Fractal biomarker of activity in patients with bipolar disorder.

BACKGROUND: The output of many healthy physiological systems displays fractal fluctuations with self-similar temporal structures. Altered fractal patterns are associated with pathological conditions. There is evidence that patients with bipolar disorder have altered daily behaviors. METHODS: To test whether fractal patterns in motor activity are altered in patients with bipolar disorder, we analyzed 2-week actigraphy data collected from 106 patients with bipolar disorder type I in a euthymic state, 73 unaffected siblings of patients, and 76 controls. To examine the link between fractal patterns and symptoms, we analyzed 180-day actigraphy and mood symptom data that were simultaneously collected from 14 patients. RESULTS: Compared to controls, patients showed excessive regularity in motor activity fluctuations at small time scales (<1.5 h) as quantified by a larger scaling exponent (α1 > 1), indicating a more rigid motor control system. α1 values of siblings were between those of patients and controls. Further examinations revealed that the group differences in α1 were only significant in females. Sex also affected the group differences in fractal patterns at larger time scales (>2 h) as quantified by scaling exponent α2. Specifically, female patients and siblings had a smaller α2 compared to female controls, indicating more random activity fluctuations; while male patients had a larger α2 compared to male controls. Interestingly, a higher weekly depression score was associated with a lower α1 in the subsequent week. CONCLUSIONS: Our results show sex- and scale-dependent alterations in fractal activity regulation in patients with bipolar disorder. The mechanisms underlying the alterations are yet to be determined.

Stability of chronotype over a 7-year follow-up period and its association with severity of depressive and anxiety symptoms.

BACKGROUND: Chronotype is an individual's preferred timing of sleep and activity, and is often referred to as a later chronotype (or evening-type) or an earlier chronotype (or morning-type). Having an evening chronotype is associated with more severe depressive and anxiety symptoms. Based on these findings it is has been suggested that chronotype is a stable construct associated with vulnerability to develop depressive or anxiety disorders. To examine this, we test the stability of chronotype over 7 years, and its longitudinal association with the change in severity of depressive and anxiety symptoms. METHODS: Data of 1,417 participants with a depressive and/or anxiety disorder diagnosis and healthy controls assessed at the 2 and 9-year follow-up waves of the Netherlands Study of depression and anxiety were used. Chronotype was assessed with the Munich chronotype questionnaire. Severity of depressive and anxiety symptoms were assessed with the inventory of depressive symptomatology and Beck anxiety inventory. RESULTS: Chronotype was found to be moderately stable (r = 0.53) and on average advanced (i.e., became earlier) with 10.8 min over 7 years (p < .001). Controlling for possible confounders, a decrease in severity of depressive symptoms was associated with an advance in chronotype (B = 0.008, p = .003). A change in severity of anxiety symptoms was not associated with a change in chronotype. CONCLUSION: Chronotype was found to be a stable, trait-like construct with only a minor level advance over a period of 7 years. The change in chronotype was associated with a change in severity of depressive, but not anxiety, symptoms.

The characteristics of psychotic features in bipolar disorder.

BACKGROUND: In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors. METHODS: In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models. RESULTS: A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (ß = -0.09, t = -3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (ß = 0.09, t = 3.04, p = 0.002). CONCLUSIONS: In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.

Efficacy of early warning signals and spectral periodicity for predicting transitions in bipolar patients: An actigraphy study.

Early-warning signals (EWS) have been successfully employed to predict transitions in research fields such as biology, ecology, and psychiatry. The predictive properties of EWS might aid in foreseeing transitions in mood episodes (i.e. recurrent episodes of mania and depression) in bipolar disorder (BD) patients. We analyzed actigraphy data assessed during normal daily life to investigate the feasibility of using EWS to predict mood transitions in bipolar patients. Actigraphy data of 15 patients diagnosed with BD Type I collected continuously for 180 days were used. Our final sample included eight patients that experienced a mood episode, three manic episodes and five depressed episodes. Actigraphy data derived generic EWS (variance and kurtosis) and context-driven EWS (autocorrelation at lag-720) were used to determine if these were associated to upcoming bipolar episodes. Spectral analysis was used to predict changes in the periodicity of the sleep/wake cycle. The study procedures were pre-registered. Results indicated that in seven out of eight patients at least one of the EWS did show a significant change-up till four weeks before episode onset. For the generic EWS the direction of change was always in the expected direction, whereas for the context-driven EWS the observed effect was often in the direction opposite of what was expected. The actigraphy data derived EWS and spectral analysis showed promise for the prediction of upcoming transitions in mood episodes in bipolar patients. Further studies into false positive rates are suggested to improve effectiveness for EWS to identify upcoming bipolar episode onsets.

ACTman: Automated preprocessing and analysis of actigraphy data.

OBJECTIVES: To introduce a novel software-library called Actigraphy Manager (ACTman) which automates labor-intensive actigraphy data preprocessing and analyses steps while improving transparency, reproducibility, and scalability over software suites traditionally used in actigraphy research practice. DESIGN: Descriptive. METHODS: Use cases are described for performing a common actigraphy task in ACTman and alternative actigraphy software. Important inefficiencies in actigraphy workflow are identified and their consequences are described. We explain how these hinder the feasibility of conducting studies with large groups of athletes and/or longer data collection periods. Thereafter, the information flow through the ACTman software is described and we explain how it alleviates aforementioned inefficiencies. Furthermore, transparency, reproducibility, and scalability issues of commonly used actigraphy software packages are discussed and compared with the ACTman package. RESULTS: It is shown that from an end-user perspective ACTman offers a compact workflow as it automates many preprocessing and analysis steps that otherwise have to be performed manually. When considering transparency, reproducibility, and scalability the design of the ACTman software is found to outperform proprietary and open-source actigraphy software suites. As such, ACTman alleviates important bottlenecks within actigraphy research practice. CONCLUSIONS: ACTman facilitates the current transition towards larger datasets containing data of multiple athletes by automating labor-intensive preprocessing and analyses steps within actigraphy research. Furthermore, ACTman offers many features which enhance user-convenience and analysis customization, such as moving window functionality and period selection options. ACTman is open-source and thus fully verifiable, in contrast with many proprietary software packages which remain a black box for researchers.

