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Abstract The influence of repeated lockdowns on mental health and social isolation is unknown. We conducted a longitudinal study of the influence of repeated mild lockdowns during two emergency declarations in Japan, in May 2020 and February 2021. The analyses included 7893 people who participated in all online surveys. During repeated mild lockdowns, mental and physical symptoms decreased overall, while loneliness increased and social networks decreased. Subgroup analyses revealed that depression and suicidal ideation did not decrease only in the younger age group (aged 18–29 years) and that younger and middle-aged people (aged 18–49 years), women, people with a history of treatment for mental illness, and people who were socially disadvantaged in terms of income had higher levels of mental and physical symptoms at all survey times. Additionally, comprehensive extraction of the interaction structure between depression, demographic attributes, and psychosocial variables indicated that loneliness and social networks were most closely associated with depression. These results indicate that repeated lockdowns have cumulative negative effects on social isolation and loneliness and that susceptible populations, such as young people and those with high levels of loneliness, require special consideration during repeated lockdown situations.

Transcranial direct current stimulation (tDCS) has been reportedly beneficial for different neurodegenerative disorders. tDCS has been reported as a potential adjunctive or alternative treatment for auditory verbal hallucination (AVH). This study aims to review the effects of tDCS on AVH in patients with schizophrenia through combining the evidence from randomized clinical trials (RCTs). The databases of PsycINFO (2000–2019), PubMed (2000–2019), EMBASE (2000–2019), CINAHL (2000–2019), Web of Science (2000–2019), and Scopus (2000–2019) were systematically searched. The clinical trials with RCT design were selected for final analysis. A total of nine RCTs were eligible and included in the review. Nine RCTs were included in the final analysis. Among them, six RCTs reported a significant reduction of AVH after repeated sessions of tDCS, whereas three RCTs did not show any advantage of active tDCS over sham tDCS. The current studies showed an overall decrease of approximately 28% of AVH after active tDCS and 10% after sham tDCS. The tDCS protocols targeting the sensorimotor frontal-parietal network showed greater treatment effects compared with the protocols targeting other regions. In this regard, cathodal tDCS over the left temporoparietal area showed inhibitory effects on AVHs. The most effective tDCS protocol on AVHs was twice-daily sessions (2 mA, 20-minute duration) over 5 consecutive days (10 sessions) with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporal area. Some patient-specific and disease-specific factors such as young age, nonsmoking status, and higher frequencies of AVHs seemed to be the predictors of treatment response. Taken together, the results of tDCS as an alternative treatment option for AVH show controversy among current literatures, since not all studies were positive. However, the studies targeting the same site of the brain showed that the tDCS could be a promising treatment option to reduce AVH. Further RCTs, with larger sample sizes, should be conducted to reach a conclusion on the efficacy of tDCS for AVH and to develop an effective therapeutic protocol for clinical setting.

To evaluate the acute effects of ingestion of 500 mg of caffeine in addition to aerobic exercise on the optimization of cognitive attention tasks and simple reaction time. Twenty men were randomly divided into two groups, caffeine (CAF) and placebo (PLA), and underwent cardiopulmonary exercise testing and cognitive testing (D2SLK, D2GZ, D2F% and TRS). Then, both ingested 500 mg of caffeine or placebo (double blind), and after 60 min performed a 30-minute continuous exercise session at 70 % VO2Max. Cognitive tests were repeated immediately after exercise, and after 30 min. D2SLK, D2GZ, D2F% and TRS scores were compared by repeated measures ANOVA. The magnitude of the effect was established, and it was considered meaningful p = 0.05. CAF is able to alter D2SLK and also reduce D2F% (0.001 - moderate effect, 0.82) and improve the task after 30 min of exercise (p = 0.014 - moderate effect 0.95). The TRS showed significant gains for the CAF group compared to PLA (0.000 - high effect 1.76). Caffeine induces significant effects in attention and reaction time domains independent of the effect of aerobic exercise.

The aim of the current overview was to present the existing literature on the recent phenomenon of eSports. Using a multifaceted approach, we focused on its definitions, historical development, and classification, drawing attention to key disputes that exist between scholars. Furthermore, we investigated the debate on whether eSports should be considered a traditional sport or not, with a particular interest in two processes that have contributed to eSports’ development as a culturally-significant addition to the world of sports, as both a game and an occupation: sportification and professionalization. Lastly, we analysed studies on spectatorship and consumption to understand why people watch and play eSports pointing out data about the recent relationship between practice and the possible development of eSport's addiction, gambling, and the related impact on individual health and wellbeing.

