Autism and ADHD have Similar Structural Defects in the Brain

Researchers at the University of Toronto have discovered that autism, attention deficit hyperactivity disorder (ADHD) and Obsessive Compulsive Disorder (OCD) all have “disruptions in the structure of the corpus callosum” in the brain. The corpus callosum is a nerve fiber bundle that links the left and right hemispheres of the brain. Results of the study were reported in the July 1, 2016 issue of the American Journal of Psychiatry.

In the study, the researchers examined the brains of 71 children with autism, 31 children with ADHD, 36 children with OCD and 62 “typical” children using diffusion tensor imaging. Diffusion tensor imaging measures the diffusion of water across the long fibers that connect the nerve cells in the brain’s white matter. There were “widespread disruptions” in the white matter structure in the brains of the children with autism and the brains of the children with ADHD. The OCD brains had “fewer alterations” than the autism or ADHD brains. Researchers also noted that the children who had the “least independence on daily tasks” (as assessed by their parents) were found to have the “most significant disruptions in white matter.”

Researchers noted two caveats. There were changes in only a small section of the corpus callosum in the autism, ADHD and OCD brains; therefore, the clinical meaning of the changes is unclear.  Secondly, “movement in the scanner” by the children could not be ruled out as affecting the differences in the three groups of children.

Sources:   Scientific American August 9, 2016 and Spectrumnews.org August 8, 2016

Sulcal Pit as a Genetic Marker for Autism

Scientists in France have identified a genetic marker for autism that they found in a “less deep fold of Broca’s area” — an area of the brain that specializes in language and communication. The scientists at the Institut de Neurosciences de la Timone, located in Marseille, focused on this “new geometric marker called the sulcal pit.” The sulcal pit is the “deepest point of the sulcus in the cerebral cortex from which points all the folds on the brain’s surface develop.”

Using MRI scans, the scientists analyzed the sulcal pits of 102 young boys aged 2-10 according to three groups:  Autism spectrum disorder, pervasive developmental disorder not otherwise specified and “normal developing” children. Comparing the three groups, the depth of the sulcal pit in the brain was less in the autism spectrum disorder group than in the other two groups. The scientists also noted in the autistic children that the deeper the sulcal pits were, the more “impaired the language production” was in the children.

Additionally, the study disproved a previously held belief that brain “cortical folding was complete at birth.” The French scientists noted that some of the brains’ “superficial folding continued to deepen with age in both the autistic and other children.”

Source:  http://www.sciencedaily.com/releases/2016/01/160113101121.htm including journal reference Brun Lucile, Auzias Guillaume, Viellard Marine, Villeneuve Nathalie, Girard Nadine, Poinso François, Da Fonseca David, Christine Deruelle. Localized misfolding within Broca’s area as a distinctive feature of autistic disorderBiological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2015; DOI: 10.1016/j.bpsc.2015.11.003 published 12 January 2016.

Autism and Abnormal Blood Vessels in the Brain

Researchers recently published a study in the Journal of Autism and Developmental Disorders called “Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum.” The study found that the brains of those with autism have “unstable blood vessels disrupting proper delivery of blood to the brain.” “Typical” brain blood vessels are stable.

The researchers conducted the study by looking microscopically at post-mortem age-matched normal brains and autistic brains. The researchers did not know which brains had had an autism diagnosis and which brains did not thus eliminating bias in their observations. The study found formation of new blood vessels (angiogenesis) in the brains from individuals who had had an autism diagnosis; no such angiogenesis was noted in the normal brains. The areas of the brain affected were the “superior temporal cortex (primary auditory cortex), fusiform cortex (face recognition center), pons/midbrain and cerebellum.” Specifically, the researchers found increased levels of the proteins nestin and CD34 which are markers of angiogenesis. Importantly, the study findings found that the angiogenesis was not the kind that caused the sprouting of new vessels but instead of splitting, thus causing continuous fluctuations in blood circulation.

Sources:  http://www.nyu.edu/about/news-publications/news/2015/12/16/scientists-find-new-vessel-for-detecting-autism.html

http://link.springer.com/article/10.1007/s10803-015-2672-6?no-access=true

Brain Anatomy Differences in Autism

The Medical Research Council UK Autism Imaging Multicentre Study which was comprised of the Institute of Psychiatry at Kings College in London, the Autism Research Centre at the University of Cambridge and the Autism Research Group at the University of Oxford analyzed the brains of males with autism versus male controls using quantitative magnetic resonance imaging. The study was comprised of 89 men with autism spectrum disorder (mean age 26 and “full-scale IQ 110”) and 89 “male control participants” (mean age 28 and “full-scale IQ 113”). The differences in the two groups were identified statistically through “partial least squares analysis.”

