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The best estimates of the incidence of schizophrenia range more than 25-fold from 3 to 80 per 100,000 person years. To what extent do differences in study design explain this wide variation? We selected all studies published between 2008-2019 reporting the incidence of schizophrenia in general populations of Northern Europe. We identified 17 estimates covering 85 million person-years and more than 15,000 individual cases. The estimates ranged from 4-72 per 100,000 person-years (median 30; interquartile range 13-41). We classified the estimates in terms of three study design factors (coverage of services, time frame, and diagnostic quality) and two population factors (urbanicity and age). A meta-regression model of the three design factors, using the two population factors as covariates, explained 91% of between-study variation. Studies performed in general psychiatric services reported similar estimates [incidence rate ratio 1.12 (95% confidence interval 0.88 to 1.43)] to those performed in specialized services. But studies applying a cumulative time frame to diagnosis reported fourfold higher estimates [4.04 (3.14 to 5.2)] than those applying a first-contact time frame. And studies based on clinical diagnoses reported lower estimates [0.55 (0.43 to 0.72)] than those based on standardized research diagnoses. The three study design factors by themselves explained 67% of between-study variation. When comparing incidence rates from different populations, distorsions arising from differences in study design can eclipse differences caused by schizophrenia risk factors, such as gender, age or migrant status. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Background Comorbidity of depressive and anxiety disorders is common and remains incompletely comprehended. This paper summarizes findings from the Netherlands Study of Depression and Anxiety (NESDA) regarding prevalence, temporal sequence, course and longitudinal patterns; sociodemographic, vulnerability and neurobiological indicators; and functional, somatic and mental health indicators of comorbidity. Methods Narrative synthesis of earlier NESDA based papers on comorbidity (n=76). Results Comorbidity was the rule in over three-quarter of subjects with depressive and/or anxiety disorders, most often preceded by an anxiety disorder. Higher severity and chronicity characterized a poorer comorbidity course. Over time, transitions between depressive and anxiety disorders were common. Consistent comorbidity risk indicators in subjects with depressive and anxiety disorders were childhood trauma, neuroticism and early age of onset. Psychological vulnerabilities, such as trait avoidance tendencies, were more pronounced in comorbid than in single disorders. In general, there were few differences in biological markers and neuroimaging findings between persons with comorbid versus single disorders. Most functional, somatic, and other mental health indicators, ranging from disability to cardiovascular and psychiatric multimorbidity, were highest in comorbid disorders. Limitations The observational design of NESDA limits causal inference. Attrition was higher in comorbid relative to single disorders. Conclusions As compared to single disorders, persons with comorbid depressive and anxiety disorders were characterized by more psychosocial risk determinants, more somatic and other psychiatric morbidities, more functional impairments, and poorer outcome. These results justify specific attention for comorbidity of depressive and anxiety disorders, particularly in treatment settings.

BackgroundBrothers and sisters growing up together share a large proportion of their genes and rearing environment. However, some siblings thrive whereas others struggle. This study investigated family-wide childhood bonding experiences with mother and father, in addition to individual-specific recollections, in relation to current depressive and anxiety symptom levels in adulthood. We examined whether extraversion and internal locus of control (iLoC) had a protective effect in this.MethodsThe sample consisted of 256 families with at least one lifetime depressed or anxious person (N = 596; ages 20–78). Multilevel modeling with cross-level interactions was used.ResultsAdult siblings showed moderate to high agreement in their childhood parental bonding (PB) recollections. Over-and-above the association between individual-specific recollections of PB and adult internalizing symptoms, family-wide poor PB was additionally linked to elevated symptom levels. Within families characterized by poor maternal bonding persons with an iLoC were relatively less anxious (but not less depressed), whereas extraversion was not protective in this context.LimitationAlthough evidence exists that poor childhood PB has an impact on (adult) psychopathology, causality cannot be determined and possible recall bias of PB should be noted. Moreover, next to their moderating effects, extraversion and LoC may also act as mediators.ConclusionsOur findings extend prior work by demonstrating the importance of siblings’ childhood PB experiences next to a person's own recollections when investigating adult internalizing symptoms, while also elucidating individual differences within families.

