Dynamic time warp analysis of individual symptom trajectories in individuals with bipolar disorder.

BACKGROUND: Manic and depressive mood states in bipolar disorder (BD) may emerge from the non-linear relations between constantly changing mood symptoms exhibited as a complex dynamic system. Dynamic Time Warp (DTW) is an algorithm that may capture symptom interactions from panel data with sparse observations over time. METHODS: The Young Mania Rating Scale and Quick Inventory of Depressive Symptomatology were repeatedly assessed in 141 individuals with BD, with on average 5.5 assessments per subject every 3-6 months. Dynamic Time Warp calculated the distance between each of the 27 × 27 pairs of standardized symptom scores. The changing profile of standardized symptom scores of BD participants was analyzed in individual subjects, yielding symptom dimensions in aggregated group-level analyses. Using an asymmetric time-window, symptom changes that preceded other symptom changes (i.e., Granger causality) yielded a directed network. RESULTS: The mean age of the BD participants was 40.1 (SD 13.5) years old, and 60% were female participants. Idiographic symptom networks were highly variable between subjects. Yet, nomothetic analyses showed five symptom dimensions: core (hypo)mania (6 items), dysphoric mania (5 items), lethargy (7 items), somatic/suicidality (6 items), and sleep (3 items). Symptoms of the "Lethargy" dimension showed the highest out-strength, and its changes preceded those of "somatic/suicidality," while changes in "core (hypo)mania" preceded those of "dysphoric mania." CONCLUSION: Dynamic Time Warp may help to capture meaningful BD symptom interactions from panel data with sparse observations. It may increase insight into the temporal dynamics of symptoms, as those with high out-strength (rather than high in-strength) could be promising targets for intervention.

Childhood trauma and anger in adults with and without depressive and anxiety disorders.

BACKGROUND: Childhood trauma (CT) is associated with severe sequelae, including stress-related mental health disorders that can perpetuate long into adulthood. A key mechanism in this relationship seems to be emotion regulation. We aimed to investigate (1) whether childhood trauma is associated with anger in adulthood, and, if so, (2) to explore which types of childhood trauma predominate in the prediction of anger in a cohort that included participants with and without current affective disorders. METHODS: In the Netherlands Study of Depression and Anxiety (NESDA), childhood trauma was assessed with a semi-structured Childhood Trauma Interview (CTI) at baseline, and analyzed in relation to anger as measured at a 4-year follow-up with the Spielberger Trait Anger Subscale (STAS), the Anger Attacks Questionnaire, and cluster B personality traits (i.e., borderline, antisocial) of the Personality Disorder Questionnaire 4 (PDQ-4), using analysis of covariance (ANCOVA) and multivariable logistic regression analyses. Post hoc analyses comprised cross-sectional regression analyses, using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) also obtained at a 4-year follow-up. RESULTS: Participants (n = 2271) were on average 42.1 years (SD = 13.1), and 66.2% were female. Childhood trauma showed a dose-response association with all anger constructs. All types of childhood trauma were significantly associated with borderline personality traits, independently of depression and anxiety. Additionally, all types of childhood trauma except for sexual abuse were associated with higher levels of trait anger, and a higher prevalence of anger attacks and antisocial personality traits in adulthood. Cross-sectionally, the effect sizes were larger compared with the analyses with the childhood trauma measured 4 years prior to the anger measures. CONCLUSIONS: Childhood trauma is linked with anger in adulthood, which could be of particular interest in the context of psychopathology. Focus on childhood traumatic experiences and adulthood anger may help to enhance the effectiveness of treatment for patients with depressive and anxiety disorders. Trauma-focused interventions should be implemented when appropriate.

[Assessment of the suicidal state with the CASE approach: a closer look at the design]. / Beoordeling van de suïcidale toestand met de CASE-benadering.

BACKGROUND: Shawn Shea's Chronological Assessment of Suicide Events (CASE approach) is worldwide, including the Netherlands, a well-known and widely used method for clinical interviewing a patient's suicidal state. However, the original description of the author is not always followed. AIM: Comparing the Dutch CASE approach with the original description. METHOD: The Dutch CASE approach has been explored on the basis of the text of the Dutch multidisciplinary guideline and current handbooks. This approach is compared with the original description. RESULTS: Three differences emerge. The main difference is that in the original CASE approach, seven validity techniques represent the foundation for investigation the suicidal state, while these are missing from the Dutch texts. Second, the chronological interview system in the Netherlands is interpreted differently than in the original CASE approach. Third, in the Netherlands, in contrast to the original approach, risk factors and protective factors are included in the study of the suicidal state. CONCLUSION: In the Netherlands, the CASE approach has been adopted in a simplified form, which is useful as a basic skill in the study of suicidal behavior. The diagnosis of suicidality can gain in depth, especially for advanced mental health professionals, by paying attention in training and education to the interviewing techniques of the original CASE approach.

