Is the mainstream construction of mood disorders resistant to systemic thinking?

IntroductionIn this study we explore how the diagnostic category of mood disorders is constructed in two handbooks of Psychopathology as an example of the mainstream construction of psychopathology. Despite the increasing criticism and lack of evidence, the debunked chemical imbalance theory of the etiology of depression still dominates the professional and pop/folk understanding and interventions.MethodsWe analysed the breadth of the inference field and the type of etiopathogenetic contents of the explanations of mood disorders using the “1to3” Coding System.ResultsOur findings show that the dominant explanations draw almost exclusively onto monadic explanations, followed by limited dyadic ones. Intrapersonal etiopathogenetic contents prevailed, and biomedical explanations were dominant in both textbooks.DiscussionWe critically discuss the underpinnings of these results and address the clinical implications of these biased representations, as well as potential alternative approaches to psychopathology

Paving the way for systemic phenomenological psychiatry - the forgotten heritage of Wolfgang Blankenburg

Phenomenological psychopathology focuses on the first-person experience of mental disorders. Although it is in principle descriptive, it also entails an explanatory dimension: single psychological symptoms are conceived as genetically arising from a holistic structure of personal experience, i.e., the patient's being-in-the-world – and of its dynamic unfolding over time. Yet both classical and current phenomenological approaches tend to identify the essential disorder or “trouble générateur” (Minkowski) of mental illness within the individual, thereby neglecting the relevance of the social context not only for the emergence of symptoms but also for their treatment. The work of Wolfgang Blankenburg on schizophrenia represents a noteworthy approach to overcome this individualistic tendency. He introduced the concept of “loss of common sense” as the structural core of schizophrenic experience and being-in-the-world and he considered the social and most importantly familial context for the emergence of schizophrenic experience. By accounting not only for personal experience but also for interactional structures of families and social milieus in which experience is embedded, Blankenburg thereby offered ways to combine phenomenological and systemic explanations of mental disorders. Beside his most renowned work on “the loss of common sense,” in this paper we also present his family studies of young persons with schizophrenia, which have so far received little if no attention. We thus discuss the different ways in which Blankenburg expanded the phenomenological approach into a more systemic and social direction. We then link Blankenburg's work with current systemic explanatory models of schizophrenia and explore the clinical and scientific implications of this link. Finally, we call for further research on the synergy effects between the two

Multiple sclerosis cortical and WM lesion segmentation at 3T MRI: a deep learning method based on FLAIR and MP2RAGE.

The presence of cortical lesions in multiple sclerosis patients has emerged as an important biomarker of the disease. They appear in the earliest stages of the illness and have been shown to correlate with the severity of clinical symptoms. However, cortical lesions are hardly visible in conventional magnetic resonance imaging (MRI) at 3T, and thus their automated detection has been so far little explored. In this study, we propose a fully-convolutional deep learning approach, based on the 3D U-Net, for the automated segmentation of cortical and white matter lesions at 3T. For this purpose, we consider a clinically plausible MRI setting consisting of two MRI contrasts only: one conventional T2-weighted sequence (FLAIR), and one specialized T1-weighted sequence (MP2RAGE). We include 90 patients from two different centers with a total of 728 and 3856 gray and white matter lesions, respectively. We show that two reference methods developed for white matter lesion segmentation are inadequate to detect small cortical lesions, whereas our proposed framework is able to achieve a detection rate of 76% for both cortical and white matter lesions with a false positive rate of 29% in comparison to manual segmentation. Further results suggest that our framework generalizes well for both types of lesion in subjects acquired in two hospitals with different scanners

Predicted vs. measured paraspinal muscle activity in adolescent idiopathic scoliosis patients: EMG validation of optimization-based musculoskeletal simulations.

