Apathy following deep brain stimulation in Parkinson's disease visualized by 7-Tesla MRI subthalamic network analysis.

BACKGROUND: Apathy is reported after subthalamic nucleus deep brain stimulation (STN DBS) and associated with a decreased quality of life in Parkinson's disease (PD) patients. Recent studies hypothesized that the location of active DBS contact point relative to the STN subdivisions (motor, associative and limbic) could be related to an increase of apathy. METHODS: 22 PD-patients that underwent STN DBS between January 2019 and February 2020 were divided in an apathy and non-apathy group using the change in the Starkstein Apathy Scale (SAS) after six months of DBS. For both groups the location of DBS electrodes was determined based on 7T MRI subthalamic network analysis, enabling visualization of the subdivisions and their projections relative to the active contact point. MDS-UPDRS III scores were included to evaluate DBS effect. RESULTS: In six patients a post-DBS increase in apathy score was assessed, versus 16 non-apathy patients. Network analysis showed that active contacts in apathy patients were more often positioned in or close to the area within the STN with high density of surrounding projections to associative cortex areas than in non-apathy patients; 63% apathy versus 42% (P = 0.02). The density of surrounding motor projections was lower in the group with increased apathy (18%) than in the group without increased apathy (38%, P = 0.01). Motor UPDRS improvement for the apathy group was 39% and for the non-apathy group 58% (n.s.) CONCLUSION: This new approach in patient-specific subthalamic 7T MRI network analysis visualized an anatomical connectivity substrate for apathy in DBS, with active electrode contacts predominantly in the associative STN.

Optimizing treatment of brain metastases in an era of novel systemic treatments: a single center consecutive series.

BACKGROUND: The multidisciplinary management of patients with brain metastases consists of surgical resection, radiation treatment and systemic treatment. Tailoring and timing these treatment modalities is challenging. This study presents real-world data from consecutively treated patients and assesses the impact of all treatment strategies and their relation with survival. The aim is to provide new insights to improve multidisciplinary decisions towards individualized treatment strategies in patients with brain metastases. METHODS: A retrospective consecutive cohort study was performed. Patients with brain metastases were included between June 2018 and May 2020. Brain metastases of small cell lung carcinoma were excluded. Overall survival was analyzed in multivariable models. RESULTS: 676 patients were included in the study, 596 (88%) received radiotherapy, 41 (6%) awaited the effect of newly started or switched systemic treatment and 39 (6%) received best supportive care. Overall survival in the stereotactic radiotherapy group was 14 months (IQR 5-32) and 32 months (IQR 11-43) in patients who started or switched systemic treatment and initially did not receive radiotherapy. In patients with brain metastases without options for local or systemic treatment best supportive care was provided, these patients had an overall survival of 0 months (IQR 0-1). Options for systemic treatment, Karnofsky Performance Score ≥ 70 and breast cancer were prognostic for a longer overall survival, while progressive extracranial metastases and whole-brain-radiotherapy were prognostic for shorter overall survival. CONCLUSIONS: Assessing prognosis in light of systemic treatment options is crucial after the diagnosis of brain metastasis for the consideration of radiotherapy versus best supportive care.

Thalamic local field potentials recorded using the deep brain stimulation pulse generator.

Background: Essential tremor (ET) is one of the most common movement disorders, and continuous deep brain stimulation (DBS) is an established treatment for medication-refractory cases. However, the need for increasing stimulation intensities, with unpleasant side effects, and DBS tolerance over time can be problematic. The advent of novel DBS devices now provides the opportunity to longitudinally record LFPs using the implanted pulse generator, which opens up possibilities to implement adaptive DBS algorithms in a real-life setting. Methods: Here we report a case of thalamic LFP activity recorded using a commercially available sensing-enabled DBS pulse generator (Medtronic Percept PC). Results: In the OFF-stimulation condition, a peak tremor frequency of 3.8 Hz was identified during tremor evoking movements as assessed by video and accelerometers. Activity at the same and supraharmonic frequency was seen in the frequency spectrum of the LFP data from the left vim nucleus during motor tasks. Coherence analysis showed that peripherally recorded tremor was coherent with the LFP signal at the tremor frequency and supraharmonic frequency. Conclusion: This is the first report of recorded tremor-related thalamic activity using the electrodes and pulse generator of an implanted DBS system. Larger studies are needed to evaluate the clinical potential of these fully implantable systems, and ultimately pulse generators with sensing-coupled algorithms driving stimulation, to really close the loop.

