Association of CYP2D6 and CYP2C19 metabolizer status with switching and discontinuing antidepressant drugs: an exploratory study.

BACKGROUND: Tailoring antidepressant drugs (AD) to patients' genetic drug-metabolism profile is promising. However, literature regarding associations of ADs' treatment effect and/or side effects with drug metabolizing genes CYP2D6 and CYP2C19 has yielded inconsistent results. Therefore, our aim was to longitudinally investigate associations between CYP2D6 (poor, intermediate, and normal) and CYP2C19 (poor, intermediate, normal, and ultrarapid) metabolizer-status, and switching/discontinuing of ADs. Next, we investigated whether the number of perceived side effects differed between metabolizer statuses. METHODS: Data came from the multi-site naturalistic longitudinal cohort Netherlands Study of Depression and Anxiety (NESDA). We selected depression- and/or anxiety patients, who used AD at some point in the course of the 9 years follow-up period (n = 928). Medication use was followed to assess patterns of AD switching/discontinuation over time. CYP2D6 and CYP2C19 alleles were derived using genome-wide data of the NESDA samples and haplotype data from the PharmGKB database. Logistic regression analyses were conducted to investigate the association of metabolizer status with switching/discontinuing ADs. Mann-Whitney U-tests were conducted to compare the number of patient-perceived side effects between metabolizer statuses. RESULTS: No significant associations were observed of CYP metabolizer status with switching/discontinuing ADs, nor with the number of perceived side effects. CONCLUSIONS: We found no evidence for associations between CYP metabolizer statuses and switching/discontinuing AD, nor with side effects of ADs, suggesting that metabolizer status only plays a limited role in switching/discontinuing ADs. Additional studies with larger numbers of PM and UM patients are needed to further determine the potential added value of pharmacogenetics to guide pharmacotherapy.

Explanatory and modifying factors of the association between sex and depression onset during adolescence: An exploratory study.

BACKGROUND: The prevalence of Major Depressive Disorder (MDD) is twice as high in women as in men and this difference already emerges during adolescence. Because the mechanisms underlying this sex-difference remain poorly understood, we took a bottom-up approach to identify factors explaining the sex-MDD relationship. METHODS: Data came from the TRacking Adolescents' Individual Lives Survey (TRAILS), a population study investigating youths' development from age 11 into adulthood. We assessed multiple baseline covariates (e.g., demographic, social and psychological) at ages 11-13 years and MDD onset at ages 19 and 25 years. In regression analyses, each covariate's role in the sex-MDD association as an effect modifier or confounder/explanatory variable was investigated. Replicability was evaluated in an independent sample. RESULTS: The analyses identified no effect-modifiers. Baseline internalizing problems, behavioral inhibition, dizziness, comfort in classroom, physical complaints, attention problems, cooperation, self/effortful control, interpersonal life events and computer use partially explained the association between sex and MDD at age 19. The association between sex and MDD at age 25 was explained by largely the same variables, but also by shyness, acne, antisocial behavior, aggression, affection from peers and time spent shopping. The explanatory roles of internalizing problems, behavioral inhibition, negative events involving gossip/rumors and leisure-time spending (computer-use/shopping) were replicated. LIMITATIONS: Potentially important baseline variables were not included or had low response rates. Gender roles or identification were not considered. Baseline MDD was not adjusted for. CONCLUSION: The sex-MDD association is partially explained by sex differences in symptoms and vulnerability factors already present in early adolescence.

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.

Effects of right prefrontal theta-burst transcranial magnetic stimulation or transcranial direct current stimulation on apathy in patients with schizophrenia: A multicenter RCT.

