To the best of our knowledge, this was the first study to investigate the prevalence and clinical correlates of insomnia symptoms, and to explore the relationship between insomnia and inflammatory markers in patients with chronic schizophrenia in China. There were several main fingings of this study: 1) we found a high rate of insomnia symptoms in patients with chronic schizophrenia; 2) compared with patients without insomnia symptoms, patients with insomnia symptoms had older age, longer duration of illness, higher proportion of hypertension, higher levels of FBG, more psychotic and depressive symptoms; 3) some demographic and clinical variables were found to be risk factors for insomnia in these patients, including more severe depressive symptoms and older age, while taking a single SGA was a beneficial factor; 4) there was no significant correlation between insomnia symptoms and any inflammatory markers.
The prevalence of insomnia symptoms in hospitalized patients with chronic schizophrenia was 38.4%, which was close to the results of previous studies in Chinese outpatients (36.0%) and community patients (28.9%) with schizophrenia [9, 18], but lower than that in a study of 175 outpatients with schizophrenia or schizophrenic affective disorder from the USA (44%), adopting more stringent criteria for insomnia with ISI ≥ 15 [28]. This difference can be considered as a considerable regional difference in the rate and severity off insomnia between Chinese and Western populations [30]. Also, this can be explained by their different hours of work and rest, or their different perception of insomnia, such as sensitivity to insomnia.
Furthermore, the prevalence of early, middle and late insomnia symptoms found in this study were very close to the corresponding 21.1%, 23.6% and 11.9%, as well as 20.5%, 19.6% and 17.7% in the previous two studies [9, 18]. These results confirmed that difficulty falling asleep and maintaining sleep are the two most common manifestations of insomnia in schizophrenia [11]. In a Chinese epidemiologic survey [31] using insomnia criteria similar to this study, the prevalence rates of early, middle, late, and any type of insomnia symptoms in general population were 7.0%, 8.0%, 4.9% and 9.2%, respectively. Therefore, the prevalence of insomnia symptoms in inpatients with schizophrenia is higher than that in normal people. As a result, hospitalized patients with schizophrenia are prone to insomnia and require more attention, even if they receive regular medical rounds and care.
Our current study found that schizophrenia patients with insomnia symptoms had significantly older age and longer duration of illness than those without insomnia symptoms. Further correlation analysis and showed that the ISI score was positively associated with the patients’ age, which was confirmed by stepwise multiple regression. These results confirmed the findings of previous studies [9, 18]. In addition, we found that ISI-3 (Satisfaction) was positively associated with duration of illness, indicating that patients with longer duration of illness had lower satisfaction with sleep in schizophrenia patients. Taken together, these findings suggest that older age and longer duration illness may be risk factors for sleep disturbances in patients with chronic schizophrenia.
Further, we found that FBG level was significantly higher in the insomnia group than that in the non-insomnia group. Moreover, FGB level was positively correlated with ISI score and ISI-2 (Severity). Our results suggest that schizophrenia patients with higher FBG levels were more likely to suffer from insomnia than those with normal FBG levels. In a large epidemiological study, about 25% patients with type 2 diabetes were diagnosed with sleep disorders, and more than 75% reported sleep symptoms [32]. A number of observational studies have shown an association between metabolic disturbance and sleep disorders [33]. These results suggest that abnormal glucose metabolism or diabetes may have a significant impact on sleep in both schizophrenia patients and general population.
In addition, we found that the proportion of hypertension in patients with insomnia symptoms was higher than that in patients without insomnia symptoms, indicating that insomnia is associated with hypertension in schizophrenia. A previous study confirmed that patients with chronic insomnia had an increased cardiovascular risk compared with healthy controls [34]. This may be related to the dysregulation of hypothalamic-pituitary axis, increased activity of sympathetic nervous system, and elevated inflammatory level [35].
Our results showed that patients with insomnia symptoms had more severe positive and general psychopathological symptoms than those without insomnia symptoms, which was consistent with the results of several previous studies. For example, a previous study found that sleep disturbances predicted the greater auditory hallucinations, paranoia and delusions the next day in schizophrenia [36], suggesting that insomnia or poor sleep quality is associated with worse psychotic symptoms in patients with schizophrenia. Moreover, several studies have found that insomnia was associated with positive [9, 18], negative [18], anxiety [9, 18] and depressive symptoms [9, 18, 28] in patients with schizophrenia. Among the schizophrenia patients in this study, the correlation remained significant after removal of the overlapping item with insomnia in CDSS. More severe depressive symptoms were independently associated with a higher risk of insomnia and higher ISI scores, suggesting that they are risk factors for insomnia. Additionally, the multiple regression showed that taking a single SGA was associated with a lower ISI score, which may be a protective factor for insomnia in the patients with schizophrenia.
Of note, we found no significant correlation between inflammatory markers and insomnia or ISI score in patients with chronic schizophrenia. In contrast, two previous studies found higher levels of inflammatory measures (neutrophil-lymphocyte and platelet-lymphocyte ratios) [16] and higher levels of CRP and IL-6 [17] in schizophrenia patients with poor sleep quality. The first study assessed inflammation and sleep quality differently from this study. And the participants in the latter study were outpatients with schizophrenia, whose lifestyles and sleep habits may differ from those of inpatients with chronic schizophrenia. Moreover, although the relationship between schizophrenia and inflammatory abnormalities has been repeatedly confirmed [37], the levels of inflammatory cytokines are easily affected by a variety of confounding factors, such as gender, stress, course of disease and the administration of different antipsychotics [37–39]. Therefore, the relationship between sleep disturbances and inflammation in patients with schizophrenia needs to be further studied.
Several methodological limitations of this study should be noted. First, this was a cross-sectional design that did not identify the direction and causal relationship between demographic or clinical variables and insomnia or ISI score in patients with schizophrenia. Second, all participants were recruited from three hospitals in the same province, which led to in a lack of nationwide representation. Third, insomnia was defined by loose criteria rather than an objective measure of sleep, such as recording through polysomnography or actigraphy. Finally, there was no healthy control group in this study, and we were unable to make a direct comparison between schizophrenia and normal populations.