by Kathleen Cason

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Intro  |  Hallmarks of schizophrenia  |  Social skills  |  
Relative risks  |  Seeing is believing

 The Cost of Madness

 A Who's Who of Schizophrenia

Relative risks

Since first-degree relatives —parents, children and full siblings — share many of the same genes, Bedwell figured that if he studied cognitive performance in relatives of schizophrenics he'd have a good chance of finding traits that could be useful in genetic studies. Those traits may help identify family members who carry schizophrenia genes but have no symptoms and thus improve the chances of finding schizophrenia-related genes. In fact, two studies by other research groups have used this approach successfully to locate genetic regions associated with eye-movement disorders and defects in filtering auditory information, both of which are biologically based markers associated with the disease. Finding genes may lead to new prevention, diagnosis and treatment strategies.

“Studying patients is problematic,” Bedwell said. “Performance differences in neuropsychological tests can be confounded by active symptoms, medication or prolonged hospitalization, which complicate interpretation of genetic brain effects.”

Healthy first-degree relatives have few psychopathologies, are not on any anti-psychotic medication and haven't been hospitalized for a psychiatric condition. Any differences in the relatives are likely to be due to genetics because they are like the controls in most every way except for the fact that they share many genes with someone who has schizophrenia, Bedwell said.

Previous research showed that people with schizophrenia have problems with attention, sensory perception, memory, and reasoning, to name a few. Joan, for example, once had a job proofreading manuscripts, but as the schizophrenia got worse, it became a struggle to read and understand a single sentence. She began making errors and eventually lost the job. The faulty wiring in her brain prevented her from keeping the words in her mind long enough to make sense of what she was reading.

Performing a complex mental task like reading requires access to lots of information. Some of that information — what the words mean, the feelings they evoke and the pictures they paint — comes from long-term storage rather like the hard drive on your computer. Other information is only stored for short periods, more like a computer's RAM. For example, if you cannot keep all the words in this sentence in your mind at once, it will be impossible to understand what the sentence means. That short-term storage — called working memory — is defective in schizophrenics.

“There's indication in the literature that people with schizophrenia have trouble paying attention over a period of time,” Bedwell said. “But then there’s other recent evidence that sustained attention was not the problem, that all along it was a deficit in how visual information is processed.”

Miller and Bedwell may be the first to put attention and visual processing head-to-head in one study. Bedwell tailored a set of neuropsychological tests to determine whether the relatives of schizophrenics experience problems with attention or visual perception and whether there was an accelerated age-related decline in performance.

In one test, one to 12 random letters flash on a computer screen every five seconds over a five-minute period and participants say if the letters “T” or “F” appear in a grouping. A poor performance on the last third of the test compared to the first third indicates declining attention span. However, stable performance but low accuracy when high numbers of letters appear on the screen points to a deficit in visual processing.

Another task checks working memory and attention. Random letters flash on a computer screen and the test taker presses a button when “K” is followed by “A.” The participant keeps the “K” briefly in mind until the next letter appears, is identified and a response is given. Again the first and last thirds of the test are compared to find any deficits in attention or visual processing.

“What I hypothesized was that the ability to process visual information would show an accelerated age-related decline in the relatives,” Bedwell said.

And that's what he observed. While the ability to process visual information declined with age for both groups, the decline was much faster in relatives of schizophrenics.

“A little bit more controversial are our findings that there is not a difference in sustained attention within those same tasks,” Miller said.

Impaired attention has been considered a core deficit in schizophrenia. Finding no difference in relatives compared with controls suggests that attention deficit in schizophrenia may not be passed on genetically. Instead the evidence points to a deficit in visual perception as the inherited trait. This implies that a different place in the brain is involved from the region implicated in attention deficit. It also left Miller and Bedwell with the task of figuring out what aspect of visual processing is problematic.

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