Not Just a Mood Disorder─Is Depression a Neurodevelopmental, Cognitive Disorder? Focus on Prefronto-Thalamic Circuits.

Depression is one of the most burdensome psychiatric disorders, affecting hundreds of millions of people worldwide. The disease is characterized not only by severe emotional and affective impairments, but also by disturbed vegetative and cognitive functions. Although many candidate mechanisms have been proposed to cause the disease, the pathophysiology of cognitive impairments in depression remains unclear. In this article, we aim to assess the link between cognitive alterations in depression and possible developmental changes in neuronal circuit wiring during critical periods of susceptibility. We review the existing literature and propose a role of serotonin signaling during development in shaping the functional states of prefrontal neuronal circuits and prefronto-thalamic loops. We discuss how early life insults affecting the serotonergic system could be important in the alterations of these local and long-range circuits, thus favoring the emergence of neurodevelopmental disorders, such as depression.

Shortcut citations in the methods section: Frequency, problems, and strategies for responsible reuse.

Methods sections are often missing essential details. Methodological shortcut citations, in which authors cite previous papers instead of describing the method in detail, may contribute to this problem. This meta-research study used 3 approaches to examine shortcut citation use in neuroscience, biology, and psychiatry. First, we assessed current practices in more than 750 papers. More than 90% of papers used shortcut citations. Other common reasons for using citations in the methods included giving credit or specifying what was used (who or what citation) and providing context or a justification (why citation). Next, we reviewed 15 papers to determine what can happen when readers follow shortcut citations to find methodological details. While shortcut citations can be used effectively, they can also deprive readers of essential methodological details. Problems encountered included difficulty identifying or accessing the cited materials, missing or insufficient descriptions of the cited method, and shortcut citation chains. Third, we examined journal policies. Fewer than one quarter of journals had policies describing how authors should report previously described methods. We propose that methodological shortcut citations should meet 3 criteria; cited resources should provide (1) a detailed description of (2) the method used by the citing authors', and (3) be open access. Resources that do not meet these criteria should be cited to give credit, but not as shortcut citations. We outline actions that authors and journals can take to use shortcut citations responsibly, while fostering a culture of open and reproducible methods reporting.

Anatomy of the left atrial appendage for the interventional cardiologist.

Exact knowledge of the anatomy of the left atrial appendage (LAA) is crucial for LAA isolation by catheter ablation and for interventional LAA occlusion in patients with atrial fibrillation. This review outlines the current anatomical understanding of LAA morphology from ostium to distal lobes, myocardial fiber orientation and wall structure, and adjacent structures such as the left upper pulmonary vein with the Coumadin ridge, the circumflex artery with its side branches, the aortic root, pulmonary artery, and the pericardial space. Insight into these details will facilitate these interventions and reduce the risk of complications.

Anatomical knowledge for the ablation of left and right atrial flutter.

The different forms of atrial flutter (AFL) and atrial macroreentrant tachycardias are strongly related to the atrial anatomy in structurally normal atria, and even more so in patients with dilated chambers or with previous interventions. Atrial anatomy, macro- and microscopic tissue disposition including myocardial fibers, conduction system and connective tissue is complex. This review summarizes knowledge of atrial anatomy for the interventional electrophysiologist to better understand the pathophysiology of and ablation options for these complex arrhythmias, as well as to perform catheter ablation procedures safely and effectively.

Structural Remodeling and Rotational Activity in Persistent/Long-Lasting Atrial Fibrillation: Gender-Effect Differences and Impact on Post-ablation Outcome.

Background: Structural and post-ablation gender differences are reported in atrial fibrillation (AF). We analyzed the gender differences in structural remodeling and AF mechanisms in patients with persistent/long-lasting AF who underwent wide area circumferential pulmonary vein isolation (WACPVI). Materials and Methods: Ultra-high-density mapping was used to study atrial remodeling and AF drivers in 85 consecutive patients. Focal and rotational activity (RAc) were identified with the CartoFinder system and activation sequence analysis. The impact of RAc location on post-ablation outcomes was analyzed. Results: This study included 64 men and 21 women. RAc was detected in 73.4% of men and 38.1% of women (p = 0.003). RAc patients had higher left atrium (LA) voltage (0.64 ± 0.3 vs. 0.50 ± 0.2 mV; p = 0.01), RAc sites had higher voltage than non-RAc sites 0.77 ± 0.46 vs. 0.53 ± 0.37 mV (p < 0.001). Women had lower LA voltage than men (0.42 vs. 0.64 mV; p < 0.001), including pulmonary vein (PV) antra (0.16 vs. 0.30 mV; p < 0.001) and posterior wall (0.34 vs. 0.51 mV; p < 0.001). RAc in the posterior atrium was recorded in few women (23.8 vs. 54.7% in men; p = 0.014). AF recurrence rate was higher in patients with RAc outside WACPVI than those with all RAc inside WACPVI or no RAc (63.4 vs. 11.1 and 31.0%; p = 0.008 and p = 0.01). Comparison of selected patients using propensity score matching confirmed lower atrial voltage (0.4 ± 0.2 vs. 0.7 ± 0.3 mV; p = 0.007) and less RAc (38 vs. 75%; p = 0.02) in women. Conclusion: Women have shown more advanced structural remodeling at ablation, which is associated with a lower incidence of RAc (usually located outside the WACPVI). These findings could explain post-ablation gender differences.

