Sleep in psychiatric disorders

Currently, we search for sleep traits in patients with various types of psychiatric disorders: schizophrenia, anxiety and mood disorders, and chronic fatigue. We want to assay the influence of sleep on the disease trajectories and define sleep microstructure characteristics by using sleep laboratory and neuroimaging studies. Our study is based on a hypothesis that sleep and circadian traits can be used for dissecting patients with psychiatric disorders into etiologically more uniform disease subclasses. Further, we hypothesize that these subclasses differ in their prognosis and response to treatment.

This study was stimulated by our recent finding of robust, sleep-based clusters among patients with psychosis in a large SUPER study in Finland as a part of the international Stanley Global Neuropsychiatric Genomic Initiative. Of note, insomnia symptoms were highly correlated with quality of life, an observation which led us also to conduct a clinical trial to treat insomnia symptoms in schizophrenia.

A longitudinal cohort study evidencing for the causality between poor sleep quality and subsequent depressed mood (Paunio 2009) and depression (Paunio 2014) has constructed a baseline for Sleep and Health.
Later, we showed deviating DNAme pattern among adolescents with depression and comorbid insomnia (Ämmälä 2019).  

We have explored genetic influences underlying schizophrenia and bipolar disorder in a national and international collaboration for more than two decades (see eg, Trubetskoy 2022, Singh 2022Sinha 2019, BPD-PGC and SZ-PRC 2019, Steinberg 2017, Peltola 2016, Marshall 2016, SWG-PGC 2014Stoll 2013). In an epidemiological sleep study of a cohort of ~10 000 individuals with major psychiatric illness from the large SUPER study in Finland as a part of the international Stanley Global Neuropsychiatric Genomic Initiative, we identified three sleep-based clusters among psychosis patients and discovered that symptoms of disturbed sleep associate robustly to subjective health and wellbeing (Cederlöf, Schizophrenia Bulletin Open, 2022 and 2023).  

Current activity:

1) Analysis of the PSG data (n=40) and the effects of substance use, medication and genetic factors of theSUPER study is underway.

2) There is an RCT ongoing in patients with chronic schizophrenia and symptoms of insomnia, in which we are testing for the effect of the evidence-based treatment for insomnia (CBT-I) we developed for HUCH Mental.hub (registered, NCT04144231).

3) To evaluate the role of sleep and circadian rhythms in the disease course in early psychosis or anxiety disorder, we are monitoring sleep, circadian rhythms, cognition and emotion regulation in cases with early psychosis and anxiety disorder and controls in a longitudinal study. High-density wake and sleep EEG (hd-EEG) monitoring is being used to characterise oscillations related to cognitive performance. Responses to emotions evoked by different video clips are being monitored in a sleep laboratory and by fMRI. In addition, blood samples (plasma and blood cells) are being collected via the Helsinki Biobank for the analysis of genetic influences and the search for biomarkers. (LINK). 

In two parallel population-based birth cohorts, Child-Sleep and FinnBrain, we have explored the development of sleep and emotional regulation, as well as the underlying genetic mechanisms. Our findings emphasize the importance of sleep, and the interplay of sleep insufficiency with genetic risk factors, in the early development. Currently, we aim to identify EEG- based biomarkers of early life indicators for vulnerability to psychiatric diseases.

We explore the development of sleep and emotion regulation and the underlying genetic mechanisms in two parallel population-based birth cohorts from Finland: Child Sleep (Paavonen 2017) and FinnBrain (Karlsson 2017) (e.g. Acosta 2020Kiviruusu 2020Mäkelä 2020, Pietikäinen 2020, Sulkava 2020, Lempainen 2021, Mäkelä 2021, Pietikäinen 2021, Kajanoja 2022, Liuhanen 2023). We identified the link between genetic liability to a diurnal preference for eveningness and longer sleep-onset during the first two years of life (Morales-Munoz 2021) and the interaction of short sleep duration and genetic risk for ADHD at 5 yrs (Morales-Munoz, 2023). Our findings emphasize the importance of sleep in the development of mental functions, and the interplay of sleep insufficiency with the genetic risk for psychiatric disorders during early development.  

Current activity

We are in the process of identifying EEG-based biomarkers of early life as indicators for vulnerability to psychiatric diseases (collaboration: Child-Sleep and FinnBrain study groups, prof. Sampsa Vanhatalo). Both birth cohorts are followed longitudinally, and our focus is to clarify the role of sleep traits as potential endophenotypes for psychiatric diseases.  

