Treatment Course Comparison Between Anxiety-Related Disorders in Adult Outpatients: A Leiden Routine Outcome Monitoring Study.

ABSTRACT: Anxiety-related disorders constitute the leading prevalent mental disorders, with major burden on patients, their relatives, and society. Moreover, there is considerable treatment nonadherence/nonresponse. We used routine outcome monitoring (ROM) data from outpatients covering four anxiety-related disorders ( DSM-IV-R , N = 470) to examine their 6-month treatment course and its predictors: generalized anxiety disorder, panic disorder with agoraphobia, obsessive-compulsive disorder, and posttraumatic stress disorder. Measures included Mini-International Neuropsychiatric Interview Plus, Brief Symptom Inventory (BSI), Montgomery-Åsberg Depression Rating Scale (MADRS), Brief Anxiety Scale (BAS), and Short Form Health Survey 36 (SF-36). On the clinician-rated instruments (MADRS/BAS), all anxiety-related disorder groups showed a significant albeit modest improvement after treatment. On the BSI self-rating, only generalized anxiety disorder and posttraumatic stress disorder showed a significant modest improvement. No anxiety-related disorder groups improved significantly regarding SF-36 physical functioning. For BSI symptom course, significant predictors were comorbid somatoform/total disorders, SF-36 physical functioning/general health, and MADRS score. Clinical implications and future research recommendations are discussed.

Translation and cross-cultural validation of the Turkish, Moroccan Arabic and Moroccan Berber versions of the 48-item Symptom Questionnaire (SQ-48).

We aimed to validate cross-culturally the Turkish, Moroccan Arabic and Moroccan Berber versions of the 48-item Symptom Questionnaire (SQ-48). Its psychometric properties were assessed in four samples: patients (n = 150) and controls (n = 103) with Turkish or Moroccan origins (n = 103) and patients (n = 189) and controls (n = 463) with native Dutch origins. Internal consistency and discriminatory power of SQ-48 subscales across groups were adequate to high. However, immigrant groups scored on average higher than Dutch native groups, but there was full configural, metric and partial scalar invariance in the immigrant groups. Although the SQ-48 is a valid measure of psychopathology in immigrant groups of Turkish and Moroccan origins, their cut-off values should likely be higher compared to natives.

Prognostic Value of Pathological Personality Traits for Treatment Outcome in Anxiety and Depressive Disorders: The Leiden Routine Outcome Monitoring Study.

ABSTRACT: Previous studies have failed to take baseline severity into account when assessing the effects of pathological personality traits (PPT) on treatment outcome. This study assessed the prognostic value of PPT (Dimensional Assessment of Personality Pathology-Short Form) on treatment outcome (Brief Symptom Inventory [BSI-posttreatment]) among patients with depressive and/or anxiety disorders ( N = 5689). Baseline symptom level (BSI-pretreatment) was taken into account as a mediator or moderator variable. Results showed significant effects of PPT on outcome, of which Emotional Dysregulation demonstrated the largest association ( ß = 0.43, p < 0.001). When including baseline BSI score as a mediator variable, a direct effect ( ß = 0.11, p < 0.001) remained approximately one-third of the total effect. The effects of Emotional Dysregulation (interaction effect ß = 0.061, p < 0.001) and Inhibition (interaction effect ß = 0.062, p < 0.001), but not Compulsivity or Dissocial Behavior, were moderated by the baseline symptom level. PPT predicts higher symptom levels, both before and after treatment, but yields relatively small direct effects on symptom decline when the effect of pretreatment severity is taken into account.

Basal and LPS-stimulated inflammatory markers and the course of anxiety symptoms.

