Early warning signals observed in motor activity preceding mood state change in bipolar disorder.

INTRODUCTION: Alterations in motor activity are well-established symptoms of bipolar disorder, and time series of motor activity can be considered complex dynamical systems. In such systems, early warning signals (EWS) occur in a critical transition period preceding a sudden shift (tipping point) in the system. EWS are statistical observations occurring due to a system's declining ability to maintain homeostasis when approaching a tipping point. The aim was to identify critical transition periods preceding bipolar mood state changes. METHODS: Participants with a validated bipolar diagnosis were included to a one-year follow-up study, with repeated assessments of the participants' mood. Motor activity was recorded continuously by a wrist-worn actigraph. Participants assessed to have relapsed during follow-up were analyzed. Recognized EWS features were extracted from the motor activity data and analyzed by an unsupervised change point detection algorithm, capable of processing multi-dimensional data and developed to identify when the statistical property of a time series changes. RESULTS: Of 49 participants, four depressive and four hypomanic/manic relapses among six individuals occurred, recording actigraphy for 23.8 ± 0.2 h/day, for 39.8 ± 4.6 days. The algorithm detected change points in the time series and identified critical transition periods spanning 13.5 ± 7.2 days. For depressions 11.4 ± 1.8, and hypomania/mania 15.6 ± 10.2 days. CONCLUSION: The change point detection algorithm seems capable of recognizing impending mood episodes in continuous flowing data streams. Hence, we present an innovative method for forecasting approaching relapses to improve the clinical management of bipolar disorder.

Antidepressive Effectiveness of Amisulpride, Aripiprazole, and Olanzapine in Patients With Schizophrenia Spectrum Disorders: A Secondary Outcome Analysis of a Pragmatic, Randomized Trial (BeSt InTro).

BACKGROUND: Depressive symptoms are frequent in schizophrenia and associated with a poorer outcome. Currently, the optimal treatment for depressive symptoms in schizophrenia remains undetermined. Amisulpride, aripiprazole, and olanzapine all have antidepressive pharmacodynamic properties, ranging from serotonergic affinities to limbic dopaminergic selectivity. Consequently, in a 12-month pragmatic, randomized clinical trial, we aimed to investigate differences in antidepressive effectiveness among amisulpride, aripiprazole, and olanzapine as a secondary outcome, measured by change in the Calgary Depression Scale for Schizophrenia sum score in patients within the schizophrenia spectrum. METHODS: Psychotic patients within the schizophrenia spectrum were included, and effectiveness was analyzed with latent growth curve modeling. RESULTS: Of the 144 patients, 51 (35%) were women, the mean age was 31.7 (SD 12.7), and 39% were antipsychotic naive. At inclusion, 68 (47%) participants had a Calgary Depression Scale for Schizophrenia sum score >6, indicating severe depressive symptoms. Across the 12-month follow-up, there was a depressive symptom reduction in all medication groups, but no statistically significant differences between the study drugs. Separate analyses of the subcohort with elevated depressive symptoms at inclusion also failed to find differences in depressive symptom reduction between study drugs. The reduction in depressive symptoms mainly occurred within 6 weeks after randomization. CONCLUSIONS: There was a reduction in depressive symptoms under treatment with amisulpride, aripiprazole, and olanzapine in acutely psychotic patients with schizophrenia spectrum disorder, but no differences between the drugs.

Objective assessment of motor activity in a clinical sample of adults with attention-deficit/hyperactivity disorder and/or cyclothymic temperament.

BACKGROUND: Most research on patterns of motor activity has been conducted on adults with mood disorders, but few studies have investigated comorbid attention-deficit/hyperactivity disorder (ADHD) or temperamental factors that may influence the clinical course and symptoms. Cyclothymic temperament (CT) is particularly associated with functional impairment. Clinical features define both disorders, but objective, biological markers for these disorders could give important insights with regard to pathophysiology and classification. METHODS: Seventy-six patients, requiring diagnostic evaluation of ADHD, mood or anxiety disorders were recruited. A comprehensive diagnostic evaluation, including the CT scale of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego - Auto-questionnaire (TEMPS-A), neuropsychological tests and actigraphy, was performed. ADHD was diagnosed according to the DSM-IV criteria. There was a range of different conditions in this clinical sample, but here we report on the presence of CT and ADHD in relation to motor activity. Twenty-nine healthy controls were recruited. We analyzed motor activity time series using linear and nonlinear mathematical methods, with a special focus on active and inactive periods in the actigraphic recordings. RESULTS: Forty patients fulfilled the criteria for ADHD, with the remainder receiving other psychiatric diagnoses (clinical controls). Forty-two patients fulfilled the criteria for CT. Twenty-two patients fulfilled the criteria for ADHD and CT, 18 patients met the criteria for ADHD without CT, and 15 patients had neither. The ratio duration of active/inactive periods was significantly lower in patients with CT than in patients without CT, in both the total sample, and in the ADHD subsample. CONCLUSIONS: CT is associated with objectively assessed changes in motor activity, implying that the systems regulating motor behavior in these patients are different from both healthy controls and clinical controls without CT. Findings suggest that actigraphy may supplement clinical assessments of CT and ADHD, and may provide an objective marker for CT.