In a search for finding biomarkers for sleep insufficiency, we identified a distinctive DNA methylation (DNAme) pattern comprising widespread loss of methylation in peripheral blood cells among those with insufficient sleep. In a longitudinal study of shift workers, we found an analogical pattern of hypomethylation linked to sleep insufficiency and disturbed circadian rhythm. 
Currently, we examine data from a sleep laboratory study to define the accumulation of DNAm changes during extended sleep loss and its effect on the diurnal rhythms of DNAm. Finding biomarkers for sleep loss would have the potential for a prognostic measure to identify individuals at-risk for long-term health hazards due to insufficient sleep. 

Find out more about our research on sleep-related biomarkers and for genetic influences for sleep and circadian rhythms: 

We identified by genome-wide association study (GWAS) a variation at vicinity for melatonin receptor 1A as a genetic vulnerability factor for exhaustion in shift work (Sulkava 2017) and, additionally, a vulnerability factor for late-onset Alzheimer’s disease (Sulkava 2018). We also identified a distinctive DNA methylation (DNAme) pattern comprising widespread loss of methylation in peripheral blood cells among those with insufficient sleep (Lahtinen 2019).  A pattern of hypomethylation was also linked to sleep insufficiency and disturbed circadian rhythm in a longitudinal study of shift workers, the data evidencing for the dynamic nature of these changes (Lahtinen 2021). In a more recent study, we investigated genetic influences for circadian preference among the general population (Merikanto   2021 and 2022). 

Current activity

1) We are currently exploring the dynamics of DNAm during a 24-hr circadian cycle, and changes in relation to accumulating sleep deprivation, in an experimental sleep laboratory study (collaboration: University of Surrey, Prof. Debra Skene).

2) In another sleep laboratory study of healthy individuals (collaboration: Washington State University, Prof. Hans van Dongen), we asked if high genetic risk for a major psychiatric disorder makes an individual vulnerable to impaired psychomotor vigilance or depressed mood after acute sleep deprivation.

3) Our hypothesis on the importance of sleep for mental health is tested by an on-going study on the general population (N~6000), in which we are searching for interaction of insufficient sleep and genetic risk for schizophrenia in an individual’s ability to work (Collaboration: Prof. Markus Perola, THL, and  Aaro Hazak, Tallinn University of Technology). 

See also to our research on sleep, stress and regulation of emotions: 

We found new genetic variants by GWAS as well as confirmed the role of previously identified MAO variation in extreme violent behavior (Tiihonen 2015) as well as antisocial personality (Rautiainen 2016, Tielbeek 2017). In an experimental study, we showed enhanced memory consolidation through automating stimulation during NREM sleep (Leminen 2016).  We identified psychological factors contributing to nonspecific somatic symptoms (Selinheimo 2019 and 2022) and performed randomized controlled trials for these stress-related symptoms (Selinheimo 2019, 2020 and 2023) as well as for stress among university students (Repo 2022). Shorter telomere length in adulthood was linked to adversity in childhood (Ämmälä 2021), but stress and/or self-reported insufficient sleep during pregnancy did not result in shorter telomere length among the newborn (Ämmälä 2020). Finally, we found association between psychological distress and dementia  (Sulkava 2022).  

Current activity

1) We are testing for the effect of a web-based rehabilitation program in an RCT on patients with persistent stress-related physical symptoms (registered, NCT04532827).

2) We are currently searching for the interplay of sleep, stress and emotions in a combined PSG and fMRI study in which emotionally loaded memories are induced by video clips and the effect of sleep on their consolidation and outcomes are followed by repeated fMRI measurements and tests (collaboration: University of Aalto, Prof. Iiro Jääskeläinen and Prof. Kimmo Kaski).  

In order to facilitate clinical sleep research, we have taken several initiatives in collaboration with UH-HUS-Aalto university. We initiated SleepDataBank at HUS which combines PSG and other sleep-related data collected at HUS for the past 10 years. The ultimate goal is to network with international databanks; however, this requires activity at multiple stakeholder levels. We have also developed a Mobile App “AidoQ” for the collection of activity data and an online survey for researchers. During the past years, we have been also active in international cooperation for sleep, for example, as Tiina Paunio a leader of the European Examination in Somnology (ESRS Sleep Medicine Examination ; Penzel, 2021; Grote, 2022), clinical Vice president for ESRS (2016-2022) or chair of the ESRS Education Committee (2014-). She is also an associate editor of the Journal of Sleep Research (IF 5.3) and Editor-in-Chief of the European Textbook for Sleep Medicine, edition 2, Wiley 2021.