The room is silent except for the soft clatter of cardboard pieces against the table. The layout of black, yellow, orange, and white jigsaw pieces lie on the table before you. These colorful small pieces are supposed to make up a large image of a butterfly. Each piece is a small but mighty clue for the next piece. The clock is ticking and a couple of hours have passed; you’ve put together only 100 of the puzzle’s 5,000 pieces. Similar to a large sprawling jigsaw puzzle, solving the mysteries of illnesses like schizophrenia—particularly its causes—requires much time and patience.
Schizophrenia is a mental illness that has remained a complex puzzle; it is a multifactorial illness that requires analysis of the patient’s genetics, neurobiology, environment, and the interplay of these factors. The latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) defines schizophrenia as a complex condition that includes a variety of mood symptoms ranging between months and years. Part of deciphering this puzzle requires looking closely at the symptoms, including hallucinations, disorganized speech, and catatonic behavior which disrupts control of movement and perception of surroundings, all of which persist during the individual’s time with this condition. Schizophrenia is characterized by one of two subtypes: bipolar and depressive. Needless to say, schizophrenia is a complex psychological condition which has affected millions of individuals in the United States alone. Worldwide, schizophrenia is one of the top 15 leading causes of disabilities. This condition motivated UC San Diego undergraduate student Paula Alconchel Albelda to compile pieces of the puzzle that reveal the connections of this neurodegenerative puzzle. Albeda wrote a literature review titled, “The role of Dopamine in Schizophrenia: Systematic Review.” Albeda’s research identifies dopamine as capable of cognitive effects, such as decline in long-term memory, and identifies related contributing factors such as brain structure.
Exploring the Structure of the Central Nervous System
To get an idea of the relevant puzzle pieces, it is important to first observe the bigger picture. Schizophrenia is a neurodegenerative disease, an illness that damages the brain’s structure. Genetics and neurobiological factors determine the brain’s early neurodevelopment in an individual’s lifespan. The brain has two main components: an outer gray matter layer and an inner white matter layer. Gray matter contains different neuronal components such as cell bodies, dendrites, and axons; all three are parts of a neuron (nerve cell) that help send signals between different neurons. Dendrites receive information from other neurons which is integrated into the cell body as signals that travel along axons. Neurons communicate predominantly through signaling molecules known as neurotransmitters which bind to dendrites to transfer signals. White matter contains myelinated axons and glial cells. Myelin surrounds neuron axons, increasing signal conduction within the axon. Glial cells are widely distributed in both white and gray matter of the central nervous system. Oligodendrocytes, a type of glial cell, are responsible for forming myelin around neuronal axons, which regulates the speed of conduction signals between neurons. Both the white and gray matter serve important functional roles in the brain. Identifying the patterns between structure and function within the brain’s matter will aid in recognizing the surrounding pieces of this jigsaw puzzle.
MRI technology is identified as a viable method to identify the patterns between structure and function. MRI scans are a type of diagnostic screening that utilizes magnets and radio waves to produce elaborate images of internal structures. Post-mortem MR (PMMR) imaging is done as an alternative to autopsies to identify diseases and structural damage. Both techniques have been used to help identify the relationship between structure and function for schizophrenia.
As Albeda points out, post-mortem studies have shown that a decrease in the outer layer of gray matter also affects the inner layer of white matter negatively, meaning that white matter axons may have trouble propagating signals through the brain. Author Paula Alconchel Albelda emphasizes the trends of negative effects that arise from a decline in the volume of gray matter of the brain in the prefrontal, medial temporal, and superior temporal regions of the cerebral cortex. Such as compromising an individual’s short- and long-term memory. Additionally, since the gray matter contains glial cells, neuronal cell bodies, and dendrites, gray matter decrease has also been linked with decreasing synaptic density and dendritic complexity. Synaptic density in this case refers to the amount of functioning synaptic clefts between two neurons. Dendritic complexity pertains to the complex structure of the dendrites which are responsible for receiving various signals from different neurons. A decrease in synaptic density and dendritic complexity has been coupled with cognitive impairment because the affected brain regions include subcortical areas that are connected to the prefrontal cortex, a structure known to play a role in decision making and reasoning. All in all, the decrease in the gray matter has been correlated with schizophrenia, negatively affecting short-term and long-term memory, attention span, learning, and decision making.
Decoding Schizophrenia through the Brain and DNA
As Albeda outlines, genetic aspects such as single nucleotide polymorphisms (SNPs) are capable of affecting an individual’s neurological structure and function. According to the National Human Genome Research Institute, SNPs are variations in DNA that can be observed in one nucleotide base position. One piece of the puzzle that has shown clues for schizophrenia is a SNP in the gene that codes for catechol-O-methyltransferase (COMT), an enzyme that directly interacts with dopamine and norepinephrine neurotransmitters. COMT regulates the amount of dopamine and norepinephrine present as it breaks down these neurotransmitters. Due to its role in the regulation of neurotransmitters, it can influence cellular processes important to the structural development of the cerebral cortex.
The cerebral cortex can be divided into 4 sections: the frontal lobe, temporal lobe, parietal lobe, and occipital lobe, which all play important sensory and motor roles in the brain. Dopamine’s role in brain dysfunction spiked researcher Albeda’s interest, which led her to research the effects of dopamine. An increase in the COMT enzyme activity will mean COMT will break down neurotransmitters at a higher rate, decreasing the amount of dopamine present within the brain. Less dopamine will affect the structure of the white matter in the brain and brain functions that require dopamine such as the basal ganglia. The basal ganglia is a specific structure that is made up of nuclei and is associated with cognitive and motor responses. The decrease in dopamine has been correlated with the cognitive impairments present within patients presenting the condition schizophrenia. Much like identifying the general area where a puzzle piece fits but struggling to find its exact placement, dopamine and the role of COMT present a similarly intricate challenge.
Conclusion
Student Paula Alconchel Albelda’s research links the structural and genetic components that affect individuals’ mental health, specifically schizophrenia. As Albeda outlined in her research, schizophrenia is linked with structural changes in the brain such as gray matter volume reduction. Additionally, Albeda identifies more specific genetic factors linked with schizophrenia, such as the COMT gene alteration, which plays an important role in the regulation of neurotransmitter dopamine. Albeda’s review emphasizes the cognitive effects of dopamine by identifying the intricacy of dopamine intercommunication with other neurotransmitters which can lead to deeper insight into the mechanisms at work. One possible limitation of this research, is that the animal models that researchers utilize do not perfectly reflect the range of symptoms experienced by humans. Therefore, this literature review is limited by which findings can be used to identify general patterns in humans.
For future exploration, Albeda suggests researchers could further examine how dopamine interacts with other neurotransmitters in individuals with schizophrenia. Additionally, linking the interactions influences the development of various symptoms. Another valuable direction would be to explore therapies that target the interactions between dopamine and other components, rather than focusing exclusively on dopamine. This direction is important as it has potential to be applicable to other dopamine-related conditions, such as Parkinson’s disease, leading to more effective treatments. All in all, by linking this mental illness to structural factors and genetic factors, this research literature review has used the bigger picture of schizophrenia to put together pieces of this puzzle.
