Evidence for mood instability in patients with bipolar disorder: Applying multilevel hidden Markov modeling to intensive longitudinal ecological momentary assessment data.

Bipolar disorder (BD) is a chronic psychiatric condition characterized by large episodic changes in mood and energy. Recently, BD has been proposed to be conceptualized as chronic cyclical mood instability, as opposed to the traditional view of alternating discrete episodes with stable periods in-between. Recognizing this mood instability may improve care and call for high-frequency measures coupled with advanced statistical models. To uncover empirically derived mood states, a multilevel hidden Markov model (HMM) was applied to 4-month ecological momentary assessment data in 20 patients with BD, yielding ∼9,820 assessments in total. Ecological momentary assessment data comprised self-report questionnaires (5 × daily) measuring manic and depressive constructs. Manic and depressive symptoms were also assessed weekly using the Altman Self-Rating Mania Scale and the Quick Inventory for Depressive Symptomatology Self-Report. Alignment between HMM-uncovered momentary mood states and weekly questionnaires was assessed with a multilevel linear model. HMM uncovered four mood states: neutral, elevated, mixed, and lowered, which aligned with weekly symptom scores. On average, patients remained < 25 hr in one state. In almost half of the patients, mood instability was observed. Switching between mood states, three patterns were identified: patients switching predominantly between (a) neutral and lowered states, (b) neutral and elevated states, and (c) mixed, elevated, and lowered states. In all, elevated and lowered mood states were interspersed by mixed states. The results indicate that chronic mood instability is a key feature of BD, even in "relatively" euthymic periods. This should be considered in theoretical and clinical conceptualizations of the disorder. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

High persistence and low treatment rates of metabolic syndrome in patients with mood and anxiety disorders: A naturalistic follow-up study.

BACKGROUND: Patients with affective and anxiety disorders are at risk of metabolic syndrome (MetS) and, consequently, cardiovascular disease and premature death. In this study, the course and treatment of MetS was investigated using longitudinal data from a naturalistic sample of affective- and anxiety-disordered outpatients (Monitoring Outcome of psychiatric PHARmacotherapy [MOPHAR]). METHODS: Demographics, clinical characteristics, medication use, and MetS components were obtained for n = 2098 patients at baseline and, in a FU-subsample of n = 507 patients, after a median follow-up (FU) of 11 months. Furthermore, pharmacological treatment rates of MetS were investigated at baseline and FU. Finally, demographic and clinical determinants of change in MetS (component) scores were investigated. RESULTS: At baseline, 34.6 % of n = 2098 patients had MetS, 41.4 % of whom received treatment. Of patients with persisting MetS, 46.1 % received treatment for one (or more) MetS component(s) at baseline, and 56.6 % received treatment at FU. Treatment rates of solely elevated blood pressure and reduced HDL-cholesterol did significantly, but modestly, improve. Higher age, male sex, smoking behavior, low education, diabetes, and depressive versus anxiety disorder were predictors of worse outcome at FU on at least one MetS component. LIMITATIONS: We did not have data on lifestyle interventions as a form of treatment, which might partly have explained the observed low pharmacotherapeutic treatment rates. CONCLUSION: MetS (components) show high persistence rates in affective- and anxiety-disordered patients, and are, despite adequate monitoring, undertreated over time. This indicates that adherence and implementation of monitoring protocols should be crucially improved in psychiatric outpatients in secondary care.

Cardiovascular risk assessment methods yield unequal risk predictions: a large cross-sectional study in psychiatric secondary care outpatients.

