[Aftershocks; about the psychological consequences of gas extraction in Groningen]. / Naschokken; over de psychische gevolgen van de gaswinning in Groningen.

BACKGROUND: In recent decades, gas extraction in Groningen has led to a lot of material and immaterial damage, including much psychological suffering, which was ignored by policymakers for years. With the publication of the report of the Parliamentary Inquiry into Natural Gas Extraction in Groningen, this is recognized and suggestions are made to repair the damage caused in the broadest sense. AIM: Description of current and expected psychological consequences, and research and treatment to be conducted focused on this specific regional phenomenon. METHOD: Describing the Groningen situation based on various sources, and identifying current and expected mental consequences based on currently available data and scientific literature. RESULTS: Psychological consequences are largely known and identified, but not yet quantified. It is most important for the well-being of inhabitants that the government takes its care task seriously and supports victims in a practical sense. Subsequently, a targeted treatment offer must be developed. CONCLUSION: The knowledge available within psychiatry and psychology about the development and treatment of psychological complaints should play a role in researching and improving the well-being and the mental health of those affected by the gas extraction problem, now and in the future.

[About quakes and biorhythms; sleeping problems in the Groningen earthquake area]. / Over bevingen en bioritme; slaapproblemen in het Groninger aardbevingsgebied.

BACKGROUND: Gas extraction-induced earthquakes have been taking place in the province of Groningen , the Netherlands, for many years. These lead to damage to homes and other buildings. This damage, and the way in which claims are handled, leads to physical and mental health problems, including sleeping problems. AIM: Drawing attention to the regional problems related to gas-extraction and, in particular, sleeping problems. METHOD: To describe of the background situation based on available sources and naming the mental consequences, especially sleep complaints. Also to calculate patterns in the course of the earthquakes related to the time of day and the season based on the KNMI (The Royal Netherlands Meteorological Institute) registrations since 12-8-2012. RESULTS: Most serious earthquakes in the last decade have occurred at night and when the sun has set. CONCLUSION: Because the most serious quakes take place during the period when it is dark during the day, this will influence sleeping behavior. Mental health care could play a role by stimulating research and treatment of these sleep complaints in order to prevent more serious complaints. Some possible suggestions are described.

Affect fluctuations examined with ecological momentary assessment in patients with current or remitted depression and anxiety disorders.

BACKGROUND: There is increasing interest in day-to-day affect fluctuations of patients with depressive and anxiety disorders. Few studies have compared repeated assessments of positive affect (PA) and negative affect (NA) across diagnostic groups, and fluctuation patterns were not uniformly defined. The aim of this study is to compare affect fluctuations in patients with a current episode of depressive or anxiety disorder, in remitted patients and in controls, using affect instability as a core concept but also describing other measures of variability and adjusting for possible confounders. METHODS: Ecological momentary assessment (EMA) data were obtained from 365 participants of the Netherlands Study of Depression and Anxiety with current (n = 95), remitted (n = 178) or no (n = 92) DSM-IV defined depression/anxiety disorder. For 2 weeks, five times per day, participants filled-out items on PA and NA. Affect instability was calculated as the root mean square of successive differences (RMSSD). Tests on group differences in RMSSD, within-person variance, and autocorrelation were performed, controlling for mean affect levels. RESULTS: Current depression/anxiety patients had the highest affect instability in both PA and NA, followed by remitters and then controls. Instability differences between groups remained significant when controlling for mean affect levels, but differences between current and remitted were no longer significant. CONCLUSIONS: Patients with a current disorder have higher instability of NA and PA than remitted patients and controls. Especially with regard to NA, this could be interpreted as patients with a current disorder being more sensitive to internal and external stressors and having suboptimal affect regulation.

Personalized ESM monitoring and feedback to support psychological treatment for depression: a pragmatic randomized controlled trial (Therap-i).