Blue-blocking glasses as additive treatment for mania: Effects on actigraphy-derived sleep parameters.

Improvement of sleep is a central treatment goal for patients in a manic state. Blue-blocking (BB) glasses as adjunctive treatment hasten overall recovery from mania. This method is an evolvement from dark therapy and builds on the discovery of the blue-light-sensitive retinal ganglion cell that signals daytime to the brain. We report effects of adjunctive BB glasses on actigraphy-derived sleep parameters for manic inpatients as compared to placebo. Hospitalized patients with bipolar disorder in a manic state aged 18-70 years were recruited from five clinics in Norway from February 2012 to February 2015. The participants were randomly allocated to wearing BB glasses or placebo (clear glasses) as an adjunctive treatment from 18:00 to 08:00 hours for seven consecutive nights. Sleep and wake were monitored by actigraphy. From 32 eligible patients, 10 patients in each group qualified for the group analyses. The BB group's mean sleep efficiency was significantly higher at night 5 as compared to the placebo group (92.6% vs. 83.1%, p = .027). The 95% confidence interval (CI) was 89.4%-95.8% in the BB group and 75.9%-90.3% in the placebo group. There were fewer nights of interrupted sleep in the BB group: 29.6% versus 43.8% in the placebo group. The BB group received less-intensive sleep-promoting pharmacological treatment and showed significantly higher sleep efficiency and more consolidated sleep as compared to the placebo group. Our findings suggest sleep-promoting effects through deactivating mechanisms. Adjunctive BB glasses seem to be useful for improving sleep for manic patients in the hospital setting.

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.

Do medical students and young physicians assess reliably their self-efficacy regarding communication skills? A prospective study from end of medical school until end of internship.

BACKGROUND: This prospective study from end of medical school through internship investigates the course and possible change of self- reported self-efficacy in communication skills compared with observers' ratings of such skills in consultations with simulated patients. METHODS: Sixty-two medical students (43 females) from four Norwegian universities performed a videotaped consultation with a simulated patient immediately before medical school graduation (T1) and after internship (internal medicine, surgery and family medicine, half a year each - T2). Before each consultation, the participants assessed their general self-efficacy in communication skills. Trained observers scored the videos and applied a well-validated instrument to rate the communication behaviour. Results from the two assessment methods were correlated at both time points and possible differences from T1 to T2 were explored. RESULTS: A close to zero correlation between self-efficacy and observed communication skills were found at T1. At T2, participants' self-efficacy scores were inversely correlated with levels of observed skills, demonstrating a lack of concordance between young physicians' own assessment of self-efficacy and observers' assessment. When dividing the sample in three groups based on the observers' scores (low <1/3-, medium 1/3 to 2/3-, high competence >2/3), the group of male physicians showed higher levels of self-efficacy than females in all the three performance groups at T1. At T2, those having a high performance score yielded a low self-efficacy, regardless of gender. CONCLUSIONS: The lack of positive correlations between self-efficacy assessment and expert ratings points to limitations in the applicability of self-assessment measures of communication skills. Due to gender differences, groups of female and male physicians should be investigated separately. Those obtaining high-performance ratings from observers, through the period of internship, may become more conscious of how demanding clinical communication with patients may be. This insight may represent a potential for growth, but could in some physicians represent too much of a self-critical attitude. Active supervision of young physicians throughout internship is important in order to help physicians to be more aware of their strengths and weaknesses, in order to gain increased mastery in the art of doctoring.

Patterns of motor activity in spontaneously hypertensive rats compared to Wistar Kyoto rats.

