Predictors of adherence to exercise interventions in people with schizophrenia.

Exercise interventions are nowadays considered as effective add-on treatments in people with schizophrenia but are usually associated with high dropout rates. Therefore, the present study investigated potential predictors of adherence from a large multicenter study, encompassing two types of exercise training, conducted over a 6-month period with individuals with schizophrenia. First, we examined the role of multiple participants' characteristics, including levels of functioning, symptom severity, cognitive performance, quality of life, and physical fitness. Second, we used K-means clustering to identify clinical subgroups of participants that potentially exhibited superior adherence. Last, we explored if adherence could be predicted on the individual level using Random Forest, Logistic Regression, and Ridge Regression. We found that individuals with higher levels of functioning at baseline were more likely to adhere to the exercise interventions, while other factors such as symptom severity, cognitive performance, quality of life or physical fitness seemed to be less influential. Accordingly, the high-functioning group with low symptoms exhibited a greater likelihood of adhering to the interventions compared to the severely ill group. Despite incorporating various algorithms, it was not possible to predict adherence at the individual level. These findings add to the understanding of the factors that influence adherence to exercise interventions. They underscore the predictive importance of daily life functioning while indicating a lack of association between symptom severity and adherence. Future research should focus on developing targeted strategies to improve adherence, particularly for people with schizophrenia who suffer from impairments in daily functioning.Clinical trials registration The study of this manuscript which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112, https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1 ) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804.

Higher Subjective Burden in Psychiatric Compared to Somatic Healthcare Workers in Germany During the first wave of the COVID-19 Pandemic.

The COVID-19 pandemic has posed unprecedented challenges for health care workers (HCWs) worldwide. While the adverse effects of the pandemic on the well-being of HCWs in general have now been established, little is known about the impact on HCWs of psychiatric hospitals (PHCWs). PHCWs are of special interest, given that they faced both an increase in infection rates among psychiatric patients as well as in mental strain of the general public due to consequences of the pandemic. The aim of the present study was to investigate how the pandemic affected PHCWs as well as possible differences between PHCWs and other health care workers (OHCWs) in Germany during the first wave of the pandemic. We conducted a country-wide anonymous online survey early during the first pandemic wave between April 15th and May 1st, 2020, to assess different aspects of subjective burden and perceived stress using 5-point Likert-scale questions. We analysed data of 1530 PHCWs and 2114 OHCWs and showed that PHCWs reported higher subjective burden and stress compared to OHCWs (p<0.001). Overall, nurses from both groups of HCWs showed higher ratings in subjective burden and stress than physicians. These higher ratings for subjective burden were even more pronounced for nurses working in psychiatric hospitals. Future research is needed to investigate the causes for PHCWs' increased stress and subjective burden, especially when taking into account the long-term effects of the pandemic, which may lead to further challenges and an ever-increasing workload, especially for PHCWs.

Effects of add-on Celecoxib treatment on patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame): study design and methodology of a multicentre randomized, placebo-controlled trial.

Neuroinflammation has been proposed to impact symptomatology in patients with schizophrenia spectrum disorders. While previous studies have shown equivocal effects of treatments with add-on anti-inflammatory drugs such as Aspirin, N-acetylcysteine and Celecoxib, none have used a subset of prospectively recruited patients exhibiting an inflammatory profile. The aim of the study is to evaluate the efficacy and safety as well as the cost-effectiveness of a treatment with 400 mg Celecoxib added to an ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. The "Add-on Celecoxib treatment in patients with schizophrenia spectrum disorders and inflammatory cytokine profile trial (TargetFlame)" is a multicentre randomized, placebo-controlled phase III investigator-initiated clinical trial with the following two arms: patients exhibiting an inflammatory profile receiving either add-on Celecoxib 400 mg/day or add-on placebo. A total of 199 patients will be assessed for eligibility by measuring blood levels of three pro-inflammatory cytokines, and 109 patients with an inflammatory profile, i.e. inflamed, will be randomized, treated for 8 weeks and followed-up for additional four months. The primary endpoint will be changes in symptom severity as assessed by total Positive and Negative Syndrome Scale (PANSS) score changes from baseline to week 8. Secondary endpoints include various other measures of psychopathology and safety. Additional health economic analyses will be performed. TargetFlame is the first study aimed at evaluating the efficacy, safety and cost-effectiveness of the antiphlogistic agent Celecoxib in a subset of patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. With TargetFlame, we intended to investigate a novel precision medicine approach towards anti-inflammatory antipsychotic treatment augmentation using drug repurposing. Clinical trial registration: http://www.drks.de/DRKS00029044 and https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00029044.