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent mental disorder with large disease burden, high levels of relapse or persistence, and overall suboptimal outcomes of protocolized pharmacological and psychotherapeutic treatments. There is an urgent need to improve treatment effectiveness, possibly through systematic treatment personalization. In psychotherapeutic treatments this can be achieved by case conceptualization. To support this process, we developed the Therap-i module, which consists of personalized Experienced Sampling Methodology (ESM) and feedback. The Therap-i module is integrated into outpatient psychotherapeutic treatment as usual (TAU) for depression. The study aim is to investigate the efficacy of the Therap-i module in decreasing symptomatology in unresponsive or relapsing patients diagnosed with MDD. We hypothesize that the Therap-i module will contribute to TAU by i) decreasing depressive symptoms, and ii) improving general functioning, therapeutic working alliance, and illness perception. This paper provides details of the study rationale, aims, procedures, and a discussion on potential pitfalls and promises of the module. METHODS: Patients diagnosed with MDD (n = 100) will enrol in a pragmatic two-armed randomized controlled trial. Randomization is stratified according to the patient's treatment resistance level assessed with the Dutch Method for quantification of Treatment Resistance in Depression (DM-TRD). All fill-out the Inventory of Depressive Symptomatology Self Report (IDS-SR), Outcome Questionnaire (OQ-45), Illness Perception Questionnaire Mental Health (IPQ-MH), and Work Alliance Inventory Self Report (WAI-SR). In the intervention arm, through close collaboration between patient, clinician, and researcher, a personalized ESM diary is developed based on the patient's case conceptualization. During the ESM monitoring period (8 weeks, 5 assessments/day), patients receive feedback three times, which is discussed among the abovementioned three parties. Both patients and clinicians will evaluate the Therap-i module. RESULTS: Data collection is ongoing. DISCUSSION: This is the first study in which personalized ESM and feedback is integrated in outpatient psychotherapeutic TAU for depression. The labour intensive procedure and methodological pitfalls are anticipated challenges and were taken into account when designing the study. When hypotheses are confirmed, the Therap-i module may advance treatment for depression by providing insights into personalized patterns driving or perpetuating depressive complaints. TRIAL REGISTRATION: Trial NL7190 (NTR7381) , registered prospectively 03-08-2018.

[Neuropsychiatric manifestations of COVID-19 in intensive care unit patients]. / Neuropsychiatrische verschijnselen bij patiënten met COVID-19 op de ic.

It has become clear that COVID-19 can lead to neuropsychiatric complications. In this article, three cases are discussed that illustrate how neuropsychiatric complications can manifest within the COVID-19 disease course. Patients are at risk to develop a severe, hyperactive delirium, which is often accompanied by anxiety and sometimes neurological symptoms. The treatment of the neuropsychiatric complications is characterized by unusually high doses of antipsychotics and sedatives. Timely psychiatric consultation is advised for adequate recognition and effective treatment of delirium and other neuropsychiatric symptoms.

Using network analysis to examine links between individual depressive symptoms, inflammatory markers, and covariates.

BACKGROUND: Studies investigating the link between depressive symptoms and inflammation have yielded inconsistent results, which may be due to two factors. First, studies differed regarding the specific inflammatory markers studied and covariates accounted for. Second, specific depressive symptoms may be differentially related to inflammation. We address both challenges using network psychometrics. METHODS: We estimated seven regularized Mixed Graphical Models in the Netherlands Study of Depression and Anxiety (NESDA) data (N = 2321) to explore shared variances among (1) depression severity, modeled via depression sum-score, nine DSM-5 symptoms, or 28 individual depressive symptoms; (2) inflammatory markers C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α); (3) before and after adjusting for sex, age, body mass index (BMI), exercise, smoking, alcohol, and chronic diseases. RESULTS: The depression sum-score was related to both IL-6 and CRP before, and only to IL-6 after covariate adjustment. When modeling the DSM-5 symptoms and CRP in a conceptual replication of Jokela et al., CRP was associated with 'sleep problems', 'energy level', and 'weight/appetite changes'; only the first two links survived covariate adjustment. In a conservative model with all 38 variables, symptoms and markers were unrelated. Following recent psychometric work, we re-estimated the full model without regularization: the depressive symptoms 'insomnia', 'hypersomnia', and 'aches and pain' showed unique positive relations to all inflammatory markers. CONCLUSIONS: We found evidence for differential relations between markers, depressive symptoms, and covariates. Associations between symptoms and markers were attenuated after covariate adjustment; BMI and sex consistently showed strong relations with inflammatory markers.