[The effect of different kinds and concentrations of disinfectants on decontamination of healing abutments]. / Het effect van verschillende soorten en concentraties desinfectantia op de decontaminatie van healing abutments.

Cross infection by remnants of microorganisms represents a latent risk in the dental practice. This study confirms that used healing abutments that have undergone the prescribed disinfection and sterilization procedures are still contaminated. Such residual contamination can be reduced by a simple, additional disinfection procedure. Different disinfectants, in increasing concentrations, were compared with a control group that had not been subject to any additional disinfection procedure. Newly supplied healing abutments were studied, as a second control. The findings show an additional disinfection procedure by immersion in a 5% sodium hypochlorite (NaOCI) solution to result in a significant reduction of contamination of healing abutments, making it a possible valuable addition to existing disinfection procedures. The results of this study might provide an impulse to investigate whether this kind of additional disinfection and sterilization of other dental materials would be of additional value.

[Nutrition and mental disorders during the life span: an overview of scientific evidence]. / Voeding bij psychische aandoeningen gedurende de levensloop; een overzicht van de evidentie.

BACKGROUND: Nutritional interventions are scarcely used in the prevention and treatment of mental disorders.
AIM: To summarize scientific evidence on the relation between nutrition and mental health, across the life span.
METHOD: An overview of the literature based on recent knowledge syntheses, meta-analyses and original studies.
RESULTS: Healthy dietary patterns are associated with a lower risk for depressive symptoms among adults and potentially also among children and adolescents. Dietary interventions can be effective in reducing depressive symptoms among high-risk groups and can have a beneficial effect in the treatment of depression. Meta-analyses of randomised studies have shown that omega-3 fatty acid supplements can be of added value in the treatment of adhd in children and of depression in adults.
CONCLUSION: Promotion of healthy dietary patterns in line with National guidelines for healthy diets is important in the entire spectrum from good mental health to a chronic disorder. More attention for improving healthy dietary patterns among patients with mental disorders can lead to important health gains.

Fatty acids and recurrence of major depressive disorder: combined analysis of two Dutch clinical cohorts.

OBJECTIVE: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acid (PUFA) alterations in patients with major depressive disorder (MDD) have been shown to persist after remission. Whether these alterations are risk factors for MDD recurrence remains unknown. Here, we examined whether fatty acids predict time until MDD recurrence in remitted MDD patients. METHODS: Data were used from remitted MDD patients of the Netherlands Study of Depression and Anxiety (n = 356) and the Depression Evaluation Longitudinal Therapy Assessment studies (n = 118). Associations of FAs with time until MDD recurrence up to 8-year follow-up were analyzed using Cox regression analyses. Study-specific estimates were pooled using mega- and meta-analysis techniques. RESULTS: 27.5% (NESDA) and 56.8% (DELTA) participants had an MDD recurrence. Pooled results showed that no FA was significantly associated with time until MDD recurrence (n-3 PUFAs: hazard ratio (HR) = 1.17, 95% confidence interval (CI) = 0.98-1.41, P = 0.082; n-6 PUFAs: HR = 1.08, 95% CI = 0.84-1.38, P = 0.55). CONCLUSION: In remitted MDD patients, circulating PUFAs were not associated with prospective risk of MDD recurrence. Consequently, circulating PUFAs are unlikely to reflect a vulnerability marker for recurrence, so correcting n-3 PUFA 'deficits' through supplementation does not seem a promising option to prevent MDD recurrence.

Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man.

Individual susceptibility to anxiety disorders after maladaptive responses to stress is not well understood. We now report that while exploring stress responses in mice after traumatic brain injury (TBI), a condition associated to stress susceptibility, we observed that the anxiogenic effects of either TBI or exposure to life-threatening experiences (predator) were blocked when both stressors were combined. Because TBI increases the entrance into the brain of serum insulin-like growth factor I (IGF-I), a known modulator of anxiety with a wide range of concentrations in the human population, we then determined whether circulating IGF-I is related to anxiety measures. In mice, anxiety-like responses to predator were inversely related to circulating IGF-I levels. Other indicators of mood regulation such as sensitivity to dexamethasone suppression and expression levels of blood and brain FK506 binding protein 5 (FKBP5), a co-chaperone of the glucocorticoid receptor that regulates its activity, were also associated to circulating IGF-I. Indeed, brain FKBP5 expression in mice was stimulated by IGF-I. In addition, we observed in a large human cohort (n = 2686) a significant relationship between plasma IGF-I and exposure to recent stressful life events, while FKBP5 expression in blood cells was significantly associated to plasma IGF-I levels. Collectively, these data indicate that circulating IGF-I appears to be involved in mood homeostasis across different species. Furthermore, the data in mice allow us to indicate that IGF-I may be acting at least in part by modulating FKBP5 expression.

