Schizophrenia and Autism: A New Connection
Autism and Schizophrenia, at first glance there probably isn’t a whole lot in common other than they are disorders that fall in that lovely book the DCM-5. The brain is a complex thing, so I guess it shouldn’t be a surprise that certain forms of Autism and Schizophrenia [don’t ask me why I capitalize them, I don’t know] share a link in what at first glance seems to be an unlikely culprit.
Using diverse methodologies, neuroscientists report that defects in Fatty Acid Binding Proteins [Or FABPs since we love to shorten things in science, FABP’s are what transfer fat to cells, since fat is hydrophobic and the body is mostly water]. This may help to explain the pathology in some cases of schizophrenia and autism spectrum disorders. After identifying mutations in FABPs from patients, the group determined that the genetic disruption of FABPs in mice mimics disease behaviors seen in patients. This work suggests that disruption of FABPs could be a common link underlying some forms of these two prevalent mental disorders.
The study reported that those fatty acid binding proteins [FABPs], a component of lipid metabolism as I stated earlier, are genetically linked to schizophrenia and autism spectrum disorder [ASD, see we like to shorten things] in humans and dysfunctional behaviors in mice. The findings provide support for the involvement of lipid metabolism in the spectrum of cognitive disorders.
The brain is composed of lipids [a fancy way of saying fat] that provide structure and signaling functions, and disruption of lipid transport to or within the brain can lead to anomalous neurological symptoms. Previous studies revealed abnormally low levels of some polyunsaturated fatty acids [PUFAs are just a particular type of fat] including essential fatty acids in schizophrenic and autistic patients but failed to identify the responsible proteins. Consequently, the team decided to investigate FABPs molecules that facilitate the transport of those PUFAs and other fatty acids the brain uses.
“Our prior study showed that disruption of Fabp7 in mice impaired neurogenesis, so we suspected that FABP7 and its family members had important roles in neurodevelopment”, said Dr. Yoshikawa, head researcher from the RIKEN Brain Science Institute.
The researchers focused on the major FABPs found in mature neurons and neuronal progenitors, FABP3, FABP5, and FABP7, to better understand their potential roles in mental disabilities.
[Loony hint: At this point if you are lost FABP3 or FABPx, where x is any number, is just a particular fatty acid binding protein. Binding proteins are specialized for certain fats, in this particular case, they looked at these particular binding proteins. It should be noted that fat is hydrophobic so to be moved into the body something needs to, for lack of a better word, protect the fat since it cannot be around water. A protein that is hydrophobic on one end, that end attaches to the fat, and hydrophilic at the other end. Hydrophilic things love water so it can then be transported in the body without any worry.]
The team found that the expression levels of FABPs in postmortem brain and blood cells of patients were altered. Using molecular analysis, the team identified specific mutations in FABP genes exclusively in patients, which caused an abnormal structure or function of these proteins, presumably preventing them from delivering the correct fatty acids to their target tissues and organelles inside cells.
To investigate the effect of FABP loss in the brain, the researchers genetically inactivated the genes in mice and conducted behavioral tests. They found that mice lacking FABPs exhibited behaviors similar to those observed in human patients. FABP3 knock-out mice showed a decrease in memory and social motivation, mirroring dysfunctional cognition and lack of interest in social communication in ASD patients.
In contrast, FABP7 knock-out mice displayed hyperactivity and anxiety, a phenotype similar to that observed in schizophrenic patients.
“Although the amino acid sequence of the FABPs is similar, we think that they interact with different fatty acids and are expressed in different cells with distinct timing during development. This is likely the reason that the behaviors in the mice are different for each member of the Fabp family”, said Dr. Yoshikawa.
Both schizophrenia and ASD are caused by many factors and conventional treatment does not work well on all patients. These findings suggest that FABPs may define one mechanism for these disorders selectively affecting lipid transport systems that may complement other etiological factors.
“Identification of FABP mutations in humans may to help us take a personalized treatment approach,” said Dr. Yoshikawa. “We hope our finding will lead to the development of tailor-made therapies, providing patients with molecules that complement deficiencies caused by their particular mutation.”
Unfortunately ASDs [Autistic spectrum disorders] are complex. Thankfully science has been knocking away at the problem and has uncovered several factors in the disorder. I thought it was interesting that certain forms of autism and schizophrenia share a common problem in the body. There have been other studies that linked the two together biologically, but with the differences in the symptoms it’s surprising they can be anywhere near related. These types of advancements give me hope that there will be better treatments coming down the pipeline to help people.
And as always, this has nothing to do with vaccination, so please, please, please vaccinate your children. To the anti-vaccination people, suck it, your fear and misinformation is doing more harm than good.
Chie Shimamoto1,, Tetsuo Ohnishi, Motoko Maekawa, Akiko Watanabe, Hisako Ohba, Ryoichi Arai, Yoshimi Iwayama, Yasuko Hisano, Tomoko Toyota, Manabu Toyoshima, Katsuaki Suzuki, Kazuhiko Nakamura, Norio Mori, Yukihiko Shirayama, Yuji Owada, Tetsuyuki Kobayashi, & Takeo Yoshikawa (2014). Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies Human Molecular Genetics : 10.1093/hmg/ddu369