[Psychedelics in the treatment of substance use disorders and psychosis]. / Psychedelica bij de behandeling van verslaving en psychose.

BACKGROUND: After psychedelics were banned in 1968, the flourishing research on the use of psychedelics in patients with a mental disorder stopped abruptly. Recently, we see a renaissance of this research.
AIM: To present an overview of what is known about the treatment of addiction and psychosis with psychedelics.
METHOD: Literature study based on Medline en PubMed publications till December 2019.
RESULTS: Studies on the effectiveness of psychedelics in the treatment of addiction and psychosis is still very limited in size and methodological quality. Nevertheless, most studies show positive effects of both classical and atypical psychedelics in a variety of addictions on motivation, craving, reduced consumption, and abstinence often following a single dose and with long-lasting benefits (3-24 months). Use of ketamine in patients with a psychosis stabilized on an antipsychotic might reduce negative symptoms.
CONCLUSION: Before psychedelics can be used in standard clinical practice for the treatment of patients with an addiction or a psychosis, larger and methodologically better studies are needed. The use of psychedelics also creates an opportunity to better understand the shared underlying pathology of many different mental disorders.

[Psychedelics in the treatment of PTSD]. / Psychedelica bij de behandeling van PTSS.

BACKGROUND: Posttraumatic stress disorder (PTSD) is often a chronic condition, despite the availability of various evidence-based treatment options. Psychedelics offer new treatment opportunities.
AIM: An overview of the current evidence, therapeutic context, and possible mechanisms of action of different types of psychedelics in the treatment of PTSD.
METHOD: A scoping review of the available literature.
RESULTS: MDMA-assisted psychotherapy has shown to produce lasting reductions in PTSD symptoms in multiple RCTs. Based on a small number of studies, ketamine administration appears to lead to temporary symptom relief. Current studies are investigating whether the use of ketamine in combination with psychotherapy can lead to lasting reductions in PTSD symptoms. Classical psychedelics (such as psilocybin and LSD) induce psychoactive effects (on behavior or experience) that could contribute to the psychotherapeutic treatment of PTSD but have not yet been investigated in controlled studies. Reported positive effects extend beyond PTSD symptoms only.
CONCLUSION: Psychedelics may have potential to serve as a catalyst for the psychotherapeutic treatment of PTSD. Most evidence exists for MDMA-supported psychotherapy; relatively little research is available on ketamine and classical psychedelics. Future research needs to show whether the use of psychedelics can be integrated into available treatment options for PTSD.

[Psychedelics for existential distress in terminally ill patients]. / Psychedelica bij existentieel lijden bij patiënten met een terminale ziekte.

BACKGROUND: Existential distress in patients with a terminal illness is often associated with (symptoms of) anxiety and depression. Psychotherapeutic interventions seem effective but effects are short-lived. There are no proven effective pharmacological interventions.
AIM: To present an overview of literature on psychedelic treatment of existential distress in patients with terminal illness.
METHOD: Literature research in PubMed/Medline databases, supplemented with cross-references.
RESULTS: 14 clinical studies have been conducted: 6 with classic psychedelics between 1960 and 1980, and 8 with classic psychedelics and ketamine after 2000. Results of early pre-post studies are promising but have serious methodological limitations. Recent clinical research with LSD, psilocybin and ketamine are also promising although limited in terms of research design and generalizability. Overall, studies show a positive effect on existential and spiritual well-being, quality of life, acceptance and (symptoms of) anxiety and depression. Mystical experiences are correlated with positive outcomes. Few adverse effects are reported.
CONCLUSION: Treatment of existential distress using classical psychedelics or ketamine in patients with terminal illness seems auspicious. Larger clinical studies in a more diverse patient population with fewer methodological limitations are needed to draw conclusions about efficacy and generalizability.

