BackgroundChildhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood... Show moreBackgroundChildhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood experiences. As first step toward a more refined analysis of the impact of CM, our objective is to revisit the relation of abuse and neglect, major subtypes of CM, with symptoms across disorders.MethodsThree longitudinal studies of major depressive disorder (MDD, N = 1240), bipolar disorder (BD, N = 1339), and schizophrenia (SCZ, N = 577), each including controls (N = 881), were analyzed. Multivariate regression models were used to examine the relation between exposure to abuse, neglect, or their combination to the odds for MDD, BD, SCZ, and symptoms across disorders. Bidirectional Mendelian randomization (MR) was used to probe causality, using genetic instruments of abuse and neglect derived from UK Biobank data (N = 143 473).ResultsAbuse was the stronger risk factor for SCZ (OR 3.51, 95% CI 2.17–5.67) and neglect for BD (OR 2.69, 95% CI 2.09–3.46). Combined CM was related to increased risk exceeding additive effects of abuse and neglect for MDD (RERI = 1.4) and BD (RERI = 1.1). Across disorders, abuse was associated with hallucinations (OR 2.16, 95% CI 1.55–3.01) and suicide attempts (OR 2.16, 95% CI 1.55–3.01) whereas neglect was associated with agitation (OR 1.24, 95% CI 1.02–1.51) and reduced need for sleep (OR 1.64, 95% CI 1.08–2.48). MR analyses were consistent with a bidirectional causal effect of abuse with SCZ (IVWforward = 0.13, 95% CI 0.01–0.24).ConclusionsChildhood abuse and neglect are associated with different risks to psychiatric symptoms and disorders. Unraveling the origin of these differences may advance understanding of disease etiology and ultimately facilitate development of improved personalized treatment strategies. Show less
BackgroundManic 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... Show moreBackgroundManic 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.MethodsThe 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.ResultsThe 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.”ConclusionDynamic 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. Show less
Hanssen, I.; Klooster, P. ten; Huijbers, M.; Bennekom, M.L. van; Boere, E.; Filali, E. el; ... ; Regeer, E. 2023
ObjectiveThis article describes the development and psychometric evaluation of the Manic Thought Inventory (MTI), a patient-driven self-report inventory to assess the presence of typical (hypo... Show moreObjectiveThis article describes the development and psychometric evaluation of the Manic Thought Inventory (MTI), a patient-driven self-report inventory to assess the presence of typical (hypo)manic cognitions. MethodsThe initial item pool was generated by patients with bipolar disorder (BD) type I and assessed for suitability by five psychiatrists specialized in treating BD. Study 1 describes the item analysis and exploratory factor structure of the MTI in a sample of 251 patients with BD type I. In study 2, the factor structure was validated with confirmatory factor analysis, and convergent and divergent validity were assessed in an independent sample of 201 patients with BD type I. ResultsStudy 1 resulted in a 50-item version of the MTI measuring one underlying factor. Study 2 confirmed the essentially unidimensional underlying construct in a 47-item version of the MTI. Internal consistency of the 47-item version of the MTI was excellent (alpha = 0.97). The MTI showed moderate to large positive correlations with other measures related to mania. It was not correlated with measures of depression. ConclusionThe MTI showed good psychometric properties and can be useful in research and clinical practice. Patients could use the MTI to select items that they recognize as being characteristic of their (hypo)manic episodes. By monitoring and challenging these items, the MTI could augment current psychological interventions for BD. Show less
Hanssen, I.; Huijbers, M.; Regeer, E.; Bennekom, M.L. van; Stevens, A.; Dijk, P. van; ... ; Speckens, A.E. 2023