BACKGROUND: Increased motor activity is a defining characteristic of patients with ADHD, and spontaneously hypertensive rats have been suggested to be an animal model of this disorder. In the present study, we wanted to use linear and non-linear methods to explore differences in motor activity patterns in SHR/NCrl rats compared to Wistar Kyoto (WKY/NHsd) rats. METHODS: A total number of 42 rats (23 SHR/NCrl and 19 WKY/NHsd, male and female) were tested. At PND 51, the animals' movements were video-recorded during an operant test procedure that lasted 90 min. Total activity level and velocity (mean and maximum), standard deviation (SD) and root mean square successive differences (RMSSD) were calculated. In addition, we used Fourier analysis, autocorrelations and two measures of complexity to characterize the time series; sample entropy and symbolic dynamics. RESULTS: The SHR/NCrl rats showed increased total activity levels in addition to increased mean and maximum velocity of movements. The variability measures, SD and RMSSD, were markedly lower in the SHR/NCrl compared to the WKY/NHsd rats. At the same time, the SHR/NCrl rats displayed a higher complexity of the time series, particularly with regard to the total activity level as evidenced by analyses of sample entropy and symbolic dynamics. Autocorrelation analyses also showed differences between the two strains. In the Fourier analysis, the SHR/NCrl rats had an increased variance in the high frequency part of the spectrum, corresponding to the time period of 9-17 s. CONCLUSION: The findings show that in addition to increased total activity and velocity of movement, the organization of behavior is different in SHR/NCrl relative to WKY/NHsd controls. Compared to controls, behavioral variability is reduced in SHR/NCrl at an aggregate level, and, concomitantly, more complex and unpredictable from moment-to-moment. These finding emphasize the importance of the measures and methods used when characterizing behavioral variability. If valid for ADHD, the results indicate that decreased behavioral variability can co-exist with increased behavioral complexity, thus representing a challenge to current theories of variability in ADHD.

Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on: data derived from a randomized clinical trial.

BACKGROUND: Patients with severe mental illness often suffer from disruptions in circadian rest-activity cycles, which might partly be attributed to ongoing psychopharmacological medication. Benzodiazepines are frequently prescribed for prolonged periods despite recommendations of only short-term usage. Melatonin, a naturally occurring nocturnal hormone, has the potential to stabilize disrupted circadian rhythmicity. Our aim was to investigate how prolonged-release melatonin affects rest-activity patterns in medicated patients with severe mental illness and if benzodiazepine dose reduction is associated with changes in circadian rhythm parameters. METHOD: Data were derived from a randomized, double-blinded clinical trial with 24 weeks follow-up. Participants were randomized to add-on treatment with prolonged-release melatonin (2 mg) or matching placebo, and usual benzodiazepine dosage was gradually tapered. Here we report the results of 72 h of actigraphic assessment of activity-rest cycles performed pre and post tapering. Changes in rest-activity rhythm parameters between the melatonin and placebo group were analyzed using the univariate general linear model. Change in activity counts per 6 h, from baseline to follow-up, in the whole sample was analyzed using paired samples t-test. RESULTS: A subsample of 48 patients participated in the actigraphic assessment: 20 in the melatonin group and 28 in the placebo group. Rest-activity cycles varied from regular to highly disrupted. Melatonin significantly increased the interdaily stability and at a trend level decreased the intradaily variability compared with placebo. Benzodiazepine dose reduction was not associated with these circadian rhythm parameters. Activity counts were generally higher after benzodiazepine dose reduction compared with pre tapering, but differences did not reach statistical significance. CONCLUSION: Our data suggest melatonin as an aid during benzodiazepine withdrawal for patients distressed by disrupted circadian rest-activity cycles. Benzodiazepine tapering might result in diminished sedentary behavior but further research is needed. TRIAL REGISTRATION: ClinicalTrials NCT01431092 , clinicaltrials.gov. Registered 31 August 2011.