[Psychedelics in the treatment of depression, anxiety, and obsessive-compulsive disorder]. / Psychedelica bij de behandeling van depressie, angst en obsessieve-compulsieve stoornis.

BACKGROUND: There is a need for new, effective treatments for patients with (treatment-resistant) depressive disorders, anxiety disorders and obsessive-compulsive disorder (ocd). At the same time, there is renewed interest in psychedelics for the treatment of psychiatric disorders.
AIM: To provide an overview of results from past and current research into psychedelics in the treatment of depression, anxiety disorders and ocd.
METHOD: Literature search in Medline and PubMed databases, supplemented with cross-references and results from recent studies.
RESULTS: There is a considerable evidence base for the atypical psychedelic ketamine. Ketamine has a rapid, beneficial effect on depression and suicidality; longer-term effects are less clear. Research into classical psychedelics for the treatment of depression and anxiety disorders is currently limited to a few small (open label) studies, although positive outcomes are reported even after a single administration, with potentially longer lasting benefits. Studies must be repeated in larger and more diverse groups of patients.
CONCLUSION: Further research into efficacy, therapeutic mechanisms and intervention models is very worthwhile; for the benefit of patients, but also to provide a deeper insight into the psychotherapeutic and neurobiological mechanisms that play a role in (the treatment of) common mental disorders.

[Ketamine as an anesthetic, analgesic and anti-depressant]. / Ketamine als anestheticum, analgeticum en als antidepressivum.

BACKGROUND: Treatment-resistance occurs in about 30% of patients with depression. Therefore, there is an urgent need to identify new treatment strategies. Ketamine, originally developed as an anesthetic, is studied and applied as treatment for patients with treatment-resistant depression.
AIM: A critical review of the current use of ketamine as an antidepressant.
METHOD: Literature study.
RESULTS: Ketamine is a proven effective acute antidepressant. However, limited information is available about maintenance of effect of ketamine, potential risks of repeated administration, and different routes of administration and treatment schedules.
CONCLUSION: Additional research on ketamine as an antidepressant is needed. Meanwhile, (off-label) treatment should only be applied after careful patient selection and under close monitoring.

The prevalence, age-of-onset and the correlates of DSM-IV psychiatric disorders in the Tianjin Mental Health Survey (TJMHS).

BACKGROUND: To effectively shape mental healthcare policy in modern-day China, up-to-date epidemiological data on mental disorders is needed. The objective was to estimate the prevalence, age-of-onset (AOO) and sociodemographic correlates of mental disorders in a representative household sample of the general population (age ⩾ 18) in the Tianjin Municipality in China. METHODS: Data came from the Tianjin Mental health Survey (TJMHS), which was conducted between July 2011 and March 2012 using a two-phase design. 11 748 individuals were screened with an expanded version of the General Health Questionnaire and 4438 subjects were selected for a diagnostic interview by a psychiatrist, using the Structured Clinical Interview for the Diagnostic and Statistical Manual - fourth edition (SCID). RESULTS: The lifetime and 1-month prevalence of any mental disorder were 23.6% and 12.8%, respectively. Mood disorders (lifetime: 9.3%; 1-month: 3.9%), anxiety disorders (lifetime: 4.5% 1-month: 3.1%) and substance-use disorders (lifetime: 8.8%; 1-month: 3.5%) were most prevalent. The median AOO ranged from 25 years [interquartile range (IQR): 23-32] for substance-use disorders to 36 years (IQR: 24-50) for mood disorders. Not being married, non-immigrant status (i.e. local 'Hukou'), being a farmer, having <6 years of education and male gender were associated with a higher lifetime prevalence of any mental disorder. CONCLUSION: Results from the current survey indicate that mental disorders are steadily reported more commonly in rapidly-developing urban China. Several interesting sociodemographic correlates were observed (e.g. male gender and non-immigrant status) that warrant further investigation and could be used to profile persons in need of preventive intervention.