Socioeconomic and ethnic inequities within organised colorectal cancer screening programmes worldwide.

OBJECTIVE: Colorectal cancer (CRC) screening programmes can reduce CRC mortality. However, the implementation of a screening programme may create or exacerbate socioeconomic and ethnic health inequities if participation varies by subgroup. We determined which organised programmes characterise participation inequities by socioeconomic and ethnic subgroups, and assessed the variation in subgroup participation among programmes collecting group-specific data. DESIGN: Employing a literature review and survey among leaders of national or regional screening programmes, this study identified published and unpublished data on participation by socioeconomic status and ethnicity. We assessed programmes offering faecal occult blood tests (FOBT) for screening. Primary outcome was screening participation rate. RESULTS: Across 24 organised FOBT-screening programmes meeting the inclusion criteria, participation rates ranged from 21% to 73%. Most programmes (13/24, 54%) did not collect data on participation by socioeconomic status and ethnicity. Among the 11 programmes with data on participation by socioeconomic status, 90% (28/31 publications) reported lower participation among lower socioeconomic groups. Differences across socioeconomic gradients were moderate (66% vs 71%) to severe (35% vs 61%). Only six programmes reported participation results by ethnicity. Ethnic differences were moderate, though only limited data were available for evaluation. CONCLUSIONS: Across organised CRC screening programmes worldwide, variation in participation by socioeconomic status and ethnicity is often not assessed. However, when measured, marked disparities in participation by socioeconomic status have been observed. Limited data were available to assess inequities by ethnicity. To avoid exacerbating health inequities, screening programmes should systematically monitor participation by socioeconomic status and ethnicity, and investigate and address determinants of low participation.

Ethnic differences in colon cancer care in the Netherlands: a nationwide registry-based study.

BACKGROUND: Ethnic differences in colon cancer (CC) care were shown in the United States, but results are not directly applicable to European countries due to fundamental healthcare system differences. This is the first study addressing ethnic differences in treatment and survival for CC in the Netherlands. METHODS: Data of 101,882 patients diagnosed with CC in 1996-2011 were selected from the Netherlands Cancer Registry and linked to databases from Statistics Netherlands. Ethnic differences in lymph node (LN) evaluation, anastomotic leakage and adjuvant chemotherapy were analysed using stepwise logistic regression models. Stepwise Cox regression was used to examine the influence of ethnic differences in adjuvant chemotherapy on 5-year all-cause and colorectal cancer-specific survival. RESULTS: Adequate LN evaluation was significantly more likely for patients from 'other Western' countries than for the Dutch (OR 1.09; 95% CI 1.01-1.16). 'Other Western' patients had a significantly higher risk of anastomotic leakage after resection (OR 1.24; 95% CI 1.05-1.47). Patients of Moroccan origin were significantly less likely to receive adjuvant chemotherapy (OR 0.27; 95% CI 0.13-0.59). Ethnic differences were not fully explained by differences in socioeconomic and hospital-related characteristics. The higher 5-year all-cause mortality of Moroccan patients (HR 1.64; 95% CI 1.03-2.61) was statistically explained by differences in adjuvant chemotherapy receipt. CONCLUSION: These results suggest the presence of ethnic inequalities in CC care in the Netherlands. We recommend further analysis of the role of comorbidity, communication in patient-provider interaction and patients' health literacy when looking at ethnic differences in treatment for CC.

Cardiovascular disease risk and secondary prevention of cardiovascular disease among patients with low health literacy.

OBJECTIVE: To explore the association between health literacy and the risk of cardiovascular disease (CVD), and to assess the differential effects by health literacy level of a nurse-coordinated secondary prevention program (NCPP) in patients with coronary artery disease (CAD). METHODS: Data were collected in two medical centres participating in the RESPONSE trial (Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists). CVD risk profiles were assessed at baseline and 12-month follow-up using the Systematic Coronary Risk Evaluation (SCORE). Health literacy was assessed by the short Rapid Estimate of Adult Literacy in Medicine (REALM-D) and the Newest Vital Sign (NVS-D); self-reported health literacy was evaluated by the Set of Brief Screening Questions (SBSQ-D). RESULTS: Among 201 CAD patients, 18% exhibited reading difficulties, 52% had difficulty understanding and applying written information, and 5% scored low on self-reported health literacy. Patients with low NVS-D scores had a higher CVD risk [mean SCORE 5.2 (SD 4.8) versus 3.3 (SD 4.1), p < 0.01]. Nurse-coordinated care seemed to reduce CVD risk irrespective of health literacy levels without significant differences. CONCLUSION: Inadequate health literacy is prevalent in CAD patients in the Netherlands, and is associated with less favourable CVD risk profiles. Where many other forms of CVD prevention fail, nurse-coordinated care seems to be effective among patients with inadequate health literacy.

