Do self-ratings of the Pittsburgh Sleep Quality Index reflect actigraphy recordings of sleep quality or variability? An exploratory study of bipolar disorders versus healthy controls.

Sleep disturbances are typical symptoms of acute episodes of bipolar disorder (BD) and differentiate euthymic BD cases from healthy controls (HC). Researchers often employ objective recordings to evaluate sleep patterns, such as actigraphy, whilst clinicians often use subjective ratings, such as the Pittsburgh Sleep Quality Index (PSQI). As evidence suggests the measures may disagree, we decided to compare subjective (PSQI) and objective (3 weeks of actigraphy) sleep profiles in BD cases and HC (n = 154). We examined whether a dimensional approach helps to illustrate different patterns of sleep disturbances and whether the concordance between subjective and objective recordings varies according to clinical status (BD versus HC). Principal component analysis (PCA) extracted two factors from the PSQI, and separate PCAs of actigraphy recordings extracted two factors for mean values of sleep parameters and one factor for intra-individual variability. Correlational and linear regression analyses of PCA-derived dimensions demonstrated that, in both BD and HC, a PSQI "Sleep duration-efficiency" factor was significantly correlated with an actigraphy "Sleep initiation-duration" factor. Furthermore, in BD cases only, the PSQI total score and a PSQI "Sleep Impairments" factor were each significantly correlated with an actigraphy "Sleep Variability" factor. Overall, we found that subjective experiences of sleep may be modulated by different components of objectively recorded sleep in BD compared with HC. Also, the use of PCA enabled us to consider the multi-dimensional nature of subjective sleep, whilst the inclusion of intra-individual sleep variability afforded a more subtle evaluation of objective sleep.

Eveningness and poor sleep quality contribute to depressive residual symptoms and behavioral inhibition in patients with bipolar disorder.

Eveningness and sleep disturbances are considered as markers of Bipolar Disorder (BD) and influence mood and emotional or behavioral states. This study investigates the associations between circadian markers and sleep quality on residual depressive symptoms and inhibition/activation dimensions during the euthymic phase. A sample of 89 euthymic adult individuals with BD was assessed for circadian preference and typology using the Composite Scale of Morningness (CSM) and the Circadian Type Inventory (CTI) and for sleep quality using the Pittsburgh Sleep Quality Index (PSQI). The Montgomery and Asberg Depression Rating Scale (MADRS) and the Multidimensional Assessment of Thymic States (MAThyS) were used to measure residual depressive symptoms and the inhibition/activation dimensions. We examined any associations between these parameters using correlations and path analyses. We identified significant associations between eveningness and poorer sleep quality that correlated to higher depressive residual symptoms and a global inhibition. The use of path analyses led us to conclude that poor sleep quality mediated the relationship between eveningness and either residual mood symptoms or behavioral inhibition (motivation, sensory perception, interpersonal interaction, and cognition). These factors should be considered in the clinical evaluation of individuals with BD, with a specific attention during the euthymic phase, in order to achieve the best functional outcome possible.

The significance of anti-neuronal antibodies for acute psychiatric disorders: a retrospective case-controlled study.

BACKGROUND: The clinical significance of anti-neuronal antibodies in patients with psychiatric disorders, but without encephalitis, remains unknown. In patients admitted to acute psychiatric inpatient care we aimed to identify clinical features distinguishing anti-neuronal antibody positive patients from matched controls. RESULTS: Patients who were serum-positive to N-methyl D-aspartate receptor (NMDAR) (n = 21), contactin-associated protein 2 (CASPR2) (n = 14) and/or glutamic acid decarboxylase 65 (GAD65) (n = 9) antibodies (cases) were age and sex matched (1:2) with serum-negative patients from the same cohort (controls). The prevalence and severity of psychiatric symptoms frequently encountered in NMDAR, CASPR2 and GAD65 antibody associated disorders were compared in cases and controls. NMDAR, CASPR2 and GAD65 antibody positive patients did not differ in their clinical presentation from matched serum negative controls. CONCLUSION: In this cohort, patients with and without NMDAR, CASPR2 and GAD65 antibodies admitted to acute psychiatric inpatient care had similar psychiatric phenotypes. This does not exclude their clinical relevance in subgroups of patients, and studies further investigating the clinical significance of anti-neuronal antibodies in patients with psychiatric symptomatology are needed.

Motor activity patterns in acute schizophrenia and other psychotic disorders can be differentiated from bipolar mania and unipolar depression.