BACKGROUND: Patients with a mental illness are more likely to develop, and die from, cardiovascular diseases (CVD), necessitating optimal CVD-risk (CVR)-assessment to enable early detection and treatment. Whereas psychiatrists use the metabolic syndrome (MetS)-concept to estimate CVR, GPs use absolute risk-models. Additionally, two PRIMROSE-models have been specifically designed for patients with severe mental illness. We aimed to assess the agreement in risk-outcomes between these CVR-methods. METHODS: To compare risk-outcomes across the various CVR-methods, we used somatic information of psychiatric outpatients from the PHAMOUS-, and MOPHAR-database, aged 40-70 years, free of past or current CVD and diabetes. We investigated: (1) the degree-of-agreement between categorical assessments (i.e. MetS-status vs. binary risk-categories); (2) non-parametric correlations between the number of MetS-criteria and absolute risks; and (3) strength-of-agreement between absolute risks. RESULTS: Seven thousand twenty-nine measurements of 3509 PHAMOUS-patients, and 748 measurements of 748 MOPHAR-patients, were included. There was systematic disagreement between the categorical CVR-assessments (all p < 0.036). Only MetS-status versus binary Framingham-assessment had a fair strength-of-agreement (κ = 0.23-0.28). The number of MetS-criteria and Framingham-scores, as well as MetS-criteria and PRIMROSE lipid-scores, showed a moderate-strong correlation (τ = 0.25-0.34). Finally, only the continuous PRIMROSE desk and lipid-outcomes showed moderate strength-of-agreement (ρ = 0.91). CONCLUSIONS: The varying methods for CVR-assessment yield unequal risk predictions, and, consequently, carry the risk of significant disparities regarding treatment initiation in psychiatric patients. Considering the significantly increased health-risks in psychiatric patients, CVR-models should be recalibrated to the psychiatric population from adolescence onwards, and uniformly implemented by health care providers. TRIAL REGISTRATION: The MOPHAR research has been prospectively registered with the Netherlands Trial Register on 19th of November 2014 (NL4779).

A multicomponent positive psychology intervention for euthymic patients with bipolar disorder to improve mental well-being and personal recovery: A pragmatic randomized controlled trial.

OBJECTIVE: Mental well-being and personal recovery are important treatment targets for patients with bipolar disorder (BD). The goal of this study was to evaluate the effectiveness of an 8-week group multicomponent positive psychology intervention (PPI) for euthymic patients with BD as an adjunct to treatment as usual (TAU) compared to TAU alone. METHODS: Patients with BD were randomized to receive TAU (n = 43) or the PPI in addition to TAU (n = 54). The primary outcome was well being measured with the Mental Health Continuum-Short Form. Personal recovery was measured with the Questionnaire about the Process of Recovery. Data were collected at baseline, mid-treatment, post-treatment and 6- and 12-month follow-up. Life chart interviews were conducted at 12 months to retrospectively assess recurrence of depression and mania. RESULTS: Significant group-by-time interaction effects for well-being and personal recovery were found favouring the PPI. At post-treatment, between-group differences were significant for well-being (d = 0.77) and personal recovery (d = 0.76). Between-group effects for well-being were still significant at 6-month follow-up (d = 0.72). Effects on well-being and personal recovery within the intervention group were sustained until 12-month follow-up. Survival analyses showed no significant differences in time to recurrence. CONCLUSIONS: The multicomponent PPI evaluated in this study is effective in improving mental well-being and personal recovery in euthymic patients with BD and would therefore be a valuable addition to the current treatment of euthymic BD patients. The fact that the study was carried out in a pragmatic RCT demonstrates that this intervention can be applied in a real-world clinical setting.

Decreased reward circuit connectivity during reward anticipation in major depression.