Linear and non-linear analyses of Conner's Continuous Performance Test-II discriminate adult patients with attention deficit hyperactivity disorder from patients with mood and anxiety disorders.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a heterogeneous disorder. Therefore it is important to look for factors that can contribute to better diagnosis and classification of these patients. The aims of the study were to characterize adult psychiatric out-patients with a mixture of mood, anxiety and attentional problems using an objective neuropsychological test of attention combined with an assessment of mood instability. METHOD: Newly referred patients (n = 99; aged 18-65 years) requiring diagnostic evaluation of ADHD, mood or anxiety disorders were recruited, and were given a comprehensive diagnostic evaluation including the self-report form of the cyclothymic temperament scale and Conner's Continuous Performance Test II (CPT-II). In addition to the traditional measures from this test we have extracted raw data and analysed time series using linear and non-linear mathematical methods. RESULTS: Fifty patients fulfilled criteria for ADHD, while 49 did not, and were given other psychiatric diagnoses (clinical controls). When compared to the clinical controls the ADHD patients had more omission and commission errors, and higher reaction time variability. Analyses of response times showed higher values for skewness in the ADHD patients, and lower values for sample entropy and symbolic dynamics. Among the ADHD patients 59 % fulfilled criteria for a cyclothymic temperament, and this group had higher reaction time variability and lower scores on complexity than the group without this temperament. CONCLUSION: The CPT-II is a useful instrument in the assessment of ADHD in adult patients. Additional information from this test was obtained by analyzing response times using linear and non-linear methods, and this showed that ADHD patients with a cyclothymic temperament were different from those without this temperament.

Prevalence and clinical features associated to bipolar disorder-migraine comorbidity: a systematic review.

BACKGROUND: The prevalence and clinical features associated with bipolar disorders (BDs)-migraine comorbidity have been reported inconsistently across different studies, therefore warranting a systematic review on the matter. METHODS: A systematic review was conducted in accordance with the PRISMA statement searching major electronic databases for documents indexed between January, 2000 and July, 2014. Eligible studies were those including quantitative data on prevalence rates and clinical features associated to BD-migraine comorbidity; case reports excluded. Three authors independently conducted searches, quality assessment of the studies and data extraction. RESULTS: Several cross-sectional studies, and a handful of retrospective follow-up studies or non-systematic reviews assessed the prevalence and/or the clinical correlates of migraine-BD comorbidity. High prevalence rates and a significant burden of BD-migraine comorbidity were common findings, particularly in case of BD-II women (point-prevalence rates up to 77%), migraine with aura (up to 53%) and/or cyclothymic temperament (up to 45% of the cases). LIMITATIONS: Some of the biases encountered in a few studies accounted by the present review may nonetheless have hampered the generalizability of the overall conclusions drawn herein. CONCLUSIONS: BD-migraine comorbidity may comprise of a sub-phenotype of BDs requiring patient-tailored therapeutic interventions to achieve an optimal outcome. Specifically, additional studies including longitudinal follow-up studies are aimed in order to shed further light on the actual prevalence rates and clinical features associated to BD-migraine comorbidity, with a special emphasis towards the clinically suggestive potential connection between mixed features, bipolar depression, migraine, and increased risk for suicidality. PROSPERO registration number: CRD42014009335.

Blocking blue light during mania - markedly increased regularity of sleep and rapid improvement of symptoms: a case report.

OBJECTIVE: Available pharmacological treatment of mania is insufficient. Virtual darkness therapy (blue light-blocking treatment by means of orange-tinted glasses) is a promising new treatment option for mania. The basis for this might be the recently identified blue light-sensitive retinal photoreceptor, which is solely responsible for light stimulus to the circadian master clock. This is the first case report describing the clinical course of a closely monitored, hospitalized patient in a manic episode first receiving clear-lensed, and then blue light-blocking glasses. METHODS: A 58-year-old Caucasian man, with bipolar I disorder and three previous manic episodes, was hospitalized during a manic episode. In addition to pharmacological treatment, he was treated with clear-lensed glasses for seven days, then one day without glasses, followed by six days of blue light-blocking glasses. During the entire observational period, he wore an actigraph with internal light sensors. RESULTS: Manic symptoms were unaltered during the first seven days. The transition to the blue-blocking regime was followed by a rapid and sustained decline in manic symptoms accompanied by a reduction in total sleep, a reduction in motor activity during sleep intervals, and markedly increased regularity of sleep intervals. The patient's total length of hospital stay was 20 days shorter than the average time during his previous manic episodes. CONCLUSIONS: The unusually rapid decline in symptoms, accompanied by uniform sleep parameter changes toward markedly increased regularity, suggest that blue-blockers might be targeting a central mechanism in the pathophysiology of mania that needs to be explored both in clinical research and in basic science.

Attention deficit hyperactivity disorder among inmates in Bergen Prison.

The aim of this study was to investigate whether clinical findings are consistent with research indicating a high prevalence of attention deficit hyperactivity disorder (ADHD) among prison inmates. Forty-three male inmates who were referred for ADHD assessment at the health service in Bergen prison participated. Although most of them reported symptoms in accordance with ADHD both in childhood and adulthood, only 35% of the referred inmates fulfilled the criteria for ADHD when a comprehensive assessment was conducted. The results emphasize the importance of a comprehensive assessment when diagnosing ADHD among prison inmates.