Apathy is a core negative symptom associated with an unfavorable functional outcome. Noninvasive brain stimulation has shown promise in the treatment of schizophrenia but has not been tested specifically for apathy. We conducted a randomized controlled trial of intermittent theta-burst (iTBS) transcranial magnetic stimulation and transcranial direct current stimulation (tDCS) targeted at the right dorsolateral prefrontal cortex (DLPFC) in patients diagnosed with a psychotic disorder suffering from apathy. The study was a multicenter, randomized, placebo-controlled, and rater-blinded trial. Patients (N = 88) were randomized into active iTBS, active tDCS, sham iTBS or sham tDCS treatment, daily for two weeks (excluding weekends). Effects were measured post-treatment and at four week and ten week follow-up. Primary outcome was apathy severity (Apathy Evaluation Scale, clinician-rated). Additional measures included assessment of negative symptoms, depression, anhedonia and quality of life. No significant difference in improvement of apathy or negative symptoms was observed for real versus sham treatment with either iTBS or tDCS, though all groups improved to a small extent. We conclude that two weeks of brain stimulation over the right DLPFC with either iTBS or tDCS is not effective for improving apathy or negative symptoms. Longer and more intensive protocols may yield different results.

Relating stability of individual dynamical networks to change in psychopathology.

One hypothesis flowing from the network theory of psychopathology is that symptom network structure is associated with psychopathology severity and in turn, one may expect that individual network structure changes with the level of psychopathology severity. However, this expectation has rarely been addressed directly. This study aims to examine (1) the stability of individual contemporaneous symptom networks over a one-year period and (2) whether network stability is associated with a change in psychopathology. We used daily diary data of n = 66 individuals, located along the psychosis severity continuum, from two separate 90-day periods, one year apart (t = 180). Based on the newly developed Individual Network Invariance Test (INIT) to assess symptom-network stability, participants were divided into two groups with stable and unstable networks and we tested whether these groups differed in their absolute change in psychopathology severity. The majority of the sample (n = 51, 77.3%) showed a stable network over time while most individuals showed a decrease in psychopathological severity. We found no significant association between a change in psychopathology severity and individual network stability. Our results call for further critical evaluation of the association between networks and psychopathology to optimize the implementation of clinical applications based on current methods.

A blended module (STAIRS) to promote functional and personal recovery in patients with a major depressive disorder in remission: study protocol of a concurrent mixed methods randomized controlled trial.

BACKGROUND: Despite the availability of a wide variety of evidence-based treatments for major depressive disorder (MDD), many patients still experience impairments in their lives after remission. Programs are needed that effectively support patients in coping with these impairments. The program Storytelling and Training to Advance Individual Recovery Skills (STAIRS) was developed to address this need and combines the use of peer contact, expert-by-experience guidance, family support and professional blended care. The aim of the planned study is (1) to assess the efficacy of the STAIRS program in patients with remitted MDD, (2) to investigate patients' subjective experiences with STAIRS, and (3) to evaluate the program's cost-effectiveness. METHODS: A concurrent mixed-methods randomized controlled trial design will be used. Patients aged between 18 and 65 years with remitted MDD (N = 140) will be randomized to either a group receiving care as usual (CAU) + the STAIRS-program or a control group receiving CAU + some basic psychoeducation. Quantitative efficacy data on functional and personal recovery and associated aspects will be collected using self-report questionnaires at the start of the intervention, immediately following the intervention, and at the six-month follow-up. Insights into patients' experiences on perceived effects and the way in which different program elements contribute to this effect, as well as the usability and acceptability of the program, will be gained by conducting qualitative interviews with patients from the experimental group, who are selected using maximum variation sampling. Finally, data on healthcare resource use, productivity loss and quality of life will be collected and analysed to assess the cost-effectiveness and cost-utility of the STAIRS-program. DISCUSSION: Well-designed recovery-oriented programs for patients suffering from MDD are scarce. If efficacy and cost-effectiveness are demonstrated with this study and patients experience the STAIRS program as usable and acceptable, this program can be a valuable addition to CAU. The qualitative interviews may give insights into what works for whom, which can be used to promote implementation. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov on 1 July 2021, registration number NCT05440812.

Increased affective reactivity among depressed individuals can be explained by floor effects: An experience sampling study.