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.

Severity, course trajectory, and within-person variability of individual symptoms in patients with major depressive disorder.

BACKGROUND: Depression shows a large heterogeneity of symptoms between and within persons over time. However, most outcome studies have assessed depression as a single underlying latent construct, using the sum score on psychometric scales as an indicator for severity. This study assesses longitudinal symptom-specific trajectories and within-person variability of major depressive disorder over a 9-year period. METHODS: Data were derived from the Netherlands Study of Depression and Anxiety (NESDA). This study included 783 participants with a current major depressive disorder at baseline. The Inventory Depressive Symptomatology-Self-Report (IDS-SR) was used to analyze 28 depressive symptoms at up to six time points during the 9-year follow-up. RESULTS: The highest baseline severity scores were found for the items regarding energy and mood states. The core symptoms depressed mood and anhedonia had the most favorable course, whereas sleeping problems and (psycho-)somatic symptoms were more persistent over 9-year follow-up. Within-person variability was highest for symptoms related to energy and lowest for suicidal ideation. CONCLUSIONS: The severity, course, and within-person variability differed markedly between depressive symptoms. Our findings strengthen the idea that employing a symptom-focused approach in both clinical care and research is of value.

Treatment course and its predictors in patients with somatoform disorders: A routine outcome monitoring study in secondary psychiatric care.

AIM: Somatoform disorders are common and often chronic. It would be helpful to distinguish those patients who are likely to have a positive treatment course from those who are likely to follow a negative course. Such studies of different somatoform disorders are scarce, especially in secondary psychiatric care. This study examined the 6-month treatment course of psychological, physical symptoms, and functioning, and its predictors in a naturalistic sample of secondary psychiatric care outpatients with somatoform disorders. METHOD: The present study used routine outcome monitoring data of patients with somatoform disorders regarding their 6-month treatment course of psychological and physical symptoms as well as functioning. The following patient groups were included: total group of somatoform disorders (N = 435), and undifferentiated somatoform disorder (N = 242), pain disorder (N = 102), body dysmorphic disorder (N = 51), and hypochondriasis (N = 40). Measures were Mini-International Neuropsychiatric Interview plus, Brief Symptom Inventory, Montgomery-Ǻsberg Depression Rating Scale, Brief Anxiety Scale, Short Form Health Survey 36, and Physical Symptom Checklist (PSC). RESULTS: The study population generally showed high co-morbidity, especially with anxiety and mood disorders. The PSC total score, body dysmorphic disorder, and hypochondriasis were significant predictors for the treatment course of symptoms (Brief Symptom Inventory), whereas the PSC total score was the only significant predictor for the course of functioning (Short Form Health Survey 36). CONCLUSION: Secondary psychiatric care outpatients with somatoform disorders showed high co-morbidity with anxiety and mood disorders, and an unfavourable 6-month course of both symptoms and functioning. Clinical implications are discussed, such as additional treatment of co-morbidity in somatoform disorders.

[Emotional scars: impact of childhood trauma on the development of depressive and anxiety disorders later in life]. / Emotionele littekens: langetermijn-gevolgen van jeugdtrauma voor angst- en depressieve stoornissen.

BACKGROUND: Childhood trauma and negative life events in childhood are risk factors for the development of anxiety and depressive disorders in adulthood.
AIM: To increase our understanding of the specific associations between trauma and negative life events in childhood and the development and course of anxiety and depressive disorders in adulthood.
METHOD: Our research findings are based on data from the Netherlands Study of Depression and Anxiety (NESDA). In our article we report on two cross-sectional and three prospective studies.
RESULTS: All domains of childhood trauma are risk factors for the development of anxiety and/or depressive disorders in adulthood. Emotional neglect is the main independent predictor of the occurrence and the course of anxiety and depressive disorders. Certain personality characteristics and more unfavorable clinical factors play an important role in mediating the relationship between childhood trauma and the course of anxiety and depressive disorders later in life.
CONCLUSION: Not only does childhood trauma increase an individual's vulnerability to the development of anxiety and depressive disorders, it is also associated with a more serious and more chronic course of these disorders. Our studies have provided new insights into the underlying mechanism that links childhood trauma and anxiety and later anxiety depressive disorders. Consequently, we feel justified in making some recommendations with regards to clinical practice and public health interventions.