Oxidative stress in major depressive and anxiety disorders, and the association with antidepressant use; results from a large adult cohort.

BACKGROUND: Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD) and anxiety disorders and may be influenced by antidepressant use. This study investigated the association of oxidative stress, measured by plasma levels of F2-isoprostanes and 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflecting oxidative lipid and DNA damage respectively, with MDD, anxiety disorders and antidepressant use in a large cohort. METHOD: Data was derived from the Netherlands Study of Depression and Anxiety including patients with current (N = 1619) or remitted (N = 610) MDD and/or anxiety disorder(s) (of which N = 704 antidepressant users) and 612 controls. Diagnoses were established with the Composite International Diagnostic Interview. Plasma 8-OHdG and F2-isoprostanes were measured using LC-MS/MS. ANCOVA was performed adjusted for sampling, sociodemographic, health and lifestyle variables. RESULTS: F2-isoprostanes did not differ between controls and patients, or by antidepressant use. Patients with current disorders had lower 8-OHdG (mean 42.1 pmol/l, 95% CI 40.4-43.8) compared to controls (45.0 pmol/l, 95% CI 42.9-47.2; p < 0.001) after adjustment for sampling, sociodemographics and lifestyle, but these differences disappeared after further adjustment for antidepressant use (p = 0.562). Antidepressant users had lower 8-OHdG levels (38.2 pmol/l, 95% CI 36.5-39.9) compared to controls (44.9 pmol/l, 95% CI 43.2-46.6; Cohen's d = 0.21, p < 0.001). Results for 8-OHdG were comparable across disorders (MDD and/or anxiety disorders), and all antidepressant types (SSRIs, TCAs, other antidepressants). CONCLUSION: Contrary to previous findings this large-scale study found no increased oxidative stress in MDD and anxiety disorders. Antidepressant use was associated with lower oxidative DNA damage, suggesting antidepressants may have antioxidant effects.

Validity of LIDAS (LIfetime Depression Assessment Self-report): a self-report online assessment of lifetime major depressive disorder.

BACKGROUND: There is a paucity of valid, brief instruments for the assessment of lifetime major depressive disorder (MDD) that can be used in, for example, large-scale genomics, imaging or biomarker studies on depression. We developed the LIfetime Depression Assessment Self-report (LIDAS), which assesses lifetime MDD diagnosis according to DSM criteria, and is largely based on the widely used Composite International Diagnostic Interview (CIDI). Here, we tested the feasibility and determined the sensitivity and specificity for measuring lifetime MDD with this new questionnaire, with a regular CIDI as reference. METHOD: Sensitivity and specificity analyses of the online lifetime MDD questionnaire were performed in adults with (n = 177) and without (n = 87) lifetime MDD according to regular index CIDIs, selected from the Netherlands Study of Depression and Anxiety (NESDA) and Netherlands Twin Register (NTR). Feasibility was tested in an additional non-selective, population-based sample of NTR participants (n = 245). RESULTS: Of the 753 invited persons, 509 (68%) completed the LIDAS, of which 419 (82%) did this online. User-friendliness of the instrument was rated high. Median completion time was 6.2 min. Sensitivity and specificity for lifetime MDD were 85% [95% confidence interval (CI) 80-91%] and 80% (95% CI 72-89%), respectively. This LIDAS instrument gave a lifetime MDD prevalence of 20.8% in the population-based sample. CONCLUSIONS: Measuring lifetime MDD with an online instrument was feasible. Sensitivity and specificity were adequate. The instrument gave a prevalence of lifetime MDD in line with reported population prevalences. LIDAS is a promising tool for rapid determination of lifetime MDD status in large samples, such as needed for genomics studies.

[Enumerating the preventive youth health care workforce: size, composition and regional variation in the Netherlands]. / Capaciteit van de jeugdgezondheidszorg in Nederland.