A cross-sectional relationship between low-grade inflammation -characterized by increased blood levels of C-reactive protein (CRP) and pro-inflammatory cytokines- and anxiety has been reported, but the potential longitudinal relationship has been less well studied. We aimed to examine whether basal and lipopolysaccharide (LPS-)induced levels of inflammatory markers are associated with anxiety symptom severity over the course of nine years. We tested the association between basal and LPS-induced inflammatory markers with anxiety symptoms (measured with the Beck's Anxiety Inventory; BAI, Fear Questionnaire; FQ and Penn's State Worry Questionnaire; PSWQ) at 5 assessment waves over a period up nine years. We used multivariate-adjusted mixed models in up to 2867 participants of the Netherlands Study of Depression and Anxiety (NESDA). At baseline, 43.6% of the participants had a current anxiety disorder, of which social phobia (18.5%) was most prevalent. Our results demonstrated that baseline inflammatory markers were significantly associated with several outcomes of anxiety at baseline over nine subsequent years. BAI subscale of somatic (arousal) symptoms of anxiety, and FQ subscale of agoraphobia demonstrated the strongest effects with standardized beta-coefficients of up to 0.14. The associations were attenuated by 25%-30% after adjusting for the presence of (comorbid) major depressive disorder (MDD), but remained statistically significant. In conclusion, we found that participants with high levels of inflammatory markers have on average high levels of anxiety consisting of physical arousal and agoraphobia, which tended to persist over a period of nine years, albeit with small effect sizes. These associations were partly driven by co-morbid depression.

Comparative responsiveness of generic versus disorder-specific instruments for depression: An assessment in three longitudinal datasets.

BACKGROUND: Routine outcome monitoring (ROM) may enhance individual treatment and is also advocated as a means to compare the outcome of different treatment programs or providers. There is debate on the optimal instruments to be used for these separate tasks. METHODS: Three sets with longitudinal data from ROM were analyzed with correlational analysis and repeated measures ANOVAs, allowing for a head-to-head comparison of measures regarding their sensitivity to detect change. The responsiveness of three disorder-specific instruments, the Beck Depression Inventory, the Inventory of Depressive Symptoms, and the Mood and Anxiety Symptoms Questionnaire, was compared to three generic instruments, the Symptom Checklist (SCL-90), the Outcome Questionnaire (OQ-45), and the Brief Symptom Inventory, respectively. RESULTS: In two of the three datasets, disorder-specific measures were more responsive compared to the total score on generic instruments. Subscale scores for depression embedded within generic instruments are second best and almost match disorder-specific scales in responsiveness. No evidence of a desynchronous response on outcome measures was found. LIMITATIONS: The present study compares measures head-to-had, and responsiveness is not assessed against an external criterion, such as clinical recovery. DISCUSSION: Disorder-specific measures yield the most precise assessment for individual treatment and are recommended for clinical use. Generic measures may allow for comparisons across diagnostic groups and their embedded subscales approach the responsiveness of disorder-specific measures.

The Assessment and Impact of Careless Responding in Routine Outcome Monitoring within Mental Health Care.

Careless responding by mental health patients on self-report assessments is rarely investigated in routine care despite the potential for serious consequences such as faulty clinical decisions. We investigated validity indices most appropriate for detecting careless responding in routine outcome monitoring (ROM) in mental health-care. First, we reviewed indices proposed in previous research for their suitability in ROM. Next, we evaluated six selected indices using data of the Brief Symptom Inventory and the Mood and Anxiety Symptom Questionnaire from 3,483 outpatients. Simulations showed that for typical ROM scales the Lmax index, Mahalanobis distance, and inter-item standard deviation may be too strongly confounded with the latent trait value to compare careless responding across patients with different symptom severity. Application of two different classification methods to the validity indices did not converge in similar prevalence estimates of careless responding. Finally, results suggest that careless responding does not have a substantial biasing effect on scale-score statistics. We recommend the lzp person-fit index to screen for random careless responding in large ROM data sets. However, additional research should further investigate methods for detecting repetitive responding in typical ROM data and assess whether there are specific circumstances in which simpler validity statistics or direct screening methods perform similarly as the lzp index.

Evaluating the Responsiveness to Therapeutic Change with Routine Outcome Monitoring: A Comparison of the Symptom Questionnaire-48 (SQ-48) with the Brief Symptom Inventory (BSI) and the Outcome Questionnaire-45 (OQ-45).