The purpose of this study was to compare 24-h motor activity patterns between and within three groups of acutely admitted inpatients with schizophrenia and psychotic disorders (n = 28), bipolar mania (n = 18) and motor-retarded unipolar depression (n = 25) and one group of non-hospitalized healthy individuals (n = 28). Motor activity was measured by wrist actigraphy, and analytical approaches using linear and non-linear variability and irregularity measures were undertaken. In between-group comparisons, the schizophrenia group showed more irregular activity patterns than depression cases and healthy individuals. The schizophrenia and mania cases were clinically similar with respect to high prevalence of psychotic symptoms. Although they could not be separated by a formal statistical test, the schizophrenia cases showed more normal amplitudes in morning to evening mean activity and activity variability. Schizophrenia constituted an independent entity in terms of motor activation that could be distinguished from the other diagnostic groups of psychotic and non-psychotic affective disorders. Despite limitations such as small subgroups, short recordings and confounding effects of medication/hospitalization, these results suggest that detailed temporal analysis of motor activity patterns can identify similarities and differences between prevalent functional psychiatric disorders. For this purpose, irregularity measures seem particularly useful to characterize psychotic symptoms and should be explored in larger samples with longer-term recordings, while searching for underlying mechanisms of motor activity disturbances.

Actigraphy as an objective intra-individual marker of activity patterns in acute-phase bipolar disorder: a case series.

BACKGROUND: Actigraphy could be an objective alternative to clinical ratings of motor activity in bipolar disorder (BD), which is of importance now that increased activity and energy are added as cardinal symptoms of (hypo)mania in the DSM-5 and commonly used rating scales give inadequate information about motor symptoms. To date, most actigraphy studies have been conducted in groups and/or used mean activity levels as the variable of interest. The novelty of this case series is therefore to indicate the potential of actigraphy and non-parametric analysis as an objective and personalized marker of intra-individual activity patterns in different phases of BD. To our knowledge, this is the first case series that provides an objective assessment of non-linear dynamics in within-person activity patterns during acute BD episodes. RESULTS: We report on three cases of bipolar I disorder with 24-h actigraphy recordings undertaken during the first few days of two or more separate admissions for an acute illness episode, including admissions for individuals in different phases of BD, or with different levels of severity in the same phase of illness. For each recording, we calculated mean activity levels over 24 h, but especially focused on key measures of variability and complexity in activity. Intra-individual activity patterns were found to be different according to phase of illness, but showed consistency within the same phase. With increasing psychotic symptoms, there was evidence of a lower overall level and greater irregularity in activity. As such, sample entropy (a measure of irregularity) may have particular utility in characterizing mania and psychotic symptoms, while assessment of the distribution of rest versus activity over 24 h may distinguish between phases of BD within an individual. CONCLUSIONS: This case series indicates that objective, intra-individual, real-time recordings of patterns of activity may have clinical impact as a valuable adjunct to clinical observation and symptom ratings. We suggest that actigraphy combined with detailed mathematical analysis provides a biological variable that could become an important tool for developing a personalized approach to diagnostics and treatment monitoring in BD.

Variability of activity patterns across mood disorders and time of day.

BACKGROUND: Few actigraphy studies in mood disorders have simultaneously included unipolar (UP) and bipolar (BD) depression or BD mixed states as a separate subgroup from mania. This study compared objectively measured activity in UP, BD depression, mania and mixed states and examined if patterns differed according to time of day and/or diagnostic group. METHODS: Eighty -eight acutely admitted inpatients with mood disorders (52 UP; 18 mania; 12 BD depression; 6 mixed states) underwent 24 hours of actigraphy monitoring. Non-parametric analyses were used to compare median activity level over 24 h (counts per minute), two time series (64-min periods of continuous motor activity) in the morning and evening, and variability in activity across and within groups. RESULTS: There was no between-group difference in 24-h median level of activity, but significant differences emerged between BD depression compared to mania in the active morning period, and between UP and mania and mixed states in the active evening period. Within-group analyses revealed that UP cases showed several significant changes between morning and evening activity, with fewer changes in the BD groups. CONCLUSIONS: Mean activity over 24 hours has limited utility in differentiating UP and BD. In contrast, analysis of non-linear variability measures of activity at different times of day could help objectively distinguish between mood disorder subgroups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01415323 , first registration July 6, 2011.

A pilot study to determine whether combinations of objectively measured activity parameters can be used to differentiate between mixed states, mania, and bipolar depression.

