Deep phenotyping towards precision psychiatry of first-episode depression - the Brain Drugs-Depression cohort.

BACKGROUND: Major Depressive Disorder (MDD) is a heterogenous brain disorder, with potentially multiple psychosocial and biological disease mechanisms. This is also a plausible explanation for why patients do not respond equally well to treatment with first- or second-line antidepressants, i.e., one-third to one-half of patients do not remit in response to first- or second-line treatment. To map MDD heterogeneity and markers of treatment response to enable a precision medicine approach, we will acquire several possible predictive markers across several domains, e.g., psychosocial, biochemical, and neuroimaging. METHODS: All patients are examined before receiving a standardised treatment package for adults aged 18-65 with first-episode depression in six public outpatient clinics in the Capital Region of Denmark. From this population, we will recruit a cohort of 800 patients for whom we will acquire clinical, cognitive, psychometric, and biological data. A subgroup (subcohort I, n = 600) will additionally provide neuroimaging data, i.e., Magnetic Resonance Imaging, and Electroencephalogram, and a subgroup of patients from subcohort I unmedicated at inclusion (subcohort II, n = 60) will also undergo a brain Positron Emission Tomography with the [11C]-UCB-J tracer binding to the presynaptic glycoprotein-SV2A. Subcohort allocation is based on eligibility and willingness to participate. The treatment package typically lasts six months. Depression severity is assessed with the Quick Inventory of Depressive Symptomatology (QIDS) at baseline, and 6, 12 and 18 months after treatment initiation. The primary outcome is remission (QIDS ≤ 5) and clinical improvement (≥ 50% reduction in QIDS) after 6 months. Secondary endpoints include remission at 12 and 18 months and %-change in QIDS, 10-item Symptom Checklist, 5-item WHO Well-Being Index, and modified Disability Scale from baseline through follow-up. We also assess psychotherapy and medication side-effects. We will use machine learning to determine a combination of characteristics that best predict treatment outcomes and statistical models to investigate the association between individual measures and clinical outcomes. We will assess associations between patient characteristics, treatment choices, and clinical outcomes using path analysis, enabling us to estimate the effect of treatment choices and timing on the clinical outcome. DISCUSSION: The BrainDrugs-Depression study is a real-world deep-phenotyping clinical cohort study of first-episode MDD patients. TRIAL REGISTRATION: Registered at clinicaltrials.gov November 15th, 2022 (NCT05616559).

Prevalence of SHOX haploinsufficiency among short statured children.

BACKGROUND: The aim of this clinical study was to determine the prevalence of SHOX haploinsufficiency in a population of short stature patients and describe their anthropometric measurements. METHODS: 574 short statured patients were evaluated in a single center (1992-2015). SHOX copy number was detected by quantitative polymerase chain reaction (qPCR) in 574 subjects, followed by multiplex ligation-dependent probe amplification (MLPA) and DNA sequencing in subjects with SHOX haploinsufficiency. We evaluated anthropometric measurements at birth, and at first examination. Skeletal abnormalities were recorded for patients with SHOX haploinsufficiency. RESULTS: Thirty-two patients were excluded due to Turner syndrome (n = 28), SRY-positive 46,XX male karyotype (n = 1), or lacked clinical follow-up information (n = 3). The prevalence of SHOX haploinsufficiency was 9 out of 542 (1.7%). The nine children had decreased height -2.85 (0.6) SD scores (SDS) (mean (SD)) and weight -2.15 (1.36) SDS, P < 0.001 and P = 0.001, respectively. The sitting height/height ratio was increased, P = 0.04. Madelung deformity was diagnosed in three patients. Mean height was -2.9 (0.4) SDS at baseline and increased by 0.25 (0.2) SDS, P = 0.046, after 1 y of growth hormone (GH) treatment. CONCLUSION: The prevalence of SHOX haploinsufficiency was 1.7%. The clinical findings indicating SHOX haploinsufficiency among the nine children were disproportionate short stature and forearm anomalies.

Default mode network functional connectivity negatively associated with trait openness to experience.

Evaluating associations between the five-factor personality domains and resting-state functional connectivity networks (e.g. default mode network, DMN) highlights distributed neurobiological systems linked to behaviorally relevant phenotypes. Establishing these associations can highlight a potential underlying role for these neural pathways in related clinical illness and treatment response. Here, we examined associations between within- and between-network resting-state functional connectivity with functional magnetic resonance imaging and the five-factor personality domains: Openness to experience (Openness), Extraversion, Neuroticism, Agreeableness and Conscientiousness. We included data from 470 resting-state scan sessions and personality assessments in 295 healthy participants. Within- and between-network functional connectivity from 32 a priori defined regions was computed across seven resting-state networks. The association between functional connectivity and personality traits was assessed using generalized least squares. Within-network DMN functional connectivity was significantly negatively associated with trait Openness (regression coefficient = -0.0010; [95% confidence interval] = [-0.0017, -0.0003]; PFWER = 0.033), seemingly driven by association with the Fantasy subfacet. Trait Extraversion was significantly negatively associated with functional connectivity between the visual and dorsal attention networks and positively associated with functional connectivity between the frontoparietal and language networks. Our findings provide evidence that resting-state DMN is associated with trait Openness and gives insight into personality neuroscience.

Extrapancreatic infections are common in acute pancreatitis and they are related to organ failure: a population-based study.

BACKGROUND: Although the impact of pancreatic infections in acute pancreatitis has been studied extensively, there are no population-based data on extrapancreatic infections and their potential relation to organ failure. We aimed to study the occurrence of pancreatic and extrapancreatic bacterial infections in acute pancreatitis and their relation to patient outcome. PATIENTS AND METHODS: All patients with first-time acute pancreatitis from 2003 to 2012 in a defined area in Sweden were retrospectively evaluated. Data on acute pancreatitis severity, organ failure, infections, and in-hospital mortality were collected. RESULTS: Overall, 304 bacterial infections occurred in 248/1457 patients (17%). Fifteen percent had extrapancreatic and 2% had pancreatic infections. The lungs (35%), the urinary tract (24%), and the bile ducts (18%) were the most common sites of extrapancreatic infections. Organ failure, severe acute pancreatitis, and in-hospital mortality were more common in patients with vs those without (pancreatic/extrapancreatic) infections (P < 0.05). Organ failure and severe acute pancreatitis occurred more frequently in pancreatic vs extrapancreatic infections (70% vs 34%, P < 0.001 and 67% vs 28%, P < 0.001), but in-hospital mortality did not differ between the two groups (7.4% vs 6.8%, P = 1.0). Both pancreatic and extrapancreatic infections were independent predictors of organ failure (P < 0.05). Out of culture-positive infections, 18% were due to antibiotic-resistant bacteria, without any significant difference between extrapancreatic vs pancreatic infections (P > 0.05). About two out of five infections were of nosocomial origin. CONCLUSION: Extrapancreatic infections occurred in 15% and pancreatic infections in 2% of patients with first-time acute pancreatitis. Both pancreatic and extrapancreatic infections were independent predictors of organ failure, leading to increased mortality.