Unlocking the Neurobiology of Schizophrenia

Summer research in Associate Professor of Neuroscience Tracie Paine’s lab is aimed at understanding the neurobiological changes that underlie the complex, less commonly recognized symptoms of schizophrenia.

May 2015 graduate Daniel Lowes and second-year student Gabriel Hitchcock are working on models to determine whether changes in the GABA neurotransmitter system, a chemical messenger that regulates anxiety, can cause schizophrenia-like changes.

Schizophrenia is a complex, long-term mental illness that interferes with a person’s ability to think clearly, manage emotions, make decisions, and relate to others. The illness is characterized by three classes of symptoms: positive, negative, and cognitive. Positive symptoms are the psychotic behaviors that most people think of when they refer to schizophrenia—hallucinations, delusions, and paranoia. Those symptoms are treated fairly well with currently available medications.

The negative symptoms can include social withdrawal or social isolation, flattened emotional responses, and a lack of self-care and personal hygiene. The cognitive symptoms include deficits in attention, memory, and decision-making. Both categories lack effective treatment, and the severity of these symptoms predicts how well afflicted individuals can live independently and maintain employment.

One current hypothesis suggests that changes in GABA (gamma-aminobutyric acid) contribute to the negative and cognitive symptoms. This hypothesis is based on the observation that there are a number of changes in GABA system in people with schizophrenia. Despite this, it is not known whether these changes in the GABA system cause the symptoms of schizophrenia. “Our past research has shown that decreasing GABA function leads to cognitive deficits—specifically, attention and decision-making deficits—and decreases in sociability,” Paine says.

The broader goal of Paine’s research, which is supported by the National Institute of Mental Health, is that it will lead to better, more targeted treatments for these symptoms of schizophrenia.

Lowes, who has been working in Paine’s lab since his second year, is continuing the work of his senior honors research project. He has designed a developmental model of schizophrenia to analyze changes in the GABA neurotransmitter.

A native of Parma Heights, Ohio, Lowes has been accepted as a PhD candidate in Columbia University’s pharmacology and molecular signaling program. He says the research and mentoring experience has been critical to shaping his career aspirations in science.

“Dan started at ground zero learning relevant techniques in the lab, and now he’s involved in experiment design, data collection and analysis and co-authoring papers. Gabe is currently learning all the relevant techniques but is pretty independent and is independently collecting all the data for his current experiment. He will become more involved in the experimental design aspects of upcoming experiments,” Paine says.

“Students in my lab get the technical skills—both in animal behavior and molecular analysis—and they learn how to properly execute an experiment with the appropriate controls. I also want students to understand why they’re doing the research, how it fits in the theoretical framework. You get that at Oberlin by working with your research mentor.”

Hitchcock, who is majoring in neuroscience and German, says he was one of those rare incoming students who knew exactly what he wanted to study. “I discovered that Oberlin has one of the first and best neuroscience programs among liberal arts schools. I auditioned in the Conservatory of Music, but I decided to focus on the sciences.”

Trained as a classical pianist, he takes piano lessons in the conservatory, and he’s a percussionist in the Arts & Sciences Orchestra. This year, he will be editor-in-chief of The Synapse, Oberlin’s student-produced science publication.

Hitchcock is working on a model of schizophrenia using a pharmacological analog of the drug PCP. “There’s strong data taken from animal studies and observations of people taking PCP that the effect mimics the behaviors of people with schizophrenia,” he says. “It’s a good model to work from to try to ameliorate the cognitive and negative symptoms.”