Background Patients with various psychiatric disorders may suffer from feelings of anger, sometimes leading to maladaptive (e.g., aggressive) behaviors. We examined to what extent depressive and anxiety disorders, relevant clinical correlates, and sociodemographics determined the level of trait anger and the prevalence of recent anger attacks. Methods In the Netherlands Study of Depression and Anxiety (NESDA), the Spielberger Trait Anger Subscale and the Anger Attacks Questionnaire were analyzed in patients with depressive (n = 204), anxiety (n = 288), comorbid (n = 222), and remitted disorders (n = 1,107), as well as in healthy controls (n = 470) based on DSM-IV criteria. Results On average, participants were 46.2 years old (SD = 13.1) and 66.3% were female. Trait anger and anger attacks were most prevalent in the comorbid group (M = 18.5, SD = 5.9, and prevalence 22.1%), followed by anxiety disorder, depressive disorder, remitted disorder, and controls (M = 12.7; SD = 2.9, and prevalence 1.3%). Major depressive disorder, social phobia, panic disorder, and generalized anxiety disorder were most strongly associated to trait anger and anger attacks. Limitations Due to a cross-sectional design, it was not possible to provide evidence for temporal or causal relationships between anger and depressive and anxiety disorders. Conclusions Trait anger and anger attacks are linked to depressive and anxiety disorders, although the strength of the relationship differed among both anger constructs.

Background: Suicidality could be associated with specific combinations of biological, social and psychologicalfactors. Therefore, depressive episodes with suicidal ideation could be different from depressive episodeswithout suicidal ideation in terms of latent variable structures.Methods: In this study we compared latent variable structures between suicidal and non-suicidal depressedpatients using confirmatory factor analysis (CFA), following a measurement invariance test procedure. Patients(N = 919) suffering from major depressive disorder were selected from the Netherlands Study of Depression andAnxiety (NESDA) and split into a group that showed no symptoms of suicidal ideation (non-SI; N = 691) and asuicidal ideation (SI) group that had one or more symptoms of suicidal ideation (N = 228). Depression andanxiety symptoms were measured using the short form of the Mood and Anxiety Symptoms Questionnaire(MASQ-D30).Results: CFA implied a difference in latent variable structures between the non-SI sample (CFI 0.957; RMSEA0.041) and the SI sample (CFI 0.900; RMSEA 0.056). Subsequent multiple-group CFA showed violations ofmeasurement invariance. The General distress and Anhedonic depression subscales were best indicated byhopelessness and lack of optimism in the SI sample and by dissatisfaction and not feeling lively in the non-SIsample. Overall, the SI sample had higher scores and lower inter-item correlations on the Anhedonic depressionitems.Limitations: We have included very mild cases of suicidal ideation in our SI sample.Conclusions: On a latent variable level, depression with suicidal ideation differs from depression without suicidalideation. Results encourage further research into the symptom structure of depression among suicidal patients

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 na?ve 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.

Trauma-related rumination and worry predict chronic PTSD. This study examined whether habitual rumination and worry measured prior to trauma exposure make persons more vulnerable to the onset of PTSD, presumably because habitual ruminators and worriers will be more prone to cognitively appraise trauma exposure in a negative way. A sample of 2981 adults aged 18–65, consisting of healthy controls and persons with past or current depressive and/or anxiety disorders were assessed at baseline and at follow-up four years later (n = 2402). At follow-up, 359 participants reported exposure to a traumatic event during the last four years of whom 52 (14.4%) had developed PTSD. Pre-trauma self-reported depression severity and trait rumination – but not trait worry-predicted onset of PTSD during follow-up, controlling for demographic and clinical history variables, as well as psychiatric diagnoses at baseline. The relation of trait rumination with onset of PTSD was partly mediated by the cognitive appraisal of the traumatic event and not by the affective reaction to trauma exposure. Repetitive negative thinking in the form of rumination may be a risk factor for onset of PTSD amenable to prevention and intervention.

Comorbidity among affective disorders is high. Rumination has been found to mediate cross-sectional and prospective relations between anxiety and depressive symptoms in adolescents and adults. We examined whether rumination and Worry, both forms of repetitive negative thinking, also explain the associations between affective disorders. This was studied using a prospective cohort study. In a mixed sample of 2981 adults (persons with a prior history of or a current affective disorder and healthy individuals) we assessed DSM-IV affective disorders (CIDI), rumination (LEIDS-R) and worry (PSWQ). All measures were repeated 2 years and 4 years later. Using structural equation models, we found that baseline rumination and worry partly mediated the association of baseline fear disorders (social anxiety disorder, panic disorder, agoraphobia) with distress disorders (dysthymia, major depressive disorder, generalized anxiety disorder). Moreover, baseline fear disorders predicted changes in distress disorders and changes in worry and rumination mediated these associations. The association between baseline distress disorders and changes in fear disorders was mediated by changes in rumination but not by changes in worry. From these results it can be concluded that repetitive negative thinking is an important transdiagnostic factor. Rumination and worry are partly responsible for the cross-sectional and prospective co-occurrence of affective disorders and may be suitable targets for treatment. (C) 2014 Elsevier Ltd. All rights reserved.