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 association between low vitamin D and depressive disorders.

It has been hypothesized that hypovitaminosis D is associated with depression but epidemiological evidence is limited. We investigated the association between depressive disorders and related clinical characteristics with blood concentrations of 25-hydroxyvitamin D [25(OH)D] in a large cohort. The sample consisted of participants (aged 18-65 years) from the Netherlands Study of Depression and Anxiety (NESDA) with a current (N=1102) or remitted (N=790) depressive disorder (major depressive disorder, dysthymia) defined according to DSM-IV criteria, and healthy controls (N=494). Serum levels of 25(OH)D measured and analyzed in multivariate analyses adjusting for sociodemographics, sunlight, urbanization, lifestyle and health. Of the sample, 33.6% had deficient or insufficient serum 25(OH)D (<50 nmol l(-1)). As compared with controls, lower 25(OH)D levels were found in participants with current depression (P=0.001, Cohen's d=0.21), particularly in those with the most severe symptoms (P=0.001, Cohen's d=0.44). In currently depressed persons, 25(OH)D was inversely associated with symptom severity (ß=-0.19, s.e.=0.07, P=0.003) suggesting a dose-response gradient, and with risk (relative risk=0.90, 95% confidence interval=0.82-0.99, P=0.03) of having a depressive disorders at 2-year follow-up. This large cohort study indicates that low levels of 25(OH)D were associated to the presence and severity of depressive disorder suggesting that hypovitaminosis D may represent an underlying biological vulnerability for depression. Future studies should elucidate whether-the highly prevalent-hypovitaminosis D could be cost-effectively treated as part of preventive or treatment interventions for depression.

Direct comparison of first-contact versus longitudinal register-based case finding in the same population: early evidence that the incidence of schizophrenia may be three times higher than commonly reported.

BACKGROUND: The incidence of schizophrenia is commonly estimated by screening for psychosis among subjects presenting to psychiatric services. This approach (using a first-contact sampling frame) cannot account for cases that did not meet criteria for schizophrenia at first contact. We compared the usual approach directly with a register-based approach (using a longitudinal sampling frame) that also includes subjects initially diagnosed with other non-schizophrenic disorders. METHOD: We compared data from the Longitudinal Psychiatric Register (LPR) of The Hague over 1980-2009 with data previously collected in a first-contact study, and applied both methods to calculate the incidence of schizophrenia for subjects aged 20-54 years in the same catchment area and over the same period (October 2000 to September 2005). We reconstructed treatment pathways and diagnostic histories up to the end of 2009 and performed sensitivity analyses. RESULTS: The LPR identified 843 first onsets of schizophrenia, corresponding to a treated incidence rate (IR) of 69 per 100,000 person-years [95% confidence interval (CI) 64-74]. The first-contact study identified 254 first onsets, corresponding to a treated IR of 21 per 100,000 person-years (95% CI 18-23). Two-thirds of the difference was accounted for by subjects treated for other disorders before the onset of psychosis, and by patients in older age groups. CONCLUSIONS: The incidence of schizophrenia was three times higher in a longitudinal register study than in a high-quality first-contact study conducted in the same population. Risk estimates based only on first-contact studies may have been affected by selection bias.

[Behavioural standard or coercive measure? Some considerations regarding the special issue on ROM]. / ROM: gedragsnorm of dwangmaatregel? Overwegingen bij het themanummer over routine outcome monitoring.

BACKGROUND: The cost of mental health care has possibly risen more than costs in other sectors of health care in the Netherlands. In an attempt to control the rising costs, new policies have been implemented that include the introduction of selective financial penalties for those in need of mental health care as well as the start of performance-based mental health care reimbursement. In order to achieve the latter goal, a nation-wide large-scale data collection was introduced based on clinical routine outcome monitoring (ROM) data, with a view to using these data for benchmarking. AIM: Closer inspection of the benchmarking efforts in terms of scientific validity. METHOD: Qualitative review and analysis. RESULTS: Analysis shows that the type of ROM data that is collected in the Netherlands is valid for tracking the outcomes of individual patients, but unsuitable for performance comparisons between institutions for reasons of case-mix, instrument-mix, bias and lack of sensitivity. CONCLUSION: Attempts to introduce benchmarking based on rom will probably have a negative impact on the practice of mental health care in the Netherlands. More input from mental health professionals and scientists is required in order to identify more rational and efficient ways of spending scarce resources.

