Arrhythmia prevalence among patients with polymyositis-dermatomyositis in the United States: An observational study.

BACKGROUND: Systemic inflammation has been associated with atherosclerotic cardiovascular diseases (ASCVD) and arrhythmia occurrence in rheumatologic conditions such as rheumatoid arthritis. Polymyositis and dermatomyositis (PD) are rare rheumatologic conditions characterized by symmetrical proximal muscle weakness and, in the case of dermatomyositis, cutaneous eruption. Although there is literature associating PD with ASCVD, no population-level studies have analyzed arrhythmia risk in PD. OBJECTIVE: The purpose of this study was to assess the prevalence of arrhythmia and its subtypes by age and sex in patients with PD and to determine associations between arrhythmia and PD. METHODS: This retrospective cohort study included adults for whom hospitalizations had been recorded in the National Inpatient Sample database in the United States between 2016 and 2018. Patients with PD were matched (1:10) by age to patients without PD. Prevalence of arrhythmia was calculated in the 2 groups and compared by sex and age groups. Associations between PD and arrhythmia were determined after adjustment for common arrhythmia risk factors. RESULTS: From 107,001,355 hospitalizations, 32,085 adults with PD were matched to 320,850 controls. Patients with PD aged <70 years had a higher prevalence of arrhythmia and higher adjusted odds of arrhythmia compared with controls. This increased risk was only seen for supraventricular arrhythmias. Adults with PD had increased odds of in-hospital mortality if they had an arrhythmia diagnosis (odds ratio 3.3; 95% confidence interval 2.5-4.5; P <.001). CONCLUSION: We found a higher prevalence and odds of arrhythmias, particularly supraventricular arrhythmias, in young and middle-aged patients with PD compared with matched controls. Arrhythmias were associated with significant mortality among patients with PD.

Neurometabolic correlates of 6 and 16 weeks of treatment with risperidone in medication-naive first-episode psychosis patients.

Antipsychotic medications are the cornerstone of treatment in schizophrenia spectrum disorders. In first-episode psychosis, the recommended time for an antipsychotic medication trial is up to 16 weeks, but the biological correlates of shorter and longer antipsychotic treatment trials in these cohorts remain largely unknown. We enrolled 29 medication-naive first-episode patients (FEP) and 22 matched healthy controls (HC) in this magnetic resonance spectroscopy (MRS) study, examining the levels of combined glutamate and glutamine (commonly referred to as Glx) in the bilateral medial prefrontal cortex (MPFC) with a PRESS sequence (TR/TE = 2000/80 ms) before initiation of antipsychotic treatment, after 6 and 16 weeks of treatment with risperidone. Data were quantified in 18 HC and 20 FEP at baseline, for 19 HC and 15 FEP at week 6, and for 14 HC and 16 FEP at week 16. At baseline, none of the metabolites differed between groups. Metabolite levels did not change after 6 or 16 weeks of treatment in patients. Our data suggest that metabolite levels do not change after 6 or 16 weeks of treatment with risperidone in FEP. It is possible that our choice of sequence parameters and the limited sample size contributed to negative findings reported here. On the other hand, longer follow-up may be needed to detect treatment-related metabolic changes with MRS. In summary, our study adds to the efforts in better understanding glutamatergic neurometabolism in schizophrenia, especially as it relates to antipsychotic exposure.

Ketamine induced changes in regional cerebral blood flow, interregional connectivity patterns, and glutamate metabolism.

Several imaging studies have attempted to characterize the contribution of glutamatergic dysfunction to functional dysconnectivity of large-scale brain networks using ketamine models. However, findings from BOLD imaging studies are conflicting, in part because the signal stems from a complex interaction between blood flow, blood volume, and oxygen consumption. We used arterial spin labelling imaging to measure regional cerebral blood flow (rCBF) in a group of healthy volunteers during a saline and during a ketamine infusion. We examined changes in rCBF and interregional connectivity patterns, as well as their associations with clinical symptom severity and Glx (glutamate + glutamine) assessed with magnetic resonance spectroscopy. We report a regionally selective pattern of rCBF changes following ketamine administration and complex changes in interregional connectivity patterns. We also found that the increase in rCBF in the bilateral putamen and left hippocampus was positively correlated with ketamine induced clinical symptom severity while anterior cingulate rCBF during the ketamine challenge was negatively correlated with change in hippocampal Glx. Our study adds to the efforts to empirically confirm putative links between an NMDA receptor blockage and dysconnectivity of large-scale brain networks, specifically the salience, executive control and default mode networks, suggesting that a glutamatergic imbalance may contribute to dysconnectivity. Development of glutamatergic compounds that alleviate disease burden, possibly through normalizing glutamate excess related increased rCBF, is direly needed.

Micro- and Macrostructural White Matter Integrity in Never-Treated and Currently Unmedicated Patients With Schizophrenia and Effects of Short-Term Antipsychotic Treatment.