Background The monitoring of patients with an anxiety disorder can benefit from Routine Outcome Monitoring (ROM). As anxiety disorders differ in phenomenology, several anxiety questionnaires are included in ROM: Brief Scale for Anxiety (BSA), PADUA Inventory Revised (PI-R), Panic Appraisal Inventory (PAI), Penn State Worry Questionnaire (PSWQ), Worry Domains Questionnaire (WDQ), Social Interaction, Anxiety Scale (SIAS), Social Phobia Scale (SPS), and the Impact of Event Scale-Revised (IES-R). We aimed to generate reference values for both ‘healthy’ and ‘clinically anxious’ populations for these anxiety questionnaires. Methods We included 1295 subjects from the general population (ROM reference-group) and 5066 psychiatric outpatients diagnosed with a specific anxiety disorder (ROM patient-group). The MINI was used as diagnostic device in both the ROM reference group and the ROM patient group. To define limits for one-sided reference intervals (95th percentile; P95) the outermost 5% of observations were used. Receiver Operating Characteristics (ROC) analyses were used to yield alternative cut-off values for the anxiety questionnaires. Results For the ROM reference-group the mean age was 40.3 years (SD=12.6), and for the ROM patient-group it was 36.5 years (SD=11.9). Females constituted 62.8% of the reference-group and 64.4% of the patient-group. P95 ROM reference group cut-off values for reference versus clinically anxious populations were 11 for the BSA, 43 for the PI-R, 37 for the PAI Anticipated Panic, 47 for the PAI Perceived Consequences, 65 for the PAI Perceived Self-efficacy, 66 for the PSWQ, 74 for the WDQ, 32 for the SIAS, 19 for the SPS, and 36 for IES-R. ROC analyses yielded slightly lower reference values. The discriminative power of all eight anxiety questionnaires was very high. Limitations Substantial non-response and limited generalizability. Conclusions For eight anxiety questionnaires a comprehensive set of reference values was provided. Reference values were generally higher in women than in men, implying the use of gender-specific cut-off values. Each instrument can be offered to every patient with MAS disorders to make responsible decisions about continuing, changing or terminating therapy.

Background Disabling medically unexplained physical symptoms occur in 16% of all patients in primary care. Objective The aim of this study was to assess the effectiveness of a cognitivebehavioral intervention by the family physician. Method In a controlled design with detailed information on patient selection, 6,409 patients were screened on somatoform disorder, and 65 participants were allocated to care-as-usual or the experimental condition. Results After 6 and 12 months, the cognitive-behavioral intervention by trained family physicians was not more effective than care-as-usual. Conclusion Possibly, the intensity of treatment was insufficient for the severe and persistent symptoms that were encountered in primary care.

Differences in the rate of metacarpal bone loss were evaluated in a 9 year population based follow-up study among 799 women initially aged 45–64 years, using initial and follow-up radiographs of the hands. Metacarpal bone loss started around the age of 50 years and was present in more than 95% of the women. The average annual rate of loss was approximately 1 % of the initial value. The prevalence of osteopenia increased from 5% for women aged 45–49 years, up to 68% for women aged 70–76. The rate of bone loss was not similar for each individual. Regression analyses of rate of change-in-RCA on initial level of RCA indicated the presence of a consistent subgroup of fast bone losers. However, osteopenia at follow-up was more accurately predicted from initial bone density than from differences in the rate of loss.

Blood pressure in women rises after menopause. In the same period of their lives many women gain weight. Both menopause and increases in body weight may influence blood pressure elevation. To study the association between changes in body weight, age at menopause and duration of menopause, and blood pressure, a prospective follow-up study was conducted in 1167 Dutch women initially aged 45-64 years. After an average follow-up period of 8.9 years 855 women, of 1009 alive at that time, were re-examined (85%). This study indicated that age at menopause and number of postmenopausal years are not directly related to blood pressure rise in middle-aged and elderly women. However, an increase in the body mass index is an important and potentially preventable determinant of increased blood pressure and incidence of hypertension in women of this age group.