Assessment of psychological distress is important, because it may help to monitor treatment effects and predict treatment outcomes. We previously developed the 48-item Symptom Questionnaire (SQ-48) as a public domain self-report psychological distress instrument and showed good internal consistency as well as good convergent and divergent validity among clinical and non-clinical samples. The present study, conducted among psychiatric outpatients in a routine clinical setting, describes additional psychometric properties of the SQ-48. The primary focus is on responsiveness to therapeutic change, which to date has been rarely examined within psychiatry or clinical psychology. Since a questionnaire should also be stable when no clinically important change occurs, we also examined test-retest reliability within a test-retest design before treatment (n = 43). A pre-treatment/post-treatment design was used for responsiveness to therapeutic change, comparing the SQ-48 with two internationally widely used instruments: the Brief Symptom Inventory (n = 97) and the Outcome Questionnaire-45 (n = 109). The results showed that the SQ-48 has excellent test-retest reliability and good responsiveness to therapeutic change, without significant differences between the questionnaires in terms of responsiveness. In sum, the SQ-48 is a psychometrically sound public domain self-report instrument that can be used for routine outcome monitoring, as a benchmark tool or for research purposes. Copyright © 2015 John Wiley & Sons, Ltd. Key Practitioner Message The SQ-48 is developed as a public domain self-report questionnaire, in line with growing efforts to develop clinical instruments that are free of charge. The SQ-48 has excellent test-retest reliability and good responsiveness to therapeutic change or patient progress. There were no significant differences in terms of responsiveness between the SQ-48 and BSI or OQ-45. The SQ-48 can be used as a routine evaluation outcome measure for quality assurance in clinical practice. Providing feedback on patient progress via outcome measures could contribute to the enhancement of treatment outcomes.

Economic Evaluation of Concise Cognitive Behavioural Therapy and/or Pharmacotherapy for Depressive and Anxiety Disorders.

BACKGROUND: Depressive and anxiety disorders cause great suffering and disability and are associated with high health care costs. In a previous conducted pragmatic randomised controlled trial, we have shown that a concise format of cognitive behavioural- and/or pharmacotherapy is as effective as standard care in reducing depressive and anxiety symptoms and in improving subdomains of general health and quality of life in secondary care psychiatric outpatients. AIMS OF THE STUDY: In this economic evaluation, we examined whether a favourable cost-utility of concise care compared to standard care was attained. METHODS: The economic evaluation was performed alongside a pragmatic randomised controlled trial. Health-related quality of life was measured using the Short-Form (SF-36) questionnaire. Cost of healthcare utilization and productivity loss (absenteeism and presenteeism) were assessed using the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness (TiC-P). A cost-utility analysis, using cost-effectiveness acceptability curves, comparing differences in societal costs and Quality-Adjusted Life Years (QALYs) at 1 year was performed. RESULTS: One year after study entry, the difference in mean cost per patient of the two primary treatments was not significant between both groups. No significant differences in other healthcare and non- healthcare costs could be detected between patients receiving concise care and standard care. Also, QALYs were not statistically different between the groups during the study period. From both the societal and healthcare perspective, the probability that concise care is more cost-effective compared to standard care remains below the turning point of 0.5 for all acceptable values of the willingness to pay for a QALY. The economic evaluation suggests that concise care is unlikely to be cost-effective compared to standard care in the treatment for depressive- and anxiety disorders in secondary mental health care during a one year follow up period. DISCUSSION: Total costs and QALYs were not significantly different between standard and concise care, with no evidence for cost-effectiveness of concise care in the first year. The longer impact of concise care for patients with mild to moderate symptoms of depressive and/or anxiety disorders compared to standard care in secondary care needs to be further studied. IMPLICATIONS: This economic evaluation failed to find significant differences in cost between concise and standard care over the study period of one year. Replication of our economic evaluation might benefit from an extended follow-up period and strict adherence to the study protocol. If concise care will be found to be cost-effective in the long term, this would have major implications for recommendations how to optimize secondary mental health care in the treatment of depressive -- and anxiety disorders.

The clinical effectiveness of a self-management intervention for patients with persistent depressive disorder and their partners/caregivers: results from a multicenter, pragmatic randomized controlled trial.