Salivary markers of stress system activation and social withdrawal in humans.

Social withdrawal is an early and common feature of psychiatric disorders. Hypothalamic-pituitary-adrenal (HPA)-axis activation through increased salivary cortisol (sC) and sympathetic activation through increased salivary alpha-amylase (sAA) may play a role. We aimed to study whether the link between increased sC and sAA on the one hand and depression on the other hand is mediated by social withdrawal. In this cross-sectional, observational study, sC and sAA measures were measured in seven saliva samples in 843 participants (231 psychiatric patients and 612 healthy controls). Social withdrawal was assessed through the Brief Symptom Inventory (BSI)-, the Short Form 36-, and the Dutch Dimensional Assessment of Personality Pathology social withdrawal subscales, and analyzed using linear regression and mediation analyses. On average, participants were 44.0 years old (SD = 12.8; 64.1% female). Basal and diurnal sAA were unrelated to any social withdrawal scale and depression. Certain sC measures were positively associated with the BSI social withdrawal subscale (i.e., area under the curve with respect to the increase, beta = 0.082, p = 0.02; evening sC value: beta = 0.110, p = 0.003; and mean sC value: beta = 0.097; p = 0.01). We found limited support for statistical mediation by social withdrawal (measured using a composite social withdrawal score) on the relationship between evening sC and depression. Thus, although we found no support for a role of basal and diurnal sAA in social withdrawal, HPA-axis activation may partly aggravate social withdrawal in depressive disorders.

Predicting the course of anxiety disorders: The role of biological parameters.

OBJECTIVE: Clinical characteristics appear limited in their ability to predict course of anxiety disorders, therefore we explored the predictive value of biological parameters on course of anxiety disorders. METHODS: 907 persons with an anxiety (panic, social phobia, generalised anxiety) disorder with a baseline and two-year follow-up measure were selected from the Netherlands Study of Depression and Anxiety (NESDA). Previously, three course trajectories were distinguished which vary in terms of symptom severity and chronicity. Baseline clinical parameters like anxiety severity, anxiety duration, and disability were limited in their ability to predict the two-year course. This study explored whether metabolic syndrome, hypothalamic-pituitary-adrenal-axis functioning, inflammation markers, and neuroplasticity were indicators of two-year course and whether these parameters improved the model containing the most predictive clinical parameters only. RESULTS: Baseline diastolic blood pressure of persons with chronic moderate symptoms was significantly higher than of persons with non-chronic mild symptoms (odds ratio [OR] = 1.18, 95% confidence interval [CI95%] 1.01 to 1.38). Baseline high-density lipid cholesterol of persons with severe chronic symptoms was significantly lower than of persons with non-chronic mild symptoms (OR = 0.77, CI95% 0.62 to 0.96). The predictive ability of both parameters was however low with concordance statistics of 0.55 and 0.57 respectively. Addition of biological parameters did not improve the predictive ability of the model containing the clinical parameters. CONCLUSIONS: In addition to clinical characteristics, biological parameters did not improve the predictive ability of the model for course trajectory of anxiety disorders. Prediction of course trajectory in anxiety disorders remains difficult and warrants further research.

Measuring treatment outcome in patients with anxiety disorders: A comparison of the responsiveness of generic and disorder-specific instruments.

