Shared and distinct abnormalities in sleep-wake patterns and their relationship with the negative symptoms of Schizophrenia Spectrum Disorder patients


Schizophrenia Spectrum Disorders (SSD), which represent a tremendous burden in terms of suffering and health care costs worldwide are currently diagnosed based on the presence of positive (i.e., hallucinations, delusions) and negative (i.e., apathy, anhedonia) symptoms. Nonetheless, disturbed sleep and activity patterns are commonly reported by SSD patients, and alterations in both sleep and rest-activity-rhythm (RAR) patterns can have clear implications for certain aspects of their physical and mental health. For example, sedentary lifestyles (i.e., less daytime activity and longer/more frequent rest periods) may contribute to an increased risk of suicide and cardiovascular disease and consequently to the shorter lifespan observed in SSD. The characterization of sleep and RAR disturbances may therefore improve prognosis and treatment outcomes in these patients.

Actigraphy can be employed to quantify disturbances in RAR and sleep parameters objectively and non-invasively. A significant increase in total sleep time and a reduction in daytime activity are some of the most consistently reported findings in SSD patients. Furthermore, SSD patients often present with irregular rest-activity patterns and fragmented sleep periods. However, an extensive characterization of sleep/RAR alterations in a large cohort of patients with SSD relative to healthy control (HC) subjects is currently lacking. Furthermore, differences in RAR parameters between residential and outpatient SSD patients that could help to disentangle disease- and environment-driven abnormalities have not been thoroughly examined. Relatedly, despite the importance of negative symptoms for the prognosis and ultimate clinical outcome in SSD patients and some evidence that certain aspects of sleep-wake patterns may relate to these symptoms, establishing the relationships between sleep-wake parameters and negative symptoms in SSD in the context of different treatment settings remains under-investigated.

In this study, we examined differences in sleep and RAR parameters differed in residential and outpatient patients with SSD relative to HC and to one another. We also assessed whether negative symptoms differed between residential and outpatient groups and whether the severity of negative symptoms was linked with sleep-wake pattern disruptions. We hypothesized that: (a) there would be shared and unique alterations in sleep and RAR parameters in residential patients and outpatients relative to HC. (b) Specific sleep and RAR parameters, including total sleep time, physical activity, and rhythm fragmentation and regularity would be more altered in residential compared to outpatient groups. (c) Negative symptoms would be worse in residential vs. outpatient individuals, and some sleep/RAR parameters that differed across SSD groups would be associated with between-group differences in negative symptom severity.

We found that residential patients and outpatients with SSD patients had longer rest periods (i.e., total sleep time and rest length) and lower activity levels (i.e., during the ten most active hours of their day, M10) compared to HC subjects. These findings confirm that individuals with SSD tend to sleep more and are overall less active than HC subjects. We also established that these alterations are present in both residential and outpatient, thus likely reflecting the pathophysiology of SSD rather than being a byproduct of environmental factors.

Residential patients had more fragmented rhythms (i.e., higher intra-daily availability, IV) along with more stability/rigidity (i.e., higher inter-daily stability, IS) and less activity (i.e., lower M10) relative to outpatients. The fact that SSD residential had higher IV, a maker of RAR fragmentation, further suggests that these findings are unlikely related to the environment, given that residential settings usually provide a more structure environment. An intriguing explanation for increased IS combined with higher IV is a more pronounced neurodegeneration occurring in inpatients relative to outpatients and control individuals. Traditionally, IS has been considered a readout of the overall greater robustness of circadian rhythmicity, and higher IS levels usually indicate a better quality of life due to the good synchronization of external timing signals. However, some studies have shown abnormally elevated IS values in clinical populations, including patients with schizophrenia. Furthermore, previous actigraphy studies in elderly HC participants have reported progressively stable, albeit more fragmented, rhythms as age increases. Higher IS in our residential patients with SSD may therefore reflect excessive rhythm regularity in the context of premature aging due to the neurodegenerative processes occurring in schizophrenia. 

Residential patients also had more severe negative symptoms than outpatients, and higher IS was associated with between SSD group differences in negative symptom severity. Negative symptoms are core features of schizophrenia that are often persistent, treatment-resistant, and lead to worse clinical outcomes and poorer quality of life in individuals with schizophrenia. IS in residential SSD patients may reflect premature aging and/or neurodegenerative processes occurring in patients with more severe forms of schizophrenia which, in turn, could contribute to the worse negative symptoms. Alternatively, individuals in the residential setting tend to have more negative symptoms, which lead to higher IS due to the inability to “get out of their routine” or do anything novel/exploratory outside of the residential environment. To further examine these different interpretations, longitudinal studies are warranted.

In sum, in this study we compared for the first time both sleep and RAR parameters in a large cohort of inpatient and outpatient SSD with each other and with control participants and investigated the links between sleep, RAR parameters and the negative symptoms of these patients. Our findings demonstrated that residential and outpatient SSD had both shared and unique abnormalities in Sleep and RAR measures vs. HC subjects and relative to one another, which also contributed to the patients’ negative symptom severity. Building on these findings, future work will help establish whether improving some of these measures may ameliorate the quality of life and the clinical symptoms of SSD patients.


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