PARIS (FRONTLINE MEDICAL NEWS) – Low physical activity in childhood and adolescence was independently associated with later development of schizophrenia and other nonaffective psychotic disorders in the large, prospective, population-based Cardiovascular Risk in Young Finns cohort study, Jarmo Hietala, MD, PhD , reported at the annual congress of the European College of Neuropsychopharmacology.

The key question now: Is this risk factor remediable? That is, will a pediatric exercise intervention that results in improved physical fitness also reduce the risk of later nonaffective psychosis? Given that there are really no downsides to physical activity, the Finnish data make a strong case for including exercise and physical activity interventions in investigational psychosis prevention programs targeting high-risk youth, according to Dr. Hietala, professor of psychiatry at the University of Turku (Finland).

The ongoing landmark Cardiovascular Risk in Young Finns study began in 1980 with enrollment of 3,596 nationally representative Finns aged 3-18 years. Their physical activity level was assessed by means of a brief, validated self-report questionnaire in 1980, 1983, and again in 1986. Based upon the questionnaire results, participants were scored on a 5-14 physical activity index, with 5 representing the most extreme sedentary end of spectrum.

Dr. Hietala and his coinvestigators tapped into comprehensive national registries in order to identify all study participants with a psychiatric diagnosis of sufficient severity to have resulted in hospitalization up to 2012. Forty-one patients were hospitalized for schizophrenia spectrum disorders, 47 for other forms of nonaffective psychosis, 43 for personality disorders, 111 for affective disorders, and 49 with alcohol and other substance use disorders.

In a multivariate analysis adjusted for sex, age, body mass index, birth weight, non-preterm birth, and maternal mental disorders, each 1-point decrement in the pediatric physical activity index was associated with a 26% increase in the risk of developing any nonaffective psychosis and, more specifically, a 43% increased risk of schizophrenia.

Moreover, nonparticipation in organized sports competitions was independently associated with a 2.58-fold increased risk of any nonaffective psychosis and a 4.88-fold increased risk of schizophrenia. And social isolation as reflected in spending less time in common activities with friends during leisure time was associated with a 71% increased risk of nonaffective psychosis and a 76% increased risk of schizophrenia.

Of note, schizophrenia was the only psychiatric disorder associated with low physical activity in childhood and adolescence. Sedentary youths were not at increased risk of later hospitalization for affective disorders or other forms of mental illness.

“Our results have relevance for preemptive psychiatry and provide rationale for including exercise in early interventions for psychosis,” the psychiatrist said.

Current programs aimed at preventing schizophrenia in youth at high risk because of family history typically emphasize avoidance of street drugs, the importance of seeking out constructive social interactions, stress reduction techniques, and cognitive-behavioral therapy aimed at promoting a positive world view.

Formal evaluation of physical activity as part of a preventive approach has a sound theoretic basis, according to Dr. Hietala. He cited an influential essay called “Rethinking Schizophrenia” by the then-director of the National Institute of Mental Health, Thomas R. Insel, MD . In that article, Dr. Insel highlights the past half-century of largely unsatisfactory results with pharmacotherapy and goes on to make the case for considering schizophrenia as a neurodevelopmental disorder in which, he argues, “psychosis is a late, potentially preventable stage of the illness” ( Nature. 2010 Nov 11;468[7321]:187-93 ).

This view of schizophrenia as a neurodevelopmental disorder has quickly come to dominate thinking within the field. Dr. Hietala noted that the schizophrenia spectrum chapter in the DSM-5 includes a greater focus on abnormal behavior and catatonia as a core domain alongside classic features, such as delusions, hallucinations, negative symptoms, and disorganized speech.

“My view of schizophrenia is that the psychotic symptoms are a secondary phenomenon, a complication of the disease that has been going on for a while. It’s a pity that we focus so much on the psychotic symptoms rather than the cognitive or negative or affective symptoms,” he said.

The hope is that a long-term physical activity intervention in at-risk youth will stimulate neurodevelopmental catch-up, thereby thwarting their predisposition to schizophrenia.

“Human development is not a linear process; it happens in spurts of rapid growth followed by consolidation periods,” Dr. Hietala said.

However, even if it turns out that an early physical activity intervention does not reduce the risk of developing schizophrenia, it might favorably alter its course in important ways, according to Dr. Hietala.

Individuals with schizophrenia are known to be at increased risk for metabolic syndrome and premature death tied to cardiovascular disease. A recent meta-analysis of 16 prospective cohort studies totaling more than 1 million men and women found that mortality during follow-up was 59% greater in those who sat for more than 8 hours per day and were in the lowest quartile of physical activity, compared with those sitting for less than 4 hours per day who were in the top quartile of physical activity, at more than 35.5 metabolic equivalent hours per week.

But there was no increased risk of mortality among those who sat for more than 8 hours per day and were also in the highest quartile of physical activity. The implication is that high levels of moderate-intensity physical activity eliminates the increased risk of death associated with high sitting time ( Lancet. 2016 Sep 24;388[10051]:1302-10 ). That’s a finding that could be applicable to patients with schizophrenia.

Dr. Hietala reported having no financial conflicts regarding the Cardiovascular Risk in Young Finns study, which is supported by the Academy of Finland, the Social Insurance Institution of Finland, and grants from nonprofit foundations.