Body image in patients with somatoform disorder.

BACKGROUND: Although body-related problems are common in patients with somatoform disorder, research focusing on how patients with somatoform disorder perceive and evaluate their body is scarce. The present study compared differences in body image between patients with somatoform disorder and respondents from a general population sample. It also examined differences within the somatoform disorder group between men and women and between the diagnostic subgroups conversion disorder, pain disorder and undifferentiated somatoform disorder. METHODS: Data were obtained from 657 patients (67.5% female) with somatoform disorder (DSM-IV-TR 300.7, 300.11, 300.81, 300.82) and 761 participants (58.6% female) from the general population. The Dresden Body Image Questionnaire (DBIQ) was used to assess body image in five domains: body acceptance, vitality, physical contact, sexual fulfilment, and self-aggrandizement. Confirmatory factor analysis and analyses of variance were performed. Since differences in age and sex were found between the somatoform disorder sample and the comparison sample, analyses were done with two samples of 560 patients with somatoform disorder and 351 individuals from the comparison sample matched on proportion of men and women and age. RESULTS: Patients scored significantly lower than the comparison sample on all DBIQ domains. Men scored higher than women. Patients with conversion disorder scored significantly higher on vitality and body acceptance than patients with undifferentiated somatoform disorder and pain disorder. CONCLUSIONS: The mostly large differences in body image between patients with somatoform disorder and the comparison sample as well as differences between diagnostic subgroups underline that body image is an important feature in patients with somatoform disorder. The results indicate the usefulness of assessing body image and treating negative body image in patients with somatoform or somatic symptom disorder.

Testosterone in human studies: Modest associations between plasma and salivary measurements.

Testosterone is involved in many processes like aggression and mood disorders. As it may easily diffuse from blood into saliva, salivary testosterone is thought to reflect plasma free testosterone level. If so, it would provide a welcome noninvasive and less stressful alternative to blood sampling. Past research did not reveal consensus regarding the strength of the association, but sample sizes were small. This study aimed to analyse the association in a large cohort. In total, 2,048 participants (age range 18-65 years; 696 males and 1,352 females) were included and saliva (using cotton Salivettes) and plasma were collected for testosterone measurements. Levels were determined by enzyme-linked immunosorbent assay and radioimmunoassay respectively. Free testosterone was calculated by the Vermeulen algorithm. Associations were determined using linear regression analyses. Plasma total and free testosterone showed a significant association with salivary testosterone in men (adjusted ß = .09, p = .01; and ß = .15, p < .001, respectively) and in women (adjusted ß = .08, p = .004; and crude ß = .09, p = .002 respectively). The modest associations indicate that there are many influencing factors of both technical and biological origin.

[rTMS for treatment resistant depression - proposal for a treatment protocol]. / Repetitieve transcraniële magnetische stimulatie bij therapieresistente depressie; voorstel voor een behandelprotocol.