Does diabetes have a protective effect on migraine?

BACKGROUND: Diabetes is associated with an increased risk of several other chronic diseases. In contrast, a previous study found an inverse relation between diabetes and migraine, whereas another large population-based study showed that the prevalence of migraine among patients with diabetes varied strongly depending on age. We aimed to investigate how the prevalence of medically treated migraine in patients with diabetes varied depending on diabetic drug treatment, sex, and age in the complete Norwegian population. METHODS: Data on all persons in Norway being prescribed medication for diabetes (n =124,649) or migraine (n = 81,225) in 2006 were obtained from the National Register of Prescriptions and analyzed in a cross-sectional design. RESULTS: Persons using diabetic drugs had an overall reduced prevalence of medically treated migraine when compared with the nondiabetic population (odds ratio [OR] = 0.72 [95% confidence interval = 0.68-0.75]). The OR was strongly associated with age. Although young persons receiving oral diabetic medication had, in fact, an increased prevalence of medically treated migraine, the prevalence declined with increasing age to about the same reduced prevalence (OR = 0.4-0.6) for all types of diabetes treatment in patients 60 to 69 years of age. The prevalence was equally decreased between men and women. CONCLUSIONS: The results suggest a markedly reduced prevalence of migraine among older patients with diabetes, when compared with the general population. One may speculate that the seemingly protective effect of diabetes on migraine could be a result of neuropathy.

The influence of glutamatergic antagonism on motor variability, and comparison to findings in schizophrenia patients.

OBJECTIVE: The primary aim of this explorative study was to investigate the influence of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine on motor activity in healthy subjects. Secondarily, we wanted to compare these data to findings in a sample of schizophrenia patients. METHODS: The healthy subjects acted as their own controls in an open-within-subject design. Motor activity was recorded with an actigraph worn for 24 h in the drug-free, and steady-state memantine conditions, respectively. Motor activity levels for 1-min intervals were analysed by means of both linear and nonlinear methods. The schizophrenia patients were monitored only once, without memantine manipulation. RESULTS: The root mean square successive differences (RMSSD) and the RMSSD/SD ratio were increased by memantine, and memantine was also associated with lower autocorrelation (lag 1) but in recordings from the right arm only. These movement patterns partly corresponded to those found in a sample of drug-treated schizophrenia patients. Total activity level, standard deviation (SD) and sample entropy were not significantly different in the memantine versus drug-free condition. CONCLUSION: The findings suggest a role for the NMDA receptor in the regulation of motor activity in healthy individuals as memantine increased the variability in the motor recordings and the alterations between adjacent motor recordings. It is suggested that the findings may be relevant to the role played by glutamate and the NMDA receptor functioning to the motor disturbances in schizophrenia.

Reduced heart rate variability during mania in a repeated naturalistic observational study.

Background: Bipolar disorder (BD) is a chronic recurrent mood disorder associated with autonomic nervous system (ANS) dysfunction, indexed by heart rate variability (HRV). Changes in HRV between mood states are sparsely studied longitudinally. We aimed to compare HRV of hospitalized manic individuals with their own euthymic selves in a naturalistic observational study. Methods: 34 individuals were included, of which 16 were lost to follow-up. Ultimately 15 patients provided reliable heart rate data in both a manic and euthymic state, using photoplethysmography (PPG) sensor wristbands overnight. We calculated HRV measures Root Mean Square of Successive Differences (RMSSD), High-frequency (HF: 0.15-0.40 Hz), Low-frequency (LF: 0.40-0.15 Hz), Very low-frequency (VLF: 0.0033-0.04 Hz), Total power and Sample Entropy in 5-min night-time resting samples. We compared HRV measures by mood state within individuals using paired t-tests and linear regression to control for age and sex. Results: HRV was lower in the manic state when compared to the euthymic state for all HRV metrics (p ≤ 0.02), with large to medium effect sizes (g = 1.24 to 0.65). HRV changes were not significantly affected by age or sex. Conclusion: This longitudinal study provides evidence of lower HRV in manic states compared to euthymia, indicating an association between ANS dysregulation and changes in bipolar mood state. This corroborates previous cross-sectional studies, although the association may be less clear or reversed in hypomanic states. Further investigation in larger longitudinal samples is warranted.

Co-prescription of medication for bipolar disorder and diabetes mellitus: a nationwide population-based study with focus on gender differences.