BACKGROUND: Persistent depressive disorder (PDD) is prevalent and debilitating. For patients with PDD, psychiatric rehabilitation using self-management interventions is advised as the next therapeutic step after multiple unsuccessful treatment attempts. The "Patient and Partner Education Program for All Chronic Diseases" (PPEP4All) is a brief, structured self-management program that focuses on functional recovery for patients and their partners/caregivers. In chronic somatic disorder populations, PPEP4All has already been shown to be clinically effective. We examined whether PPEP4All adapted for PDD (PPEP4All-PDD, nine weekly group or individual sessions) is also clinically effective for adults/elderly with PDD and their partners/caregivers compared to care-as-usual (CAU) in specialized mental healthcare. METHODS: In this mixed-method multicenter pragmatic randomized controlled trial, 70 patients with PDD and 14 partners/caregivers were allocated to either PPEP4All-PDD (patients, n = 37; partners/caregivers, n = 14) or CAU (patients, n = 33; partners/caregivers, not included) and completed questionnaires at 0, 3, 6, and 12 months regarding depressive symptoms, psychopathology, psychosocial burden, mental resilience, and happiness/well-being. Qualitative data were collected regarding treatment satisfaction. Data were analyzed using mixed model analyses and an intention-to-treat (ITT) approach. RESULTS: There was no statistically significant difference in any outcome regarding clinical effectiveness between PPEP4All-PDD and CAU. Subgroup analysis for depressive symptoms did not show any interaction effect for any subgroup. Although 78% of participants recommended PPEP4All-PDD, there was no difference in treatment satisfaction between PPEP4All-PDD (score = 6.6; SD = 1.7) and CAU (score = 7.6; SD = 1.2), p = 0.06. CONCLUSION: Although depressive symptoms did not improve relative to CAU, this only confirmed that treatment for patients with treatment-resistant PDD should move from symptom reduction to functional recovery. Also, functional recovery may be reflected in other outcomes than psychosocial burden, such as self-empowerment, in patients with treatment-resistant PDD. Future research on PPEP4All-PDD could focus on a longer-term program and/or online program that may also be offered earlier in the treatment process as an empowerment intervention.  TRIAL REGISTRATION: Netherlands Trial Register Identifier NL5818. Registered on 20 July 2016 https://clinicaltrialregister.nl/nl/trial/20302.

The role of injury and trauma-related variables in the onset and course of symptoms of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) affects a minority of trauma-exposed persons and is associated with significant impairment. This longitudinal study examined risk factors for PTSD. We tested whether the presence of injuries resulting from trauma exposure predicted the course of PTSD symptoms. In addition, we tested whether gender, trauma type, perceived life threat, and peritraumatic dissociation predicted the onset of PTSD symptoms. 236 trauma-exposed civilians were assessed for PTSD symptoms with a structured interview at four occasions during 6 months posttrauma. Path analysis showed that a model in which the female gender, assault, perceived life threat, and peritraumatic dissociation predicted PTSD severity at 1 week, and injury predicted PTSD severity 8 weeks after the traumatic event showed the best fit. However, a similar model without injury showed comparable fit. It is concluded that injuries have a negligible effect on the course of PTSD.

Musicians seeking psychiatric help: a preliminary study of psychiatric characteristics.

Musicians are at increased risk for mental disorders, in particular performance anxiety. Likely causes are high levels of occupational stress, special personality traits, and coping skills. In this cross-sectional study, routine outcome monitoring (ROM) data on clinical and psychosocial characteristics were collected from the first 50 musicians visiting our outpatient psychiatric clinic for performing artists and were compared to those of a large sample of psychiatric outpatients (n=1,498) and subjects from the general population. Of the musician outpatients, 82% (n=41) met the criteria of an Axis I psychiatric disorder. Performance anxiety could not be accurately diagnosed with the MINI-plus, and in a few cases it masked different psychiatric disorders. Musician outpatients scored significantly better on functional scales despite their Axis I disorder, with equal scores on scales measuring distress compared to general outpatients. Musicians displayed significantly higher mean scores on the DAPP-sf subscale measuring narcissistic personality traits than general outpatients and non-patient controls (p=0.001). Diagnostic challenges, in particular regarding performance anxiety, of musicians seeking psychiatric care are thoroughly discussed. Musicians with psychiatric disorders may constitute a group of patients with specific characteristics who may benefit from specialized psychiatric care, and health professionals should be aware of the high prevalence of psychiatric disorders in musicians.

A proof of principle for using adaptive testing in Routine Outcome Monitoring: the efficiency of the Mood and Anxiety Symptoms Questionnaire -Anhedonic Depression CAT.

