Insomnia disorder subtypes derived from life history and traits of affect and personality

Abstract

Background Insomnia Disorder (ID) is the second-most prevalent mental disorder and a primary risk factor for depression. Inconsistent clinical and biomarker findings suggest heterogeneity and unrecognized subtypes. Previous top-down proposed subtypes had insufficient validity. The present large-scale study aimed to reveal robust subtypes using data-driven analyses on a high-dimensional set of biologically based traits. Methods Netherlands Sleep Registry participants (N=4,322; 2,224 with probable ID) completed up to 34 trait questionnaires. ID subtypes were identified using latent class analyses. Validity was evaluated in an independent sample and by assessing within-subject stability over years. Clinical relevance was extensively assessed in all subtypes for the development of sleep complaints, comorbidities including depression and response to benzodiazepines, and in two subtypes for an EEG biomarker and effectiveness of cognitive behavioral therapy. To facilitate implementation, a concise subtype questionnaire was constructed and validated in an independent sample. Outcomes Five novel ID subtypes were identified: one labelled as highly distressed, two as moderately distressed with either intact or weak responses to pleasurable emotions, and two as low distressed with either high or low reactivity to environment and life time events. A participant could be classified with high probability to only one subtype, and also in an independent replication sample five subtypes were again optimal (posterior probabilities 0•91-1•00). Participants reassessed 4•8±1•6 years later (N=215) maintained their subtype with high probability (0•87); indicating high stability. Clinical relevance showed from subtype differences in developmental etiology, response to treatment, an EEG biomarker, and up to five-fold differing risk of depression. Interpretation High-dimensional data-driven subtyping of people with insomnia solved an unmet need of heterogeneity reduction. Subtyping facilitates progress in finding mechanisms, developing personalized treatment, and selecting cases with the highest risk of depression for inclusion in preventive trials. Funding European Research Council (ERC-ADG-2014-671084-INSOMNIA); Netherlands Organization for Scientific Research (VICI-453-07-001). 4322 Sleep Registry database search for ISI and one additional questionnaire completed 2224 probable ID; Latent Class Analysis 2098 excluded ISI < 10 control reference values 1046 probable ID; subtype profiles and interpretation 1178 excluded for interpretation completed < 10 questionnaires 215 probable ID; Latent Transition Analysis 831 lost to follow-up 614 Sleep Registry database search for completed Insomnia Type Questionnaire and ISI 251 independent non-overlapping probable ID; Latent Class Analysis 363 excluded were included in original probable ID sample to develop model 244 received DSM-5 face-to-face diagnosis to validate ISI cutoff

Internet-guided cognitive, behavioral and chronobiological interventions in depression-prone insomnia subtypes: protocol of a randomized controlled prevention trial

“…The RCT aims to include 120 people with ID of the subtypes with increased risk of developing depression. Inclusion criteria are: 1) meeting the criteria of ID according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DMS-5) [35], and the International Classification of Sleep Disorders, 3rd edition (ICSD-3) [36]; 2) an Insomnia Severity Index score (ISI) ≥ 10 [37]; 3) classification as insomnia type 1, 2, or 3 according to the Insomnia Type Questionnaire [8]; and 4) age between 18 and 70 years. Exclusion criteria are: a) current major depressive disorder according to self-report, a clinical diagnosis, or the Composite International Diagnostic Interview Short Form (CIDI-SF) [38]; b) current treatment with antidepressant medication; c) current CBT-I treatment; d) a diagnosis of or probable severe obstructive sleep apnea syndrome (Apnea Hypopnea Index ≥15 [39], or high risk according to the Berlin questionnaire [40]), moderate to severe restless legs syndrome (International Restless Legs Scale > 15 [41]), or severe periodic limb movement disorder (Periodic Limb Movement Index ≥ 25); e) a self-reported diagnosis of a severe neurological or psychiatric disorder; f) selfreported severe physical or mental impairment due to stroke, or traumatic head injury; g) night work or rotating shift-work; h) a known eye condition incompatible with light exposure; i) a history of light-induced migraine or epilepsy, or severe side effects to bright light in the past; or j) MRI contraindications such as non-MR compatible metal implants, claustrophobia, or pregnancy.…”

“…This trial is embedded in a larger study, where we aim to explore the multivariate predictors of the development of depression in people with ID. Apart from the 120 participants with ID with a subtype prone to develop a depression, we include 30 people with ID of one of the two subtypes that is less prone to develop a depression [8], and 30 age and sex matched controls. Ancillary assessments at baseline (T0) include 9 days of experience sampling and ambulatory recordings (actigraphy, light exposure, heart rate), and one night of High-Density (256 channel) Electroencephalography (HD-EEG) sleep recordings.…”

“…Insomnia plays an important role in developing and maintaining depressive symptoms [3] and may be the best modifiable risk factor of depression [4][5][6][7]. It has recently been revealed that insomnia comes in five different stable subtypes, of which three have an increased risk of lifetime depression [8]. The current randomized controlled trial (RCT) therefore evaluates the effects of internet-guided Cognitive Behavioral Therapy for Insomnia (CBT-I), Chronobiological Therapy (CT), and their combination on insomnia and the development of depressive symptoms in people with the type of Insomnia Disorder (ID) that are most prone to develop depression.…”

“…It has recently been discovered that ID is not a uniform disorder. Rather, people with ID represent a heterogeneous mix of at least five different subtypes, of which three are more prone to developing depression [8]. It is unknown which environmental, psychological, or biological markers of vulnerability underlie the subtypes of ID that are prone to develop depression.…”

“…The recent finding that insomnia comes in different subtypes [8] could propel the development of individualized treatment: what is effective for one subtype may not be effective for another subtype. For the three insomnia subtypes that are most prone to develop depression, it is highly relevant to evaluate whether CBT-I or CT interventions aimed at sleep improvement could also prevent worsening of depressive symptoms or the onset of a major depressive episode.…”