What do healthcare workers need? A qualitative study on support strategies to protect mental health of healthcare workers during the SARS-CoV-2 pandemic.

BACKGROUND: To support healthcare workers (HCWs) during the increased burden caused by the SARS-CoV-2 pandemic, numerous recommendations for action and possible interventions have been developed. However, the actual protective factors, needs and desires of those affected, as well as potential barriers to implementing psychological interventions, have been insufficiently examined. This study addresses this research gap and captures HCWs' experiences and views. METHODS: Medical personnel including nursing staff and physicians were recruited for a qualitative study regarding protective factors as well as barriers to the implementation of support services. We conducted 21 individual, semi-structured interviews with members of the medical staff at tertiary care center in Germany. The collected data were analyzed using a qualitative content analysis. RESULTS: The analyses showed that social interaction in the professional and private context was rated as helpful in coping with the challenges of everyday work amplified by the SARS-CoV-2 pandemic. The results also suggest that the available support services, despite being highly valued, were rarely accessed. Possible barriers included the fear of negative consequences when asking for support. It could be deduced that the fear and shame of admitting one's own mistakes as well as the work-related tradition of showing no weakness could be the underlying factors for this fear. RESULTS: The results of this study suggest that medical staff need a more extensive range of low-threshold support services, which should be adapted to the respective needs of the professional groups. The study also provides indications that the norms and expectations represented in the hospital system require critical reflection.

Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia.

BACKGROUND: Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the relationship of these abnormalities with functional outcome remains unclear. METHODS: In two independent cohorts (C1, C2), patients with SZ were divided into two subgroups: patients with higher cognitive performance (SZ-HCP-C1, n = 25; SZ-HCP-C2, n = 24) and patients with lower cognitive performance (SZ-LCP-C1, n = 25; SZ-LCP-C2, n = 24). Healthy controls (HC) were included in both cohorts (HC-C1, n = 52; HC-C2, n = 27). We compared fractional anisotropy (FA) of the whole-brain WM skeleton between the three groups (SZ-LCP, SZ-HCP, HC) by a whole-brain exploratory approach and an atlas-defined WM regions-of-interest approach via tract-based spatial statistics. In addition, we explored whether FA values were associated with Global Assessment of Functioning (GAF) scores in the SZ groups. RESULTS: In both cohorts, mean FA values of whole-brain WM skeleton were significantly lower in the SCZ-LCP group than in the SCZ-HCP group. Whereas in C1 the FA of the frontal part of the left inferior fronto-occipital fasciculus (IFOF) was positively correlated with GAF score, in C2 the FA of the temporal part of the left IFOF was positively correlated with GAF score. CONCLUSIONS: We provide robust evidence for WM microstructural abnormalities in SZ. These abnormalities are more prominent in patients with low cognitive performance and are associated with the level of functioning.

Association between aerobic fitness and the functional connectome in patients with schizophrenia.