Physical exercise is seen as the main ally for health promotion, preventing and protecting the organism from several diseases. According to WHO, there is a tendency of constant growth in the elderly population in the coming years. The regular practice of exercises by the elderly becomes relevant to minimize the deleterious effects of the aging process and to increase the fitness index. Recently, the world population started a confrontation against Corona Virus Disease (COVID-19), which is the most significant public health challenge globally. Although social isolation is a reasonable measure in an attempt to stop contamination by COVID-19, this measure has limited the ability of individuals to exercise outdoors or in gyms and health clubs, which increased the risk of developing chronic illnesses related to a sedentary lifestyle. The critical point is that the recent recommendations on exercise prescription to combat the potentially harmful effects of COVID-19 failure to adequately address resistance exercise interventions as home-based exercise strategy. Thus, in this paper, we discussed the physical exercise as medicine if the training status is enough to protect the elderly against COVID-19 infection, about the role of physical activity on immunosuppression. Possible risks for COVID-19 infection, and the old training methods, such as no-load resistance training as possible resistance exercise strategies and high-intensity interval training, as new proposals of home-based exercise interventions, could perform during the current COVID-19 pandemic.

BackgroundDepression is a common threat to children and adolescents in terms of affecting psychosocial development and increasing their risk of suicide. Apart from conventional treatments for depression, physical exercise has become a promising alternative. This paper aims to systematically review the existing meta-analyses that focus on the impact of physical exercise on clinical and nonclinical depression in children and adolescents.MethodsA systematic literature search was conducted using PsycINFO, PsycARTICLES, MedLine, PubMed, and hand searching. Risk of bias analysis, effect sizes calculations, and evaluation of the methodological characteristics (AMSTAR 2) were carried out.ResultsFour meta-analyses met the inclusion criteria. After analysing the overlap, the total sample contained 30 single studies (mostly including gender mixed samples) and 2,110 participants (age range 5–20 years). The medium duration of the interventions was 11.5 weeks. The sessions had a medium length of 41 min, and the frequency of implementation was three sessions per week. The most implemented intervention type was aerobic exercise, while control groups mainly continued with their regular routine, among other related options. The overall mean effect of physical exercise on depression was medium (d = −0.50). The additional analysis in clinically depressed samples documented a small to medium mean effect (d = −0.48) in favor of the intervention.ConclusionThe small to medium but consistently positive effects that were found in the present study place physical exercise as a promising and helpful alternative for children and adolescents with clinical and nonclinical depression. The limited literature focused on children and adolescents in comparison with adult samples points to the need for further research.

Aim: The following work aims to investigate the putative correlation between early trauma and cognitive functions, as well as psychotic symptoms and cognitive functions, in individuals diagnosed with schizophrenia.Methods: A quantitative assessment was performed with 20 individuals diagnosed with schizophrenia according to the 5th edition of the Diagnostic and Statistical Manual (DSM-5) criteria and who were in ongoing outpatient treatment in Psychosocial Care Centres in Brazil. Clinical measurements comprised a semistructured clinical interview, a screening questionnaire for common mental disorders, the Positive and Negative Syndrome Scale (PANSS), and the Early Trauma Inventory Self-Report—Short Form (ETISR-SF). Cognitive assessment included Beta III test, Concentrated Attention (CA) test, Color Trails Test (CTT), and Visual Face Memory (VFM) test.Results: Age-adjusted analysis showed a negative correlation between early trauma and visual memory performance (r = −0.585, p = 0.007) and negative symptoms and attention performance (r = −0.715, p = 0.000).Conclusion: Although a cause–effect relationship cannot be firmly stated, an association between early trauma experience and cognitive impairment such as visual memory, as well as a relationship between negative symptoms and attention domains, is suggested by our preliminary findings. Future studies with larger sample sizes and prospective design will clarify the long-term effects of early exposure to trauma and its clinical meaning in terms of developing psychotic-related illness.

There is preliminary evidence suggesting that hippocampal functioning is associated with attachment style. However, it is unknown if attachment is also associated with hippocampal-related cognitive function such as spatial learning and recall. This study aims to verify if attachment dimensions are associated with spatial learning and recall. Sixty-five female participants were recruited and were evaluated using the Adult Attachment Scale-R and tested on a virtual maze navigation task (VMT) at one moment (exploratory trial + 3 trials) and 24 h later (3 trials). There was a significant Moment × Trial × Close-Depend interaction for the outcome time, F(2,126) = 3.807, p = 0.025, with post hoc analysis indicating that the High Close-Depend group displayed significant improvements between Trial 1 and Trial 3 in the post-test assessment. Conversely, the Low Close-Depend group displayed significant improvements between Trial 1and Trial 3 but on the pre-test assessment. Furthermore, the Low Close-Depend group presented significant better performance in pre-test Trial 3 in comparison to the High Close-Depend group. Thereby, it seems that low comfort with proximity and trust in others is associated with reduced spatial recall, although spatial learning performance was actually superior in these participants. It is possible that reduced exposure to social interaction and meaningful relationships may be reduced in the Low Close-Depend group, leading to modifications in hippocampal function and, ultimately, reduced spatial recall. Oppositely, participants in the High Close-Depend group may not display typical spatial learning in the proposed task as they are more willing to freely explore the presented environment.