An important symptom of major depressive disorder (MDD) is the inability to experience pleasure, possibly due to a dysfunction of the reward system. Despite promising insights regarding impaired reward-related processing in MDD, circuit-level abnormalities remain largely unexplored. Furthermore, whereas studies contrasting experimental conditions from incentive tasks have revealed important information about reward processing, temporal difference modeling of reward-related prediction error (PE) signals might give a more accurate representation of the reward system. We used a monetary incentive delay task during functional MRI scanning to explore PE-related striatal and ventral tegmental area (VTA) activation in response to anticipation and delivery of monetary rewards in 24 individuals with MDD versus 24 healthy controls (HCs). Furthermore, we investigated group differences in temporal difference related connectivity with a generalized psychophysiological interaction (gPPI) analysis with the VTA, ventral striatum (VS) and dorsal striatum (DS) as seeds during reward versus neutral, both in anticipation and delivery. Relative to HCs, MDD patients displayed a trend-level (p = 0.052) decrease in temporal difference-related activation in the VS during reward anticipation and delivery combined. Moreover, gPPI analyses revealed that during reward anticipation, MDD patients exhibited decreased functional connectivity between the VS and anterior cingulate cortex / medial prefrontal cortex, anterior cingulate gyrus, angular/middle orbital gyrus, left insula, superior/middle frontal gyrus (SFG/MFG) and precuneus/superior occipital gyrus/cerebellum compared to HC. Moreover, MDD patients showed decreased functional connectivity between the VTA and left insula compared to HC during reward anticipation. Exploratory analysis separating medication free patients from patients using antidepressant revealed that these decreased functional connectivity patterns were mainly apparent in the MDD group that used antidepressants. These results suggest that MDD is characterized by alterations in reward circuit connectivity rather than isolated activation impairments. These findings represent an important extension of the existing literature since improved understanding of neural pathways underlying depression-related reward dysfunctions, may help currently unmet diagnostic and therapeutic efforts.

A Web-Based Application for Personalized Ecological Momentary Assessment in Psychiatric Care: User-Centered Development of the PETRA Application.

BACKGROUND: Smartphone self-monitoring of mood, symptoms, and contextual factors through ecological momentary assessment (EMA) provides insights into the daily lives of people undergoing psychiatric treatment. Therefore, EMA has the potential to improve their care. To integrate EMA into treatment, a clinical tool that helps clients and clinicians create personalized EMA diaries and interpret the gathered data is needed. OBJECTIVE: This study aimed to develop a web-based application for personalized EMA in specialized psychiatric care in close collaboration with all stakeholders (ie, clients, clinicians, researchers, and software developers). METHODS: The participants were 52 clients with mood, anxiety, and psychotic disorders and 45 clinicians (psychiatrists, psychologists, and psychiatric nurses). We engaged them in interviews, focus groups, and usability sessions to determine the requirements for an EMA web application and repeatedly obtained feedback on iteratively improved high-fidelity EMA web application prototypes. We used human-centered design principles to determine important requirements for the web application and designed high-fidelity prototypes that were continuously re-evaluated and adapted. RESULTS: The iterative development process resulted in Personalized Treatment by Real-time Assessment (PETRA), which is a scientifically grounded web application for the integration of personalized EMA in Dutch clinical care. PETRA includes a decision aid to support clients and clinicians with constructing personalized EMA diaries, an EMA diary item repository, an SMS text message-based diary delivery system, and a feedback module for visualizing the gathered EMA data. PETRA is integrated into electronic health record systems to ensure ease of use and sustainable integration in clinical care and adheres to privacy regulations. CONCLUSIONS: PETRA was built to fulfill the needs of clients and clinicians for a user-friendly and personalized EMA tool embedded in routine psychiatric care. PETRA is unique in this codevelopment process, its extensive but user-friendly personalization options, its integration into electronic health record systems, its transdiagnostic focus, and its strong scientific foundation in the design of EMA diaries and feedback. The clinical effectiveness of integrating personalized diaries via PETRA into care requires further research. As such, PETRA paves the way for a systematic investigation of the utility of personalized EMA for routine mental health care.

Lithium surveillance by community pharmacists and physicians in ambulatory patients: a retrospective cohort study.