The results of the study showed significant brain anatomy differences between the two groups although the adults with autism spectrum disorder did not “differ significantly from the controls in overall brain volume.” Study individuals with autism did have “significantly increased gray matter volume in the anterior temporal and dorsolateral prefrontal regions and significant reductions in the occipital and medial parietal regions as compared with controls.” The importance of these regional differences in neuroanatomy is that there was a “significant correlation between these differences and the severity of specific autistic symptoms.” Additional differences between those with autism spectrum disorder and the male controls were that those with autism had “spatially distributed reductions in white matter volume.”

In summary, quantitative MRI showed that although the overall brain volume of those with autism spectrum disorder and the controls (commonly referred to as the neurotypical) is not significantly different, there are significant brain anatomy differences in gray matter volume as well as white matter volume in those with autism spectrum disorder compared to the neurotypical; and further, the regional differences correlated with autistic symptom severity.

Source: Journal of the Archives of General Psychiatry; Jan. 2, 2012; copyrighted by the American Medical Association as detailed on the Nuffield Department of Clinical Neurosciences Medical Sciences Division of University of Oxford website: http://www.ndcn.ox.ac.uk/publications/343223.

Brain Inflammation a Key Finding in Autism

A collaborative study between Johns Hopkins School of Medicine and the University of Alabama concerning an analysis of autopsied autism and control brains was published in the December 2014 journal Nature Communications. The study found that although there are many different combinations of genetic traits that can cause autism, brains that are affected by autism show “genes responsible for inflammation responses seemed to be perpetually turned on.”1

The study involved 104 brain samples from 72 individuals where the researchers analyzed gene expression. They found that a “specific type of support cell known as a microglial cell” appeared to be “perpetually activated in the autism brains.” According to Dan Arking, Ph.D., an associate professor in the McKusick-Nathans Institute for Genetic Medicine at the Johns Hopkins School of Medicine, “inflammation is unlikely to be [autism’s] root cause…rather a downstream consequence of upstream gene mutation…” and that the “next step would be to find out whether treating the inflammation could ameliorate symptoms of autism.” Another researcher involved in the study, Andrew West, Ph.D., an associate professor of neurology at the University of Alabama, noted further that “this type of inflammation is not well understood, but it highlights the lack of current understanding about how innate immunity controls neural circuits.”1

So what is this microglia?

Microglial cells are the primary immune cells of the central nervous system. They respond to pathogens or injury by becoming “activated” where they change form and structure, increase greatly in number and migrate to the site of the injury or pathogen. At the site, they phagocytose and remove pathogens or damaged cells. Their secretions increase and direct the immune response. Though microglia often have a “protective role, they also have been studied for their harmful roles in neurodegenerative diseases and brain injuries, such as Alzheimer’s disease, Parkinson’s disease, ischemic injury, and traumatic brain injuries.”2

 

Sources: 1 Hopkinsmedicine.org/news/media/releases/

2 Faculty.sites.uci.edu/kimgreen/bio/microglia-in-the-healthy-brain/

What Can be Learned about Brain Cancer from Autism

On February 9, 2015, a physiology professor, Rajini Rao, Ph.D, at Johns Hopkins University School of Medicine announced his research group’s findings through the journal Nature Communications regarding the problems with a protein involved in cargo transport within the cells of people with certain forms of autism and people with a deadly form of brain cancer. The research involved a protein called NHE9 which is on the surface of endosomes (“cargo carriers”) that regulate the delivery of and removal of important proteins from cells. The research suggests that drugs developed to target NHE9 could help fight the most common and deadly form of brain cancer, glioblastoma.

Dr. Rao’s team first studied cargo transport inside the cells of patients with autism. The endosomes’ function is to carry new proteins to certain areas throughout the cell and remove old proteins for destruction. The research found that “autism-associated defects in the protein NHE9 cause this protein to clog the leaks leaving the endosomes too acidic and making them race to remove cargo from the cell membrane” thus destroying the protein too soon. The acidity level inside the endosomes is key to the speed of the transport of proteins in and leaks out.

Next in the research regarding NHE9, the team researched through patient databases and found that elevated levels of NHE9 are associated with “resistance to radiation, chemotherapy and poorer prognosis for patients with glioblastoma.” Dr. Rao then teamed up with a neurosurgeon at Johns Hopkins, Alfredo Quinones-Hinojosa, M.D., to examine NHE9 in the tumor cells from several patients. Research found that the cells with the most NHE9 travelled fastest when placed on a “surface mimicking the brain” suggesting high odds of metastasis. This theory was confirmed when cells manipulated to have low or high levels of NHE9 were transplanted into the brains of mice.

Further studies revealed that in contrast to autism, NHE9 is overactive in brain cancer. The result is the endosomes leak too much and the endosome becomes too alkaline which causes “cancer-promoting cargo” to stay on the cell surface too long. Dr. Quinones-Hinojosa stated that the research results give researchers a better idea of what to target to make glioblastoma “less aggressive and devastating.”

Source: Hopkinsmedicine.org/news/media/releases/