BACKGROUND: Schizophrenia is accompanied by widespread alterations in static functional connectivity associated with symptom severity and cognitive deficits. Improvements in aerobic fitness have been demonstrated to ameliorate symptomatology and cognition in people with schizophrenia, but the intermediary role of macroscale connectivity patterns remains unknown. OBJECTIVE: Therefore, we aim to explore the relation between aerobic fitness and the functional connectome in individuals with schizophrenia. Further, we investigate clinical and cognitive relevance of the identified fitness-connectivity links. METHODS: Patients diagnosed with schizophrenia were included in this cross-sectional resting-state fMRI analysis. Multilevel Bayesian partial correlations between aerobic fitness and functional connections across the whole brain as well as between static functional connectivity patterns and clinical and cognitive outcome were performed. Preliminary causal inferences were enabled based on mediation analyses. RESULTS: Static functional connectivity between the subcortical nuclei and the cerebellum as well as between temporal seeds mediated the attenuating relation between aerobic fitness and total symptom severity. Functional connections between cerebellar seeds affected the positive link between aerobic fitness and global cognition, while the functional interplay between central and limbic seeds drove the beneficial association between aerobic fitness and emotion recognition. CONCLUSION: The current study provides first insights into the interactions between aerobic fitness, the functional connectome and clinical and cognitive outcome in people with schizophrenia, but causal interpretations are preliminary. Further interventional aerobic exercise studies are needed to replicate the current findings and to enable conclusive causal inferences. TRIAL REGISTRATION: The study which the manuscript is based on is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Aberrant computational mechanisms of social learning and decision-making in schizophrenia and borderline personality disorder.

Psychiatric disorders are ubiquitously characterized by debilitating social impairments. These difficulties are thought to emerge from aberrant social inference. In order to elucidate the underlying computational mechanisms, patients diagnosed with major depressive disorder (N = 29), schizophrenia (N = 31), and borderline personality disorder (N = 31) as well as healthy controls (N = 34) performed a probabilistic reward learning task in which participants could learn from social and non-social information. Patients with schizophrenia and borderline personality disorder performed more poorly on the task than healthy controls and patients with major depressive disorder. Broken down by domain, borderline personality disorder patients performed better in the social compared to the non-social domain. In contrast, controls and major depressive disorder patients showed the opposite pattern and schizophrenia patients showed no difference between domains. In effect, borderline personality disorder patients gave up a possible overall performance advantage by concentrating their learning in the social at the expense of the non-social domain. We used computational modeling to assess learning and decision-making parameters estimated for each participant from their behavior. This enabled additional insights into the underlying learning and decision-making mechanisms. Patients with borderline personality disorder showed slower learning from social and non-social information and an exaggerated sensitivity to changes in environmental volatility, both in the non-social and the social domain, but more so in the latter. Regarding decision-making the modeling revealed that compared to controls and major depression patients, patients with borderline personality disorder and schizophrenia showed a stronger reliance on social relative to non-social information when making choices. Depressed patients did not differ significantly from controls in this respect. Overall, our results are consistent with the notion of a general interpersonal hypersensitivity in borderline personality disorder and schizophrenia based on a shared computational mechanism characterized by an over-reliance on beliefs about others in making decisions and by an exaggerated need to make sense of others during learning specifically in borderline personality disorder.

The two-way relationship between nicotine and cortical activity: a systematic review of neurobiological and treatment aspects.

Nicotine intake and cortical activity are closely related, as they can influence each other. Nicotine is implicated in the induction and modification of cortical plasticity and excitability, whereas a change on cortical plasticity and excitability can also lead to a modification of the smoking behaviour of an individual. The aim of this systematic review was, on the one hand, to evaluate the effects of nicotinergic modulation on cortical excitability and plasticity, and, on the other hand, to assess if modifying the brain's excitability and plasticity could influence one's smoking behaviour. Two systematic literature searches in the PubMed/MEDLINE and PsycINFO databases were conducted. Studies focusing either on the impact of nicotinergic modulation on cortical activity or the treatment effect of non-invasive brain stimulation techniques (NIBS) on smoking behaviour were included. A total of 22 studies for the first systematic search and 35 studies for the second one were included after full-text screening. Nicotine's effect on cortical activity appeared to depend on smoking status of the individual. While deprived smokers seem to generally profit from nicotine consumption in terms of cortical excitability and plasticity, the contrary was true for non-smokers. Regarding the questions of how changes in cortical excitability can influence smoking behaviour, a trend points towards NIBS being a potential intervention technique for smoking cessation.