BACKGROUND: For routine outcome monitoring, generic (i.e., broad-based) and disorder-specific instruments are used to monitor patient progress. While disorder-specific instruments may be more sensitive to therapeutic change, generic measures can be applied more broadly and allow for an assessment of therapeutic change, irrespective of a specific anxiety disorder. Our goal was to investigate whether disorder-specific instruments for anxiety disorders are a valuable (or even necessary) addition to generic instruments for an appropriate assessment of treatment outcome in groups of patients. METHODS: Data were collected from 2002 to 2013 from psychiatric outpatients in treatment for Social Phobia (SP; n = 834), Generalized Anxiety Disorder (GAD; n = 661), Panic Disorder (PD; n = 944), Obsessive-Compulsive Disorder (OCD; n = 460), and Posttraumatic Stress Disorder (PTSD; n = 691). Instruments used were the generic Brief Symptom Inventory (BSI), The Mood and Anxiety Symptoms Questionnaire (MASQ), and several disorder-specific instruments (e.g., Social Interaction Anxiety Scale, Social Phobia Scale, Panic Appraisal Inventory, etc.). Responsiveness (i.e., sensitivity to therapeutic change) was examined through correlational analyses, effect sizes (ES), and analysis of variance for repeated measures. RESULTS: The MASQ appeared generally more responsive than the BSI, except for the BSI Anxiety subscale for PD. Disorder-specific measures equaled the MASQ and BSI in responsiveness. When statistically significant differences occurred, the ES was small. DISCUSSION/CONCLUSIONS: For most anxiety disorder groups (i.e., SP, PD and OCD), the MASQ or BSI was equally suited as disorder-specific instruments to detect change at group level. Exceptions are GAD and PTSD. These findings suggest limited incremental information value of disorder-specific instruments over the MASQ and BSI for measuring change.

Personality traits and the risk of incident (hypo)mania among subjects initially suffering from depressive and anxiety disorders in a 9-year cohort study.

BACKGROUND: Bipolar disorder (BD) is characterized by the alternating occurrence of (hypo)manic and depressive episodes. The aim of the current study was to determine whether personality traits independently predicted the subsequent development of (hypo)manic episodes within a group of patients who were initially diagnosed with depressive and anxiety disorders. METHODS: The Netherlands Study of Depression and Anxiety is a cohort study with measurements taken at baseline and at 2-, 4-, 6-, and 9-year follow-up. Development of a (hypo)manic episode during follow-up was assessed with the Composite International Diagnostic Interview and (hypo)manic symptoms were evaluated with the Mood Disorder Questionnaire. The Big Five personality traits were the independent variables in multivariable Cox regression analyses. RESULTS: There were 31 incident cases of (hypo)manic episodes (n = 1888, mean age 42.5 years, 68.3% women), and 233 incident cases of (hypo)manic symptoms (n = 1319, mean age 43.1, 71.9% women). In multivariable analyses, low agreeableness was independently associated with an increased risk of developing a (hypo)manic episode, with a hazard ratio (HR) of 0.54 (p = 0.002, 95% CI [0.37, 0.78]). This finding was consistent with the development of (hypo)manic symptoms (HR 0.77, p = 0.001, 95% CI [0.66, 0.89]). LIMITATIONS: The 2-year lag-time analysis reduced the number of participants at risk of a (hypo)manic episode. CONCLUSIONS: We conclude that low agreeableness is a personality-related risk factor for incident (hypo)mania among subjects initially suffering from depressive and anxiety disorders. Increased attention to personality deviances could help to recognize BD at an early stage.

Clinical and sociodemographic associations with treatment selection in major depression.

OBJECTIVE: To investigate treatment selection in a naturalistic sample of MDD outpatients and the factors influencing treatment selection in specialized psychiatric care. METHOD: Multinomial Logistic Regression analysis investigated associations between treatment selection and patients' sociodemographic and clinical characteristics, using retrospective chart review data and Routine Outcome Monitoring (ROM) data of MDD outpatients. RESULTS: Of the patients included for analyses (N = 263), 34% received psychotherapy, 32% received an antidepressant (AD) and 35% received a combination. Men were more likely than women to receive AD with reference to psychotherapy (ORAD = 5.57, 95% CI 2.38-13.00). Patients with severe depression and patients with AD use upon referral, prescribed by their general practitioner, were more likely to receive AD (ORsevere depression = 5.34, 95% CI 1.70-16.78/ORAD GP = 9.26, 95% CI 2.53-33.90) or combined treatment (ORsevere depression = 6.32, 95% CI 1.86-21.49/ORAD GP = 22.36, 95% CI 5.89-83.59) with respect to psychotherapy. More severe patients with AD upon referral received combined treatment less often compared to psychotherapy (OR = 0.14, 95% CI 0.03-0.68). CONCLUSION: AD prescriptions in primary care, severity and gender influenced treatment selection for depressive disorders in secondary psychiatric care. Other factors such as the accessibility of treatment and patient preferences may have played a role in treatment selection in this setting and need further investigation.

Elevated salivary alpha-amylase levels at awakening in patients with depression.