Experience sampling studies into daily-life affective reactivity indicate that depressed individuals react more strongly to both positive and negative stimuli than non-depressed individuals, particularly on negative affect (NA). Given the different mean levels of both positive affect (PA) and NA between patients and controls, such findings may be influenced by floor/ceiling effects, leading to violations of the normality and homoscedasticity assumptions underlying the used statistical models. Affect distributions in prior studies suggest that this may have particularly influenced NA-reactivity findings. Here, we investigated the influence of floor/ceiling effects on the observed PA- and NA-reactivity to both positive and negative events. Data came from 346 depressed, non-depressed, and remitted participants from the Netherlands Study of Depression and Anxiety (NESDA). In PA-reactivity analyses, no floor/ceiling effects and assumption violations were observed, and PA-reactivity to positive events, but not negative events, was significantly increased in the depressed and remitted groups versus the non-depressed group. However, NA-scores exhibited a floor effect in the non-depressed group and naively estimated models violated model assumptions. When these violations were accounted for in subsequent analyses, group differences in NA-reactivity that had been present in the naive models were no longer observed. In conclusion, we found increased PA-reactivity to positive events but no evidence of increased NA-reactivity in depressed individuals when accounting for violations of assumptions. The results indicate that affective-reactivity results are very sensitive to modeling choices and that previously observed increased NA-reactivity in depressed individuals may (partially) reflect unaddressed assumption violations resulting from floor effects in NA.

Concentration gradients of monoamines, their precursors and metabolites in serial lumbar cerebrospinal fluid of neurologically healthy patients determined with a novel LC-MS/MS technique.

BACKGROUND: Potential biomarkers for neuropsychiatric disorders are cerebrospinal fluid (CSF) monoamines and their corresponding precursors and metabolites. During CSF sampling, CSF flows towards the lumbar sampling site from more cranial regions. To compare the results of studies in which different CSF volumes were acquired, it is important to know if ventricular-lumbar concentration gradients exist. This has only been addressed for a few biogenic amines, and almost exclusively in neurologically unwell patients due to the burden of a lumbar puncture (necessary to obtain CSF). The aim of our study was to determine if concentration gradients exist for routinely measured CSF constituents and biogenic amines in neurologically healthy patients. We applied a novel ultrasensitive liquid chromatography mass spectrometry (LC-MS/MS) method for the simultaneous quantification of multiple monoamines, precursors and metabolites in CSF and plasma. METHODS: CSF and blood samples were collected from twenty neurologically healthy patients undergoing spinal anaesthesia. Ten mL of lumbar CSF was collected in five consecutive two mL fractions. We determined leucocyte and erythrocyte counts, glucose, albumin and protein concentrations and quantified monoamines, precursors and metabolites on each of the fractions using LC-MS/MS. RESULTS: In twenty patients (60% male; median age: 46 years), dopamine, DOPAC, 3-MT, HVA, noradrenaline, normetanephrine and 5-HIAA concentrations increased from the first to the last CSF fraction (all p < 0.001). CSF adrenaline concentrations were below the detection limit, whereas serotonin measurements were regarded as unreliable. Albumin and total protein levels decreased significantly across CSF fractions. CONCLUSIONS: A ventricular-lumbar CSF concentration gradient existed for most of the investigated analytes. This is a novel finding for dopamine, noradrenaline, 3-MT and normetanephrine. These results contribute to the understanding of the neurobiology and underline the importance of standardized procedures for CSF handling to allow comparisons between studies.

Serum free thiols in recently diagnosed patients with schizophrenia spectrum disorder: A potentially useful biomarker of oxidative stress.

Schizophrenia spectrum disorders (SSD) have been linked to oxidative stress (OS). Recent findings from our group show that serum free thiols (R-SH, sulfhydryl groups) can function as an accurate biomarker of systemic OS, since they are readily oxidized by reactive species (ROS), thereby serving as potent antioxidants. The aim of this study is to investigate if reduced R-SH levels can be demonstrated in recently diagnosed patients with SSD compared to healthy controls (HC). In this study, 102 patients with recently diagnosed SSD (< three years), and 42 HC were included. Levels of R-SH were quantified and studied for correlations with age, C-reactive protein (CRP) as proxy of inflammation as well as body mass index (BMI) and total cholesterol as indices of metabolic health. R-SH levels were significantly lower in patients when compared to HC. When correcting for age the difference was borderline significant (p=0.05). Moreover, R-SH correlated significantly with age (r = -0.29) and CRP (r = -0.29) in patients with SSD, but not in the HC. R-SH levels are reduced in SSD as compared to HC and correlate negatively with CRP and age in SSD. Future studies are required to further investigate R-SH and its role in SSD.