OBJECTIVE: The progress in workforce planning in preventive youth health care (YHC) is hampered by a lack of data on the current workforce. This study aimed to enumerate the Dutch YHC workforce. To understand regional variations in workforce capacity we compared these with the workforce capacity and the number of children and indicators of YHC need per region. METHODS: A national survey was conducted using online questionnaires based on WHO essential public health operations among all YHC workers. Respondents (n=3220) were recruited through organisations involved in YHC (participation: 88%). RESULTS: The YHC workforce is multi-disciplinary, 62% had > 10 years working experience within YHC and only small regional variations in composition existed. The number of children per YHC professional varied between regions (range: 688-1007). All essential public health operations were provided. Regional differences in the number of children per YHC professional were unrelated to the indicators of YHC need. CONCLUSION: The essential public health operations provided by the YHC workforce and the regional variations in children per YHC professional were not in line with indicators of YHC needs, indicating room for improvement of YHC workforce planning. The methodology applied in this study is probably relevant for use in other countries.

[Healthcare for teenagers: are we working together?]. / Gezondheidszorg voor tieners: trekken we samen op?

There are about 1.8 million children between 10 and 18 years of age in the Netherlands in 2016. These teenagers account for approximately 10% of the total population. Teenagers are relatively healthy and do not make much use of curative care. However, they are an important group in terms of public health, because a basis for good health in later life is created in the teenage years. Good health in teenagers is also important for education, relationships and employment, and their health has an influence on the health of the next generation. Child and adolescent healthcare plays an important part in preventive care for teenagers. Better cooperation and exchange of information between paediatricians, specialists in child and adolescent healthcare and general practitioners are important in order to optimise care for teenagers.

Serum proteomic profiles of depressive subtypes.

Depression is a highly heterogeneous disorder. Accumulating evidence suggests biological and genetic differences between subtypes of depression that are homogeneous in symptom presentation. We aimed to evaluate differences in serum protein profiles between persons with atypical and melancholic depressive subtypes, and compare these profiles with serum protein levels of healthy controls. We used the baseline data from the Netherlands Study of Depression and Anxiety on 414 controls, 231 persons with a melancholic depressive subtype and 128 persons with an atypical depressive subtype for whom the proteomic data were available. Depressive subtypes were previously established using a data-driven analysis, and 171 serum proteins were measured on a multi-analyte profiling platform. Linear regression models were adjusted for several covariates and corrected for multiple testing using false discovery rate q-values. We observed differences in analytes between the atypical and melancholic subtypes (9 analytes, q<0.05) and between atypical depression and controls (23 analytes, q<0.05). Eight of the nine markers differing between the atypical and melancholic subtype overlapped with markers from the comparison between atypical subtype and controls (mesothelin, leptin, IGFBP1, IGFBP2, FABPa, insulin, C3 and B2M), and were mainly involved in cellular communication and signal transduction, and immune response. No markers differed significantly between the melancholic subtype and controls. To conclude, although some uncertainties exist in our results as a result of missing data imputation and lack of proteomic replication samples, many of the identified analytes are inflammatory or metabolic markers, which supports the notion of atypical depression as a syndrome characterized by metabolic disturbances and inflammation, and underline the importance and relevance of subtypes of depression in biological and genetic research, and potentially in the treatment of depression.

[We are living longer, but are these additional years spent in good health?]. / We leven langer, maar wat zijn dat voor jaren?

Life expectancy in western countries has increased continuously over recent years. The issue at stake is if this rise includes healthy years. The answer depends on the health indicator used, e.g., perceived health, disability, or cognitive impairment. A study by Jagger et al. (2016) provides evidence for an increase in life expectancy without cognitive impairment and an absolute compression of cognitive impairment between 1991 and 2011. Information on life expectancy without cognitive impairment is not yet available for the Netherlands. Similar to England, Dutch trends in life expectancy in excellent or good self-perceived health and in life expectancy without severe disability are favourable, although less pronouncedly so. Dutch and English data suggest that the additional years lived by the population are at least partly spent in good health.

Knowledge and Informed Decision-Making about Population-Based Colorectal Cancer Screening Participation in Groups with Low and Adequate Health Literacy.