BACKGROUND: Shared care agreements between clinical pharmacists and physicians can improve suboptimal lithium monitoring in in- and outpatient settings. However, it is unknown whether incorporating community pharmacists in such agreements can also improve lithium monitoring in an outpatient setting. AIM: To assess the necessity for a shared care agreement for lithium monitoring in our region by investigating: intervention rates by community pharmacists and whether those are sufficient; lithium monitoring by physicians in ambulatory patients; the extent of laboratory parameter exchange to community pharmacists. METHOD: Patient files of lithium users were surveyed in a retrospective cohort study among 21 community pharmacies in the Northern Netherlands. Outcome was the intervention rate by community pharmacists and whether those were deemed sufficient by an expert panel. Additionally, we investigated both the percentages of patients monitored according to current guidelines and of laboratory parameters exchanged to community pharmacists. RESULTS: 129 patients were included. Interventions were performed in 64.4% (n = 29), 20.8% (n = 5), and 25.0% (n = 1) of initiations, discontinuations, and dosage alterations of drugs interacting with lithium, respectively. The expert panel deemed 40.0% (n = 14) of these interventions as "insufficient". Physicians monitored 40.3% (n = 52) of the patients according to current guidelines for lithium serum levels and kidney functions combined. Approximately half of the requested laboratory parameters were available to the community pharmacist. CONCLUSION: Intervention rates by community pharmacists and lithium monitoring by physicians can be improved. Therefore, a shared care agreement between community pharmacists, clinical pharmacists, and physicians is needed to improve lithium monitoring in ambulatory patients.

Anticipating manic and depressive transitions in patients with bipolar disorder using early warning signals.

BACKGROUND: In bipolar disorder treatment, accurate episode prediction is paramount but remains difficult. A novel idiographic approach to prediction is to monitor generic early warning signals (EWS), which may manifest in symptom dynamics. EWS could thus form personalized alerts in clinical care. The present study investigated whether EWS can anticipate manic and depressive transitions in individual patients with bipolar disorder. METHODS: Twenty bipolar type I/II patients (with ≥ 2 episodes in the previous year) participated in ecological momentary assessment (EMA), completing five questionnaires a day for four months (Mean = 491 observations per person). Transitions were determined by weekly completed questionnaires on depressive (Quick Inventory for Depressive Symptomatology Self-Report) and manic (Altman Self-Rating Mania Scale) symptoms. EWS (rises in autocorrelation at lag-1 and standard deviation) were calculated in moving windows over 17 affective and symptomatic EMA states. Positive and negative predictive values were calculated to determine clinical utility. RESULTS: Eleven patients reported 1-2 transitions. The presence of EWS increased the probability of impending depressive and manic transitions from 32-36% to 46-48% (autocorrelation) and 29-41% (standard deviation). However, the absence of EWS could not be taken as a sign that no transition would occur in the near future. The momentary states that indicated nearby transitions most accurately (predictive values: 65-100%) were full of ideas, worry, and agitation. Large individual differences in the utility of EWS were found. CONCLUSIONS: EWS show theoretical promise in anticipating manic and depressive transitions in bipolar disorder, but the level of false positives and negatives, as well as the heterogeneity within and between individuals and preprocessing methods currently limit clinical utility.

Individual and common patterns in the order of symptom improvement during outpatient treatment for major depression.

BACKGROUND: Research so far provided few clues on the order in which depressive symptoms typically remit during treatment. This study examined which depressive symptoms improve first, and whether symptoms changed before, simultaneous with, or after the core symptoms of depression (i.e., sad mood, loss of pleasure, and loss of interest). METHODS: Participants were 176 patients with Major Depressive Disorder (MDD) receiving outpatient treatment (a combination of pharmacotherapy and psychological interventions) for depression. Participants filled out the Inventory of Depressive Symptomatology - Self Report (IDS-SR) for 16 to 20 consecutive weeks. For each symptom, the timing of onset of a persistent improvement was determined for each single-subject separately. RESULTS: Which symptoms improved first differed markedly across patients. The core depression symptoms improved 1.5 to 2 times more often before (48% - 60%) than after (19% -28%) depressive cognitions ('view of myself' and 'view of the future'), anxiety symptoms ('feeling irritable' and 'feeling anxious / tense') and vegetative symptoms ('loss of energy', 'slowed down', and 'physical energy'). Only improvements in suicidal thoughts were more likely to occur before (46% - 48%) than after (29%) improvements in the depression core symptoms. LIMITATIONS: Not all 'core depression-non-core symptom' combinations could be tested because some symptoms did not improve in a sufficient number of patients. CONCLUSIONS: Which improvements mark the start of symptom remission differed between patients. Improvements in the core depression symptoms 'sad mood', 'loss of interest', and 'loss of pleasure' were more likely to occur before than after improvements in non-core symptoms.