BACKGROUND: Studies have shown a correlation between bipolar disorder and diabetes mellitus. It is unclear if this correlation is a part of common pathophysiological pathways, or if medication for bipolar disorder has negative effects on blood sugar regulation. METHODS: The Norwegian prescription database was analyzed. Prescriptions for lithium, lamotrigine, carbamazepine and valproate were used as proxies for bipolar disorder. Prescriptions for insulin and oral anti-diabetic agents were used as proxies for diabetes mellitus. We explored the association between medication for bipolar disorder and diabetes medication by logistic regression RESULTS: We found a strong association between concomitant use of medication to treat diabetes mellitus and mood stabilizers for the treatment of bipolar disorder. Females had a 30% higher risk compared to men of being treated for both disorders. Persons using oral anti-diabetic agents had higher odds of receiving valproate than either lithium or lamotrigine. Use of insulin as monotherapy seemed to have lower odds than oral anti-diabetic agents of co-prescription of mood stabilizers, compared to the general population. CONCLUSIONS: This study showed a strong association between the use of mood stabilizers and anti-diabetic agents. The association was stronger among women than men.

Complexity and variability analyses of motor activity distinguish mood states in bipolar disorder.

Changes in motor activity are core symptoms of mood episodes in bipolar disorder. The manic state is characterized by increased variance, augmented complexity and irregular circadian rhythmicity when compared to healthy controls. No previous studies have compared mania to euthymia intra-individually in motor activity. The aim of this study was to characterize differences in motor activity when comparing manic patients to their euthymic selves. Motor activity was collected from 16 bipolar inpatients in mania and remission. 24-h recordings and 2-h time series in the morning and evening were analyzed for mean activity, variability and complexity. Lastly, the recordings were analyzed with the similarity graph algorithm and graph theory concepts such as edges, bridges, connected components and cliques. The similarity graph measures fluctuations in activity reasonably comparable to both variability and complexity measures. However, direct comparisons are difficult as most graph measures reveal variability in constricted time windows. Compared to sample entropy, the similarity graph is less sensitive to outliers. The little-understood estimate Bridges is possibly revealing underlying dynamics in the time series. When compared to euthymia, over the duration of approximately one circadian cycle, the manic state presented reduced variability, displayed by decreased standard deviation (p = 0.013) and augmented complexity shown by increased sample entropy (p = 0.025). During mania there were also fewer edges (p = 0.039) and more bridges (p = 0.026). Similar significant changes in variability and complexity were observed in the 2-h morning and evening sequences, mainly in the estimates of the similarity graph algorithm. Finally, augmented complexity was present in morning samples during mania, displayed by increased sample entropy (p = 0.015). In conclusion, the motor activity of mania is characterized by altered complexity and variability when compared within-subject to euthymia.

Innovative approaches in investigating inter-beat intervals: Graph theoretical method suggests altered autonomic functioning in adolescents with ADHD.

Cardiac inter-beat intervals (IBIs) are considered to reflect autonomic functioning and self-regulatory abilities and are often investigated by traditional time- and frequency domain analyses. These analyses investigate IBI fluctuations across relatively long time series. The similarity graph algorithm is a nonlinear method that analyzes segments of IBI time series (i.e., time windows)-possibly being more sensitive to transient and spontaneous IBI fluctuations. We hypothesized that the similarity graph algorithm would detect differences between Attention-Deficit/Hyperactivity Disorder (ADHD) and control groups. Resting electrocardiogram (ECG) recordings were collected in 10-18-year-olds with ADHD (n = 37) and controls (n = 36). IBIs were converted to graphs that were subsequently investigated for similarity. We varied the criterion for defining IBIs as similar, assessing which setting best distinguished ADHD and control groups. Using this setting, we applied the similarity graph algorithm to time windows of 2-5, 6-13 and 12-25 s, respectively. We also performed traditional IBI analyses. Independent samples t tests assessed group differences. Results showed that a 1.5% criterion of similarity and a time window of 2-5 s best distinguished adolescents with ADHD and controls. The similarity graph algorithm showed a higher number of edges, maximum edges and cliques, and lower edges10+10/edges2+2 in the ADHD group compared to controls. The results suggested more similar IBIs in the ADHD group compared to the controls, possibly due to altered vagal activity and less effective regulation of heart rate. Traditional analyses did not detect any group differences. Consequently, the similarity graph algorithm might complement traditional IBI analyses as a marker of psychopathology.