Demystifying Psychiatry

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Brain Dysfunction Common to Schizophrenia & Bipolar Disorder

Are we getting closer to understanding psychotic symptoms?

As mentioned in an earlier post (Bipolar Disorder and Schizophrenia - Similar and Different, 3/5/13), schizophrenia and bipolar disorder have some overlapping symptoms and brain abnormalities. People with either disorder can experience psychotic symptoms, including hallucinations (such as hearing voices or seeing visions), delusions (fixed false beliefs), or various forms of thought disorder characterized by speech that is rambling and hard to follow. Until recently, brain abnormalities responsible for psychotic symptoms had not been identified. Whether the brain abnormalities underlying psychotic symptoms in schizophrenia are the same brain abnormalities underlying psychosis in bipolar disorder is also unknown. Recent research examining the function of brain networks is beginning to shed light on these questions.

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A brain network is a group of interconnected brain regions that work in harmony in order to regulate certain functions, including thinking (cognition), emotion, motivation, and behavior. Scientists are characterizing an increasing number of brain networks in hopes of better understanding human behavior. For example, a network called the emotional salience network appears to be involved in regulating emotional responses. This network has been implicated in an illness called behavioral variant frontotemporal dementa, where the breakdown of the emotional salience network leads to markedly disinhibited (crude and embarrassing) behaviors gradually followed by deterioration in speech, organizational skills, and eventually memory

The default network and the dorsal attention network are two other brain networks that have been identified. These two networks have very different roles. The default network is active when we are daydreaming, i.e., when we are not thinking about anything in particular. In reality, when we daydream, we are actually exploring a variety of thoughts, memories, and ideas. Thus, the default network is involved in broad-based introspective thinking. In contrast, the dorsal attention network helps us focus on performing specific tasks that require concentration and attention. This system is driven by external (outside the body) cues as opposed to the default network, which responds largely to internal cues. When one of these two systems is active, the other is much less active.

The frontoparietal control network (FPCN) is another recently characterized brain network. It has the role of coordinating the relative activity of the internally driven default network and the externally responsive dorsal attention network. As a person shifts from introspection to focus on a specific task, he or she must disconnect from daydreaming, which utilizes internal information such as stored memories and images, and engage in interpreting external events, which requires focus on the external environment via sensory systems involving sight, sound, etc. This shift from introspection to focused attention is facilitated by the FPCN.

What would happen if the FPCN malfunctioned? Is it possible that the separation between our internal and external worlds would become blurred? Could malfunction of this network lead to psychotic symptoms such as hallucinations and delusions?

A team from Harvard has been studying these questions in a sample of patients who suffer from either schizophrenia or bipolar disorder with psychosis. Results from this study were recently reported by Justin Baker and colleagues in JAMA-Psychiatry. By utilizing advanced brain imaging techniques, these researchers found that patients with these two illnesses have marked abnormalities in the function of the FPCN. Furthermore, the patterns of abnormalities were similar in patients with schizophrenia and patients with bipolar disorder. The researchers suggest that psychotic symptoms in both of these disorders may involve malfunction of the same brain regions.

When does this breakdown in the FPCN begin? If this system starts to malfunction prior to clinical symptoms, can examining the integrity of the FPCN be used to predict whether an individual will develop psychotic symptoms? Why does this system break down, and can we develop specific treatments to reverse the structural or functional changes in the brain regions involved? Are there differences in the malfunctioning of the FPCN in patients suffering from schizophrenia versus those with bipolar disorder?

This work has profound clinical implications and would have been impossible without decades of prior neuroscience research that has helped define and understand brain networks. All this work was dependent on the development of advanced brain imaging techniques and the quantitative methods required to analyze network activity. Such investments in basic scientific research lead to advances in our understanding and treatment of illnesses. In the long run, this investment has the potential to improve lives and save money, hopefully diminishing the disability and mortality associated with severe psychiatric disorders.

This column was written by Eugene Rubin MD, PhD and Charles Zorumski MD

Eugene Rubin, M.D., Ph.D., is Professor and Vice-Chair for Education in the Department of Psychiatry at Washington University in St. Louis - School of Medicine.

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