Social jetlag and depression status: Results obtained from the Netherlands Study of Depression and Anxiety.

Social jetlag, the misalignment between the internal clock and the socially required timing of activities, is highly prevalent, especially in people with an evening chronotype and is hypothesized to be related to the link between the evening chronotype and major depressive disorder. Although social jetlag has been linked to depressive symptoms in non-clinical samples, it has never been studied in patients with major depressive disorder (MDD). This study is aimed to study social jetlag in patients with major depressive disorder and healthy controls, and to further examine the link between social jetlag and depressive symptomatology. Patients with a diagnosis of MDD (n = 1084) and healthy controls (n = 385), assessed in a clinical interview, were selected from the Netherlands Study of Depression and Anxiety. Social jetlag was derived from the Munich Chronotype Questionnaire, by calculating the absolute difference between the midsleep on free days and midsleep on work days. Depression severity was measured with the Inventory of Depressive Symptomatology. It was found that patients with MDD did not show more social jetlag compared to healthy controls, neither in a model without medication use (ß = 0.06, 95% CI: -0.03-0.15, p = 0.17) nor in a model where medication use is accounted for. There was no direct association between the amount of social jetlag and depressive symptoms, neither in the full sample, nor in the patient group or the healthy control group. This first study on social jetlag in a clinical sample showed no differences in social jetlag between patients with MDD and healthy controls.

An actigraphy study investigating sleep in bipolar I patients, unaffected siblings and controls.

OBJECTIVES: Disturbances in sleep and waking patterns are highly prevalent during mood episodes in bipolar disorder. The question remains whether these disturbances persist during phases of euthymia and whether they are heritable traits of bipolar disorder. The current study investigates objective sleep measures in a large sample of bipolar I patients, non-affected siblings and controls. METHODS: A total of 107 bipolar disorder I patients, 74 non-affected siblings, and 80 controls were included. Sleep was measured with actigraphy over the course of 14 days. Seven sleep parameters were analyzed for group differences and their relationship with age at onset, number of episodes and psychotic symptoms using linear mixed model analysis to account for family dependencies. RESULTS: Patients had a longer sleep duration and later time of sleep offset compared to the non-affected siblings but these differences were entirely attributable to differences in mood symptoms. We found no difference between patients and controls or siblings and controls when the analyses were restricted to euthymic patients. None of the bipolar illness characteristics were associated with sleep. LIMITATIONS: Medication use was not taken into account which may have influenced our findings and controls were younger compared to non-affected siblings. CONCLUSIONS: In the largest study to date, our findings suggest that recovered bipolar I patients and their siblings do not experience clinically significant sleep disturbances. Sleep disturbances are primarily a reflection of current mood state, but are unrelated to the course of the disorder.

The relation between chronotype and treatment outcome with light therapy on a fixed time schedule.

BACKGROUND: Seasonal affective disorder (SAD) is characterized by recurrent episodes of major depression in a seasonal pattern. The therapy of choice is light therapy (LT). It is suggested that LT should be administered relative to the chronotype of the patient, with the optimal timing earlier for morning than for evening types. This study aims to retrospectively investigate the relation between chronotype and the effect of LT on a fixed time in the morning in a population of SAD patients. METHODS: Data from four different studies conducted at the University Center of Psychiatry in Groningen, the Netherlands was used. Data from 132 patients was used (103 women). Depression score was determined by a structured interview (SIGH-SAD) prior to LT and after LT. Prior to LT morningness/eveningness preference of the patient was determined by the 'Morningness/Eveningness Questionnaire' (MEQ). All patients received LT at 8:00 AM at the clinic, independent of chronotype. RESULTS: Patients had an average MEQ score of 51.5±8.2. There was no significant relationship between MEQ score and therapy success as measured with the SIGH-SAD (F2,129=0.05, ns). When patients were divided by chronotype (ranging from definite morning to moderate evening) no significant relation between MEQ score and therapy success was found (F2,129=0.02, ns). LIMITATIONS: Retrospective design. CONCLUSIONS: The lack of a significant relationship between chronotype, as measured with the MEQ, and therapy success with LT at a fixed timepoint may indicate that the anti-depressive effect of morning light in SAD patients is not explained by a phase shift of the biological clock.

Coping with a life event in bipolar disorder: ambulatory measurement, signalling and early treatment.

Disruption of the biological rhythm in patients with bipolar disorder is a known risk factor for a switch in mood. This case study describes how modern techniques using ambulatory assessment of sleep parameters can help in signalling a mood switch and start early treatment. We studied a 40-year-old woman with bipolar disorder experiencing a life event while wearing an actigraph to measure sleep-wake parameters. The night after the life event the woman had sleep later and shorter sleep duration. Adequate response of both the woman and the treating psychiatrist resulted in two normal nights with the use of 1 mg lorazepam, possibly preventing further mood disturbances. Ambulatory assessment of the biological rhythm can function as an add-on to regular signalling plans for prevention of episodes in patients with bipolar disorder. More research should be conducted to validate clinical applicability, proper protocols and to understand underlying mechanisms.