Recommendations for the use of long-term experience sampling in bipolar disorder care: a qualitative study of patient and clinician experiences.

BACKGROUND: Self-monitoring has been shown to improve the self-management and treatment of patients with bipolar disorder. However, current self-monitoring methods are limited to once-daily retrospectively assessed mood, which may not suit the rapid mood fluctuations in bipolar disorder. The experience sampling method (ESM), which assesses mood in real-time several times a day, may overcome these limitations. This study set out to assess the experiences of patients and clinicians with the addition of ESM monitoring, real-time alerts, and personalized feedback to clinical care. Participants were twenty patients with bipolar disorder type I/II and their clinicians. For four months, patients completed five ESM assessments per day on mood, symptoms, and activities. Weekly symptom questionnaires alerted patients and clinicians to potential episodes. After the monitoring, a personalized feedback report based on the patient's data was discussed between patient and clinician. Three months later, patient and clinician were both interviewed. RESULTS: Thematic analysis of the transcripts resulted in four themes: perceived effects of the monitoring, alerts, and feedback, and recommendations for implementation of ESM. ESM was perceived as helping patients to cope better with their disorder by increasing awareness, offering new insights, and encouraging life style adjustments. ESM was further believed to facilitate communication between patient and clinician and to lead to new treatment directions. However, high assessment burden and pre-occupation with negative mood and having a disorder were also described. Patients and clinicians advocated for increased personalization and embedding of ESM in care. CONCLUSIONS: This study demonstrates that long-term ESM monitoring, alerts, and personalized feedback are perceived as beneficial to the treatment and self-management of patients with bipolar disorder. Future research should further test the clinical utility of ESM. Clinically relevant feedback and technology need to be developed to enable personalized integration of ESM in clinical care.

Design and methods of the 'monitoring outcomes of psychiatric pharmacotherapy' (MOPHAR) monitoring program - a study protocol.

BACKGROUND: At many outpatient departments for psychiatry worldwide, standardized monitoring of the safety of prescribed psychotropic drugs is not routinely performed in daily clinical practice. Therefore it is unclear to which extent the drugs used by psychiatric outpatients are prescribed effectively and safely. These issues warrant structured monitoring of medication use, (pre-existing) co-morbidities, effectiveness and side effects during psychiatric outpatient treatment. Improvement of monitoring practices provides an opportunity to ensure that somatic complications and adverse drug effects are detected and dealt with in a timely manner. Structural support for data collection and follow-up tests seems essential for improvement of monitoring practices in psychiatric outpatients. The implementation of a structured somatic monitoring program as part of routine clinical practice, as we describe in this study protocol, may be a solution. METHODS: In order to address these issues, we developed the innovative program 'Monitoring Outcomes of Psychiatric Pharmacotherapy (MOPHAR)'. MOPHAR is an infrastructure for implementation of standardized routine outcome monitoring (ROM; including standardized monitoring of treatment effect), monitoring of adverse psychotropic medication effects in psychiatric outpatients, encompassing both somatic adverse effects (e.g. metabolic disturbances) and subjective adverse effects (e.g. sedation or sexual side effects) and medication reconciliation. DISCUSSION: In the MOPHAR monitoring program, a nurse performs general and psychotropic drug-specific somatic screenings and provides the treating mental health care providers with more and better information on somatic monitoring for treatment decisions. Given our experience regarding implementation of the MOPHAR program, we expect that the MOPHAR program is feasible and beneficial for patients in any MHS organisation. This paper describes the objectives, target population, setting and the composition and roles of the treatment team. It also indicates what measurements are performed at which time points during outpatient treatment in the MOPHAR monitoring program, as well as the research aspects of this project. TRIAL REGISTRATION: MOPHAR research has been prospectively registered with the Netherlands Trial Register on 19th of November 2014. ( NL4779 ).

