4.1 Study I: Sleep disturbances in schizophrenia spectrum and bipolar disorders – a transdiagnostic perspective
In a sample of 1057 clinical participants (617 with schizophrenia spectrum disorders and 440 with bipolar disorders) and 173 healthy controls we investigated the type and frequency of three different sleep disturbances in and across severe mental disorders compared to healthy controls. We also investigated the frequency of these sleep disturbances across treatment history, as well as the relationship between any sleep disturbance and clinical symptoms and functioning while adjusting for possible confounding factors.
We found a high percentage of any type of sleep disturbance across all groups: 78% of participants in the schizophrenia group, 69% of participants in the bipolar disorder group and 39% of healthy controls. Any type of sleep disturbance was significantly higher in schizophrenia spectrum compared to bipolar disorder. Insomnia was the most frequent sleep disturbance across all groups, reported in
½ of both schizophrenia and bipolar disorder, and in ⅓ of the healthy controls. Hypersomnia presented the largest difference in frequency between clinical groups (28%) and healthy controls (3%). Delayed sleep phase was reported in 11% of the schizophrenia group, in 4% of the bipolar group, but in none of the healthy controls.
When analyzing factors that might influence sleep disturbances, we found that younger age was associated with any sleep disturbance, hypersomnia and delayed sleep phase. Recent substance use was associated with lower frequency of any sleep disturbance, hypersomnia, and delayed sleep phase, whilst substance abuse/dependency was associated with a higher frequency of any sleep disturbance. Recent use of alcohol and a history of alcohol dependency was only associated a higher
46
insomnia frequency. Use of medication with sedative effects was associated with higher frequency of any sleep disturbance and hypersomnia. Gender and BMI were not associated with any of the sleep disturbances.
The only sleep disturbance related to differences in treatment history was hypersomnia, with a significant interaction effect between treatment history and diagnostic group related to risk of hypersomnia, also significantly influenced by medication with sedative effects. Higher frequency of hypersomnia was found in previously treated schizophrenia and in first treatment bipolar disorder.
Participants with any sleep disturbance had overall more severe symptoms and poorer functioning than participants without any sleep disturbance. Follow-up analyses further showed that participants with any sleep disturbance had significantly more negative and depressive/anxiety symptoms, as well as poorer functioning than participants without any sleep disturbance, also after adjusting for age, diagnostic group, history of drug dependency and medication with sedative effects.
4.2 Study II: Do sleep disturbances contribute to cognitive impairments in schizophrenia spectrum and bipolar disorders?
In this study we had a sample of 797 clinical participants (457 with schizophrenia spectrum disorders, and 340 with bipolar disorders) and 182 healthy controls. We explored the relationship between sleep disturbances and cognitive impairments both in and across severe mental disorders, adjusting for the influence of potential confounders. We also investigated whether the relationship to
cognitive impairments varied between the different sleep disturbances. Lastly, we explored if the relationship between sleep disturbances and cognition differed between severe mental disorders and healthy controls.
The results showed that clinical participants with any sleep disturbance had overall poorer cognitive performance compared to those without any sleep disturbance. Further analyses of the eight separate cognitive domains revealed that clinical participants with any sleep disturbance performed
47
significantly poorer on processing speed and inhibition compared to those without any sleep disturbance. These analyses withstood adjustments for covariates including age, diagnostic group, positive and negative symptoms and medication with sedative effects.
Results from the analyses of potential differences in the relationship between any sleep disturbance and cognition between schizophrenia and bipolar disorder showed no significant overall interaction effect between any sleep disturbance and diagnostic group. Thus, the association between sleep disturbance and cognition was found to be similar across schizophrenia and bipolar disorder.
Analyses of the different sleep disturbances and cognition revealed main effects of both insomnia and hypersomnia (compared to those without) on both processing speed and inhibition, but no main effect of delayed sleep phase.
Separate analyses of the relationship between any sleep disturbance and cognition were conducted in healthy controls. These analyses revealed no significant overall or specific domain-related
difference between those with and without any sleep disturbance.
4.3 Study III: Sleep disturbance mediates the link between childhood trauma and clinical outcome in severe mental disorders
In this study the sample consisted of 766 participants with severe mental disorders (418 with
schizophrenia spectrum and 348 with bipolar disorders). We explored the relationship between sleep disturbances and childhood trauma and investigated whether sleep disturbance mediates the
relationship between childhood trauma and severity of clinical symptoms and poorer functioning, also examining the influence of potential confounding factors.
Having a history of childhood trauma was found in half of the study sample. There was no significant difference in frequency of any sleep disturbance between those with or without childhood trauma experiences. However, a significantly higher frequency of insomnia was reported in those with childhood trauma experiences compared to those without. Around one fourth (26%) of the sample reported the experience of both childhood trauma and insomnia. For hypersomnia, the findings were
48
in the opposite direction; those with childhood trauma experiences reported significantly less hypersomnia compared to those without childhood trauma experiences. There were no differences in frequency of delayed sleep phase in participants with and without childhood trauma experiences.
Follow-up analyses conducted to investigate possible differences between schizophrenia and bipolar disorder, showed that in both diagnostic groups only insomnia was significantly more frequent in those with childhood trauma experiences compared to those without.
Results for the analyses of the different childhood trauma subtypes and the different sleep disturbances showed that childhood trauma total, physical abuse, emotional abuse and emotional neglect were significantly higher in participants with insomnia compared to those without, but significantly lower in those with hypersomnia compared to those without. There were no significant differences in the level of sexual abuse and physical neglect between participants with or without either insomnia or hypersomnia. Analyses of participants with and without delayed sleep phase revealed no differences in the level of childhood trauma total or any of the childhood trauma subtypes. Whilst the magnitude of childhood trauma total, physical abuse, emotional abuse and emotional neglect were significantly higher in participants with insomnia compared to those without in schizophrenia, the magnitude of emotional abuse was the only childhood trauma subtype found to be significantly higher in participants with insomnia compared to those without in bipolar disorder.
As insomnia appears to be frequent in participants with childhood trauma experiences and is
associated with three childhood trauma subtypes, insomnia was selected as the possible mediator in the mediation model.
In terms of clinical outcome, positive, depressive/anxiety symptoms and functioning were significantly associated with both childhood trauma total and insomnia total. Three separate
mediation analyses were therefore conducted to investigate if insomnia total mediated the effect of childhood trauma total on positive and depressive/anxiety symptoms and functioning, respectively.
Statistically significant indirect effect of childhood trauma total via insomnia total were found for all
49
three clinical outcome measures. These findings withstood after adjustments for covariates,
including age, recent intake of drugs and history of drug dependency. Calculations of the proportion of the total effect mediated revealed that insomnia mediated 25% of the effect of childhood trauma on positive symptoms, 26% of the effect on depressive/anxiety symptoms, and 12% of the effect on functioning.