Improving Outcomes for Persons with Schizophrenia

What core deficits should be targeted when treating schizophrenia?

Posted Jan 11, 2021

Successful treatment of hallucinations and delusions associated with schizophrenia does not reverse many of the long-term consequences of this illness. Rene Kahn convincingly explains why this is so in an excellent review published in the American Journal of Psychiatry entitled “On the Origins of Schizophrenia.”

Kahn points out that antipsychotic medications are successful in decreasing psychotic symptoms for many individuals with schizophrenia. Despite this, 90 percent of persons with this illness are unable to hold gainful employment. Their life expectancy is decreased by an average of 15 years, and many find it difficult to establish a family.  

Why aren’t these outcomes reversed with today’s treatments? One reason may be poor medication compliance, but Kahn proposes “that the principal reason that we have not been able to materially ameliorate the outcome in schizophrenia is that we have been barking up the wrong tree; we have mistakenly focused on psychosis.”

It is likely that the major core deficits associated with schizophrenia involve cognitive dysfunction, for example, deficits in abstract reasoning, attentional abilities, working memory, organizational skills, and language. Reversing psychotic symptoms will not alter these underlying cognitive deficits.

The concept that schizophrenia is primarily a cognitive disorder was espoused by psychiatrists who defined this set of illnesses in the late 1800s and early 1900s, including Emil Kraepelin and Eugen Bleuler. Evidence that impaired cognitive abilities are core features of schizophrenia and precede psychotic symptoms by several years has accumulated over the last decade. Kahn reviews research suggesting the following progression.

First, abnormal brain maturation in childhood and early adolescence leads to changes in the way brain regions connect with each other. This abnormal connectivity is associated with changes in brain structure and function resulting in cognitive deficits. Psychotic symptoms develop later. Successful treatment of psychotic symptoms, although beneficial, does little to treat underlying cognitive deficits, and these deficits are associated with poor long-term outcomes.

There is little doubt that psychotic symptoms can be dramatic and are associated with behaviors that may frighten patients along with anyone witnessing such symptoms, including families and friends. Successful treatment of psychotic symptoms leads to the illness being less visible to the public, and patients with schizophrenia feel better when psychotic symptoms are diminished. However, cognitive deficits continue to interfere with individuals’ abilities to process information, focus, and plan, resulting in illness-associated dysfunction and disability. The development of treatments that prevent or ameliorate cognitive deficits has the potential to markedly improve the long-term outcomes of those with schizophrenia.

Such treatments may need to be initiated prior to or during adolescence before chronic dysfunction is manifest. Thus, early recognition of schizophrenia, including identification of biomarkers that predict who will become symptomatic during young adulthood, is of vital importance, as is the development of effective treatments that improve cognition.

This column was written by Eugene Rubin MD, Ph.D., and Charles Zorumski MD.

References

Kahn, R.S. (2020 April). On the origins of schizophrenia. Am J Psychiatry. 177:291-297.