Deconstructing Schizophrenia Offers Hope for Better Treatment

“Alex” (not his real name) said he was having a hard time keeping up in school. At 30, he was working full time and taking classes at the University of Toronto.

He is a striver, a perfectionist perhaps, intent on doing well and making good. “When things get hectic and I push myself to the limit, I get real stressed out, and I start to isolate,” he said.

And there were occasional voices he heard. “I was working in the kitchen, cleaning my stove,” he recalled, “when I heard the voice of my mother saying very loud, 'Good job! Good job!' I was shocked and I was scared, but I just kept going.”

Alex said it was his girlfriend, concerned that he was talking to himself a lot, who urged him to seek the attention of a mental health professional. A psychologist in the Toronto area, recognizing his symptoms as suggestive of a thought disorder, referred him to the PRIME (Prevention Through Risk Identification, Management, and Education) Clinic in downtown Toronto, at the Centre for Addiction and Mental Health, Canada's leading addiction and mental health teaching hospital.

Following extensive testing, Alex was found to have the signs of“ prodromal” schizophrenia, the pre-psychotic stage that schizophrenia researchers believe precedes an acute psychotic episode. Now he comes to the clinic periodically to talk to therapists and to psychometric“ raters” who assess his progress (or his deterioration) and to participate in a multicenter study looking at the efficacy of alternative methods for preventing or delaying the onset of schizophrenia.

Alex is a beneficiary of, and participant in, a unique public health effort on a far frontier of schizophrenia research. PRIME in Toronto is one of approximately 20 schizophrenia prevention clinics in North America, and one of eight receiving funding from the National Institute of Mental Health as part of the North American Prodrome Longitudinal Study (NAPLS).

“We get young people aged 14 to 30 who are having perceptual abnormalities of some kind,” said Jean Addington, Ph.D., lead investigator at PRIME Clinic. “They won't be having full-blown psychosis, but they may think they are hearing things and that it's happening more often than it should.

“You get a range of symptoms from very mild to quite severe within this not-yet-psychotic stage, and the condition is usually accompanied by a decline in functioning,” she said. “They may be suspicious and feel that they need to be watchful, but at the same time they know it's kind of strange to think that way.”

'Is Something Not Quite Right?'

Alex's pathway to PRIME was paved with good fortune—the helpful girlfriend, the knowledgeable psychologist, and his own driven nature, determined to do well and to be an effective worker and student. His presence at the clinic—and the likely fact that countless others at risk for schizophrenia will never make it there—highlights the importance to prevention efforts of sustained and vigorous outreach to the community.

Andrea Reynolds, education coordinator at PRIME, told Psychiatric News that reaching the public in the greater Toronto area with the message about prevention has required a wide range of strategies that include canvassing hospitals, specialists, general practitioners, mental health professionals, staff at public high schools, guidance counselors, and print and broadcast media.

At one time, Toronto subway commuters might have seen a PRIME Clinic poster in the train depicting a group of smiling teenagers with a headline above:“ Is Something Not Quite Right?” Aimed at the adolescent who knows somehow that he or she doesn't fit into the portrait of happy adolescence, the poster targets individuals who are experiencing the symptoms of prodromal schizophrenia and encourages them to contact PRIME (see poster).

“Finding the people in the community is the biggest challenge in this work,” said Scott Woods, M.D., principal investigator in the Enhancing the Prospective Prediction of Psychosis study at Yale University, one of the eight NAPLS sites. “There isn't a DSM category for prodromal schizophrenia, and your average mental health professional doesn't know that much about it. We go out in the community and give between 50 and 100 talks every year in the community, focusing on the local area of New Haven.”

Staff at PRIME Clinic say the shooting in April at Virginia Tech and the ensuing publicity about the shooter's untreated mental illness may give the cause of prevention some new traction. In the meantime, they wonder whom they are missing in their outreach efforts, particularly since their numbers don't match the generally accepted prevalence rate of 1 percent for schizophrenia, even assuming that everyone being seen at the prevention clinic were to convert to psychosis.

“My guess is that we are getting the squeaky wheel that requires grease,” said PRIME Clinic psychiatrist Irvin Epstein, M .D. “T he se a re people who are more likely to tell someone that they are having problems or who really aren't doing well.”

