Dynamic time warp analysis of individual symptom trajectories in individuals with bipolar disorder.

BACKGROUND: Manic and depressive mood states in bipolar disorder (BD) may emerge from the non-linear relations between constantly changing mood symptoms exhibited as a complex dynamic system. Dynamic Time Warp (DTW) is an algorithm that may capture symptom interactions from panel data with sparse observations over time. METHODS: The Young Mania Rating Scale and Quick Inventory of Depressive Symptomatology were repeatedly assessed in 141 individuals with BD, with on average 5.5 assessments per subject every 3-6 months. Dynamic Time Warp calculated the distance between each of the 27 × 27 pairs of standardized symptom scores. The changing profile of standardized symptom scores of BD participants was analyzed in individual subjects, yielding symptom dimensions in aggregated group-level analyses. Using an asymmetric time-window, symptom changes that preceded other symptom changes (i.e., Granger causality) yielded a directed network. RESULTS: The mean age of the BD participants was 40.1 (SD 13.5) years old, and 60% were female participants. Idiographic symptom networks were highly variable between subjects. Yet, nomothetic analyses showed five symptom dimensions: core (hypo)mania (6 items), dysphoric mania (5 items), lethargy (7 items), somatic/suicidality (6 items), and sleep (3 items). Symptoms of the "Lethargy" dimension showed the highest out-strength, and its changes preceded those of "somatic/suicidality," while changes in "core (hypo)mania" preceded those of "dysphoric mania." CONCLUSION: Dynamic Time Warp may help to capture meaningful BD symptom interactions from panel data with sparse observations. It may increase insight into the temporal dynamics of symptoms, as those with high out-strength (rather than high in-strength) could be promising targets for intervention.

Personality traits and the risk of incident (hypo)mania among subjects initially suffering from depressive and anxiety disorders in a 9-year cohort study.

BACKGROUND: Bipolar disorder (BD) is characterized by the alternating occurrence of (hypo)manic and depressive episodes. The aim of the current study was to determine whether personality traits independently predicted the subsequent development of (hypo)manic episodes within a group of patients who were initially diagnosed with depressive and anxiety disorders. METHODS: The Netherlands Study of Depression and Anxiety is a cohort study with measurements taken at baseline and at 2-, 4-, 6-, and 9-year follow-up. Development of a (hypo)manic episode during follow-up was assessed with the Composite International Diagnostic Interview and (hypo)manic symptoms were evaluated with the Mood Disorder Questionnaire. The Big Five personality traits were the independent variables in multivariable Cox regression analyses. RESULTS: There were 31 incident cases of (hypo)manic episodes (n = 1888, mean age 42.5 years, 68.3% women), and 233 incident cases of (hypo)manic symptoms (n = 1319, mean age 43.1, 71.9% women). In multivariable analyses, low agreeableness was independently associated with an increased risk of developing a (hypo)manic episode, with a hazard ratio (HR) of 0.54 (p = 0.002, 95% CI [0.37, 0.78]). This finding was consistent with the development of (hypo)manic symptoms (HR 0.77, p = 0.001, 95% CI [0.66, 0.89]). LIMITATIONS: The 2-year lag-time analysis reduced the number of participants at risk of a (hypo)manic episode. CONCLUSIONS: We conclude that low agreeableness is a personality-related risk factor for incident (hypo)mania among subjects initially suffering from depressive and anxiety disorders. Increased attention to personality deviances could help to recognize BD at an early stage.

[Bipolar disorder and alcohol use disorder: practical recommendations for treatment, based on a literature review]. / Bipolaire stoornissen en alcoholafhankelijkheid; praktische aanbevelingen voor behandeling op basis van een systematische literatuurstudie.