Metabolic Syndrome at an Outpatient Clinic for Bipolar Disorders: A Case for Systematic Somatic Monitoring.

OBJECTIVES: The primary objective of the study was to determine whether the Monitoring Outcomes of Psychiatric Pharmacotherapy (MOPHAR) program improved somatic monitoring practices at an outpatient clinic for bipolar disorders in the Netherlands. The secondary objective was to determine in MOPHAR the frequency of metabolic syndrome (compared with its measurability before MOPHAR) and treatment thereof. METHODS: Frequencies of physical examinations and laboratory tests before (retrospectively) and after (prospectively) the active introduction of MOPHAR were compared among adult patients (N=155). RESULTS: A median of three measurements (range 0-19) per patient were performed before MOPHAR, compared with 24 measurements (range 3-24) after MOPHAR (p<0.001). MOPHAR revealed somatic abnormalities previously unknown to treating physicians. Metabolic syndrome was present in 53% of patients; of these, 98% were not known to have metabolic syndrome before MOPHAR. CONCLUSIONS: Introducing a monitoring program largely improved knowledge regarding metabolic abnormalities, which are frequently present among patients with bipolar disorder.

Correction to: Weight changes associated with antiepileptic mood stabilizers in the treatment of bipolar disorder.

In the original version of this article unfortunately two tables have been missing. By mistake they have been published as Supplementary Material. We apologize for any inconvenience caused. The original article has been corrected.

Weight changes associated with antiepileptic mood stabilizers in the treatment of bipolar disorder.

OBJECTIVE: To present up-to-date information and recommendations on the management of body weight changes during the use of antiepileptic mood stabilizers in bipolar disorder to help clinicians and patients make well-informed, practical decisions. DATA SOURCES: Umbrella review. Systematic reviews and meta-analyses on the prevention, treatment, and monitoring of body weight changes as a side effect of the mood stabilizers valproate, lamotrigine, topiramate, and carbamazepine were identified in Embase (2010-2015, no language restrictions). STUDY SELECTION: The search yielded 18 relevant publications on antiepileptic mood stabilizers and weight changes in bipolar disorder. DATA EXTRACTION: Relevant scientific evidence was abstracted and put into a clinical perspective by a multidisciplinary expert panel of clinicians with expertise in the treatment of bipolar disorders across all age groups and a patient representative. RESULTS: Valproate has been proven to be associated with weight gain in up to 50% of its users, and can be detected 2-3 months after initiation. Carbamazepine has been proven to have a low risk of weight gain. Lamotrigine and topiramate are associated with weight loss. Other option for this sentence = Weigth gain has been proven to be associated with valproate use in up to 50% of its users, and can be detected within 2-3 months after initiation. CONCLUSION: Each antiepileptic mood stabilizer has specific effects on body weight and accordingly requires a discrete education, prevention, monitoring, and treatment strategy. Clinicians are recommended to adopt an active, anticipatory approach, educating patients about weight change as an important side effect in order to come to informed shared decisions about the most suitable mood stabilizer.

Monitoring of somatic parameters at outpatient departments for mood and anxiety disorders.