Subjective burden and perspectives of German healthcare workers during the COVID-19 pandemic.

Healthcare workers (HCW) face tremendous challenges during the COVID-19 pandemic. Little is known about the subjective burden, views, and COVID-19 infection status of HCWs. The aim of this work was to evaluate the subjective burden, the perception of the information policies, and the agreement on structural measures in a large cohort of German HCW during the COVID-19 pandemic. This country-wide anonymous online survey was carried out from April 15th until May 1st, 2020. 25 content-related questions regarding the subjective burden and other dimensions were evaluated. We evaluated different dimensions of subjective burden, stress, and perspectives using 5-point Likert-scale questions. Moreover, the individual COVID-19 infection status, the amount of people infected in circle of friends and acquaintances and the hours working overtime were assessed. A total of 3669 HCWs provided sufficient responses for analyses. 2.8% of HCWs reported to have been tested positive for COVID-19. Nurses reported in principle higher ratings on all questions of subjective burden and stress than doctors and other hospital staff. Doctors (3.6%) and nurses (3.1%) were more likely to be tested positive for COVID-19 than other hospital staff (0.6%, Chi (2) 2 = 17.39, p < 0.0005). HCWs who worked in a COVID-19 environment reported higher levels of subjective burden and stress compared to all other participants. Working in a COVID-19 environment increased the likelihood to be tested positive for COVID-19 (4.8% vs. 2.3%, Chi (1) 2 = 12.62, p < 0.0005) and the severity of the subjective burden. During the COVID-19 pandemic, nurses experience more stress than doctors. Overall, German HCWs showed high scores of agreement with the measures taken by the hospitals.

Aerobic endurance training to improve cognition and enhance recovery in schizophrenia: design and methodology of a multicenter randomized controlled trial.

Even today, patients with schizophrenia often have an unfavorable outcome. Negative symptoms and cognitive deficits are common features in many patients and prevent recovery. In recent years, aerobic endurance training has emerged as a therapeutic approach with positive effects on several domains of patients' health. However, appropriately sized, multicenter randomized controlled trials that would allow better generalization of results are lacking. The exercise study presented here is a multicenter, rater-blind, two-armed, parallel-group randomized clinical trial in patients with clinically stable schizophrenia being conducted at five German tertiary hospitals. The intervention group performs aerobic endurance training on bicycle ergometers three times per week for 40-50 min/session (depending on the intervention week) for a total of 26 weeks, and the control group performs balance and tone training for the same amount of time. Participants are subsequently followed up for 26 weeks. The primary endpoint is all-cause discontinuation; secondary endpoints include psychopathology, cognition, daily functioning, cardiovascular risk factors, and explorative biological measures regarding the underlying mechanisms of exercise. A total of 180 patients will be randomized. With currently 162 randomized participants, our study is the largest trial to date to investigate endurance training in patients with schizophrenia. We hypothesize that aerobic endurance training has beneficial effects on patients' mental and physical health, leading to lower treatment discontinuation rates and improving disease outcomes. The study results will provide a basis for recommending exercise interventions as an add-on therapy in patients with schizophrenia.The study is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Effects of 1 mA and 2 mA transcranial direct current stimulation on working memory performance in healthy participants.