Musculoskeletal (MSK) models offer great potential for predicting the muscle forces required to inform more detailed simulations of vertebral endplate loading in adolescent idiopathic scoliosis (AIS). In this work, simulations based on static optimization were compared with in vivo measurements in two AIS patients to determine whether computational approaches alone are sufficient for accurate prediction of paraspinal muscle activity during functional activities. We used biplanar radiographs and marker-based motion capture, ground reaction force, and electromyography (EMG) data from two patients with mild and moderate thoracolumbar AIS (Cobb angles: 21° and 45°, respectively) during standing while holding two weights in front (reference position), walking, running, and object lifting. Using a fully automated approach, 3D spinal shape was extracted from the radiographs. Geometrically personalized OpenSim-based MSK models were created by deforming the spine of pre-scaled full-body models of children/adolescents. Simulations were performed using an experimentally controlled backward approach. Differences between model predictions and EMG measurements of paraspinal muscle activity (both expressed as a percentage of the reference position values) at three different locations around the scoliotic main curve were quantified by root mean square error (RMSE) and cross-correlation (XCorr). Predicted and measured muscle activity correlated best for mild AIS during object lifting (XCorr's ≥ 0.97), with relatively low RMSE values. For moderate AIS as well as the walking and running activities, agreement was lower, with XCorr reaching values of 0.51 and comparably high RMSE values. This study demonstrates that static optimization alone seems not appropriate for predicting muscle activity in AIS patients, particularly in those with more than mild deformations as well as when performing upright activities such as walking and running

Biomechanics of the lumbar spine after dynamic stabilization

Target of the study was to predict the biomechanics of the instrumented and adjacent levels due to the insertion of the DIAM spinal stabilization system (Medtronic Ltd). For this purpose, a 3-dimensional finite element model of the intact L3/ S1 segment was developed and subjected to different loading conditions (flexion, extension, lateral bending, axial rotation). The model was then instrumented at the L4/L5 level and the same loading conditions were reapplied. Within the assumptions of our model, the simulation results suggested that the implant caused a reduction in range of motion of the instrumented level by 17% in flexion and by 43% in extension, whereas at the adjacent levels, no significant changes were predicted. Numerical results in terms of intradiscal pressure, relative to the intact condition, predicted that the intervertebral disc at the instrumented level was unloaded by 27% in flexion, by 51% in extension, and by 6% in axial rotation, while no variations in pressure were caused by the device in lateral bending. At the adjacent levels, a change of relative intradiscal pressure was predicted in extension, both at the L3/L4 level, which resulted unloaded by 26% and at the L5/S1 level, unloaded by 8%. Furthermore, a reduction in terms of principal compressive stress in the annulus fibrosus of the L4/L5 instrumented level was predicted, as compared with the intact condition. These numerical predictions have to be regarded as a theoretical representation of the behavior of the spine, because any finite element model represents only a simplification of the real Structure

The utility of existing passerine microsatellite markers for genetic studies in endangered species: as demonstrated for a critically endangered forest bird endemic to Réunion Island, the Réunion cuckooshrike (Coracina newtoni)

Genetic data are increasingly recognized for their utility in conservation programs. However, many endangered species belong to families that have been understudied. Due to the urgency of their conservation status it is important to quickly identify polymorphic microsatellite loci from available resources. We show for the Re´union Cuckoo shrike Coracina newtoni, that this strategy can be very useful. Using 110 passerine microsatellite primer sets we identified eighteen polymorphic loci and tested them in 25 C. newtoni individuals. Following a Bonferroni correction one pair of loci displayed linkage disequilibriu

GAMER MRI: Gated-attention mechanism ranking of multi-contrast MRI in brain pathology.