BACKGROUND: Schizophrenia is associated with progressive white matter changes, but it is unclear whether antipsychotic medications contribute to these. Our objective was to characterize effects of short-term treatment with risperidone on white matter diffusion indices. METHODS: We recruited 42 patients with schizophrenia (30 never treated and 12 currently untreated) and 42 matched healthy control subjects in this prospective case-control neuroimaging study. Patients received a 6-week trial of risperidone. Using diffusion tensor imaging, we assessed microstructural (fractional anisotropy, mean diffusivity, and radial diffusivity) and macrostructural (radial fiber trophy) white matter integrity deficits in unmedicated patients compared with control subjects and change in white matter integrity in patients before and after antipsychotic treatment (mean risperidone dose at end point was 3.73 ± 1.72 mg). RESULTS: At baseline, fractional anisotropy was decreased in the left medial temporal white matter (cluster extent: 123 voxels; Montreal Neurological Institute peak coordinates: x = -51, y = -44, z = -7; α < .05), and mean diffusivity was increased in the fusiform/lingual gyrus white matter extending to the hippocampal part of the cingulum (cluster extent: 185 voxels; peak coordinates: x = -27, y = -49, z = 2; α < .04) in patients compared with control subjects. Radial diffusivity and macrostructure were not abnormal. None of the diffusion indices showed a significant change after 6 weeks of treatment with both voxelwise and whole-brain white matter analyses. CONCLUSIONS: We demonstrate microstructural white matter integrity abnormalities in the absence of macrostructural impairment in unmedicated patients with primarily early-stage schizophrenia. In our data, we found no significant white matter changes after short-term treatment with risperidone.

Hippocampal-parietal dysconnectivity and glutamate abnormalities in unmedicated patients with schizophrenia.

Abnormalities in resting state connectivity in schizophrenia (SZ) are now well established, but the biological substrates of these functional alterations remain to be elucidated. We performed a combined functional magnetic resonance imaging and magnetic resonance spectroscopy study in 22 unmedicated patients with SZ and 22 matched healthy controls (HCs) to evaluate resting state functional connectivity of the hippocampus and Glx/Cr (a combined glutamate + glutamine peak normalized to creatine) in the hippocampus and investigate functional and neurometabolic abnormalities and examine the relationship between these. Functional connectivity between the left hippocampus and bilateral precuneus was significantly decreased in unmedicated patients with SZ when compared to HCs [t(4.22), cluster extent (kE) = 751, PFDRcorr = 0.001, Montreal Neurological Institute coordinates: x = -4, y = -56, z = 44]. Glx/Cr in the hippocampus was significantly elevated in SZ (HC: mean = 0.60+/-0.10 SZ: 0.67+/-0.10; F = 5.742; P = 0.02), but was not correlated with functional connectivity deficits (P > 0.05). In this study, we found hippocampal resting state functional connectivity deficits to the precuneus in unmedicated patients with SZ and an increase of Glx/Cr in the hippocampus, but did not observe a direct relationship between these abnormalities. However, our findings do not exclude the possibility of a shared underlying pathology, which warrants further investigation.

Delay discounting and task performance consistency in patients with schizophrenia.

To study impaired goal-oriented behavior in schizophrenia (SZ), we used a delay discounting task, which consists of a series of choices between receiving a small immediate or larger delayed reward. Few studies of delay discounting have evaluated response consistency (R(2)), which is especially relevant in SZ because of documented inconsistency in task performance. We calculated the rate of discounting (k) and R(2) in SZ (n=35) and healthy controls (HC; n=21). Using a criterion value of R(2)>0.60 to define consistent performance allowed us to compare discounting in consistent SZ and HC, as well as in inconsistent SZ. Groups did not differ significantly in smoking. Compared to HC, consistent SZ showed greater delay discounting. Both groups exhibited similar patterns of decreasing immediate choices across trial categories, although the decrease was less for SZ. Separate analyses on smokers and non-smokers showed that this group difference was carried by the non-smokers. Inconsistent SZ discounted more than HC and consistent SZ, but their aberrant pattern of choices casts doubt on the validity of their calculated k values.

An fMRI investigation of delay discounting in patients with schizophrenia.

Schizophrenia (SZ) is associated with a reduced ability to set meaningful goals to reach desired outcomes. The delay-discounting (DD) task, in which one chooses between sooner smaller and later larger rewards, has proven useful in revealing executive function and reward deficits in various clinical groups. We used fMRI in patients with SZ and healthy controls (HC) to compare brain activation during performance of a DD task. Prior to the neuroimaging session, we obtained each participant's rate of DD, k, on a DD task and used it to select a version of the DD task for each participant's fMRI session. Because of the importance of comparing fMRI results from groups matched on performance, we used a criterion value of R (2) > 0.60 for response consistency on the DD task to analyze fMRI activation to DD task versus control trials from consistent SZ (n = 14) and consistent HC (n = 14). We also compared activation between the groups on contrasts related to trial difficulty. Finally, we contrasted the inconsistent SZ (n = 9) with the consistent HC and consistent SZ; these results should be interpreted with caution because of inconsistent SZ's aberrant performance on the task. Compared with consistent HC, consistent SZ showed reduced activation to DD task versus control trials in executive function and reward areas. In contrast, consistent SZ showed more activation in the precuneus and posterior cingulate, regions of the default mode network (DMN) that are typically deactivated during tasks, and in the insula, a region linked to emotional processing. Furthermore, consistent SZ had abnormal activation of lateral and medial frontal regions in relation to trial difficulty. These results point to disruption of several neural networks during decision making, including the executive, reward, default mode, and emotional networks, and suggest processes that are impaired during decision making in schizophrenia.