BACKGROUND: Until recently, actigraphy studies in bipolar disorders focused on sleep rather than daytime activity in mania or depression, and have failed to analyse mixed episodes separately. Furthermore, even those studies that assessed activity parameters reported only mean levels rather than complexity or predictability of activity. We identified cases presenting in one of three acute phases of bipolar disorder and examined whether the application of non-linear dynamic models to the description of objectively measured activity can be used to predict case classification. METHODS: The sample comprised 34 adults who were hospitalized with an acute episode of mania (n = 16), bipolar depression (n = 12), or a mixed state (n = 6), who agreed to wear an actiwatch for a continuous period of 24 h. Mean level, variability, regularity, entropy, and predictability of activity were recorded for a defined 64-min active morning and active evening period. Discriminant function analysis was used to determine the combination of variables that best classified cases based on phase of illness. RESULTS: The model identified two discriminant functions: the first was statistically significant and correlated with intra-individual fluctuation in activity and regularity of activity (sample entropy) in the active morning period; the second correlated with several measures of activity from the evening period (e.g. Fourier analysis, autocorrelation, sample entropy). A classification table generated from both functions correctly classified 79% of all cases based on phase of illness (χ 2 = 36.21; df 4; p = 0.001). However, 42% of bipolar depression cases were misclassified as being in manic phase. CONCLUSIONS: The findings should be treated with caution as this was a small-scale pilot study and we did not control for prescribed treatments, medication adherence, etc. However, the insights gained should encourage more widespread adoption of statistical approaches to the classification of cases alongside the application of more sophisticated modelling of activity patterns. The difficulty of accurately classifying cases of bipolar depression requires further research, as it is unclear whether the lower prediction rate reflects weaknesses in a model based only on actigraphy data, or if it reflects clinical reality i.e. the possibility that there may be more than one subtype of bipolar depression.

Mood and motor activity in euthymic bipolar disorder with sleep disturbance.

BACKGROUND: The aims of this observational study of patients with euthymic bipolar disorder and sleep disturbance were to 1) compare characteristics related to mood and sleep between two groups with stable and unstable rest-activity cycles and 2) detect between-group differences in motor activity patterns. METHODS: 43 patients wore an actigraph for 6-8 days while reporting daily mood and sleep. Patients were defined as having an unstable rest-activity cycle if their diurnal active period duration presented variation above 2h from the mean during one week: 22 patients had stable and 21 unstable rest-activity cycles. Mood variability was defined as at least moderate symptoms and a change across two levels on a 7-point mood scale during one week. RESULTS: Patients with unstable rest-activity cycles were younger (37 vs. 48 years, p=0.01) and displayed more mood variability (p=0.02). Ten of 11 patients diagnosed with delayed sleep phase disorder were in the unstable group (p<0.01), and the unstable group had later and more variable get-up-times and bedtimes. In actigraphy recordings, the mean activity counts per minute did not differ between groups, but the minute-to-minute variability was elevated (p=0.04) and increased relative to the overall variability (p=0.03). LIMITATIONS: A relatively small study sample and a 1-week study period prevent exploration of long-term clinical implications of results. CONCLUSIONS: A subgroup of euthymic patients with bipolar disorder displayed unstable rest-activity cycles combined with mood variability and motor activity patterns that resemble findings in affective episodes.

Actigraphically assessed activity in unipolar depression: a comparison of inpatients with and without motor retardation.

OBJECTIVE: To compare the activity patterns of inpatients with unipolar depression, who had been divided into groups with and without motor retardation prior to actigraphy monitoring. METHOD: Twenty-four-hour actigraphy recordings from 52 consecutively, acutely admitted inpatients with unipolar depression (ICD-10) were compared to recordings from 28 healthy controls. The patients, admitted between September 2011 and April 2012, were separated into 2 groups: 25 with motor retardation and 27 without motor retardation. Twenty-eight healthy controls were also included. Twenty-four-hour recordings, 9-hour daytime sequences, and 64-minute periods of continuous motor activity in the morning and evening were analyzed for mean activity, variability, and complexity. RESULTS: Patients with motor retardation had a reduced mean activity level (P = .04) and higher intraindividual variability, as shown by increased standard deviation (SD) (P = .003) and root mean square successive difference (RMSSD) (P = .025), during 24 hours compared to the patients without motor retardation. Both patient groups demonstrated significantly lower mean activity compared to healthy controls (P < .001) as well as higher SD (P < .02) and RMSSD (P < .001) and a higher RMSSD/SD ratio (P = .04). In the active morning period, the patients without motor retardation displayed significantly increased complexity compared to motor-retarded patients (P = .006). CONCLUSIONS: The patients with and without motor retardation differ in activity patterns. Findings in depressed inpatients without motor retardation closely resemble those of inpatients with mania.

Actigraphic assessment of motor activity in acutely admitted inpatients with bipolar disorder.