During the last decade, a multitude of novel quantitative and semiquantitative MRI techniques have provided new information about the pathophysiology of neurological diseases. Yet, selection of the most relevant contrasts for a given pathology remains challenging. In this work, we developed and validated a method, Gated-Attention MEchanism Ranking of multi-contrast MRI in brain pathology (GAMER MRI), to rank the relative importance of MR measures in the classification of well understood ischemic stroke lesions. Subsequently, we applied this method to the classification of multiple sclerosis (MS) lesions, where the relative importance of MR measures is less understood. GAMER MRI was developed based on the gated attention mechanism, which computes attention weights (AWs) as proxies of importance of hidden features in the classification. In the first two experiments, we used Trace-weighted (Trace), apparent diffusion coefficient (ADC), Fluid-Attenuated Inversion Recovery (FLAIR), and T1-weighted (T1w) images acquired in 904 acute/subacute ischemic stroke patients and in 6,230 healthy controls and patients with other brain pathologies to assess if GAMER MRI could produce clinically meaningful importance orders in two different classification scenarios. In the first experiment, GAMER MRI with a pretrained convolutional neural network (CNN) was used in conjunction with Trace, ADC, and FLAIR to distinguish patients with ischemic stroke from those with other pathologies and healthy controls. In the second experiment, GAMER MRI with a patch-based CNN used Trace, ADC and T1w to differentiate acute ischemic stroke lesions from healthy tissue. The last experiment explored the performance of patch-based CNN with GAMER MRI in ranking the importance of quantitative MRI measures to distinguish two groups of lesions with different pathological characteristics and unknown quantitative MR features. Specifically, GAMER MRI was applied to assess the relative importance of the myelin water fraction (MWF), quantitative susceptibility mapping (QSM), T1 relaxometry map (qT1), and neurite density index (NDI) in distinguishing 750 juxtacortical lesions from 242 periventricular lesions in 47 MS patients. Pair-wise permutation t-tests were used to evaluate the differences between the AWs obtained for each quantitative measure. In the first experiment, we achieved a mean test AUC of 0.881 and the obtained AWs of FLAIR and the sum of AWs of Trace and ADC were 0.11 and 0.89, respectively, as expected based on previous knowledge. In the second experiment, we achieved a mean test F1 score of 0.895 and a mean AW of Trace = 0.49, of ADC = 0.28, and of T1w = 0.23, thereby confirming the findings of the first experiment. In the third experiment, MS lesion classification achieved test balanced accuracy = 0.777, sensitivity = 0.739, and specificity = 0.814. The mean AWs of T1map, MWF, NDI, and QSM were 0.29, 0.26, 0.24, and 0.22 (p < 0.001), respectively. This work demonstrates that the proposed GAMER MRI might be a useful method to assess the relative importance of MRI measures in neurological diseases with focal pathology. Moreover, the obtained AWs may in fact help to choose the best combination of MR contrasts for a specific classification problem

Association of Spinal Cord Atrophy and Brain Paramagnetic Rim Lesions With Progression Independent of Relapse Activity in People With MS.

Progression independent of relapse activity (PIRA) is a crucial determinant of overall disability accumulation in multiple sclerosis (MS). Accelerated brain atrophy has been shown in patients experiencing PIRA. In this study, we assessed the relation between PIRA and neurodegenerative processes reflected by (1) longitudinal spinal cord atrophy and (2) brain paramagnetic rim lesions (PRLs). Besides, the same relationship was investigated in progressive MS (PMS). Last, we explored the value of cross-sectional brain and spinal cord volumetric measurements in predicting PIRA. From an ongoing multicentric cohort study, we selected patients with MS with (1) availability of a susceptibility-based MRI scan and (2) regular clinical and conventional MRI follow-up in the 4 years before the susceptibility-based MRI. Comparisons in spinal cord atrophy rates (explored with linear mixed-effect models) and PRL count (explored with negative binomial regression models) were performed between: (1) relapsing-remitting (RRMS) and PMS phenotypes and (2) patients experiencing PIRA and patients without confirmed disability accumulation (CDA) during follow-up (both considering the entire cohort and the subgroup of patients with RRMS). Associations between baseline MRI volumetric measurements and time to PIRA were explored with multivariable Cox regression analyses. In total, 445 patients with MS (64.9% female; mean [SD] age at baseline 45.0 [11.4] years; 11.2% with PMS) were enrolled. Compared with patients with RRMS, those with PMS had accelerated cervical cord atrophy (mean difference in annual percentage volume change [MD-APC] -1.41; p = 0.004) and higher PRL load (incidence rate ratio [IRR] 1.93; p = 0.005). Increased spinal cord atrophy (MD-APC -1.39; p = 0.0008) and PRL burden (IRR 1.95; p = 0.0008) were measured in patients with PIRA compared with patients without CDA; such differences were also confirmed when restricting the analysis to patients with RRMS. Baseline volumetric measurements of the cervical cord, whole brain, and cerebral cortex significantly predicted time to PIRA (all p ≤ 0.002). Our results show that PIRA is associated with both increased spinal cord atrophy and PRL burden, and this association is evident also in patients with RRMS. These findings further point to the need to develop targeted treatment strategies for PIRA to prevent irreversible neuroaxonal loss and optimize long-term outcomes of patients with MS