BackgroundMindfulness-based cognitive therapy (MBCT) seems a promising intervention for bipolar disorder (BD), but there is a lack of randomised controlled trials (RCT) investigating this. The... Show moreBackgroundMindfulness-based cognitive therapy (MBCT) seems a promising intervention for bipolar disorder (BD), but there is a lack of randomised controlled trials (RCT) investigating this. The purpose of this multicentre, evaluator blinded RCT was to investigate the added value of MBCT to treatment as usual (TAU) in BD up to 15 months follow-up (NCT03507647). MethodsA total of 144 participants with BD type I and II were randomised to MBCT + TAU (n = 72) and TAU (n = 72). Primary outcome was current depressive symptoms. Secondary outcomes were current (hypo)manic and anxiety symptoms, recurrence rates, rumination, dampening of positive affect, functional impairment, mindfulness skills, self-compassion, and positive mental health. Potential moderators of treatment outcome were examined. ResultsMBCT + TAU was not more efficacious than TAU in reducing current depressive symptoms at post-treatment (95% CI [-7.0 to 1.8], p = 0.303, d = 0.24) or follow-up (95% CI [-2.2 to 6.3], p = 0.037, d = 0.13). At post-treatment, MBCT + TAU was more effective than TAU in improving mindfulness skills. At follow-up, TAU was more effective than MBCT + TAU in reducing trait anxiety and improving mindfulness skills and positive mental health. Exploratory analysis revealed that participants with higher depressive symptoms and functional impairment at baseline benefitted more from MBCT + TAU than TAU. ConclusionsIn these participants with highly recurrent BD, MBCT may be a treatment option in addition to TAU for those who suffer from moderate to severe levels of depression and functional impairment. Show less
Psychological problems like procrastination, perfectionism, low self-esteem, test anxiety and stress are common among college students. There are evidence-based interventions available for these... Show morePsychological problems like procrastination, perfectionism, low self-esteem, test anxiety and stress are common among college students. There are evidence-based interventions available for these problems that not only have direct effects on these problems, but also indirect effects on mental disorders such as depression and anxiety disorders. Targeting these psychological problems may offer new opportunities to prevent and treat mental disorders in a way that is less stigmatizing to students. In this study we examined the association of five psychological problems with five common mental disorders (panic, generalized anxiety, bipolar, major depressive, and substance use disorder) in a sample of 2,449 students from two Dutch universities. Psychological problems were measured with one item for each problem and mental disorders were measured with the Composite International Diagnostic Interview Screening Scales. Associations were examined with Poisson regression models as relative risks (RR) of the disorders as a function of the psychological problems. The population attributable fraction (PAF) indicates by what percentage the prevalence of the mental disorder would be reduced if the psychological problem was addressed successfully by an intervention. Especially generalized anxiety disorder was strongly associated with psychological problems (strong associations with stress and low self-esteem and moderately with test anxiety). The group with three or more psychological problems had a strongly increased risk for generalized anxiety (RR = 11.25; 95% CI: 7.51-16.85), and a moderately increase risk for major depression (RR = 3.22; 95% CI: 2.63-3.95), panic disorder (RR = 3.19; 95% CI: 1.96-5.20) and bipolar disorder (RR = 3.66; 95% CI: 2.40-5.58). The PAFs for having any of the psychological problems (one or more) were considerable, especially for generalized anxiety (60.8%), but also for panic disorder (35.1%), bipolar disorder (30.6%) and major depression (34.0%). We conclude that common psychological problems are associated with mental disorders and with each other. After adjustment, psychological problems are associated with different patterns of mental disorders. If the impact of the psychological problems could be taken away, the prevalence of several mental disorders would be reduced considerably. The psychological problems may provide a promising target to indirectly prevent and intervene in psychopathology in hard to reach college students with mental disorders. Show less
Koenders, M.; Mesbah, R.; Spijker, A.; Boere, E.; Leeuw, M. de; Hemert, B. van; Giltay, E. 2021