BACKGROUND: In Routine Outcome Monitoring (ROM) there is a high demand for short assessments. Computerized Adaptive Testing (CAT) is a promising method for efficient assessment. In this article, the efficiency of a CAT version of the Mood and Anxiety Symptom Questionnaire, - Anhedonic Depression scale (MASQ-AD) for use in ROM was scrutinized in a simulation study. METHODS: The responses of a large sample of patients (N = 3,597) obtained through ROM were used. The psychometric evaluation showed that the items met the requirements for CAT. In the simulations, CATs with several measurement precision requirements were run on the item responses as if they had been collected adaptively. RESULTS: CATs employing only a small number of items gave results which, both in terms of depression measurement and criterion validity, were only marginally different from the results of a full MASQ-AD assessment. CONCLUSIONS: It was concluded that CAT improved the efficiency of the MASQ-AD questionnaire very much. The strengths and limitations of the application of CAT in ROM are discussed.

Reference values for generic instruments used in routine outcome monitoring: the Leiden Routine Outcome Monitoring Study.

INTRODUCTION: The Brief Symptom Inventory (BSI), Mood & Anxiety Symptom Questionnaire -30 (MASQ-D30), Short Form Health Survey 36 (SF-36), and Dimensional Assessment of Personality Pathology-Short Form (DAPP-SF) are generic instruments that can be used in Routine Outcome Monitoring (ROM) of patients with common mental disorders. We aimed to generate reference values usually encountered in 'healthy' and 'psychiatrically ill' populations to facilitate correct interpretation of ROM results. METHODS: We included the following specific reference populations: 1294 subjects from the general population (ROM reference group) recruited through general practitioners, and 5269 psychiatric outpatients diagnosed with mood, anxiety, or somatoform (MAS) disorders (ROM patient group). The outermost 5% of observations were used to define limits for one-sided reference intervals (95th percentiles for BSI, MASQ-D30 and DAPP-SF, and 5th percentiles for SF-36 subscales). Internal consistency and Receiver Operating Characteristics (ROC) analyses were performed. RESULTS: Mean age for the ROM reference group was 40.3 years (SD=12.6) and 37.7 years (SD=12.0) for the ROM patient group. The proportion of females was 62.8% and 64.6%, respectively. The mean for cut-off values of healthy individuals was 0.82 for the BSI subscales, 23 for the three MASQ-D30 subscales, 45 for the SF-36 subscales, and 3.1 for the DAPP-SF subscales. Discriminative power of the BSI, MASQ-D30 and SF-36 was good, but it was poor for the DAPP-SF. For all instruments, the internal consistency of the subscales ranged from adequate to excellent. DISCUSSION AND CONCLUSION: Reference values for the clinical interpretation were provided for the BSI, MASQ-D30, SF-36, and DAPP-SF. Clinical information aided by ROM data may represent the best means to appraise the clinical state of psychiatric outpatients.

The structure of peritraumatic dissociation: a cross validation in clinical and nonclinical samples.

Empirical data have challenged the unidimensionality of the Peritraumatic Dissociative Experiences Questionnaire (PDEQ), a widely used measure for peritraumatic dissociation. The aim of this study was to assess the factor structure of the PDEQ in 3 trauma-exposed samples: (a) trauma-exposed police officers (N = 219); (b) trauma-exposed civilians (N = 158); and (c) treatment-seeking trauma-exposed civilians (N = 185). Confirmatory factor analyses using measurement invariance testing supported a 2-factor structure (CFIs .96-.98; RMSEAs .07-.09), but excluded 2 of the original items. Factor 1 was termed Altered Awareness; Factor 2 was termed Derealization. Altered Awareness reflected disturbances in information processing during the traumatic event, whereas Derealization reflected distortions in perception. Hierarchical linear regression analysis showed that Derealization predicted posttraumatic stress severity at 26.5 weeks follow-up only in the sample of police officers (R(2) = .45). Future longitudinal research shortly following trauma is required to elucidate causality and underlying mechanisms of peritraumatic dissociation, which may contribute to the development of more accurate screening strategies, as well as more effective strategies for prevention and early intervention.

The clinical and cost-effectiveness of a self-management intervention for patients with persistent depressive disorder and their partners/caregivers: study protocol of a multicenter pragmatic randomized controlled trial.