BACKGROUND: A fairly large proportion (25-50%) of patients with bipolar disorder (bd) also suffer from comorbid alcohol use disorder (aud). However, little is known how this type of morbidity should be treated. It is also unclear whether the current guidelines on bd have been influenced by aud.
AIM: To provide an overview of recent literature concerning the diagnosis and treatment of comorbid bd and aud.
METHOD: We systematically reviewed studies that have addressed three treatment options for this group of patients: pharmaco-therapy, psychological interventions and self-management techniques.
RESULTS: If health professionals decide to treat bd using a pharmaco-therapeutic intervention, they must proceed with caution because the patient may also be suffering from aud. From the very limited number of published articles on this subject, we conclude that the best solution to the problem is to add valproate to the lithium-based treatment. There is also limited evidence that other effective treatments may include the use of integrated psychological interventions, cognitive behavioural therapy and self-management techniques, but these possibilities need further investigation.
CONCLUSION: Treatment of patients suffering from both bd and aud should always focus on both disorders, either simultaneously or separately. If this approach is successful it is vitally important that care is better organised and that there is cooperation between institutions involved in treating addiction disorders and departments that specialise in the care of bd. These improvements are likely to lead to further developments and to more research into new forms of integrated treatment.

A mathematical model of cell equilibrium and joint cell formation in multiple myeloma.

In Multiple Myeloma Bone Disease healthy bone remodelling is affected by tumour cells by means of paracrine cytokinetic signalling in such a way that osteoclast formation is enhanced and the growth of osteoblast cells inhibited. The participating cytokines are described in the literature. Osteoclast-induced myeloma cell growth is also reported. Based on existing mathematical models for healthy bone remodelling a three-way equilibrium model is presented for osteoclasts, osteoblasts and myeloma cell populations to describe the progress of the illness in a scenario in which there is a secular increase in the cytokinetic interactive effectiveness of paracrine processes. The equilibrium state for the system is obtained. The paracrine interactive effectiveness is explored by parameter variation and the stable region in the parameter space is identified. Then recently-discovered joint myeloma-osteoclast cells are added to the model to describe the populations inside lytic lesions. It transpires that their presence expands the available parameter space for stable equilibrium, thus permitting a detrimental, larger population of osteoclasts and myeloma cells. A possible relapse mechanism for the illness is explored by letting joint cells dissociate. The mathematics then permits the evaluation of the evolution of the cell populations as a function of time during relapse.

A Network Approach to Bipolar Symptomatology in Patients with Different Course Types.

OBJECTIVE: The longitudinal mood course is highly variable among patients with bipolar disorder(BD). One of the strongest predictors of the future disease course is the past disease course, implying that the vulnerability for developing a specific pattern of symptoms is rather consistent over time. We therefore investigated whether BD patients with different longitudinal course types have symptom correlation networks with typical characteristics. To this end we used network analysis, a rather novel approach in the field of psychiatry. METHOD: Based on two-year monthly life charts, 125 patients with complete 2 year data were categorized into three groups: i.e., a minimally impaired (n = 47), a predominantly depressed (n = 42) and a cycling course (n = 36). Associations between symptoms were defined as the groupwise Spearman's rank correlation coefficient between each pair of items of the Young Mania Rating Scale (YMRS) and the Quick Inventory of Depressive Symptomatology (QIDS). Weighted symptom networks and centrality measures were compared among the three groups. RESULTS: The weighted networks significantly differed among the three groups, with manic and depressed symptoms being most strongly interconnected in the cycling group. The symptoms with top centrality that were most interconnected also differed among the course group; central symptoms in the stable group were elevated mood and increased speech, in the depressed group loss of self-esteem and psychomotor slowness, and in the cycling group concentration loss and suicidality. CONCLUSION: Symptom networks based on the timepoints with most severe symptoms of bipolar patients with different longitudinal course types are significantly different. The clinical interpretation of this finding and its implications are discussed.

The bidirectional impact of perceived and enacted support on mood in bipolar outpatients: A two-year prospective study.

Bipolar disorder (BD) is a chronic illness, and a great need has been expressed to elucidate factors affecting the course of the disease. Social support is one of the psychosocial factors that is assumed to play an important role in the course of BD, but it is largely unknown whether the depressive and/or manic symptoms also affect the patients' support system. Further, the perception of one's social support appears to have stronger effects on disease outcomes than one's enacted or received support, but whether this also applies to BD has not been investigated. The objective of this study is to examine temporal, bidirectional associations between mood states (depression and mania) and both enacted and perceived support in BD patients. The current study was conducted among 173 BD I and II outpatients, with overall light to mild mood symptoms. Severity of mood symptoms and social support (enacted as well as perceived) were assessed every 3months, for 2years (1146 data points). Multilevel regression analyses (linear mixed-models) showed that lower perceived support during 3months was associated with subsequent higher levels of depressive, but not of manic symptoms in the following 3months. Vice versa, depressive symptoms during 3months were associated with less perceived support in the following 3months. Further, manic symptoms during 3months were associated with less enacted support in the subsequent 3 months. The current study suggests that perceived, but not enacted, support is consistently related to depressive symptoms in a bidirectional way, while mania is specifically associated with a subsequent loss of enacted support. Clinical implications of the current findings are discussed.

