Specific Childhood Deficits Tied to Schizophrenia Risk

Children who develop schizophrenia as young adults appear on average to begin primary school with intellectual deficits and fall further behind their peers as they grow into adolescence due to impairments in working memory, information processing, and attention.

Those are the findings of a large prospective study of the developmental dynamics of cognitive deficits among children aged 7 to 13 who later experience psychosis. The report appears in the February American Journal of Psychiatry (AJP).

That cognitive deficits precede the onset of schizophrenia, often by many years, is not new. But the AJP study is unique for its disaggregation of cognition into sub-domains and its exploration of the dynamic interplay of deficits in these domains over the period preceding adolescence.

The picture that emerges from the study is of children who begin primary school with low IQ and deficits in knowledge acquisition, verbal fluency, and vocabulary, with these core intellectual deficits remaining stable over time. But in later years, these children fall farther behind their peers due to a failure of what is sometimes referred to as “online” thinking skills—information processing, visual-spatial problem solving, and working memory.

“In very practical terms, what this tells us about children who later develop schizophrenia is that they begin their primary school years struggling with a lot of verbal deficits, but fall even further behind in their working memory and attention,” study co-author Avshalom Caspi, Ph.D., told Psychiatric News. He is the Edward M. Arnett Professor of Psychology and Neuroscience at Duke University School of Medicine.

The findings deepen the understanding of the developmental trajectory of individuals at risk for psychosis and point in the direction of early identification. But researchers are quick to point out that the findings do not suggest that IQ testing be used to identify at-risk kids.

“Low IQ can signal later problems of all kinds but in a very nonspecific way,” Caspi said. “Low IQ doesn't tell you whether a child is at risk for schizophrenia. There is currently no single test of cognitive functioning that we can pick up at any one point in time to tell us what the future looks like for a child. Rather, what our findings suggest is a very complex developmental unfolding in the brains of future schizophrenia patients.”

The AJP report draws on a large sample from a multidisciplinary, longitudinal study carried out in individuals born in Dunedin, New Zealand, in 1972 and 1973.

In the study, 1,037 males and females underwent evaluations at specific intervals from ages 3 to 32, with a 96 percent retention rate. The Revised Wechsler Intelligence Scale for Children (WISC), a composite IQ test, was administered to cohort members within one month of their birthdays at ages 7, 9, 11, and 13 years.

Follow-up evaluations were also conducted at ages 15, 18, 21, 26, and 32. However, the current AJP paper reports on results for cognitive function only up to age 13, the last age at which children received IQ testing.

Assessment for schizophrenia began at the follow-up at age 21. By age 32, 1 percent of the sample (n=11) met criteria for schizophrenia and had been hospitalized and prescribed antipsychotic medications.

In addition, 2.5 percent (n=24) met criteria for schizophrenia, had hallucinations, and suffered significant life impairment but had not yet been registered with the New Zealand health service as schizophrenia patients.

Cognitive assessments showed that the average childhood IQ at age 7 was 94 for cohort members who met diagnostic criteria for schizophrenia as an adult, 98 for those who met criteria for recurrent depression as an adult, and 101 for healthy comparison subjects.

Researchers then disaggregated IQ into specific cognitive functions and tested three hypotheses for how those functions might change between ages 7 and 13: a “decline” hypothesis, under which function would deteriorate; a “deficit” hypothesis positing deficits that remained stable over time; and a “lag” hypothesis, under which certain functions would improve but at a steadily slower rate than normal.

They found there was no deterioration in cognitive function, but that the early deficits in knowledge acquisition and language fluency remained stable over time.

However, on tests indexing processing speed, attention, visual-spatial problem-solving ability, and working memory, individuals who later developed schizophrenia experienced a lag—meaning their improvement over time between the ages of 7 and 13 was slower relative to healthy comparison subjects. For each year between the ages of 7 and 13, the children who later received a diagnosis of schizophrenia lost between 0.17 and 0.26 years in mental age when compared with the children who did not develop schizophrenia.

“Developmentally what really distinguishes these future patients is how they fall behind in their ability to monitor and manipulate information,” Caspi said. “That delay coming on top of early core intellectual deficits makes for a complicated picture when they begin to develop positive symptoms of schizophrenia.”

James Gold, Ph.D., a neuropsychologist at the Maryland Psychiatric Research Center who reviewed the report, said the study is noteworthy for its prospectively studied sample followed over many years and because it confirms data about cognitive deficits from studies with less rigorously studied cohorts.

“What's somewhat new is the level of detail in examining the tests of sub-domains of cognitive function over time,” Gold told Psychiatric News. He added that it will be important to see analysis of how those trends continue past age 13.

Study coauthor Richard Keefe, Ph.D., a professor of psychiatry and behavioral sciences at Duke University Medical Center, said the findings from the study contribute to efforts at early identification and intervention with the aim of delaying or preventing a psychotic break.

“If we are really going to [decrease the incidence of schizophrenia], it is because we are able to figure out what is happening in the brains of these children before the onset of the disorder and can do something, pharmacologically or behaviorally, to alter the trajectory,” he told Psychiatric News.

“Static and Dynamic Cognitive Deficits in Childhood Preceding Adult Schizophrenia: A 30-Year Study” is posted at <http://ajp.psychiatryonline.org/cgi/content/abstract/167/2/160>.