INTRODUCTION: Somatic complications account for the majority of the 13-30 years shortened life expectancy in psychiatric patients compared to the general population. The study aim was to assess to which extent patients visiting outpatient departments for mood and anxiety disorders were monitored for relevant somatic comorbidities and (adverse) effects of psychotropic drugs-more specifically a) metabolic parameters, b) lithium safety and c) ECGs-during their treatment. METHODS: We performed a retrospective clinical records review and cross-sectional analysis to assess the extent of somatic monitoring at four outpatient departments for mood and anxiety disorders in The Netherlands. We consecutively recruited adult patients visiting a participating outpatient department between March and November 2014. The primary outcome was percentage of patients without monitoring measurements. Secondary outcomes were number of measurements per parameter per patient per year and time from start of treatment to first measurement. RESULTS: We included 324 outpatients, of whom 60.2% were female. Most patients were treated for depressive disorders (39.8%), anxiety disorders (16.7%) or bipolar or related disorders (11.7%) and 198 patients (61.1%) used at least one psychotropic drug. For 186 patients (57.4%), no monitoring records were recorded (median treatment period 7.3 months, range 0-55.6). The median number of measurements per parameter per year since the start of outpatient treatment for patients with monitoring measurements was 0.31 (range 0.0-12.9). The median time to first monitoring measurement per parameter for patients with monitoring measurements was 3.8 months (range 0.0-50.7). DISCUSSION: Somatic monitoring in outpatients with mood and anxiety disorders is not routine clinical practice. Monitoring practices need to be improved to prevent psychiatric outpatients from undetected somatic complications.

Anxiety disorders and CRP in a population cohort study with 54,326 participants: The LifeLines study.

OBJECTIVES: Growing evidence indicates that inflammatory processes may play a role in the pathogenesis of anxiety disorders. Nevertheless, much remains to be learned about the involvement of inflammation, including C-reactive protein (CRP), in specific anxiety disorders. This study examines the relation between anxiety disorders and CRP. METHODS: Associations of serum CRP with anxiety disorders were determined in a large population study (n = 54,326 participants, mean age = 47 years; 59% female), the LifeLines cohort. Depressive and anxiety disorders (generalized anxiety disorder, social anxiety phobia, panic disorder with or without agoraphobia and agoraphobia without panic disorder) were assessed using the Mini-International Neuropsychiatric Interview. RESULTS: Anxiety disorders, with the exception of social anxiety disorder, were significantly associated with increased CRP. After adjusting for demographics, life style factors, health factors, medication use, depression, and psychological stressors, CRP remained significantly associated with panic disorder with agoraphobia (ß = 0.01, P = .013). Moreover, CRP levels were significantly higher in people with panic disorder with agoraphobia compared to other anxiety disorders, independent of all covariates (F = 3.00, df = 4, P = .021). CONCLUSIONS: Panic disorder with agoraphobia is associated with increased CRP, although the effect size of this association is small. This indicates that neuroinflammatory mechanisms may play a potential role in its pathophysiology.

Gray matter volume and white matter lesions in chronic kidney disease: exploring the association with depressive symptoms.

OBJECTIVE: Chronic kidney disease (CKD) is associated with structural brain damage and with a high prevalence of depression. We therefore investigated structural brain alterations in both gray and white matter in CKD patients, focusing on depression-related (frontal-subcortical) regions. METHOD: This cross-sectional MRI study in 24 CKD patients and 24 age- and sex-matched controls first tested whether CKD was associated with regionally lower gray matter (GM) volumes and more severe white matter lesions (WMLs). In exploratory subanalyses, we examined whether differences were more pronounced in CKD patients with depressive symptoms. RESULTS: CKD patients showed lower global GM volume (P=.04) and more severe WMLs (P=.04) compared to controls. In addition, we found substantial clusters of lower GM in the bilateral orbitofrontal-cortex for CKD patients, which were however nonsignificant after proper multiple-comparison correction. In exploratory analyses for depressed CKD patients, reduced GM clusters were mainly detected within the frontal lobe. WML severity was unrelated to depression. CONCLUSION: CKD was characterized by differences in brain structure. Although subthreshold, lower GM volumes were observed in depression-related brain areas and were more pronounced for depressed patients. There is a need for replication in larger and longitudinal studies to investigate whether WMLs and regional GM reductions may render CKD patients more susceptible for depression.

Does tryptophan degradation along the kynurenine pathway mediate the association between pro-inflammatory immune activity and depressive symptoms?

