Schizophrenia affects about 1 percent of the world’s population and is the #1 cause of medical disability in the United States. The biggest reason for this high rate of disability is severe impairment in cognition, which makes it difficult to work or perform activities of daily living. Unfortunately, the cause of these cognitive impairments is poorly understood.

A recent paper by graduate student Lindsay Morra, which Strauss supervised, found that medical conditions such as diabetes, a high waist-to-hip ratio and especially high blood pressure were “particularly associated with a range of cognitive deficits” that occur in schizophrenia. This finding is significant because it suggests that general health problems that affect the body also affect the brain and cognition in schizophrenia. Earlier studies mostly focused on structural or neurochemical abnormalities that affect the brain broadly. The research from Strauss’ lab raised an important possibility that treating metabolic abnormalities, such as hypertension, may improve cognition in schizophrenia.

“The brain is intricately wired to receive blood from arteries,” Strauss says. “In people with schizophrenia, who often have had high blood pressure for 20 to 40 years, there is a systemic effect on the brain caused by a hardening of the arteries, which affects the brain’s ability to efficiently distribute blood throughout the brain.”

Several potential mechanisms complicate the interpretation of the finding in Morra’s study, Strauss says. “One is actually, unfortunately, the antipsychotic medications,” he notes. “They can cause the metabolic abnormalities to come about.”

Most of the recent drug therapies carry risks of elevated blood sugar, high blood pressure, weight gain and higher cholesterol. The new study was unable to follow the participants longitudinally to determine the cause-effect role of the antipsychotics.

All of this is not to say that high blood pressure causes schizophrenia or vice versa. Correlation isn’t causation, as the saying goes, and Strauss emphasizes that “metabolic abnormalities only predict a small proportion of the cognitive impairment in schizophrenia.”

Another potential explanation for cognitive impairment, which Strauss is investigating with a new grant from the American Psychological Foundation, is what he calls a “motivational impairment,” or abnormal interaction of the brain’s reward system with the prefrontal cortex that can cause a certain kind of reward process to go haywire.

Strauss explains it like this: For years, clinicians have thought that patients suffering from schizophrenia were cognitively impaired because something in the brain was demotivating them. “We’ve explored that, and we basically don’t think that that’s true,” he says. “What we think happens is that they try adequately but they’re inefficient at allocating their efforts.”

Healthy individuals, he says, engage in a labor-leisure tradeoff. When it’s necessary, psychiatrically healthy individuals ramp up their brain’s efforts when confronted with a hard task, but automatically ease off when that task gets easier or ends. They do this unconsciously, and it’s why you might like to play a mindless video game after a hard day at work.

By using brain recording techniques and pupillometry — the measurement of pupil diameter, which is a way to assess the amount of cognitive effort that someone exerts — Strauss and his students have found that it’s not that the brains of those suffering from schizophrenia aren’t expending as much effort; they’re ramping up and down their efforts inefficiently.

“They basically end up in the state of mental fatigue really quickly because they expend their effort inefficiently, and they can’t overcome it,” says Strauss, who received Early Career Awards for Research last year from the National Academy of Neuropsychology and the American Psychological Foundation.

By researching motivational mechanisms that can cause the cognitive impairments, Strauss hopes that he and his students might be able to design “cognitive rehabilitation training programs,” similar to some of the online brain games you’ve probably heard of.

“What we’re working toward,” he says, “is developing new cognitive training programs that actually target the motivational mechanisms that are inherent to schizophrenia and cause them to become mentally fatigued more quickly.”

Mark F. Lenzenweger, a distinguished professor of clinical science, neuroscience and cognitive psychology at Binghamton University, says he has a good response to this troubling question and ideas about how to find those answers.

In his latest book, Schizotypy and Schizophrenia: The View from Experimental Psychopathology (Guilford Press, 2010), Lenzenweger explores lessons he has learned in the psychological science laboratory while probing the broader questions of how to think about and conduct psychopathology research.

“The liability for schizophrenia is relatively prevalent and common in our population,” Lenzenweger says. “Therefore, understanding why someone goes on to develop the illness is a high-priority research question. I firmly believe that those who harbor this liability but do not develop the full-blown illness of schizophrenia may hold the key to this puzzle.

“Since this is an ongoing challenge for our society, training the next generation in how to think about and conduct psychopathology research is just as vital. So what I’ve tried to do is combine both of those elements in a way that I hope will appeal to both the experienced researcher and those just starting out.”

The book traces Lenzenweger’s intense efforts to find answers using laboratory and statistical procedures by examining a host of related conceptual issues, data analysis strategies and methodical viewpoints that he has found helpful in his more than 25 years of laboratory study. Lenzenweger, who relies on clinical anecdotes and research recollections, hopes that readers will develop an appreciation for issues related to the causes of schizophrenia and related disorders.

“Schizophrenia is perhaps the costliest form of mental illness,” Lenzenweger says. “In addition, it has a strong genetic component; about 80 percent of what determines schizophrenia is related to genetic influences. All people with schizophrenia share a personality organization known as schizotypy. And the person who carries shizotypy is known as a schizotype. Yet not all schizotypes are schizophrenic. In fact, the vast majority of schizotypes do not go on to develop the illness. So it stands to reason that the study of schizotypic individuals offers a unique perspective on what might cause the illness.”

Lenzenweger says advancing our understanding of the causes and development of schizophrenia will be difficult.

“There will be no simple solution or discovery that remedies the entire problem,” he says. “But I hope that my book will chart the course for the field as it stands currently and show the way forward for the generation to come.”