BACKGROUND: At present, the use of repetitive transcranial magnetic stimulation (rtms) for treatment-resistant depression is sufficiently substantiated to be applied in clinical practice. In the Netherlands, it will be reimbursed when offered in combination with cognitive behavior therapy.
AIM: Proposal for a clinical treatment protocol for rtms in The Netherlands.
METHOD: A study of the literature and a critical appraisal of available international guidelines for rtms.
RESULTS: rtms is a safe treatment for patients suffering from a moderate to severe depressive disorder that is relatively treatment-resistant. The duration of the effect is still unknown. It is advised to stimulate the left dorsolateral prefrontal cortex using an intensity of 120% of the resting motor threshold, with a frequency of 10 Hz and using 3000 pulses per session during a total of 20-30 sessions.
CONCLUSION: The proposed treatment protocol is favored based on the available evidence when rtms is used as a treatment aimed to acutely decrease the severity of depressive symptoms. It is further proposed to systematically collect technical and outcome data on treatment with rtms to further improve treatment with rtms in clinical practice.

Testing a machine-learning algorithm to predict the persistence and severity of major depressive disorder from baseline self-reports.

Heterogeneity of major depressive disorder (MDD) illness course complicates clinical decision-making. Although efforts to use symptom profiles or biomarkers to develop clinically useful prognostic subtypes have had limited success, a recent report showed that machine-learning (ML) models developed from self-reports about incident episode characteristics and comorbidities among respondents with lifetime MDD in the World Health Organization World Mental Health (WMH) Surveys predicted MDD persistence, chronicity and severity with good accuracy. We report results of model validation in an independent prospective national household sample of 1056 respondents with lifetime MDD at baseline. The WMH ML models were applied to these baseline data to generate predicted outcome scores that were compared with observed scores assessed 10-12 years after baseline. ML model prediction accuracy was also compared with that of conventional logistic regression models. Area under the receiver operating characteristic curve based on ML (0.63 for high chronicity and 0.71-0.76 for the other prospective outcomes) was consistently higher than for the logistic models (0.62-0.70) despite the latter models including more predictors. A total of 34.6-38.1% of respondents with subsequent high persistence chronicity and 40.8-55.8% with the severity indicators were in the top 20% of the baseline ML-predicted risk distribution, while only 0.9% of respondents with subsequent hospitalizations and 1.5% with suicide attempts were in the lowest 20% of the ML-predicted risk distribution. These results confirm that clinically useful MDD risk-stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models.

Gene expression in major depressive disorder.

The search for genetic variants underlying major depressive disorder (MDD) has not yet provided firm leads to its underlying molecular biology. A complementary approach is to study gene expression in relation to MDD. We measured gene expression in peripheral blood from 1848 subjects from The Netherlands Study of Depression and Anxiety. Subjects were divided into current MDD (N=882), remitted MDD (N=635) and control (N=331) groups. MDD status and gene expression were measured again 2 years later in 414 subjects. The strongest gene expression differences were between the current MDD and control groups (129 genes at false-discovery rate, FDR<0.1). Gene expression differences across MDD status were largely unrelated to antidepressant use, inflammatory status and blood cell counts. Genes associated with MDD were enriched for interleukin-6 (IL-6)-signaling and natural killer (NK) cell pathways. We identified 13 gene expression clusters with specific clusters enriched for genes involved in NK cell activation (downregulated in current MDD, FDR=5.8 × 10(-5)) and IL-6 pathways (upregulated in current MDD, FDR=3.2 × 10(-3)). Longitudinal analyses largely confirmed results observed in the cross-sectional data. Comparisons of gene expression results to the Psychiatric Genomics Consortium (PGC) MDD genome-wide association study results revealed overlap with DVL3. In conclusion, multiple gene expression associations with MDD were identified and suggest a measurable impact of current MDD state on gene expression. Identified genes and gene clusters are enriched with immune pathways previously associated with the etiology of MDD, in line with the immune suppression and immune activation hypothesis of MDD.

Six-year longitudinal course and outcomes of subtypes of depression.