BACKGROUND: Several studies have suggested that induced tryptophan (TRP) degradation through the kynurenine (KYN) pathway by the enzyme indoleamine 2,3-dioxygenase (IDO) is implicated in the relation between depression and inflammation. We investigated the role of tryptophan degradation in the relationship between inflammatory markers and depressive symptoms in the Netherlands Study of Depression and Anxiety (NESDA) and hypothesized that tryptophan degradation would mediate (part of) this association. METHODS: 2812 Participants of NESDA were included in this study including 1042 persons with current major depressive disorder (MDD). Assessments of C-reactive protein (CRP), interleukin (IL)-6, tumor-necrosis factor (TNF)-α, KYN and TRP were obtained from fasting blood samples at the baseline assessment. Tryptophan degradation was estimated by calculating the ratio [KYN/TRP]. Depressive symptoms were measured with the Inventory of Depressive Symptomatology. RESULTS: Significant associations between inflammation and depressive symptoms were found for CRP and IL-6, for the total group and the subgroup of patients with current MDD. Adjustment for KYN/TRP did not attenuate these associations. There were no significant indirect effects for CRP on depressive symptoms mediated by KYN/TRP for the whole group (B=-0.032; 95% CI: -0.103 to 0.028) and for the subgroup of patients with current MDD (B=0.059; 95% CI: -0.037 to 0.165). Also IL-6 did not indirectly affect depressive symptoms through KYN/TRP in the total group (B=-0.023; 95% CI: -0.093 to 0.045) and in the MDD subgroup B=0.052; 95% CI: -0.019 to 0.144). Finally, no significant relation between depressive symptoms and KYN/TRP was found in the whole group (ß=-0.019, p=0.311) nor in the subgroup with MDD (ß=0.025, p=0.424). CONCLUSIONS: We did not find indications for tryptophan degradation, measured by KYN/TRP, to mediate the relationship between inflammation and depressive symptoms.

Comparing cognitive and somatic symptoms of depression in myocardial infarction patients and depressed patients in primary and mental health care.

Depression in myocardial infarction patients is often a first episode with a late age of onset. Two studies that compared depressed myocardial infarction patients to psychiatric patients found similar levels of somatic symptoms, and one study reported lower levels of cognitive/affective symptoms in myocardial infarction patients. We hypothesized that myocardial infarction patients with first depression onset at a late age would experience fewer cognitive/affective symptoms than depressed patients without cardiovascular disease. Combined data from two large multicenter depression studies resulted in a sample of 734 depressed individuals (194 myocardial infarction, 214 primary care, and 326 mental health care patients). A structured clinical interview provided information about depression diagnosis. Summed cognitive/affective and somatic symptom levels were compared between groups using analysis of covariance, with and without adjusting for the effects of recurrence and age of onset. Depressed myocardial infarction and primary care patients reported significantly lower cognitive/affective symptom levels than mental health care patients (F (2,682) = 6.043, p = 0.003). Additional analyses showed that the difference between myocardial infarction and mental health care patients disappeared after adjusting for age of onset but not recurrence of depression. These group differences were also supported by data-driven latent class analyses. There were no significant group differences in somatic symptom levels. Depression after myocardial infarction appears to have a different phenomenology than depression observed in mental health care. Future studies should investigate the etiological factors predictive of symptom dimensions in myocardial infarction and late-onset depression patients.

[No quetiapine for sleeping disorders]. / Geen quetiapine bij slaapstoornissen.

The prescribing of low doses of quetiapine for the treatment of sleeping disorders appears to be widespread. Recently, in a systematic literature review on low-dose quetiapine use for the treatment of sleeping disorders, it was concluded that evidence for its efficacy is currently lacking. Furthermore, quetiapine is probably associated with potentially severe adverse effects, also at low doses. In conclusion, sufficient scientific evidence that justifies the current practice of off-label prescribing of low-dose quetiapine for the treatment of sleeping disorders is insufficient; further research into its efficacy and safety is needed.