The Use of the Health of the Nation Outcome Scales for Assessing Functional Change in Treatment Outcome Monitoring of Patients with Chronic Schizophrenia.

Schizophrenia is a severe mental disorder that is characterized not only by symptomatic severity but also by high levels of functional impairment. An evaluation of clinical outcome in treatment of schizophrenia should therefore target not only assessing symptom change but also alterations in functioning. This study aimed to investigate whether there is an agreement between functional- and symptom-based outcomes in a clinical sample of admissions with chronic forms of schizophrenia. A full 3-year cohort of consecutive inpatient admissions for schizophrenia (N = 205) was clinically rated with the Positive and Negative Symptom Scale (PANSS) and the Health of the Nation Outcome Scales (HoNOS) as measures of functioning at the time of admission and discharge. The sample was stratified twofold: first, according to the degree of PANSS symptom improvement during treatment with the sample being divided into three treatment response groups: non-response, low response, and high response. Second, achievement of remission was defined using the Remission in Schizophrenia Working Group criteria based on selected PANSS symptoms. Repeated measures analyses were used to compare the change of HoNOS scores over time across groups. More than a half of all admissions achieved a symptom reduction of at least 20% during treatment and around one quarter achieved remission at discharge. Similarly, HoNOS scores improved significantly between admission and discharge. Interaction analyses indicated higher functional improvements to be associated with increasing levels of treatment response. Functional improvement in individuals treated for schizophrenia was linked to a better clinical outcome, which implies a functional association. Thus, improvement of functioning represents an important therapeutic target in the treatment of schizophrenia

Ketamine decreases resting state functional connectivity between networks via the dorsal nexus: implications for major depression

Question: Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate modulating NMDA receptor antagonist ketamine [1, 2]. Targeting the glutamatergic system might thus provide a novel therapeutic strategy for antidepressant drug treatment [3]. Since glutamate is the most abundand and major excitatory neurotransmitter in the human brain, pathophysiological changes in glutamatergic signalling are likely to affect neurobehavioural plasticity, information processing and large-scale changes in functional brain connectivity underlying certain symptoms of major depressive disorder (MDD) [4]. Using resting state functional MRI (rsfMRI), the „dorsal nexus“ (DN) was recently identified as a bilateral dorsal medial prefrontal cortex (DMPFC) region showing dramatically increased depression-associated fMRI connectivity with large portions of the cognitive control network (CCN), the default mode network (DMN), and the affective network (AN) [5]. Hence, Sheline and colleagues [5] proposed that reducing increased connectivity of the DN might play a critical role in reducing depressive symptomatology and thus represent a potential therapeutic target for affective disorders. Since little is known about how ketamine affects large-scale neural network dynamics in the human brain, we aimed to test the hypothesis that ketamine as an antidepressant glutamatergic agent decreases resting state connectivties via the DN. Methods: Study design: 17 healthy subjects (mean age, 40.5 +/- 7.5 [SD]; 9 males) completed four resting state fMRI sessions in a double-blind, randomized, crossover study design (s. Fig 1). The baseline scan was followed by an intravenous infusion (45 mins) of either S-ketamine (0.25 mg/kg) or placebo (saline) outside the scanner. Since the antidepressant effect of ketamine is most prominent after one day [1], the followup scans were scheduled 24 hours after the ketamine or placebo infusion in order to assess the mid-term effects on neuronal network dynamics that might contribute to its antidepressant efficacy. To avoid a possible carry-over effect, the time lag between the two baseline measurements was set to at least 10 days. rsfMRI data acquisition and analysis: Measurements were performed on a Philips Achieva TX 3-T whole-body MR unit equipped with an 8-channel SENSE head coil. During each session a total of 200 functional images were collected in 10 minute runs (eyes closed) using the following acquisition parameters: TE = 35 ms, TR = 3000 ms (θ = 82°), FOV = 22 cm, acquisition matrix = 80 x 80 interpolated to 128 x 128, voxel size = 2.75 x 2.75 x 4 mm, 32 contiguous axial slices (placed along the anterior-posterior commissure plane), and sensitivity-encoded acceleration factor R = 2.0. A 3-dimensional T1-weighted anatomical scan was obtained for structural reference. Data were analyzed using the SPM8 (Wellcome Trust Center for Neuroimaging, London, England) based data processing assistant for resting state fMRI (DPARSF, by Yan Chao-Gan et al.) which includes a resting state fMRI data analysis toolkit (REST, by Song Xiao-Wei et al.). The postprocessing steps followed the standard protocol described by Yan and Zang (2010) [6]. Results: To test our hypothesis, we created a seed region of interest in the left and right DMPFC (10 mm sphere at ± 6 51 24) representing the DN. 24 h following ketamine administration, functional connectivity was exclusively reduced to the posterior cingulate cortex (PCC), to the subgenual anterior cingulate cortex (sgACC), and to anterior and mediodorsal parts of the thalamus (compared to placebo). The backprojection from a seed in the PCC confirmed these results and revealed an additional significant reduction of functional connectivity to the pregenual ACC (PACC) and medioprefrontal cortex (MPFC). For details, see Fig. 2 A, B and bar diagrams (functional connectivity change, paired t tests). Conclusion: While pharmacological effects of ketamine on task induced fMRI BOLD signals have been studied extensively, this is the first randomized, placebo-controlled, double-blind, crossover study demonstrating changes in resting state functional connectivity in response to ketamine administration in healthy subjects. Here, we report a significant decrease in functional connectivity of the sgACC (AN) and the PCC (DMN) via the DN 24 hours following ketamine administration, thus reflecting a neuronal pattern of normalization with regard to MDD where increased connectivities of the AN and DMN via the DN have been observed [5]. As critical hub of the AN, the sgACC plays an important role in mood regulation. Subgenual cortical activity was shown to be elevated in MDD and effective antidepressant treatment was associated with a reduction in sgACC activity [for review see ref. 7]. In addition, the observed reduction in functional connectivity between anterior (PACC/MPFC) and posterior parts of the DMN (PCC) may partially reverse the disrupted neurobehavioral homeostasis in MDD where a failure to normally down-regulate activity within the DMN during emotional stimulation was found [8], with increasing levels of DMN dominance being associated with higher levels of maladaptive, depressive rumination and lower levels of adaptive, reflective rumination [9]. Finally, reductions in cortico-thalamic connectivity may reflect functional alterations in thalamocortical loops via the prefrontal cortex. Based on the fact that the antidepressant effect of ketamine peaks one day after a single intravenous administration [1], we conclude that pharmacologically reducing the hyperconnectivity via the DN may play a critical role in reducing depressive symptomatology and in representing a systems level mechanism of treatment response for major depression

