 and CA3 and lower numbers of somatostatin- and parvalbumin-positive neurones.
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Dsyfunction In Blood Vessel Walls Could Be Risk Factor For Alzheimer's As Well As Heart Disease
This study showed that inhibition of endiothelial nitric oxide synthase in blood vessel walls triggered a cascade leading to increased production of APP and higher levels of BACE1. Cerebral circulation problems could be at the root of Alzheimer's disease. Indeed, carotid artery atherosclerosis is observed in a large number of Alzheimer's patients (Refs ) as is atherosclerosis of the circle of Willis and other cerebral arteries Refs :
Thus far, Beta amyloid -based therapies have not been successful, but these atherosclerotic problems are detectable and to some extent treatable.
Thus far, Beta amyloid -based therapies have not been successful, but these atherosclerotic problems are detectable and to some extent treatable.
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