Epstein believes that some of these with the most severe symptoms—like Alex with his occasional episodes of hearing voices—are those who are experiencing the precursors to the more frightening positive symptoms of psychosis.

“Where we aren't doing such a great job is in reaching those people who are experiencing the softer, negative symptoms,” Epstein said.“ These are people who, instead of hearing voices, may be withdrawing from their friends, feeling uncomfortable around others, and lacking in motivation or direction.”

If the behavioral manifestations are only subtly different, the underlying neuroanatomical differences are not, Epstein said, noting that functional imaging studies have shown changes in the dorsolateral prefrontal cortex to be responsible for negative symptoms and changes in personality and executive functioning.

“These are much more dangerous because they are the symptoms that are usually refractory to treatment,” he said. “But these are the same people who don't typically get to our clinic.”

Schizophrenia Gets Deconstructed

So, where is the line between prodromal psychosis and full-blown schizophrenia?

Maria Haarmans, M.A., a therapist at PRIME who works with Alex and other clients, said that a distinguishing feature of those who have converted to psychosis is a conviction about the reality of their abnormal experiences: the prodromal client may hear a voice and know it isn't real, while the patient is convinced it is.

Woods observed, “The prodromal symptom is like schizophrenia, but instead of hallucinations, people experience milder perceptual abnormalities that don't have as much content. Instead of believing the FBI is monitoring their thoughts, feelings, and actions, they may simply think that people are watching them.”

But if the line between those nameless individuals in the community with a“ quieter” form of psychosis who never come to clinical attention and a patient like Alex with disturbing and disrupting symptoms is a faint but scientifically valid one—and if the line between Alex's prodromal symptoms and full-blown schizophrenia is equally valid scientifically—then it would seem to suggest that the symptoms of schizophrenia, as a developmental disorder, exist along a continuum.

Today a popular theme at scientific conferences is“ deconstructing” schizophrenia, breaking it down into stages or domains of pathology along the continuum and developing interventions appropriately targeted to each stage or domain. The concept has ignited a debate about the validity of the traditional categorical description of the disorder according to rigid DSM criteria and spurred interest in the development of a “dimensional” definition that might include the prodrome as a distinct dimension of schizophrenia.

The July issue of the Schizophrenia Bulletin, which can be accessed at<www.schizophreniabulletin.oxfordjournals.org>, featured several articles on the theme “Deconstructing Psychosis.”

Addington said that the idea of schizophrenia existing along a continuum suggests that just as it is possible to be “a little bit depressed,” it may be possible to be a “little bit psychotic.” At the farthest, or earliest, end of the developmental continuum, symptoms may “fade to normal,” consisting of unusual thoughts or beliefs that never cause them to come to the attention of others. These individuals find a way to live quietly with the symptoms and never seek treatment.

She believes the idea can help to destigmatize psychosis, diluting its toxic associations with bizarre or violent or criminal behavior, and also points the way to future research.

“What happens to the persons who don't go on to develop psychosis?” she wonders. “Among those people we are seeing with a 'little bit of psychosis,' are there protective factors that keep them from become fully psychotic?”

Alex's prognosis remains uncertain, but he said that PRIME Clinic has taught him skills for taking the heat off when the stress of his own endeavors gets too high—“positive chilling out,” he called it—and he looks forward to taking a break someday from the hectic atmosphere of busy Toronto.

He expressed relief that he found PRIME before the vigorous party scene in Toronto found him, saying it might have spelled his ruin. “I wouldn't be sitting here with you today,” Alex said.

He added that his mother and family, as well as his girlfriend, have been extraordinarily supportive of the help he receives at the clinic.

But how would he feel about telling his friends he was at risk for schizophrenia?

“I would be embarrassed a little to tell friends, but I would be able to explain it,” he replied. “I would use it as an opportunity to talk about it and deal with it.

“At first I was scared, but it has really changed my perspective,” he said. “[The staff at the clinic] have helped me to know other people feel the same kind of stresses and that the stuff I go through is normal. I don't ignore my problems, but I don't focus on them either.”

More information on PRIME Clinic is posted at<www.camh.net/Care_Treatment/Program_Descriptions/Mental_Health_Programs/PRIME_Clinic/index.html>.▪