Personality traits and coping strategies in recent-onset psychosis: Associations with symptom severity and psychosocial functioning.

BACKGROUND: Personality and coping may be related to symptom severity and psychosocial functioning in patients with recent-onset psychosis. This study aimed to investigate associations of personality traits and coping strategies with concurrent and follow-up symptom severity and functioning in those patients, and identify whether coping mediates relations between personality and symptoms or functioning. METHODS: At baseline, 527 recent-onset psychosis patients (73 % male, mean age = 28 years) received assessments on personality (Neuroticism-Extraversion-Openness - Five-Factor Inventory), coping (Utrecht Coping List), symptom severity (Positive And Negative Syndrome Scale) and psychosocial functioning (Global Assessment of Functioning Scale). Of those, 149 also received symptom and functioning assessments at follow-up. Multivariable linear regression analyses were performed to assess cross-sectional associations of personality and coping with symptoms and functioning at baseline. Longitudinal associations of baseline personality and coping with follow-up symptomatic remission and functioning were analyzed with multivariable linear and binary logistic regression analyses, respectively. Lastly, it was investigated whether coping mediated associations between personality and symptoms or functioning. RESULTS: Higher baseline Agreeableness (B = -0.019, [95%CI: -0.031; -0.007]) and Neuroticism (B = -0.017, [95%CI: -0.028; -0.006]) were associated with lower concurrent symptom severity. Reassuring Thoughts were associated with better functioning at baseline (B = 0.833, [95%CI: 0.272; 1.393]). Neither personality nor coping were associated with follow-up symptomatic remission or functioning. Coping did not mediate associations between personality and symptoms or functioning. CONCLUSION: Only the coping strategy Reassuring Thoughts is associated with better baseline functioning in patients with recent-onset psychosis. Personality traits seem to have limited clinically relevant relations with symptom severity or functioning.

Storytelling and training to advance individual recovery skills (STAIRS). A feasibility study of a blended program to support personal recovery among patients with a major depressive disorder in remission.

Because major depressive disorder (MDD) has a strong negative impact on patients' lives, well-designed treatment programs are needed that address the lasting effects of MDD. Previous work has shown that such programs should not only focus on symptomatic recovery, but also on the subsequent personal recovery process. Currently, few programs with this specific focus exist. Therefore, this study aimed to assess the feasibility of a newly developed blended program to support the personal recovery process of MDD patients: Storytelling and Training to Advance Individual Recovery Skills (STAIRS). STAIRS is a program using peer support and guidance by experts by experience and clinicians, which can be added to regular depression treatment when symptomatic recovery is almost reached. Topics addressed in this program are: (1) effects of depression and treatment; (2) structure; (3) (self) stigma; (4) self-image; (5) meaning of life; (6) connection to others; (7) physical health; (8) relaxation; and (9) preventing relapse. Experiences with the STAIRS program were collected from five participating patients with questionnaires and a focus-group interview, as well as from four trainers using semi-structured interviews. Participants valued the topics addressed in STAIRS, the used working methods, the presence of an expert by experience and the ability to share experiences with peers. The use of an online platform and the involvement of others is seen as potentially supportive but turned out to be more challenging. Perceived effects of STAIRS include positive changes in participants' daily lives and their contacts with others. Overall, the results indicate that when implemented accessibly, STAIRS is a promising and feasible program to foster personal recovery among patients recovering from MDD.

Loneliness associates strongly with anxiety and depression during the COVID pandemic, especially in men and younger adults.

