When I was 20, I worked at what was then called the Clarke Institute of Psychiatry in Toronto, volunteering as a research assistant on a study of the relationship between puberty and schizophrenia. I was lucky to be supervised by one of the smartest and kindest women I had ever met, Dr. Mary Seeman. Because I was pre-med and interested in becoming a psychiatrist myself, she organized opportunities for me to spend some time on the various wards of the hospital; the most memorable of which was my week on the acute psychotic episode ward, where patients who were experiencing psychotic symptoms for the first time were being diagnosed and treated. Psychosis in patients with schizophrenia generally appears when patients are in their early twenties, and  I was struck by how similar many of the patients were to me; they were experiencing delusions, hallucinations and disorganized thinking for the first time and they were my age. The trouble with delusions and other symptoms of schizophrenia is that they feel just as real as any other cognitive, perceptual or emotional experience. These patients described their delusions in the same language that I would use to describe the feelings that I experience in stressful situations.

A Fish’s Delusion from sonpham32 (www.photobucket.com)

Let’s say, for example, that a patient falsely believes that he is being monitored by the state: that someone has implanted a microchip into his brain that transmits his thoughts to a computer located in a branch of the Canadian equivalent of the CIA (CSIS). If that were true, one can imagine how frightening it might be. Hearing the patient describe his emotional reaction to this belief, I couldn’t help but sympathize. His emotional reaction was entirely appropriate, even though the cause of it was not real. I couldn’t sleep at night because I kept imagining how frightening it must be to have those irrational thoughts, or hallucinatory experiences.  Many patients, after responding well to pharmacological treatments of their symptoms, know that their delusions and hallucinations are caused by disease rather than the outside world, and they can describe them with the insight that an actor has when describing what a character that she is playing experiences. But most actors can readily turn off feelings induced by their skills; patients with schizophrenia live with the fear that they cannot control their thoughts and emotions so easily.  I have to admit that throughout my twenties, I lived with a small, nagging fear that at any time, my own psyche could betray me and symptoms of schizophrenia could just as easily tear apart my life as they had the lives of many of the young people that I encountered on that ward.

Like virtually all psychiatric disorders, the symptoms of schizophrenia arise from the building blocks of healthy mental processes. The fact that hallucinations and delusions use the same brain regions and mechanisms as normal perceptions and beliefs makes the disease so devastating.  Given this problem, it’s amazing that any drugs at all can target disease symptoms without destroying healthy thoughts and perceptions.

The different symptoms of schizophrenia are likely caused by different pathologies: some resulting from changes in dopamine receptors in the prefrontal cortex, others from changes in the way that the brain cells respond to acetylcholine, serotonin, GABA and/or other neurotransmitters. The pharmacological treatment for schizophrenia these days revolves around a cocktail of drugs targeting specific symptoms, which is why psychiatrists have such a hard time finding the right doses and combinations of drugs to maximize benefits and minimize their side effects.

Perhaps because the disease is so heterogeneous, I found that every patient with whom I interacted was first and foremost a unique individual, rather than a textbook case. Each person’s experience was different, and the problem of diagnosis dominated the conversation in the clinic. Yet I found myself relating to the experiences of these patients much more quickly than I would have expected, given how strange their symptoms sound when listed in a textbook.

My primary interest in neuroscience has been to understand the narrative and constructive nature of memory. In the course of my recent work on the topic, I came across a computational model of some of the cognitive symptoms of schizophrenia, aptly named DISCERN. In the journal Biological Psychiatry, Hoffman and colleagues developed a computer model of the cognitive symptoms of schizophrenia, and then tested both the model and real patients on a test of memory for stories (delayed story recall task). Patients with schizophrenia often have trouble remembering stories and some neuroscientists think that this episodic memory breakdown might lead to delusional thinking (click here for a paper reviewing the relationship between memory biases and delusions in schizophrenia).

What’s fascinating about the computational model is that the best predictor of errors made by patients with schizophrenia was a version that used hyperlearning as the mechanism of disruption. That is, delusions in patients with schizophrenia might be the result of an inability to forget, or to suppress irrelevant information from memory. Which reminds me, once again, of why the way in which our memory works is so fascinating: somehow, when functioning optimally, our minds ‘know’ or ‘learn’ to discriminate between details of our experiences, those that should be remembered and those that should be forgotten, so that we can make sense of the world and, with some accuracy, make predictions about the future. The vast majority of our brain’s operations seem to happen outside of our consciousness. We might know relatively little about our brains, but they sure do know a lot about us.

Tags: schizophrenia, dISCERN, delusions, hallucinations, episodic memory