Association of age with clinical features and ablation outcomes of paroxysmal supraventricular tachycardias.

OBJECTIVE: The role of age in clinical characteristics and catheter ablation outcomes of atrioventricular nodal re-entrant tachycardia (AVNRT) or orthodromic atrioventricular re-entrant tachycardia (AVRT) has been assessed in retrospective studies categorising age by arbitrary cut-offs, but contemporary analyses of age-related trends are lacking. We aimed to study the relationship of age with epidemiological, clinical features and catheter ablation outcomes of AVNRT and AVRT. METHODS: We recruited 600 patients (median age 56 years, 60% female) with a confirmed diagnosis of AVNRT (n=455) or AVRT (n=145) by means of an electrophysiological study. They were interrogated for arrhythmia-related symptoms with a structured questionnaire and followed up to 1 year. We analysed age as a continuous variable using regression models and adjusting for relevant covariables. RESULTS: Both typical and atypical forms of AVNRT upraised with age while AVRT decreased (p<0.001 by regression). Female sex predominance in AVNRT was not observed in older patients. Overall, these tachycardias became more symptomatic with ageing despite a longer tachycardia cycle length (p<0.001) and regardless of the presence of structural heart disease, with a higher proportion of dizziness, syncope, chest pain or dyspnoea (p<0.005 for all) and a lower presence of palpitations or neck pounding (p<0.001 for both). Age was not associated with catheter ablation acute success, periprocedural complications or 1-year recurrence rates (p>0.05 for all). CONCLUSIONS: Age, evaluated as a continuous variable, had a significant association with the clinical profile of patients with AVNRT and AVRT. Nevertheless, catheter ablation outcomes and complications were not significantly related to patients' age.

Magnetic Resonance Imaging-Guided Fibrosis Ablation for the Treatment of Atrial Fibrillation: The ALICIA Trial.

BACKGROUND: Myocardial fibrosis is key for atrial fibrillation maintenance. We aimed to test the efficacy of ablating cardiac magnetic resonance (CMR)-detected atrial fibrosis plus pulmonary vein isolation (PVI). METHODS: This was an open-label, parallel-group, randomized, controlled trial. Patients with symptomatic drug-refractory atrial fibrillation (paroxysmal and persistent) undergoing first or repeat ablation were randomized in a 1:1 basis to receive PVI plus CMR-guided fibrosis ablation (CMR group) or PVI alone (PVI-alone group). The primary end point was the rate of recurrence (>30 seconds) at 12 months of follow-up using a 12-lead ECG and Holter monitoring at 3, 6, and 12 months. The analysis was conducted by intention-to-treat. RESULTS: In total, 155 patients (71% male, age 59±10, CHA2DS2-VASc 1.3±1.1, 54% paroxysmal atrial fibrillation) were allocated to the PVI-alone group (N=76) or CMR group (N=79). First ablation was performed in 80% and 71% of patients in the PVI-alone and CMR groups, respectively. The mean atrial fibrosis burden was 12% (only ≈50% of patients had fibrosis outside the pulmonary vein area). One hundred percent and 99% of patients received the assigned intervention in the PVI-alone and CMR group, respectively. The primary outcome was achieved in 21 patients (27.6%) in the PVI-alone group and 22 patients (27.8%) in the CMR group (odds ratio: 1.01 [95% CI, 0.50-2.04]; P=0.976). There were no differences in the rate of adverse events (3 in the CMR group and 2 in the PVI-alone group; P=0.68). CONCLUSIONS: A pragmatic ablation approach targeting CMR-detected atrial fibrosis plus PVI was not more effective than PVI alone in an unselected population undergoing atrial fibrillation ablation with low fibrosis burden. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02698631.