Loneliness is associated with major depressive disorder (MDD), and likely also with generalized anxiety disorder (GAD). It is unclear if these associations are moderated by age, sex, or genetic susceptibility for MDD. We included 75,279 individuals from the Lifelines COVID-19 study, a longitudinal study of a Dutch population-based cohort. Participants completed up to sixteen digital questionnaires between March 2020 and January 2021, yielding a total of 616,129 observations. Loneliness was assessed with the Three-Item Loneliness Scale, and MDD and GAD with the Mini-International Neuropsychiatric Interview. We used generalized estimating equations to investigate the association between loneliness and MDD and GAD, and whether this association varied across time, age, sex and MDD polygenic risk. Loneliness was strongly associated with all MDD and GAD outcomes. Individuals with the highest loneliness scores were around 14 times more likely to have MDD, and 11 times more likely to have GAD, compared to individuals who reported the least loneliness. The association between loneliness and MDD symptoms was stronger in men, younger individuals, and increased across time. While MDD polygenic risk predicted MDD and GAD outcomes, we did not find an interaction effect with loneliness. Our study, which is the largest to date, confirms that loneliness is an important risk factor for MDD, GAD, depressive and anxiety symptoms, especially in men and younger individuals. Future studies should investigate the mechanisms of these associations and explore loneliness-based interventions to prevent and treat MDD and GAD.

Female sex and femininity independently associate with common somatic symptom trajectories.

BACKGROUND: Multiple predictors have been associated with persistent somatic symptoms. However, previous studies problematically defined the persistence of symptoms, conflated participants' sex and gender, and focused on patient populations. Therefore, we studied associations between predictors, especially sex and gender, and longitudinal patterns of somatic symptoms in the general adult population. We also assessed whether predictors for persisting symptoms differ between sexes. METHOD: To identify developmental trajectories of somatic symptoms, assessed by the SCL-90 SOM, we used latent class trajectory modeling in the Dutch Lifelines Cohort Study [N = 150 494; 58.6% female; median time to follow-up: 46.0 (min-max: 22.0-123.0) months]. To identify predictors of trajectories, we applied multiple logistic regression analyses. Predictors were measured by surveys at baseline and a composite gender index was previously developed. RESULTS: A five-class linear LCGA model fitted the data best: 93.7% of the population had a stable symptom trajectory, whereas 1.5% and 4.8% of the population had a consistently increasing or decreasing symptom trajectory, respectively. Female sex predicted severe, stable symptom severity (OR 1.74, 95% CI 1.36-2.22), but not increasing symptom severity (OR 1.15, 95% CI 0.99-1.40). Femininity was protective hereof (OR 0.60, 95% CI 0.44-0.82 and OR 0.66, 95% CI 0.51-0.85, respectively). Merely a few predictors of symptom severity, for instance hours of paid employment and physical functioning, differed in strength between sexes. Yet, effect sizes were small. CONCLUSION: Female sex and femininity predict symptom trajectories. No large sex differences in the strength of additional predictors were found, thus it may not be clinically useful to distinguish between predictors specific to male or female patients of persistent somatic symptoms.

Investigating data-driven biological subtypes of psychiatric disorders using specification-curve analysis.

BACKGROUND: Cluster analyses have become popular tools for data-driven classification in biological psychiatric research. However, these analyses are known to be sensitive to the chosen methods and/or modelling options, which may hamper generalizability and replicability of findings. To gain more insight into this problem, we used Specification-Curve Analysis (SCA) to investigate the influence of methodological variation on biomarker-based cluster-analysis results. METHODS: Proteomics data (31 biomarkers) were used from patients (n = 688) and healthy controls (n = 426) in the Netherlands Study of Depression and Anxiety. In SCAs, consistency of results was evaluated across 1200 k-means and hierarchical clustering analyses, each with a unique combination of the clustering algorithm, fit-index, and distance metric. Next, SCAs were run in simulated datasets with varying cluster numbers and noise/outlier levels to evaluate the effect of data properties on SCA outcomes. RESULTS: The real data SCA showed no robust patterns of biological clustering in either the MDD or a combined MDD/healthy dataset. The simulation results showed that the correct number of clusters could be identified quite consistently across the 1200 model specifications, but that correct cluster identification became harder when the number of clusters and noise levels increased. CONCLUSION: SCA can provide useful insights into the presence of clusters in biomarker data. However, SCA is likely to show inconsistent results in real-world biomarker datasets that are complex and contain considerable levels of noise. Here, the number and nature of the observed clusters may depend strongly on the chosen model-specification, precluding conclusions about the existence of biological clusters among psychiatric patients.

Predictors of new onsets of irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia: the lifelines study.