The use of the prospective NIMH Life Chart Method as a bipolar mood assessment method in research: a systematic review of different methods, outcome measures and interpretations.

BACKGROUND: The severity of bipolar disorder can be assessed using the daily prospective National Institute of Mental Health׳s Life Chart Method (LCM-p). Also for scientific research the LCM-p, has been used frequently. However, processing and analyzing the LCM-p for research purposes, are challenging because of the multitude of complex measures that can be derived from the data. In the current paper we review the different LCM-p course variables (mood episodes, average severity, proportion of time ill and mood switches) and their definitions. Strengths and limitations and the impact of the use of different LCM-p course measures and definitions on the research results are described. METHOD: A systematic review of original papers on the LCM was conducted using 9 electronic databases for literature between January 1996 and December 2014. Papers using other prospective charting procedures were not evaluated in the current study. RESULTS: The initial literature search led to 1352 papers of which 21 were eventually selected. A relatively wide variety of definitions of LCM-p course variables was used across the studies. Especially for the calculation of number of episodes and mood switch no univocal definition seems to exist. Across studies several different durations and severity criteria are applied to calculate these variables. We describe which variables and definitions are most suitable for detecting specific bipolar disease course characteristics and patterns. CONCLUSION: In the absence of a golden standard for the calculation of LCM-p course variables, researchers should report the exact method they applied to their LCM-p data, and clearly motivate why this is their method of first choice considering their research aim.

Stressful life events in bipolar I and II disorder: cause or consequence of mood symptoms?

BACKGROUND: Life events are assumed to be triggers for new mood episodes in bipolar disorder (BD). However whether life events may also be a result of previous mood episodes is rather unclear. METHOD: 173 bipolar outpatients (BD I and II) were assessed every three months for two years. Life events were assessed by Paykel׳s self-report questionnaire. Both monthly functional impairment due to manic or depressive symptomatology and mood symptoms were assessed. RESULTS: Negative life events were significantly associated with both subsequent severity of mania and depressive symptoms and functional impairment, whereas positive life events only preceded functional impairment due to manic symptoms and mania severity. These associations were significantly stronger in BD I patients compared to BD II patients. For the opposite temporal direction (life events as a result of mood/functional impairment), we found that mania symptoms preceded the occurrence of positive life events and depressive symptoms preceded negative life events. LIMITATIONS: The use of a self-report questionnaire for the assessment of life events makes it difficult to determine whether life events are cause or consequence of mood symptoms. Second, the results can only be generalized to relatively stable bipolar outpatients, as the number of severely depressed as well as severely manic patients was low. CONCLUSIONS: Life events appear to precede the occurrence of mood symptoms and functional impairment, and this association is stronger in BD I patients. Mood symptoms also precede the occurrence of life event, but no differences were found between BD I and II patients.

The incremental response of random aggregates of identical round particles.

This paper is concerned with a dense, randomly packed, granular material that consists of identical spheres or disks with elastic, frictional interactions, that is first isotropically compressed and subsequently loaded along an arbitrary stress path. An analytical relationship between the overall stress and strain increments is determined for the pre-failure regime. The purpose of the modelling is to understand how this relation depends upon the features of the packing and the particle interactions. From the outset it is recognised that the packing and interactive properties for these materials may vary substantially from grain to grain and the heterogeneity introduced in this manner is fully accounted for. Moment equilibrium equations are solved for each particle and force equilibrium equations are solved for each neighbourhood. Then, the heterogeneity of the aggregate is taken into account by introducing means and fluctuations in the description of the local deformations and the measures of the particles and interactions. The general development is illustrated with an example in two dimensions in which the packing and contact interactions are approximated by angular distributions and the heterogeneity is introduced by variations in these. For an isotropic medium with constant contact stiffnesses the theory provides predictions that compare well with results obtained from numerical simulations.