BACKGROUND: Specific Major Depressive Disorder (MDD) biomarkers could help improve our understanding of MDD pathophysiology and aid in the refinement of current MDD criteria. While salivary cortisol (SC) can differentiate between healthy controls and patients with psychiatric disorders, salivary alpha amylase (sAA), may be a putative candidate biomarker for MDD specifically. METHODS: In a naturalistic cohort of consecutive out-patients and healthy controls, sAA and SC were determined in 833 participants (97 MDD patients, 142 patients with other mood, anxiety, and/or somatoform (MAS-) disorders, and 594 healthy controls). Samples were collected at 7 different time points (at awakening, after 30, 45, and 60 min, at 10:00 p.m., at 11:00 p.m., and at awakening on day 2). RESULTS: The mean age of the sample was 43.8 years (SD = 12.9; 63.9% female). Concerning sAA, MDD patients had higher sAA levels upon awakening on two consecutive days (p = 0.04, p = 0.01 respectively), as well as a higher area under the curve with respect to the increase (AUCi; p = 0.04) in comparison to both controls and the other MAS-disorders group. Regarding SC, mean levels of evening SC were elevated in MDD patients (p = 0.049) in comparison to both controls and the other MAS-disorders group. SC values on day 2 after ingestion of dexamethasone were elevated in both MDD patients and the other MAS-disorders group (p = 0.04, p = 0.047 respectively). CONCLUSIONS: sAA at awakening and not cortisol differentiates MDD from other psychiatric disorders in outpatients. This suggests that sAA may be a valuable candidate biomarker specifically for MDD.

Agreement between clinical and MINI diagnoses in outpatients with mood and anxiety disorders.

BACKGROUND: Standardized Diagnostic Interviews (SDIs) such as the Mini International Neuropsychiatric Interview (MINI) are widely used to systematically screen for psychiatric disorders in research. To support generalizability of results to clinical practice, we assessed agreement between the MINI and clinical diagnoses. METHODS: Agreement was assessed in a large, real life dataset (n = 7016) using concordance statistics such as sensitivity, specificity, efficiency and area under the curve (AUC). RESULTS: 41.5% of clinical diagnoses were mood disorders, 26.5% were anxiety disorders. Overall, we found moderate agreement between MINI and clinical diagnoses (median efficiency: 0.92, median AUC: 0.79). For mood disorders, the AUC for all participants showed a range between 0.55 and 0.81 (median: 0.73), and for anxiety disorders the AUC ranged from 0.78 to 0.88 (median: 0.83). The AUC showed better agreement for mood disorders in the single diagnosis group than in the total group (median 0.77 vs. 0.71). For anxiety disorders, the AUC for the single diagnosis group was comparable to the AUC of the total group (median: 0.81 vs. 0.83 respectively). Numbers of false positives were high for both mood and anxiety diagnoses, but less so in the single diagnosis group. LIMITATIONS: Time lag between MINI and clinical diagnosis, the availability of only the primary clinical diagnosis, and relatively high severity of the current sample are limitations of the current study. CONCLUSIONS: Agreement between MINI and clinical diagnoses was moderate at best, which partly reflects the difference between the different measures used in the current study.

Large normal-range TBP and ATXN7 CAG repeat lengths are associated with increased lifetime risk of depression.

Depression is one of the most prevalent and debilitating psychiatric disorders worldwide. Recently, we showed that both relatively short and relatively long cytosine-adenine-guanine (CAG) repeats in the huntingtin gene (HTT) are associated with an increased risk of lifetime depression. However, to what extent the variations in CAG repeat length in the other eight polyglutamine disease-associated genes (PDAGs) are associated with depression is still unknown. We determined the CAG repeat sizes of ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, ATN1 and AR in two well-characterized Dutch cohorts-the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons-including 2165 depressed and 1058 non-depressed individuals-aged 18-93 years. The association between PDAG CAG repeat size and the risk for depression was assessed via binary logistic regression. We found that the odds ratio (OR) for lifetime depression was significantly higher for individuals with >10, compared with subjects with ≤10, CAG repeats in both ATXN7 alleles (OR=1.90, confidence interval (CI) 1.26-2.85). For TBP we found a similar association: A CAG repeat length exceeding the median in both alleles was associated with an increased risk for lifetime depression (OR=1.33, CI 1.00-1.76). In conclusion, we observed that carriers of either ATXN7 or TBP alleles with relatively large CAG repeat sizes in both alleles had a substantially increased risk of lifetime depression. Our findings provide critical evidence for the notion that repeat polymorphisms can act as complex genetic modifiers of depression.