BACKGROUND: It has been claimed that functional somatic syndromes share a common etiology. This prospective population-based study assessed whether the same variables predict new onsets of irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS) and fibromyalgia (FM). METHODS: The study included 152 180 adults in the Dutch Lifelines study who reported the presence/absence of relevant syndromes at baseline and follow-up. They were screened at baseline for physical and psychological disorders, socio-demographic, psycho-social and behavioral variables. At follow-up (mean 2.4 years) new onsets of each syndrome were identified by self-report. We performed separate analyses for the three syndromes including participants free of the relevant syndrome or its key symptom at baseline. LASSO logistic regressions were applied to identify which of the 102 baseline variables predicted new onsets of each syndrome. RESULTS: There were 1595 (1.2%), 296 (0.2%) and 692 (0.5%) new onsets of IBS, CFS, and FM, respectively. LASSO logistic regression selected 26, 7 and 19 predictors for IBS, CFS and FM, respectively. Four predictors were shared by all three syndromes, four predicted IBS and FM and two predicted IBS and CFS but 28 predictors were specific to a single syndrome. CFS was more distinct from IBS and FM, which predicted each other. CONCLUSIONS: Syndrome-specific predictors were more common than shared ones and these predictors might form a better starting point to unravel the heterogeneous etiologies of these syndromes than the current approach based on symptom patterns. The close relationship between IBS and FM is striking and requires further research.

Early-Life Environmental and Child Factors Associated with the Presence of Disruptive Behaviors in Seven-Year-Old Children with Autistic Traits in the Avon Longitudinal Study of Parents and Children.

We studied the association of early-life environmental and child factors with disruptive behaviors in children with autistic traits around age 7, in the Avon Longitudinal Study of Parents and Children (n = 6,401). Logistic regression with the least absolute shrinkage and selection operator indicated that disruptive behaviors were associated with prenatal smoking, no seafood-consumption during pregnancy, breech presentation at delivery, neonatal feeding problems, low social-economic situation, suboptimal preschool family environment, maternal depression, maternal antisocial behavior, male sex, and difficult child temperament. Compared to controls, male sex, maternal depression, and suboptimal preschool family environment were related to autistic traits without disruptive behaviors. Thus, there may be a difference in early-life factors related to autism spectrum disorder with and without disruptive behaviors.

Identifying mismatch and match between clinical needs and mental healthcare use trajectories in people with anxiety and depression: Results of a longitudinal study.

BACKGROUND: Mismatch between need and mental healthcare (MHC) use (under-and overuse) has mainly been studied with cross-sectional designs, not accurately capturing patterns of persistence or change in clinical burden and MHC-use among persons with depressive and/or anxiety disorders. AIMS: Determining and describing [mis]match of longitudinal trajectories of clinical burden and MHC-use. METHODS: Six-year longitudinal burden and MHC-use data came from the Netherlands Study of Depression and Anxiety (n=2981). The sample was split into four subgroups: I) no clinical burden but constant MHC use, II) constant clinical burden but no MHC-use, III) changing clinical burden and MHC-use, and IV) healthy non-users. Within subgroups I)-III), specific clinical burden and MHC trajectories were identified (growth mixture modeling). The resulting classes' associations with predisposing, enabling, and need factors were investigated (regression analysis). RESULTS: Subgroups I-III revealed different trajectories. I) increasing MHC without burden (4.1%). II) slightly increasing (1.9%), strongly increasing (2.4%), and decreasing (9.5%) burden without MHC. III) increasing (41.4%) or decreasing (19.4%) burden and concurrently increasing MHC use (first underuse, then matched care), thus revealing delayed MHC-use. Only having suicidal ideation (p<.001, Cohen's d= .6-1.5) was a significant determinant of being in latter classes compared to underusers (strongly increasing burden without MHC-use). LIMITATIONS: More explanatory factors are needed to explain [mis]match. CONCLUSION: Mismatch occurred as constant underuse or as delayed MHC-use in a high-income country (Netherlands). Additionally, no meaningful class revealed constantly matched care on average. Presence of suicidal ideation could influence the probability of symptomatic individuals receiving matched MHC or not.

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.