Potential Biomarkers for Schizophrenia

Schizophrenia is among a large array of psychological disorders that are just that – psychological. Specifically, researchers struggle to find biological factors, or biomarkers, that are consistent across patients diagnosed with schizophrenia. Associative biomarkers allow doctors to diagnose a patient more discerningly and accurately. This increased accuracy leads to better patient treatment and to the development of a causal cure. But again, these biomarkers are scarce, especially in psychological disorders.

However, two potential biomarkers have recently been reported. The first is a genetic correlation between the C₄ gene and synaptic pruning published by Beth Stevens, Steve McCarroll and their colleagues at Harvard Medical School and its Broad Institute’s Stanley Center for Psychiatric Research. During human brain development, humans undergo a process called synaptic pruning in which the brain degrades certain neural connections. The C₄ gene was specifically studied due to a preliminary human genome inquiry. C₄ is located on chromosome six in an area associated with the immune system. Researchers found that increased C₄ activity correlates to schizophrenic patients. To experimentally test this correlation, researchers manipulated the genes in mice. From these manipulations, they saw that when the C₄ gene is deleted, synaptic pruning goes wrong, and when C₄  activity increases, synaptic pruning increases as well. From these observations, researchers concluded that the C₄ gene acts to increase the tagging of neural connections to be pruned, resulting in detrimental deletion. So, it is speculated that because people with schizophrenia show increased C₄ activity, which correlates to increased synaptic pruning, humans with schizophrenia experience this increased pruning and incorrect development. In addition, human’s synaptic pruning occurs during adolescence, which is also when schizophrenic symptoms start to appear. Therefore, C₄’s activity level is a potential biomarker for schizophrenia.

Another possible biomarker for schizophrenia is suggested by Dr. Lei Wang and his colleagues at Northwestern’s Medical School. In his presentation, “Deep Brain Structural Shape as Biomarkers for Neuropsychiatric Disorders,” Wang discussed four deep brain structures: the hippocampus, the amygdala, the thalamus, and the basal ganglia including its subdivisions. In connection to schizophrenia, he specifically discussed deceased gray matter in the thalamic nuclei and basal ganglia due to a decreased number of NADPH-d neurons. With these aspects in mind, Wang researched the shape and volume differences of these deep brain structures in patients diagnosed with schizophrenia. He reported that the hippocampus, thalamus, and basal ganglia in schizophrenic patients had significantly different shapes compared to controls. However, he found no significant difference in the volume of these areas. In addition, Wang analyzed correlations of these deformed shapes with participants’ non-psychotic siblings. He found a significant correlation between the siblings’ deep brain structure shapes compared to unrelated and control participants. Wang hesitated to say that these structure deformities are consistent biomarkers for schizophrenia but he concluded that these deformities allude to schizophrenia possibly being a disorder of “network disorganization” (Wang, 2019). 

Perhaps, Wang’s idea of “network disorganization” directly connects to Stevens and McCarroll’s idea of amplified synaptic pruning. The C₄  activity increases, causing excessive tagging for synaptic pruning, in which an excessive amount of neural connections are eliminated, resulting in a disorganized neural network.

Overall, research indicates that there is something different about a person with schizophrenia’s brain compared to the normal developed population. Yet schizophrenic associative biological factors are lacking. Although the researchers mentioned did not state that their findings are definite schizophrenic biomarkers, their findings provide hopeful conclusions and areas for future research. Perhaps even a schizophrenic causal cure will be developed, targeting the initial activity of the C₄ gene and effectively inhibiting corrupt synaptic pruning and all of its downstream effects.

References:

Carey, Benedict. “Scientists Move Closer to Understanding Schizophrenia's Cause.” The New York Times, The New York Times, 27 Jan. 2016, www.nytimes.com/2016/01/28/health/schizophrenia-cause-synaptic-pruning-brain-psychiatry.html.

Rettner, Rachael. “‘Schizophrenia Gene’ Discovery Sheds Light on Possible Cause.” Scientific American, LiveScience, 28 Jan. 2016,  www.scientificamerican.com/article/schizophrenia-gene-discovery-sheds-light-on-possible-cause/.

Wang, Lei Dr. “Deep Brain Structural Shape as Biomarkers for Neuropsychiatric Disorders.” Loyola University Chicago Neuroscience Seminar. 5 Feb. 2019, Chicago, Loyola University Chicago.