Are exposure to cytomegalovirus and genetic variation on chromosome 6p joint risk factors for schizophrenia?

BACKGROUND: Published data support genetic variants, as well as certain infectious agents, as potential risk factors for schizophrenia. Less is known about interactions between the risk factors. AIM: To evaluate exposure to infectious agents and host genetic variation as joint risk factors. METHODS: We investigated four infectious agents: cytomegalovirus (CMV), herpes simplex viruses 1 and 2 (HSV1, HSV2), and Toxoplasma gondii (TOX). We initially compared exposure using specific serum antibodies, among simplex and multiplex nuclear families (one or more than one affected offspring, respectively). If interactions between infectious agents and host genetic variation are important risk factors for schizophrenia, we reasoned that they would be more prominent among multiplex versus simplex families. We also evaluated the role of variation at chromosome 6p21-p23 in conjunction with exposure. We used 22 short tandem repeat polymorphisms (STRPs) dispersed across this region. RESULTS: Though exposure to all four agents was increased among multiplex families versus simplex families, the difference was consistently significant only for CMV (odds of exposure to CMV in multiplex families: 2.47, 95% CI: 1.48-5.33). Transmission disequilibrium tests and case-control comparisons using STRPs revealed significant linkage/association with D6S2672 among CMV+ schizophrenia patients. CONCLUSIONS: Polymorphisms near D6S2672 could confer risk for schizophrenia in conjunction with CMV exposure.

Circadian phase variation in bipolar I disorder.

Abnormalities in circadian rhythms are prominent features of bipolar I disorder (BD1). To investigate circadian variation in BD1, we evaluated morningness-eveningness (M/E), a stable trait reflecting circadian phase, using the composite scale (CS) among BD1 patients (DSM IV criteria; n = 75), unscreened controls (n = 349), and patients with schizophrenia (SZ) or schizoaffective disorder (SZA) (n = 81). Our analyses showed that CS scores correlated significantly with age but did not differ by gender among the controls. BD1 patients differed significantly from controls and from SZ/SZA patients when age was considered. CS scores were distributed bi-modally among BD1 cases. There are several possible reasons for the observed heterogeneity. Younger BD1 patients, and those with rapid mood swings, were significantly more likely to have lower CS scores (i.e., to score in the 'evening' range and to have later circadian phase). CS scores were also positively correlated with the age at onset and the duration of the most severe depressive episodes. These relationships were not observed among the SZ/SZA groups. Thus, distinct patterns of M/E were noted among BD1 patients and among BD1 subgroups. The impact of medication, mood state, and chronicity on CS scores needs to be considered.