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.</p

The functional connectome of 3,4‐methyldioxymethamphetamine‐related declarative memory impairments

The chronic intake of 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) bears a strong risk for sustained declarative memory impairments. Although such memory deficits have been repeatedly reported, their neurofunctional origin remains elusive. Therefore, we here investigate the neuronal basis of altered declarative memory in recurrent MDMA users at the level of brain connectivity. We examined a group of 44 chronic MDMA users and 41 demographically matched controls. Declarative memory performance was assessed by the Rey Auditory Verbal Learning Test and a visual associative learning test. To uncover alterations in the whole brain connectome between groups, we employed a data‐driven multi‐voxel pattern analysis (MVPA) approach on participants' resting‐state functional magnetic resonance imaging data. Recent MDMA use was confirmed by hair analyses. MDMA users showed lower performance in delayed recall across tasks compared to well‐matched controls with moderate‐to‐strong effect sizes. MVPA revealed a large cluster located in the left postcentral gyrus of global connectivity differences between groups. Post hoc seed‐based connectivity analyses with this cluster unraveled hypoconnectivity to temporal areas belonging to the auditory network and hyperconnectivity to dorsal parietal regions belonging to the dorsal attention network in MDMA users. Seed‐based connectivity strength was associated with verbal memory performance in the whole sample as well as with MDMA intake patterns in the user group. Our findings suggest that functional underpinnings of MDMA‐related memory impairments encompass altered patterns of multimodal sensory integration within auditory processing regions to a functional heteromodal connector hub, the left postcentral gyrus. In addition, hyperconnectivity in regions of a cognitive control network might indicate compensation for degraded sensory processing

Psyche und Sport in Zeiten von COVID-19

Die Weltgesundheitsorganisation (WHO) betont in ihren Empfehlungen «Coping with stress du-ring the 2019-nCoV outbreak» die Bedeutung von Bewegung und der Beibehaltung eines gesunden Lebensstils (11). Diese Empfehlungen gehören zu Informationsmaterial, das die WHO während der COVID-19-Pandemie zu verschiedenen Aspek-ten der psychischen Gesundheit herausgegeben h a t (1 2)

Infectious, atopic and inflammatory diseases, childhood adversities and familial aggregation are independently associated with the risk for mental disorders: Results from a large Swiss epidemiological study.

To examine the associations between mental disorders and infectious, atopic, inflammatory diseases while adjusting for other risk factors. We used data from PsyCoLaus, a large Swiss Population Cohort Study (n = 3720; age range 35-66). Lifetime diagnoses of mental disorders were grouped into the following categories: Neurodevelopmental, anxiety (early and late onset), mood and substance disorders. They were regressed on infectious, atopic and other inflammatory diseases adjusting for sex, educational level, familial aggregation, childhood adversities and traumatic experiences in childhood. A multivariate logistic regression was applied to each group of disorders. In a complementary analysis interactions with sex were introduced via nested effects. Associations with infectious, atopic and other chronic inflammatory diseases were observable together with consistent effects of childhood adversities and familial aggregation, and less consistent effects of trauma in each group of mental disorders. Streptococcal infections were associated with neurodevelopmental disorders (men), and measles/mumps/rubella-infections with early and late anxiety disorders (women). Gastric inflammatory diseases took effect in mood disorders (both sexes) and in early disorders (men). Similarly, irritable bowel syndrome was prominent in a sex-specific way in mood disorders in women, and, moreover, was associated with early and late anxiety disorders. Atopic diseases were associated with late anxiety disorders. Acne (associations with mood disorders in men) and psoriasis (associations with early anxiety disorders in men and mood disorders in women) contributed sex-specific results. Urinary tract infections were associated with mood disorders and, in addition, in a sex-specific way with late anxiety disorders (men), and neurodevelopmental and early anxiety disorders (women). Infectious, atopic and inflammatory diseases are important risk factors for all groups of mental disorders. The sexual dimorphism of the associations is pronounced

