Delaying Treatment May Not Worsen Schizophrenia Symptoms

Young people developing schizophrenia wait, on average, a year and a half before seeking treatment. Does this tardiness allow the illness to unleash more brain damage than it would otherwise inflict?

A number of scientific studies have said yes, some others no. And now a new investigation, reported in the January American Journal of Psychiatry, adds, for the most part, to the nays.

The study was conducted by Beng-Choon Ho, M.D., clinical director of the University of Iowa Schizophrenia Research Center, and coworkers.

Ho and his team feel confident that their results have merit since they used more subjects in their study than have been used before to examine the question of late schizophrenia treatment and brain toxicity and also since state-of-the-art magnetic resonance imaging was used to assess the brain anatomy of their subjects.

Ho and his colleagues selected 156 persons, average age 26, who had been diagnosed at the University of Iowa’s Mental Health Clinical Research Center for early schizophrenia or early schizophrenia-like illness. One hundred and fourteen had schizophrenia, 36 had schizophreniform disorder, and six had schizoaffective disorder.

The subjects were then given 36 neuropsychological tests spanning nine cognitive domains—verbal memory, nonverbal memory, working memory, language skills, visuospatial skills, problem solving, initiation and speed, sustained and selected attention, and motor skills. Magnetic resonance imaging was also performed on 101 of the 156 subjects to measure 21 aspects of brain anatomy—the volume of cerebral tissue, cerebellar tissue, lateral ventricles, and surface cerebrospinal fluid; total cerebral gray matter, frontal lobe gray matter, temporal lobe gray matter, parietal lobe gray matter, and occipital lobe gray matter; total cerebral white matter, frontal lobe white matter, temporal lobe white matter, parietal lobe white matter, and occipital lobe white matter; cerebral cortical depth, sulcal cortical depth, gyral cortical depth, sulcal curvature index, gyral curvature index, cerebral surface area, and surface complexity index.

The researchers then compared the psychological test results of the 156 subjects with those of the mentally healthy controls and found, not surprisingly, that the former performed worse on average than the controls in every domain tested.

But did the length of time that the 156 subjects had experienced psychosis before seeking treatment have any influence on their psychological test scores? The investigators attempted to answer this question, defining “untreated initial psychosis” as the period from the onset of the “full psychotic syndrome” to the initiation of treatment with antipsychotic medication. “Full psychotic syndrome” was defined as the presence of any one of five positive symptoms—delusions, hallucinations, bizarre behaviors, positive formal thought disorder, or catatonic motor behavior—rated at a severity level of moderate or worse. The average duration of untreated initial psychosis among the subjects was 74 weeks, although it ranged from as little as 12 weeks to more than 76 weeks.

The investigators found a mild link between longer untreated initial psychosis and poorer verbal memory and between longer untreated initial psychosis and poorer problem-solving skills, but neither link was strong enough to be statistically significant.

The scientists then divided the subjects into two groups based on median duration of untreated initial psychosis and attempted to see whether the group with a short duration of untreated initial psychosis—fewer than 13 weeks—had test results that differed from those of the group with a long duration of untreated initial psychosis—more than 13 weeks. The only statistically significant difference they could find between the two groups was in verbal memory: The group with a short duration of untreated initial psychosis had less impairment.

The researchers then attempted to see, in the 102 subjects who had had magnetic resonance imaging of various areas of the brain, whether they could find any links between the duration of their untreated initial psychosis and their magnetic resonance imaging results. The strongest link was found for the lateral ventricle volume, with larger ventricles related to longer duration of untreated initial psychosis. However, neither this association nor any of the others reached statistical significance.

Finally, the investigators compared the magnetic resonance imaging results from the group with a short duration of untreated initial psychosis with the results from the group with a long duration of untreated initial psychosis. They found only one statistically significant difference between the two groups—in cortical sulcal depth. The group that had gone without treatment for a shorter period had significantly thicker sulci.

Taking these results together, the researchers concluded that delaying treatment for schizophrenia or related disorders does not seem to result in any dramatic brain damage. If this is indeed the case, they reasoned, then treating such illnesses early will probably not lessen brain damage.

Nonetheless, early treatment is justified for another reason, they believe, and that is to stanch emotional suffering by patients and their families.

Psychiatric News asked Ho whether he and his colleagues will be conducting any more research on the subject of duration of untreated psychosis. He replied: “We are in the process of designing a study that will look at the relationship between duration of untreated psychosis and hippocampal volumes. The hippocampus is an especially plastic region of the brain and may be most sensitive to any ‘toxicity’ from untreated psychosis.”

The study was financed in part by National Institute of Mental Health grants.

The study, “Untreated Initial Psychosis: Relation to Cognitive Deficits and Brain Morphology in First-Episode Schizophrenia,” is posted on the Web at http://ajp.psychiatryonline.org/cgi/content/full/160/1/142?. ▪

Am J Psychiatry 2003 160 142