Anodal transcranial current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) has been shown to enhance working memory (WM) in neuropsychiatric patients. In healthy populations, however, tDCS obtains inconclusive results, mostly due to heterogeneous study and stimulation protocols. Here, we approached these issues by investigating effects of tDCS intensity on simultaneous WM performance with three cognitive loads by directly comparing findings of two double-blind, cross-over, sham-controlled experiments. TDCS was administrated to the left DLPFC at intensity of 1 mA (Experiment 1) or 2 mA (Experiment 2), while participants completed a verbal n-back paradigm (1-, 2-, 3-back). Analysis showed no overall effects of tDCS on WM, but a significant interaction with cognitive load. The present study suggests that cognitive load rather than tDCS intensity could be a decisive factor for effects on WM. Moreover, it emphasizes the need of thorough investigation on study parameters to develop more efficient stimulation protocols.

T1-MPRAGE and T2-FLAIR segmentation of cortical and subcortical brain regions-an MRI evaluation study.

PURPOSE: Development of a warp-based automated brain segmentation approach of 3D fluid-attenuated inversion recovery (FLAIR) images and comparison to 3D T1-based segmentation. METHODS: 3D FLAIR and 3D T1-weighted sequences of 30 healthy subjects (mean age 29.9 ± 8.3 years, 8 female) were acquired on the same 3T MR scanner. Warp-based segmentation was applied for volumetry of total gray matter (GM), white matter (WM), and 116 atlas regions. Segmentation results of both sequences were compared using Pearson correlation (r). RESULTS: Correlation of GM segmentation results based on FLAIR and T1 was overall good for cortical structures (mean r across all cortical structures = 0.76). Comparatively weaker results were found in the occipital lobe (r = 0.77), central region (mean r = 0.58), basal ganglia (mean r = 0.59), thalamus (r = 0.30), and cerebellum (r = 0.73). FLAIR segmentation underestimated volume of the central region compared to T1, but showed a better anatomic concordance with the occipital lobe on visual review and subcortical structures, when also compared to manual segmentation. Visual analysis of FLAIR-based WM segmentation revealed frequent misclassification of regions of high signal intensity as GM. CONCLUSION: Warp-based FLAIR segmentation yields comparable results to T1 segmentation for most cortical GM structures and may provide anatomically more congruent segmentation of subcortical GM structures. Selected cortical regions, especially the central region and total WM, seem to be underestimated on FLAIR segmentation.

Characterizing cognitive subtypes in schizophrenia using cortical curvature.

Cognitive deficits are a core symptom of schizophrenia, but research on their neural underpinnings has been challenged by the heterogeneity in deficits' severity among patients. Here, we address this issue by combining logistic regression and random forest to classify two neuropsychological profiles of patients with high (HighCog) and low (LowCog) cognitive performance in two independent samples. We based our analysis on the cortical features grey matter volume (VOL), cortical thickness (CT), and mean curvature (MC) of N = 57 patients (discovery sample) and validated the classification in an independent sample (N = 52). We investigated which cortical feature would yield the best classification results and expected that the 10 most important features would include frontal and temporal brain regions. The model based on MC had the best performance with area under the curve (AUC) values of 76% and 73%, and identified fronto-temporal and occipital brain regions as the most important features for the classification. Moreover, subsequent comparison analyses could reveal significant differences in MC of single brain regions between the two cognitive profiles. The present study suggests MC as a promising neuroanatomical parameter for characterizing schizophrenia cognitive subtypes.

Effects of Exercise on Structural and Functional Brain Patterns in Schizophrenia-Data From a Multicenter Randomized-Controlled Study.