BACKGROUND: Clinical and aetiological heterogeneity have impeded our understanding of depression. AIMS: To evaluate differences in psychiatric and somatic course between people with depression subtypes that differed clinically (severity) and aetiologically (melancholic v. atypical). METHOD: Data from baseline, 2-, 4- and 6-year follow-up of The Netherlands Study of Depression and Anxiety were used, and included 600 controls and 648 people with major depressive disorder (subtypes: severe melancholic n = 308; severe atypical n = 167; moderate n = 173, established using latent class analysis). RESULTS: Those with the moderate subtype had a significantly better psychiatric clinical course than the severe melancholic and atypical subtype groups. Suicidal thoughts and anxiety persisted longer in those with the melancholic subtype. The atypical subtype group continued to have the highest body mass index and highest prevalence of metabolic syndrome during follow-up, although differences between groups became less pronounced over time. CONCLUSIONS: Course trajectories of depressive subtypes mostly ran parallel to each other, with baseline severity being the most important differentiator in course between groups.

The network structure of major depressive disorder, generalized anxiety disorder and somatic symptomatology.

BACKGROUND: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) often co-occur with somatic symptomatology. Little is known about the contributions of individual symptoms to this association and more insight into their relationships could help to identify symptoms that are central in the processes behind the co-occurrence. This study explores associations between individual MDD/GAD symptoms and somatic symptoms by using the network approach. METHOD: MDD/GAD symptoms were assessed in 2704 participants (mean age 41.7 years, 66.1% female) from the Netherlands Study of Depression and Anxiety using the Inventory of Depressive Symptomatology. Somatic symptoms were assessed with the somatization scale of the Four-Dimensional Symptom Questionnaire. The technique eLasso was used to estimate the network of MDD/GAD and somatic symptoms. RESULTS: The network structure showed numerous associations between MDD/GAD and somatic symptoms. In general, neurovegetative and cognitive/affective MDD/GAD symptoms showed a similar strength of connections to the somatic domain. However, associations varied substantially across individual symptoms. MDD/GAD symptoms with many and strong associations to the somatic domain included anxiety and fatigue, whereas hypersomnia and insomnia showed no connections to somatic symptoms. Among somatic symptoms, excessive perspiration and pressure/tight feeling in chest were associated with the MDD/GAD domain, while muscle pain and tingling in fingers showed only a few weak associations. CONCLUSIONS: Individual symptoms show differential associations in the co-occurrence of MDD/GAD with somatic symptomatology. Strongly interconnected symptoms are important in furthering our understanding of the interaction between the symptom domains, and may be valuable targets for future research and treatment.

Casting wider nets for anxiety and depression: disability-driven cross-diagnostic subtypes in a large cohort.

BACKGROUND: In search of empirical classifications of depression and anxiety, most subtyping studies focus solely on symptoms and do so within a single disorder. This study aimed to identify and validate cross-diagnostic subtypes by simultaneously considering symptoms of depression and anxiety, and disability measures. METHOD: A large cohort of adults (Lifelines, n = 73 403) had a full assessment of 16 symptoms of mood and anxiety disorders, and measurement of physical, social and occupational disability. The best-fitting subtyping model was identified by comparing different hybrid mixture models with and without disability covariates on fit criteria in an independent test sample. The best model's classes were compared across a range of external variables. RESULTS: The best-fitting Mixed Measurement Item Response Theory model with disability covariates identified five classes. Accounting for disability improved differentiation between people reporting isolated non-specific symptoms ['Somatic' (13.0%), and 'Worried' (14.0%)] and psychopathological symptoms ['Subclinical' (8.8%), and 'Clinical' (3.3%)]. Classes showed distinct associations with clinically relevant external variables [e.g. somatization: odds ratio (OR) 8.1-12.3, and chronic stress: OR 3.7-4.4]. The Subclinical class reported symptomatology at subthreshold levels while experiencing disability. No pure depression or anxiety, but only mixed classes were found. CONCLUSIONS: An empirical classification model, incorporating both symptoms and disability identified clearly distinct cross-diagnostic subtypes, indicating that diagnostic nets should be cast wider than current phenomenology-based categorical systems.