Background The coronavirus disease 2019 (COVID-19) pandemic interfered in the daily lives of people and is assumed to adversely affect mental health. However, the effects on mood (in)stability of... Show moreBackground The coronavirus disease 2019 (COVID-19) pandemic interfered in the daily lives of people and is assumed to adversely affect mental health. However, the effects on mood (in)stability of bipolar disorder (BD) patients and the comparison to pre-COVID-19 symptom severity levels are unknown. Method Between April and September, 2020, symptoms and well-being were assessed in the Bipolar Netherlands Cohort (BINCO) study of recently diagnosed patients with BD I and II. The questionnaire contained questions regarding manic and depressive symptoms (YMRS and ASRM, QIDS), worry (PSWQ), stress (PSS), loneliness, sleep, fear for COVID-19, positive coping, and substance use. As manic, depressive and stress symptoms levels were assessed pre-COVID-19, their trajectories during the lockdown restrictions were estimated using mixed models. Results Of the 70 invited BD patients, 36 (51%) responded at least once (mean age of 36.7 years, 54% female, and 31% BD type 1) to the COVID-19 assessments. There was a significant increase (X-2 = 17.06; p = .004) in (hypo)manic symptoms from baseline during the first COVID-19 wave, with a decrease thereafter. Fear of COVID-19 (X-2 = 18.01; p = .003) and positive coping (X-2 = 12.44; p = .03) were the highest at the start of the pandemic and decreased thereafter. Other scales including depression and stress symptoms did not vary significantly over time. Conclusion We found a meaningful increase in manic symptomatology from pre-COVID-19 into the initial phases of the pandemic in BD patients. These symptoms decreased along with fear of COVID-19 and positive coping during the following months when lockdown measures were eased. Show less
Hebbrecht, K.; Skorobogatov, K.; Giltay, E.J.; Coppens, V.; Picker, L. de; Morrens, M. 2021
Objective Tryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a meta-analysis of... Show moreObjective Tryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a meta-analysis of TRYCAT levels in bipolar disorder (BD) patients compared to healthy controls.MethodsA systematic literature search in seven electronic databases (PubMed, Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier) was conducted on TRYCAT levels in cerebrospinal fluid or peripheral blood according to the PRISMA statement. A minimum of three studies per TRYCAT was required for inclusion. Standardized mean differences (SMD) were computed using random effect models. Subgroup analyses were performed for BD patients in a different mood state (depressed, manic). The methodological quality of the studies was rated using the modified Newcastle-Ottawa Quality assessment Scale.ResultsTwenty-one eligible studies were identified. Peripheral levels of tryptophan (SMD = -0.44; p < 0.001), kynurenine (SMD = - 0.3; p = 0.001) and kynurenic acid (SMD = -.45; p = < 0.001) were lower in BD patients versus healthy controls. In the only three eligible studies investigating TRP in cerebrospinal fluid, tryptophan was not significantly different between BD and healthy controls. The methodological quality of the studies was moderate. Subgroup analyses revealed no significant difference in TRP and KYN values between manic and depressed BD patients, but these results were based on a limited number of studies.ConclusionThe TRYCAT pathway appears to be downregulated in BD patients. There is a need for more and high-quality studies of peripheral and central TRYCAT levels, preferably using longitudinal designs. Show less
Mesbah, R.; Bles, N. de; Rius Ottenheim, N.; Does, A.J.W. van der; Penninx, B.W.J.H.; Hemert, A.M. van; ... ; Koenders, M. 2021
Introduction Feelings of anger and irritability are prominent symptoms of bipolar disorder (BD) that may occur during hypomanic, depressive and, especially, during mixed mood states. We aimed to... Show moreIntroduction Feelings of anger and irritability are prominent symptoms of bipolar disorder (BD) that may occur during hypomanic, depressive and, especially, during mixed mood states. We aimed to determine whether such constructs are associated with the conversion to BD in subjects with a history of unipolar depression.Methods Data were derived from the depressed participants of Netherlands Study of Depression and Anxiety with 9 years of follow-up. Hypomania was ascertained using the Composite International Diagnostic Interview at 2, 4, 6, and 9 years follow-up. Cross-sectionally, we studied the association between prevalent hypomania and anger related constructs with the "Spielberger Trait Anger subscale," the "Anger Attacks" questionnaire, the cluster B personality traits part of the "Personality Disorder Questionnaire," and "aggression reactivity." Prospectively, we studied whether aggression reactivity predicted incident hypomania using Cox regression analyses.Results Cross-sectionally, the bipolar conversion group (n = 77) had significantly higher scores of trait anger and aggression reactivity, as well as a higher prevalence on "anger attacks," "antisocial traits," and "borderline traits" compared to current (n = 349) as well as remitted (n = 1159) depressive patients. In prospective analyses in 1744 participants, aggression reactivity predicted incident hypomania (n = 28), with a multivariate-adjusted hazard ratio of 1.4 (95% confidence interval: 1.02-1.93; p = .037).Conclusion Anger is a risk factor for conversion from unipolar depression to BD. In addition, patients who converted to BD showed on average anger, agitation and irritability than people with a history of unipolar depression who had not converted. Show less
