Background-Significant alterations in γ-aminobutyric acid (GABA) and glutamate levels have been previously reported in symptomatic and remitted major depressive disorder (MDD); however, no studies to date have investigated potential associations between these amino acid neurotransmitters and treatment-resistance.

Chronic fatigue syndrome (CFS), a complex illness characterized by fatigue, impaired concentration, and musculoskeletal pain, is often misdiagnosed as a psychiatric illness due to the overlap of its symptoms with mood and anxiety disorders. Using proton magnetic resonance spectroscopic imaging ((1)H MRSI), we previously measured levels of the major brain metabolites in CFS, in generalized anxiety disorder (GAD), and in healthy control subjects, and found significantly higher levels of ventricular cerebrospinal fluid (CSF) lactate in CFS compared to the other two groups. In the present study, we sought to assess the specificity of this observation for CFS by comparing ventricular lactate levels in a new cohort of 17 CFS subjects with those in 19 healthy volunteers and in 21 subjects with major depressive disorder (MDD), which, like GAD, is a neuropsychiatric disorder that has significant symptom overlap with CFS. Ventricular CSF lactate was significantly elevated in CFS compared to healthy volunteers, replicating the major result of our previous study. Ventricular lactate measures in MDD did not differ from those in either CFS or healthy volunteers. We found a significant correlation between ventricular CSF lactate and severity of mental fatigue that was specific to the CFS group. In an exploratory analysis, we did not find evidence for altered levels of the amino acid neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate + glutamine ('Glx'), in CFS compared to MDD or healthy controls. Future (1)H MRS studies with larger sample sizes and well-characterized populations will be necessary to further clarify the sensitivity and specificity of neurometabolic abnormalities in CFS and MDD.

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Aims Develop, calibrate and evaluate with clinical data a human electromechanical modelling and simulation framework for multiscale, mechanistic investigations in healthy and post-myocardial infarction (MI) conditions, from ionic to clinical biomarkers. Methods and results Human healthy and post-MI electromechanical simulations were conducted with a novel biventricular model, calibrated and evaluated with experimental and clinical data, including torso/biventricular anatomy from clinical magnetic resonance, state-of-the-art human-based membrane kinetics, excitation–contraction and active tension models, and orthotropic electromechanical coupling. Electromechanical remodelling of the infarct/ischaemic region and the border zone were simulated for ischaemic, acute, and chronic states in a fully transmural anterior infarct and a subendocardial anterior infarct. The results were compared with clinical electrocardiogram and left ventricular ejection fraction (LVEF) data at similar states. Healthy model simulations show LVEF 63%, with 11% peak systolic wall thickening, QRS duration and QT interval of 100 ms and 330 ms. LVEF in ischaemic, acute, and chronic post-MI states were 56%, 51%, and 52%, respectively. In linking the three post-MI simulations, it was apparent that elevated resting potential due to hyperkalaemia in the infarcted region led to ST-segment elevation, while a large repolarization gradient corresponded to T-wave inversion. Mechanically, the chronic stiffening of the infarct region had the benefit of improving systolic function by reducing infarct bulging at the expense of reducing diastolic function by inhibiting inflation. Conclusion Our human-based multiscale modelling and simulation framework enables mechanistic investigations into patho-physiological electrophysiological and mechanical behaviour and can serve as testbed to guide the optimization of pharmacological and electrical therapies.

Background: Hypertrophic cardiomyopathy (HCM) remains the commonest cause of sudden cardiac death among young athletes. Differentiating between physiologically adaptive left ventricular (LV) hypertrophy observed in athletes' hearts and pathological HCM remains challenging. By quantifying the diffusion of water molecules, diffusion tensor imaging (DTI) MRI allows voxelwise characterization of myocardial microstructure. Purpose: To explore microstructural differences between healthy volunteers, athletes, and HCM patients using DTI. Study Type: Prospective cohort. Population: Twenty healthy volunteers, 20 athletes, and 20 HCM patients. Field Strength/Sequence: 3T/DTI spin echo. Assessment: In-house MatLab software was used to derive mean diffusivity (MD) and fractional anisotropy (FA) as markers of amplitude and anisotropy of the diffusion of water molecules, and secondary eigenvector angles (E2A)-reflecting the orientations of laminar sheetlets. Statistical Tests: Independent samples t-tests were used to detect statistical significance between any two cohorts. Analysis of variance was utilized for detecting the statistical difference between the three cohorts. Statistical tests were twotailed. A result was considered statistically significant at P ≤ 0.05. Results: DTI markers were significantly different between HCM, athletes, and volunteers. HCM patients had significantly higher global MD and E2A, and significantly lower FA than athletes and volunteers. (MD HCM = 1.52 ± 0.06 × 10 −3 mm 2 /s, MD Athletes = 1.49 ± 0.03 × 10 −3 mm 2 /s, MD volunteers = 1.47 ± 0.02 × 10 −3 mm 2 /s, P < 0.05; E2A HCM = 58.8 ± 4 , E2A athletes = 47 ± 5 , E2A volunteers = 38.5 ± 7 , P < 0.05; FA HCM = 0.30 ± 0.02, FA Athletes = 0.35 ± 0.02, FA volunteers = 0.36 ± 0.03, P < 0.05). HCM patients had significantly higher E2A in their thickest segments compared to the remote (E2A thickest = 66.8 ± 7, E2A remote = 51.2 ± 9, P < 0.05). Data Conclusion: DTI depicts an increase in amplitude and isotropy of diffusion in the myocardium of HCM compared to athletes and volunteers as reflected by increased MD and decreased FA values. While significantly higher E2A values in HCM and athletes reflect steeper configurations of the myocardial sheetlets than in volunteers, HCM patients