INTRODUCTION: Mania is associated with increased activity, whereas psychomotor retardation is often found in bipolar depression. Actigraphy is a promising tool for monitoring phase shifts and changes following treatment in bipolar disorder. The aim of this study was to compare recordings of motor activity in mania, bipolar depression and healthy controls, using linear and nonlinear analytical methods. MATERIALS AND METHODS: Recordings from 18 acutely hospitalized inpatients with mania were compared to 12 recordings from bipolar depression inpatients and 28 healthy controls. 24-hour actigraphy recordings and 64-minute periods of continuous motor activity in the morning and evening were analyzed. Mean activity and several measures of variability and complexity were calculated. RESULTS: Patients with depression had a lower mean activity level compared to controls, but higher variability shown by increased standard deviation (SD) and root mean square successive difference (RMSSD) over 24 hours and in the active morning period. The patients with mania had lower first lag autocorrelation compared to controls, and Fourier analysis showed higher variance in the high frequency part of the spectrum corresponding to the period from 2-8 minutes. Both patient groups had a higher RMSSD/SD ratio compared to controls. In patients with mania we found an increased complexity of time series in the active morning period, compared to patients with depression. The findings in the patients with mania are similar to previous findings in patients with schizophrenia and healthy individuals treated with a glutamatergic antagonist. CONCLUSION: We have found distinctly different activity patterns in hospitalized patients with bipolar disorder in episodes of mania and depression, assessed by actigraphy and analyzed with linear and nonlinear mathematical methods, as well as clear differences between the patients and healthy comparison subjects.

Cognitive behavioral therapy for insomnia in euthymic bipolar disorder: study protocol for a randomized controlled trial.

BACKGROUND: Patients with bipolar disorder experience sleep disturbance, even in euthymic phases. Changes in sleep pattern are frequent signs of a new episode of (hypo)mania or depression. Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment for primary insomnia, but there are no published results on the effects of CBT-I in patients with bipolar disorder. In this randomized controlled trial, we wish to compare CBT-I and treatment as usual with treatment as usual alone to determine its effect in improving quality of sleep, stabilizing minor mood variations and preventing new mood episodes in euthymic patients with bipolar disorder and comorbid insomnia. METHODS: Patients with euthymic bipolar I or II disorder and insomnia, as verified by the Structured Clinical Interview for DSM Disorders (SCID-1) assessment, will be included. The patients enter a three-week run-in phase in which they complete a sleep diary and a mood diary, are monitored for seven consecutive days with an actigraph and on two of these nights with polysomnography in addition before randomization to an eight-week treatment trial. Treatment as usual consists of pharmacological and supportive psychosocial treatment. In this trial, CBT-I will consist of sleep restriction, psychoeducation about sleep, stabilization of the circadian rhythm, and challenging and correcting sleep state misperception, in three to eight sessions. DISCUSSION: This trial could document a new treatment for insomnia in bipolar disorder with possible effects on sleep and on stability of mood. In addition, more precise information can be obtained about the character of sleep disturbance in bipolar disorder. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01704352.

Prevalence of the metabolic syndrome in Danish psychiatric outpatients treated with antipsychotics.

BACKGROUND: The incidence of the metabolic syndrome, a major risk factor for diabetes and cardiovascular disease, is increasing worldwide and is suggested to be higher among psychiatric patients, especially those on antipsychotic treatment. AIMS: To assess the prevalence of the metabolic syndrome in Danish psychiatric outpatients and compare it with the general population. METHODS: In a cross-sectional, observational study in 2007-08, 170 Danish outpatients on antipsychotic drug treatment were monitored for the prevalence of the metabolic syndrome based on the International Diabetes Federation (IDF) definition and compared with a general population group of 3303 randomly selected Danes. RESULTS: Of the antipsychotic-treated patients 48.2% fulfilled the IDF criteria for the metabolic syndrome, compared with 29.6% of the general population. The antipsychotic-treated patients had higher rates of increased waist circumference, triglyceride and glucose levels, and lower high-density lipoprotein cholesterol. Compared with the general population, the odds ratio (OR) of the metabolic syndrome among antipsychotic-treated patients was 2.2. After adjustment for age and sex, the OR increased to 2.7. In the antipsychotic-treated group, statistically different rates of the metabolic syndrome for patients in monopharmacy vs. polypharmacy, and for patients in monotherapy with first-generation vs. second-generation antipsychotics, could not be found. CONCLUSION: The metabolic syndrome is highly prevalent among a Danish outpatient population treated with antipsychotics compared with the general population. Monitoring of lipid and glucose levels, blood pressure and waist circumference before start-up and during treatment with antipsychotic medication is of pivotal importance in order to prevent diabetes and cardiovascular disease in this patient population.