New Findings about Comorbid Conditions

Functional somatic syndromes comprise a group of disorders that are primarily symptom-based, multisystemic in presentation and may involve alterations in mind-brain-body interactions. They are distinct from psychiatric disorders. Yet Functional somatic and psychiatric disorders share clinical features, such as fatigue, pain, sleep disturbance and cognitive impairment and can often occur together. It’s not known whether this co-occurrence is explained by a common underlying mechanism(s) or whether there are unique biologic aspects to these comorbid conditions.

A recent paper by Kenji Kato, PhD, and colleagues published in Psychological Medicine uses the Swedish Twin Registry to examine how genetic and environmental factors influence four somatic syndromes: chronic widespread pain, chronic fatigue, irritable bowel syndrome, and recurrent headache, as well as two psychiatric disorders: major depression and generalized anxiety disorder. This study is the first to find both common and unique genetic and environmental influences underlying the mechanisms of these comorbid conditions. It’s also significant because of it’s use of a large study population of twins.

One of the most powerful ways to examine the influence of genetics and environment on human health is to study twins. Twins can be monozygotic, coming from a single fertilized egg and sharing all genes, or dizygotic, coming from two separately fertilized eggs and on average sharing half the genes. By comparing monozygotic to dizygotic twins, investigators can estimate the relative importance of genes and environment.

The study by Kato, used 31,318 subjects from the Swedish Twin Registry who responded to questions by telephone interview. Chronic widespread pain, chronic fatigue, irritable bowel syndrome and recurrent headache were assessed using previously reported criteria, algorithms and validated questionnaires. The criteria the investigators used for identifying chronic fatigue closely emulated the 1994 diagnostic criteria for CFS.

Major depression and generalized anxiety disorder were assessed using the Computerized Composite International Diagnostic Interview (CIDI), a comprehensive, standardized interview that can be used to assess mental disorders according to specific, widely accepted definitions and criteria.

Once all the study subjects were assessed for the six conditions, structural equation modeling--a statistical approach for estimating causal relationships--was used to compare the monozygotic and dizygotic twins to identify any common and distinct genetic and environmental factors. The analysis focused on women since data was scarce for two of the syndromes in men.

From this comparative analysis, the investigators were able to construct a model to explain the frequent co-occurrence of the somatic syndromes and psychiatric disorders. The model indicated that the two psychiatric disorders, grouped together and, were more influenced by genetic factors than the four somatic syndromes. These genetic factors could influence predisposition for depression and anxiety and likely reflect a biologic mechanism (for example the serotonergic system). Furthermore, even though the genetic factors were common to all six conditions, they were not as important in chronic fatigue and the other somatic syndromes as were the environmental influences.

This study provides evidence for shared genetic factors that shed plausible mechanistic light on why CFS can co-occur with pain and psychiatric disorders. Importantly, it also provides strong evidence for the importance of environment factors in influencing and distinguishing CFS from other comorbid conditions.

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