Feel it in my bones: Composing multimodal experience through tissue conduction

We outline here the feasibility of coherently utilising tissue conduction for spatial audio and tactile input. Tissue conduction display-specific compositional concerns are discussed; it is hypothesised that the qualia available through this medium substantively differ from those for conventional artificial means of appealing to auditory spatial perception. The implications include that spatial music experienced in this manner constitutes a new kind of experience, and that the ground rules of composition are yet to be established. We refer to results from listening experiences with one hundred listeners in an unstructured attribute elicitation exercise, where prominent themes such as “strange”, “weird”, “positive”, “spatial” and “vibrations” emerged. We speculate on future directions aimed at taking maximal advantage of the principle of multimodal perception to broaden the informational bandwidth of the display system. Some implications for composition for hearing-impaired are elucidated.n/

Solar System Processes Underlying Planetary Formation, Geodynamics, and the Georeactor

Only three processes, operant during the formation of the Solar System, are responsible for the diversity of matter in the Solar System and are directly responsible for planetary internal-structures, including planetocentric nuclear fission reactors, and for dynamical processes, including and especially, geodynamics. These processes are: (i) Low-pressure, low-temperature condensation from solar matter in the remote reaches of the Solar System or in the interstellar medium; (ii) High-pressure, high-temperature condensation from solar matter associated with planetary-formation by raining out from the interiors of giant-gaseous protoplanets, and; (iii) Stripping of the primordial volatile components from the inner portion of the Solar System by super-intense solar wind associated with T-Tauri phase mass-ejections, presumably during the thermonuclear ignition of the Sun. As described herein, these processes lead logically, in a causally related manner, to a coherent vision of planetary formation with profound implications including, but not limited to, (a) Earth formation as a giant gaseous Jupiter-like planet with vast amounts of stored energy of protoplanetary compression in its rock-plus-alloy kernel; (b) Removal of approximately 300 Earth-masses of primordial gases from the Earth, which began Earth's decompression process, making available the stored energy of protoplanetary compression for driving geodynamic processes, which I have described by the new whole-Earth decompression dynamics and which is responsible for emplacing heat at the mantle-crust-interface at the base of the crust through the process I have described, called mantle decompression thermal-tsunami; and, (c)Uranium accumulations at the planetary centers capable of self-sustained nuclear fission chain reactions.Comment: Invited paper for the Special Issue of Earth, Moon and Planets entitled Neutrino Geophysics Added final corrections for publicatio

Effects of the PPAR-β/δ agonist GW0742 during resuscitated porcine septic shock.

BACKGROUND: In un-resuscitated rodent models of septic shock, the peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ) agonist GW0742 improved visceral organ function. Therefore, we tested the hypothesis whether GW0742 would attenuate kidney injury during long-term, resuscitated, porcine polymicrobial septic shock. METHODS: Six, 12, and 18 h after the induction of fecal peritonitis by inoculation of autologous feces, anesthetized, mechanically ventilated, and instrumented male pigs with pre-existing atherosclerosis resulting from familial hypercholesteremia and atherogenic diet randomly received either vehicle (dimethyl sulfoxide, n = 12) or GW0742 (n = 10). Resuscitation comprised hydroxyethyl starch and norepinephrine infusion titrated to maintain mean arterial pressure at baseline values. RESULTS: Despite aggressive fluid resuscitation, fecal peritonitis was associated with arterial hypotension requiring norepinephrine infusion, ultimately resulting in progressive lactic acidosis and acute kidney injury. GW0742 did not beneficially affect any parameter of systemic and regional hemodynamics, gas exchange, metabolism, or organ function. The parameters of inflammation, oxidative and nitrosative stress, and organ injury (post-mortem analysis for histomorphology and markers of apoptosis) were not influenced either. Immunohistochemistry of pre-shock kidney biopsies from a previous study in this swine strain showed markedly lower PPAR-β/δ receptor expression than in healthy animals. CONCLUSIONS: In swine with pre-existing atherosclerosis, the PPAR-β/δ agonist GW0742 failed to attenuate septic shock-induced circulatory failure and kidney dysfunction, most likely due to reduced receptor expression coinciding with cardiovascular and metabolic co-morbidity