BACKGROUND: After regular treatment, patients with persistent depressive disorder (PDD) may remain in specialized psychiatric outpatient care without achieving remission. Lacking other options, these patients often receive long-term, non-protocolized care as usual (CAU) that does not involve the partner/caregiver of the patient. Although the revised depression treatment guidelines suggest focusing on psychiatric rehabilitation and self-management as the next treatment step for PDD, an evidence-based cost-effective self-management protocol for PDD is lacking. This study investigates the "Patient and Partner Education Program for All Chronic Illnesses" (PPEP4All) as a brief self-management protocol that could lead to lower costs, higher quality of life, and less disease burden in PDD patients and their partners/caregivers. METHODS: Presented is the rationale and methods of a multicenter pragmatic randomized controlled trial to evaluate the clinical efficacy and cost-effectiveness of PPEP4All for patients with PDD and their partners/caregivers. In accordance with current recommendations, a mixed methods research approach is used with both quantitative and qualitative data. A total of 178 eligible outpatients with PDD and their partners/caregivers are recruited and randomized to either PPEP4All or CAU. Those assigned to PPEP4All receive nine weekly self-management sessions with a trained PPEP4All therapist. Primary and secondary outcome measurements are at 0, 3, 6, and 12 months. DISCUSSION: This project will result in the implementation of a self-management intervention for patients with PDD, meeting an urgent need in mental healthcare. Using PPEP4All can optimize the quality and efficiency of care for both patients with PDD and their partners/caregivers. TRIAL REGISTRATION: Netherlands Trial Register Identifier NTR5973 . Registered on 20 July 2016.

Predicting the 9-year course of mood and anxiety disorders with automated machine learning: A comparison between auto-sklearn, naïve Bayes classifier, and traditional logistic regression.

BACKGROUND: Predicting the onset and course of mood and anxiety disorders is of clinical importance but remains difficult. We compared the predictive performances of traditional logistic regression, basic probabilistic machine learning (ML) methods, and automated ML (Auto-sklearn). METHODS: Data were derived from the Netherlands Study of Depression and Anxiety. We compared how well multinomial logistic regression, a naïve Bayes classifier, and Auto-sklearn predicted depression and anxiety diagnoses at a 2-, 4-, 6-, and 9-year follow up, operationalized as binary or categorical variables. Predictor sets included demographic and self-report data, which can be easily collected in clinical practice at two initial time points (baseline and 1-year follow up). RESULTS: At baseline, participants were 42.2 years old, 66.5% were women, and 53.6% had a current mood or anxiety disorder. The three methods were similarly successful in predicting (mental) health status, with correct predictions for up to 79% (95% CI 75-81%). However, Auto-sklearn was superior when assessing a more complex dataset with individual item scores. CONCLUSIONS: Automated ML methods added only limited value, compared to traditional data modelling when predicting the onset and course of depression and anxiety. However, they hold potential for automatization and may be better suited for complex datasets.

The 9-year clinical course of depressive and anxiety disorders: New NESDA findings.

BACKGROUND: In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective disorders over a nine-year period, comparing a categorical approach using diagnoses to a dimensional approach using symptom severity. METHOD: Patients with a current depressive and/or anxiety disorder at baseline (N = 1701) were selected from the Netherlands Study of Depression and Anxiety (NESDA). Using psychiatric diagnoses, we described 'consistently recovered,' 'intermittently recovered,' 'intermittently recurrent', and 'consistently chronic' at two-, four-, six-, and nine-year follow-up. Additionally, latent class growth analysis (LCGA) using depressive, anxiety, fear, and worry symptom severity scores was used to identify distinct classes. RESULTS: Considering the categorical approach, 8.5% were chronic, 32.9% were intermittently recurrent, 37.6% were intermittently recovered, and 21.0% remained consistently recovered from any affective disorder at nine-year follow-up. In the dimensional approach, 66.6% were chronic, 25.9% showed partial recovery, and 7.6% had recovered. LIMITATIONS: 30.6% of patients were lost to follow-up. Diagnoses were rated by the interviewer and questionnaires were completed by the participant. CONCLUSIONS: Using diagnoses alone as discrete categories to describe clinical course fails to fully capture the persistence of affective symptoms that were observed when using a dimensional approach. The enduring, fluctuating presence of subthreshold affective symptoms likely predisposes patients to frequent relapse. The commonness of subthreshold symptoms and their adverse impact on long-term prognoses deserve continuous clinical attention in mental health care as well further research.

