Schizophrenia through the ages: from childhood risk factors to middle-aged comorbidity

People in the prospective North Finland 1966 Birth Cohort Study who went on to have a diagnosis of schizophrenia had a far higher incidence of endocrine, nutritional and metabolic diseases (16% vs 9%) than those born in the same year who did not have a schizophrenia diagnosis. These data were reported by Jussi Seppala (University of Oulu, Finland). Among people with schizophrenia, there was also a statistically significant increase in incidence of haematological diseases (11% vs 5%).

Surprisingly – in the light of previous studies – a schizophrenia diagnosis in this birth cohort of more than twelve thousand individuals was not associated with increased risk of cardiovascular disease. And musculoskeletal problems were less common.

Adverse metabolic effects of treatment

Given that they were evident at the relatively young age of 46, the rates of endocrine and metabolic disorder are disturbingly high, Professor Seppala suggested. Despite national guidelines, these findings show that at-risk patients are not being adequately screened and treated. We need more co-ordinated care.

These findings should be seen in the wider context. Although the majority of patients with schizophrenia survive into old age, their average life expectancy is reduced by 10-25 years compared with the non-schizophrenia population. A wide range of studies suggests that risk of cardiovascular disease is increased 2-3 fold, and risk of type 2 diabetes by 4-5 times.

Potential causes include a lifestyle that is more likely to include smoking, excessive alcohol use, physical inactivity and poor diet. But the risk of adverse endocrine and metabolic effects caused by antipsychotic medication should not be ignored, Professor Seppala said.

Teasing apart genes and environment

Evolving data from the Western Australian cohort study, which has followed half a million children since birth, strongly support previous evidence that a maternal diagnosis of schizophrenia is a highly significant risk factor for psychotic illness in offspring.

But, according to data presented by Vera Morgan (University of Western Australia, Perth, Australia), the hazard ratio of 5.7 is reduced to 3.9 when potentially confounding environmental risk factors – which are more frequent in the offspring of mothers with schizophrenia -- are taken into account by multivariate analysis.

This suggests that inherited genetic risk, although considerable, can be reduced by targeting potentially modifiable environmental factors that are associated with it.

On initial analysis, birth complications (Hazard Ration[HR] 1.1), Aboriginal heritage (HR 2.5), lower sociodemographic status (HR 1.6 for the most disadvantaged group) and death of a parent (HR 1.7) were all significant risk factors for psychosis. The presence of documented childhood abuse produced a HR of 5.3.

Multivariate analysis for these variables has still to be completed, but the HR for abuse is so large that it will probably remain a significant independent factor, Dr Morgan told the symposium.

Can technology aid outcome in treatment-resistant schizophrenia?

Though definitions of treatment resistant schizophrenia (TRS) vary, somewhere between 10% and 30% of patients have little or no improvement in symptoms despite trial of several antipsychotics of different pharmacological classes, Dr Katja Rubinstein (Tel Aviv, Israel) told the symposium audience.

Imaging and pre-morbid characteristics suggest TRS patients may represent a distinct subgroup of people with the disease, but this question is still unresolved. It is certain, though, that current standards of care do not prevent a poor outcome for such patients. We should be improving management of TRS and patients’ quality of life.

The m-RESIST project, part-funded by the European Union and still in an early phase, aims to do this by taking advantage of smart, wearable devices to monitor patients during the all-important periods between consultations. One example is detecting sleep irregularities that depart significantly from an individual patient’s usual pattern and may signal the onset of a psychotic exacerbation.

Such continuous monitoring may not be accepted by patients of a paranoid disposition, of course; and this was pointed out from the audience. But Dr Rubinstein was confident that there would be some TRS patients who might accept the potential benefit of using smart technology to detect the early signs of clinical deterioration.