BACKGROUND AND HYPOTHESIS: Aerobic exercise interventions in people with schizophrenia have been demonstrated to improve clinical outcomes, but findings regarding the underlying neural mechanisms are limited and mainly focus on the hippocampal formation. Therefore, we conducted a global exploratory analysis of structural and functional neural adaptations after exercise and explored their clinical implications. STUDY DESIGN: In this randomized controlled trial, structural and functional MRI data were available for 91 patients with schizophrenia who performed either aerobic exercise on a bicycle ergometer or underwent a flexibility, strengthening, and balance training as control group. We analyzed clinical and neuroimaging data before and after 6 months of regular exercise. Bayesian linear mixed models and Bayesian logistic regressions were calculated to evaluate effects of exercise on multiple neural outcomes and their potential clinical relevance. STUDY RESULTS: Our results indicated that aerobic exercise in people with schizophrenia led to structural and functional adaptations mainly within the default-mode network, the cortico-striato-pallido-thalamo-cortical loop, and the cerebello-thalamo-cortical pathway. We further observed that volume increases in the right posterior cingulate gyrus as a central node of the default-mode network were linked to improvements in disorder severity. CONCLUSIONS: These exploratory findings suggest a positive impact of aerobic exercise on 3 cerebral networks that are involved in the pathophysiology of schizophrenia. CLINICAL TRIALS REGISTRATION: The underlying study of this manuscript was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112, https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Polygenic risk for schizophrenia converges on alternative polyadenylation as molecular mechanism underlying synaptic impairment.

Schizophrenia (SCZ) is a genetically heterogenous psychiatric disorder of highly polygenic nature. Correlative evidence from genetic studies indicate that the aggregated effects of distinct genetic risk factor combinations found in each patient converge onto common molecular mechanisms. To prove this on a functional level, we employed a reductionistic cellular model system for polygenic risk by differentiating induced pluripotent stem cells (iPSCs) from 104 individuals with high polygenic risk load and controls into cortical glutamatergic neurons (iNs). Multi-omics profiling identified widespread differences in alternative polyadenylation (APA) in the 3' untranslated region of many synaptic transcripts between iNs from SCZ patients and healthy donors. On the cellular level, 3'APA was associated with a reduction in synaptic density of iNs. Importantly, differential APA was largely conserved between postmortem human prefrontal cortex from SCZ patients and healthy donors, and strongly enriched for transcripts related to synapse biology. 3'APA was highly correlated with SCZ polygenic risk and affected genes were significantly enriched for SCZ associated common genetic variation. Integrative functional genomic analysis identified the RNA binding protein and SCZ GWAS risk gene PTBP2 as a critical trans-acting factor mediating 3'APA of synaptic genes in SCZ subjects. Functional characterization of PTBP2 in iNs confirmed its key role in 3'APA of synaptic transcripts and regulation of synapse density. Jointly, our findings show that the aggregated effects of polygenic risk converge on 3'APA as one common molecular mechanism that underlies synaptic impairments in SCZ.

Smoking status ameliorates cholinergic impairments in cortical inhibition in patients with schizophrenia.

RATIONALE: Modulation of cortical excitability, in particular inhibition, is impaired in patients with schizophrenia. Chronic nicotine consumption, which is prevalent in this group, has been shown to alter cortical excitability in healthy individuals and to increase inhibitory activity. Thus, beneficial effects of smoking on impaired cortical excitability in patients with schizophrenia have been proposed, though direct experimental evidence is still lacking. OBJECTIVES: We aimed to explore the effect of chronic smoking on cortical excitability by comparing smoking and non-smoking patients with schizophrenia. METHOD: Twenty-six smoking and 19 non-smoking patients diagnosed with schizophrenia were included. Transcranial magnetic stimulation (TMS) applied to the primary motor cortex served as experimental paradigm for measuring corticospinal and intracortical excitability as follows: Resting motor threshold (RMT) and the input/output curve (I/O curve) were obtained to assess corticospinal excitability. Intracortical excitability was explored using paired-pulse TMS techniques (intracortical facilitation (ICF), short-latency intracortical inhibition (SICI) and short-latency afferent inhibition (SAI)). RESULTS: A significantly stronger inhibition in the cholinergically driven SAI protocol was observed in smokers compared to non-smokers. All other measures did not show significant differences between groups. CONCLUSION: Our results suggest an increased inhibition within cholinergic circuits due to chronic nicotine consumption in schizophrenia. This increase may compensate impaired cholinergic neurotransmission and could explain the high rate of smokers in schizophrenia.

Exercise as an add-on treatment in individuals with schizophrenia: Results from a large multicenter randomized controlled trial.