Objectives Studies in children of patients affected with bipolar disorder (BD; bipolar offspring) are at high risk to develop mood disorders. Our aim is to investigate how environmental factors... Show moreObjectives Studies in children of patients affected with bipolar disorder (BD; bipolar offspring) are at high risk to develop mood disorders. Our aim is to investigate how environmental factors such as childhood trauma and family functioning relate to the development of mood disorders in offspring at familial risk for BD.Design The current study is part of a longitudinal prospective cohort study among offspring of parents with BD.Methods The current study is part of the Dutch Bipolar Offspring Study, an ongoing prospective cohort study among adolescent offspring of a parent with BD. Bipolar offspring were psychiatrically evaluated at baseline and at 1-, 5-, and 12-year follow-up. Complete follow-up data over de 12-year follow-up were available for 102 offspring. Childhood trauma was measured with the Childhood Trauma Questionnaire (CTQ) and filled out by the offspring. Family functioning was reported by the mother with the 130-item Questionnaire for Family Problems (QFP).Results Emotional maltreatment was significantly associated (HR = 1.82, CI 1.18-2.82, p = .007) with mood disorder onset in bipolar offspring. No association was found with the family functioning total score (HR = 1.04, CI 0.94-15, p = .085) nor its subscales.Conclusions The current study suggests that emotional maltreatment is associated with mood disorder development in bipolar offspring. Remarkably, the association of offspring-reported emotional maltreatment and mood disorder onset was not reflected in parent-reported family functioning (e.g., support and communication, openness or involvement). Possible explanations are discussed and warrant further study.Practitioner pointsOffspring of bipolar patients are at increased risk of developing mood disorders across the life-time.Emotional trauma contributes to the likelihood of developing mood disorders in bipolar offspring.In the daily treatment of bipolar patients having children, attention should be given to parental style and difficulties.Further research using multiple informant methods on childhood trauma an family functioning is needed to further disentangle the effects of these variables on the onset of psychopathology in bipolar offspring. Show less
Background. Individuals with autism spectrum disorder (ASD) appear to be at increased risk of non-affective psychotic disorder (NAPD) and bipolar disorder (BD). However, most previous studies... Show moreBackground. Individuals with autism spectrum disorder (ASD) appear to be at increased risk of non-affective psychotic disorder (NAPD) and bipolar disorder (BD). However, most previous studies examined the co-occurrence of ASD and NAPD or BD, ignoring possible diagnostic bias and selection bias. We used longitudinal data from Dutch psychiatric case registers to assess the risk of NAPD or BD among individuals with ASD, and compared the results to those obtained for the Dutch population in earlier studies.Methods. Individuals with ASD (n = 17 234) were followed up between 16 and 35 years of age. Kaplan-Meier estimates were used to calculate the risk of NAPD or BD. We conducted separate analyses to reduce possible bias, including an analysis among individuals diagnosed with ASD before age 16 years (n = 8337).Results. Of the individuals with ASD, 23.50% (95% confidence interval 21.87-25.22) were diagnosed with NAPD and 3.79% (3.06-4.69) with BD before age 35 years. The corresponding figures for the general population were 0.91% (0.63-1.28) and 0.13% (0.08-0.20). Risk estimates were substantially lower, but still higher than general population estimates, when we restricted our analyses to individuals diagnosed with ASD before age 16, with 1.87% (1.33-2.61) being diagnosed with NAPD and 0.57% (0.21-1.53) with BD before age 25 years. The corresponding figures for the general population were 0.63% (044-0.86) and 0.08% (0.05-0.12).Conclusions. Individuals with ASD are at increased risk of NAPD or BD. This is likely not the result of diagnostic or selection bias. Show less
