Editorial- Autism and the brain: the vital contribution of postmortem research

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects approximately 1% of the global population. It presents in diverse ways, but the core features typically include challenges with social interaction and communication, as well as repetitive behaviors and focused interests. Despite these shared characteristics, individuals with autism can vary significantly in how the condition initially manifests and progresses. Unfortunately, the causes of autism are usually not determined, and the biological mechanisms underlying the condition remain poorly understood. This gap in knowledge can result in suboptimal care for affected individuals and, consequently, has ramifications for family members. To address this, it is crucial to gain a deeper understanding of the brain processes involved in autism. One important way to achieve this is through postmortem brain research that is made possible through the donation of brain tissue for scientific study.

Why is studying human brain tissue important in autism research?

There are many ways to study autism, including epidemiological studies, clinical analyses, genetic research, and neuroimaging of living individuals. These methods have provided valuable insights, such as the recognition that autism is a highly heritable and heterogeneous condition, both in terms of its causes and its clinical presentations. Studies have also identified genetic variations associated with autism, particularly those affecting aspects of brain development and function. Given these advances, one might wonder why it is still essential to study brain tissue directly.

The answer lies in the fact that the brain is the primary organ affected by autism. While many individuals with autism have other co-occurring medical conditions, the brain is central to the condition’s core features. To understand how, where, and when the brain is affected by autism, it is necessary to study brain tissue directly. Some aspects of brain biology, such as cellular organization, connectivity, and neurotransmitter systems, can only be fully understood through this type of investigation.

What can be learned from studying human brain tissue?

Studying brain tissue from individuals with autism allows researchers to explore a range of questions that cannot be answered through other means. Three key areas of study are histological analysis, gene expression studies, and biochemical analysis.

Histological and histochemical analysis. By examining brain tissue, scientists can observe how neurons and other cells are organized and connected, which may reveal abnormalities in neural networks. These networks are crucial for communication, behavior, and cognition. Additionally, studies of neurotransmitter systems in the brain can shed light on potential chemical imbalances that contribute to autism’s symptoms. Understanding these aspects can lead to new pharmacological treatments. Furthermore, brain tissue research can provide insights into brain plasticity, or the brain’s ability to change in response to experiences, which is particularly relevant in understanding how autism develops and responds to interventions.

Gene expression studies. Gene expression analysis in brain tissue has provided important information about how genes are regulated in the autistic brain. This includes understanding which genes are upregulated or downregulated in comparison to non-autistic brains. Brain gene expression can be affected by inherited or newly occurring genetic variants or by environmental factors such as hormones, infections, nutritional factors, or toxins. Research has identified various gene expression changes in the autistic brain, some of which point to specific pathways and processes that may be disrupted in autism. These studies are increasingly being refined through the use of techniques like laser microdissection, which allows for the examination of gene expression in individual brain cells.

Biochemical analysis. Biochemical studies of autistic brain tissue involve analyzing specific proteins, metabolites, or other molecules. These studies can reveal how altered gene expression translates into changes in the brain’s biochemistry, bringing us closer to understanding the biological basis of autism. These studies hold great promise for furthering our understanding of the biological underpinnings of autism and for uncovering new targets for treatment.

Challenges in brain tissue research for autism

Despite the significant insights gained from studying autistic brain tissue, there are several challenges that researchers face. One major issue is the limited availability of brain tissue for study. Compared to other conditions like Alzheimer or Parkinson diseases, there are far fewer donated brains available for autism research. This scarcity is compounded by the fact that some donated tissues are of poor quality or lack comprehensive medical information about the donor, limiting their usefulness for research.

The NIH NeuroBioBank, a National Institutes of Health network of brain banks dedicated to supporting brain research on autism and numerous other brain disorders through the provision of donated brain specimens, houses over 3,200 brain specimens from Alzheimer patients but has only 106 brains from autistic individuals. Similarly, the Autism BrainNet network, a network of brain banks dedicated to autism research, holds just 204 samples. This stark disparity, particularly when considering the high prevalence of autism, underscores the urgent need to increase the number of autism brain specimens available for research. Expanding this resource is essential for advancing our understanding of autism and developing more effective treatments.

How can families contribute to autism research through brain donation?

For families considering brain donation, it is important, when possible, to have discussions about this in advance. This can be a difficult decision, influenced by personal, religious, or cultural beliefs. However, making arrangements ahead of time can ease the process during the challenging and emotional period when a loved one has just passed.

The Autism BrainNet network offers resources and a 24-hour hotline (www.AutismBrainNet.org; 877-333-0999) to guide families through the donation process. They ensure that the donation meets research criteria and handle the logistical aspects of obtaining the brain tissue.

The NIH NeuroBioBank, which is accessible through the Brain Donor Project, www.BrainDonorProject.org; 513-393-7878, also facilitates brain donations for various neurological conditions, including autism. The participating institutions include the Universities of Maryland (800-847-1539), Miami (800-UM-BRAIN), and Pittsburgh (513-393-7878), along with Harvard (800-BRAIN-Bank), Mount Sinai (212-807-5541), and the Human Brain and Spinal Fluid Resource Center (310-268-3330).

Both networks encourage pre-registration, making it easier for families to proceed with donation when the time comes. Both also accept donations from neurotypical individuals, which are critical for control studies.

Conclusion

Donating brain tissue for research is vital for advancing our understanding of autism. Current technologies cannot study the living brain at the level of cellular and molecular detail needed to uncover the detailed biological underpinnings of autism. Postmortem brain research provides insights that can lead to better therapeutic approaches, ultimately transforming lives. Families who choose to contribute in this way are making a profound impact on the future of autism science.

This article originally appeared in Autism Research Review International, Vol. 38, No. 3, 2024