Current treatment methods do not achieve recovery for most individuals with schizophrenia, and symptoms such as negative symptoms and cognitive deficits often persist. Aerobic endurance training has been suggested as a potential add-on treatment targeting both physical and mental health. We performed a large-scale multicenter, rater-blind, parallel-group randomized controlled clinical trial in individuals with stable schizophrenia. Participants underwent a professionally supervised six-month training comprising either aerobic endurance training (AET) or flexibility, strengthening, and balance training (FSBT, control group), follow-up was another six months. The primary endpoint was all-cause discontinuation (ACD); secondary endpoints included effects on psychopathology, cognition, functioning, and cardiovascular risk. In total, 180 participants were randomized. AET was not superior to FSBT in ACD and most secondary outcomes, with dropout rates of 59.55% and 57.14% in the six-month active phase, respectively. However, both groups showed significant improvements in positive, general, and total symptoms, levels of functioning and in cognitive performance. A higher training frequency additionally promoted further memory domains. Participants with higher baseline cognitive abilities were more likely to respond to the interventions. Our results support integrating exercise into schizophrenia treatment, while future studies should aim to develop personalized training recommendations to maximize exercise-induced benefits.

Single session gamma transcranial alternating stimulation does not modulate working memory in depressed patients and healthy controls.

OBJECTIVES: Gamma transcranial alternating current stimulation (gamma tACS) is considered a non-invasive brain stimulation technique for modulation of cognitive performance and for treatment of psychiatric disorders. There is heterogeneous data on its effectiveness in improving working memory. METHODS: In this randomized crossover study, we tested 22 patients with major depression and 21 healthy volunteers who received 20 min of active and sham 40 Hz gamma tACS over bilateral dorsolateral prefrontal cortex during a computerized n-back task in a cross-over design. RESULTS: We showed no improvement in reaction time and accuracy of working memory during active or sham stimulation in both groups, and no interaction between cognitive load and stimulation conditions. CONCLUSION: The present study suggests that a single session of gamma tACS does not affect cognition in depression. However, the bilateral electrode montage and learning or ceiling effects may have affected results. Overall, this study is in line with the heterogeneous results of previous gamma tACS studies, emphasizing that methodologies and study designs should be harmonized.

Anodal transcranial direct current stimulation sustainably increases EEG alpha activity in patients with schizophrenia.

AIMS: Transcranial direct current stimulation (tDCS) applied to the prefrontal cortex has been frequently used to elicit behavioral changes in patients with schizophrenia. However, the interaction between prefrontal tDCS and electrophysiological changes remains largely uncharted. The present study aimed to investigate cortical electrophysiological changes induced by tDCS in frontal areas by means of repeated electroencephalography (EEG) in patients with schizophrenia. METHODS: In total, 20 patients with schizophrenia received 13 minutes of anodal tDCS (1 mA) applied to the left dorsolateral prefrontal cortex (DLPFC). Repeated resting EEG was recorded before (once) and following (at five follow-up time-bins) tDCS to trace post-tDCS effects. We used sLORETA for source reconstruction to preserve the localization of brain signals with a low variance and to analyze frequency changes. RESULTS: We observed significant changes after the stimulation in areas highly connected with the stimulated DLPFC areas. The alpha 1 (8.5-10.0 Hz) activity showed a highly significant, long-lasting, increase for up to 1 hour after the stimulation in the postcentral gyrus (Brodmann area 2, 3, and 40). Significant yet unstable changes were also seen in the alpha-2 frequency band precentral at 10 minutes, in the beta-1 frequency band occipital at 20 minutes, and in the beta-3 frequency band temporal at 40 minutes. CONCLUSION: We were able to show that anodal tDCS can induce stable EEG changes in patients with schizophrenia. The results underline the potential of tDCS to induce long-lasting neurophysiological changes in patients with schizophrenia showing the possibility to induce brain excitability changes in this population.