Objective. To analyze and compare decision-relevant knowledge, decisional conflict, and informed decision-making about colorectal cancer (CRC) screening participation between potential screening participants with low and adequate health literacy (HL), defined as the skills to access, understand, and apply information to make informed decisions about health. Methods. Survey including 71 individuals with low HL and 70 with adequate HL, all eligible for the Dutch organized CRC screening program. Knowledge, attitude, intention to participate, and decisional conflict were assessed after reading the standard information materials. HL was assessed using the Short Assessment of Health Literacy in Dutch. Informed decision-making was analyzed by the multidimensional measure of informed choice. Results. 64% of the study population had adequate knowledge of CRC and CRC screening (low HL 43/71 (61%), adequate HL 47/70 (67%), p > 0.05). 57% were informed decision-makers (low HL 34/71 (55%), adequate HL 39/70 (58%), p > 0.05). Intention to participate was 89% (low HL 63/71 (89%), adequate HL 63/70 (90%)). Respondents with low HL experienced significantly more decisional conflict (25.8 versus 16.1; p = 0.00). Conclusion. Informed decision-making about CRC screening participation was suboptimal among both individuals with low HL and individuals with adequate HL. Further research is required to develop and implement effective strategies to convey decision-relevant knowledge about CRC screening to all screening invitees.

Oxidative stress, anti-oxidants and the cross-sectional and longitudinal association with depressive symptoms: results from the CARDIA study.

Depression may be accompanied by increased oxidative stress and decreased circulating anti-oxidants. This study examines the association between depressive symptoms, F2-isoprostanes and carotenoids in a US community sample. The study includes 3009 participants (mean age 40.3, 54.2% female) from CARDIA (Coronary Artery Risk Development in Young Adults). Cross-sectional analyses were performed on data from the year 15 examination (2000-2001) including subjects whose depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) and had measurements of plasma F2-isoprostanes (gas chromatography/mass spectrometry) or serum carotenoids (high-performance liquid chromatography). Carotenoids zeaxanthin/lutein, ß-cryptoxanthin, lycopene, α-carotene, ß-carotene were standardized and summed. Longitudinal analyses were conducted using the data from other examinations at 5-year intervals. Cross-lagged analyses investigated whether CES-D predicted F2-isoprostanes or carotenoids at the following exam, and vice versa. Regression analyses were controlled for sociodemographics, health and lifestyle factors. F2-isoprostanes were higher in subjects with depressive symptoms (CES-D ⩾ 16) after adjustment for sociodemographics (55.7 vs 52.0 pg ml(-1); Cohen's d = 0.14, P < 0.001). There was no difference in F2-isoprostanes after further adjustment for health and lifestyle factors. Carotenoids were lower in those with CES-D scores ⩾ 16, even after adjustment for health and lifestyle factors (standardized sum 238.7 vs 244.0, Cohen's d = -0.16, P < 0.001). Longitudinal analyses confirmed that depression predicts subsequent F2-isoprostane and carotenoid levels. Neither F2-isoprostanes nor carotenoids predicted subsequent depression. In conclusion, depressive symptoms were cross-sectionally and longitudinally associated with increased F2-isoprostanes and decreased carotenoids. The association with F2-isoprostanes can largely be explained by lifestyle factors, but lower carotenoids were independently associated with depressive symptoms.

Serum biomarkers predictive of depressive episodes in panic disorder.

Panic disorder with or without comorbid agoraphobia (PD/PDA) has been linked to an increased risk to develop subsequent depressive episodes, yet the underlying pathophysiology of these disorders remains poorly understood. We aimed to identify a biomarker panel predictive for the development of a depressive disorder (major depressive disorder and/or dysthymia) within a 2-year-follow-up period. Blood serum concentrations of 165 analytes were evaluated in 120 PD/PDA patients without depressive disorder baseline diagnosis (6-month-recency) in the Netherlands Study of Depression and Anxiety (NESDA). We assessed the predictive performance of serum biomarkers, clinical, and self-report variables using receiver operating characteristics curves (ROC) and the area under the ROC curve (AUC). False-discovery-rate corrected logistic regression model selection of serum analytes and covariates identified an optimal predictive panel comprised of tetranectin and creatine kinase MB along with patient gender and scores from the Inventory of Depressive Symptomatology (IDS) rating scale. Combined, an AUC of 0.87 was reached for identifying the PD/PDA patients who developed a depressive disorder within 2 years (n = 44). The addition of biomarkers represented a significant (p = 0.010) improvement over using gender and IDS alone as predictors (AUC = 0.78). For the first time, we report on a combination of biological serum markers, clinical variables and self-report inventories that can detect PD/PDA patients at increased risk of developing subsequent depressive disorders with good predictive performance in a naturalistic cohort design. After an independent validation our proposed biomarkers could prove useful in the detection of at-risk PD/PDA patients, allowing for early therapeutic interventions and improving clinical outcome.