Basal and LPS-stimulated inflammatory markers and the course of individual symptoms of depression.

Multiple studies show an association between inflammatory markers and major depressive disorder (MDD). People with chronic low-grade inflammation may be at an increased risk of MDD, often in the form of sickness behaviors. We hypothesized that inflammation is predictive of the severity and the course of a subset of MDD symptoms, especially symptoms that overlap with sickness behavior, such as anhedonia, anorexia, low concentration, low energy, loss of libido, psychomotor slowness, irritability, and malaise. We tested the association between basal and lipopolysaccharide (LPS)-induced inflammatory markers with individual MDD symptoms (measured using the Inventory of Depressive Symptomatology Self-Report) over a period of up to 9 years using multivariate-adjusted mixed models in 1147-2872 Netherlands Study of Depression and Anxiety (NESDA) participants. At baseline, participants were on average 42.2 years old, 66.5% were women and 53.9% had a current mood or anxiety disorder. We found that basal and LPS-stimulated inflammatory markers were more strongly associated with sickness behavior symptoms at up to 9-year follow-up compared with non-sickness behavior symptoms of depression. However, we also found significant associations with some symptoms that are not typical of sickness behavior (e.g., sympathetic arousal among others). Inflammation was not related to depression as a unified syndrome but rather to the presence and the course of specific MDD symptoms, of which the majority were related to sickness behavior. Anti-inflammatory strategies should be tested in the subgroup of MDD patients who report depressive symptoms related to sickness behavior.

Approaches to denote treatment outcome: Clinical significance and clinical global impression compared.

OBJECTIVES: The authors of a previous study proposed a statistically based approach to denote treatment outcome, translating pretest and posttest scores into clinically relevant categories, such as recovery and reliable improvement. We assessed the convergent validity of the Jacobson-Truax (JT) approach, using T-score based cutoff values, with ratings by an independent evaluator. METHODS: Pretest and retest scores on the Brief Symptom Inventory (BSI) and clinical global impression improvement (CGI-I) ratings were collected repeatedly through routine outcome monitoring from 5,900 outpatients with common mental disorders. Data were collected in everyday practice in a large mental health care provider. RESULTS: Continuous pretest-to-retest BSI change scores had a stronger association with CGI-I than the categorical variable based on JT. However, JT categorization and improvement according to CGI converged substantially with association indices (Somers' D) ranging from D = .50 to .56. Discordance was predominantly due to a more positive outcome according to JT than on CGI-I ratings. CONCLUSION: Converting continuous outcome variables into clinically meaningful categories comes at the price of somewhat diminished concurrent validity with CGI-I. Nevertheless, support was found for the proposed threshold values for reliable change and recovery, and the outcome denoted in these terms corresponded with CGI improvement for most patients.

Neuroticism and chronicity as predictors of 9-year course of individual depressive symptoms.

BACKGROUND: The large between-person differences in symptomatology suggest that major depressive disorder (MDD) is a heterogeneous psychiatric disorder. However, symptom-specific prospective studies are scarce. We hypothesized that chronicity (i.e., being depressed for 24 months during a patient's preceding 48 months at baseline) and neuroticism at baseline would predict adverse course trajectories over 9 years of follow up with differential magnitudes for individual depressive symptoms. METHODS: In total, 560 patients with a current MDD were included from the Netherlands Study of Depression and Anxiety (NESDA-cohort). We used a multivariate linear mixed model with repeated measures, with a history of chronicity and neuroticism separately as main independent variables and with Inventory of Depressive Symptomatology self-report (IDS-SR) item scores as outcome variables. For each individual symptom, the model was adjusted for age, gender, and baseline depression severity. RESULTS: Patients were on average 42.7 (SD = 12.1) years old and 64.7% were women. Patients with chronic depression or high levels of neuroticism showed similar absolute rates of decline over time compared to their counterparts. However, because symptoms had higher starting points for mood, cognitive, and somatic/vegetative symptoms (in that order), symptom severity remained higher over time. Chronicity and neuroticism were especially linked to persistent low self-esteem and high interpersonal sensitivity. LIMITATIONS: Neuroticism is partly state dependent and likely affected by depression severity. CONCLUSIONS: Chronicity and neuroticism predict long-term persistence of diverse psychiatric symptoms, in particular low self-esteem and high interpersonal sensitivity.