Background: The neurophysiological mechanisms of cognitive reactivity, the primary vulnerability factor of major depressive disorder (MDD) recurrence, remain unclear in individuals with recovered MDD (rMDD). Because gamma-band responses (GBRs) can be used to measure cognitive processing, they may also be useful for elucidating the mechanisms underlying cognitive reactivity. Identifying these mechanisms may permit the development of an index for predicting and preempting MDD recurrence. Here, to identify the neurophysiological mechanisms of cognitive reactivity, we examined the characteristics of the GBRs evoked/induced by emotional words in participants with and without rMDD after inducing a negative mood.Methods: Thirty-three healthy control participants and 18 participants with rMDD completed a lexical emotion identification task during electroencephalography along with assessments of cognitive reactivity after negative mood induction.Results: No between-group differences were identified for the task reaction times; however, the rMDD group had significantly higher cognitive reactivity scores than did the control group. Furthermore, the power of late GBRs to positive words was significantly greater in the rMDD group, with the greater power of late GBRs being related to higher cognitive reactivity.Limitations: Considering the population studied, our findings cannot be completely generalized to populations other than adolescents, people with rMDD, and those without a history of co-morbid disorders and early life stress.Conclusions: Our findings indicate that the dysfunction of neural circuits related to higher-order processes like memory and attention might underlie cognitive reactivity. Altered late GBRs to positive information may be persistent biomarkers of the depression recurrence risk.

Abstract Background Cannabidiol (CBD), the non-psychotropic compound from Cannabis sativa, shows positive results on controlling several health disturbances; however, comparable data regarding additional chemical from C. sativa, such as cannabidiolic acid (CBDA), is scarce due to its instability. To address this limitation, a stable CBDA analogue, CBDA methyl ester (HU-580), was synthetized and showed CBDA-like effects. Recently, we described that HU-580 increased wakefulness and wake-related neurochemicals. Objective To extend the comprehension of HU-580´s properties on waking, the c-Fos and NeuN expression in a wake-linked brain area, the hypothalamus was evaluated. Methods c-Fos and NeuN expression in hypothalamic sections were analyzed after the injections of HU-580 (0.1 or 100 μg/kg, i.p.). Results Systemic administrations of HU-580 increased c-Fos and neuronal nuclei (NeuN) expression in hypothalamic nuclei, including the dorsomedial hypothalamic nucleus dorsal part, dorsomedial hypothalamic nucleus compact part, and dorsomedial hypothalamic nucleus ventral part. Conclusion HU-580 increased c-Fos and NeuN immunoreactivity in hypothalamus nuclei suggesting that this drug might modulate the sleep–wake cycle by engaging the hypothalamus.

BackgroundThe effectiveness of physical activity (PA) as an intervention against anxiety disorders and depression is undeniable in clinical psychology. Therefore, the question arose whether these effects also occur when a fear stimulus, like the COVID-19 pandemic, affects otherwise healthy adolescents. Boredom is closely linked to symptoms of fear and anxiety, but the connection between PA, boredom and fear is partly unclear.MethodsA cross-sectional online study was conducted that involved 122 students. Participants were 13–19 years old (Mage = 15.83, SD = 1.73). The survey was available online from April 27th to May 3rd, 2020. At this time, schools in Germany had already been closed for 6 weeks. A self-report questionnaire was used to measure physical activity, boredom, and fear of COVID-19. A multiple linear regression model was conducted.ResultsThe reported fear of COVID-19 significantly correlates with total PA, quantity of strenuous PA, and boredom. Furthermore, a significant regression equation was found. The variables boredom, PA, and age contribute significantly to predicting the fear of COVID-19 [R2 = 0.127, F(3,118) = 6.876, p < 0.000], among adolescents.ConclusionOur results indicate that there is an association between PA, boredom and the quarantine experience of adolescents. Students who were physically more active, especially with strenuous intensity, did not feel bored and showed less fear of COVID-19.

Abstract Background Latest research demonstrates a significant improvement in stress-related symptoms in psychological disorders as a result of exercise training (ET). Controlled clinical trials further validate the significance of ET by demonstrating lower salivary cortisol levels in patients with post-traumatic stress disorder (PTSD) after intervention. A significant change in cortisol and dehydroepiandrosterone (DHEA) levels can already be found after an 8–12-week ET program. The proposed study aims to investigate the impact of an 8-week ET on PTSD symptoms and changes in cortisol levels in a juvenile refugee sample from the Democratic Republic of the Congo (DRC) at an Ugandan refugee settlement. It is the first to implement an ET intervention in a resource-poor, post-conflict setting. Methods/design In a randomized controlled trial, 198 adolescent participants aged 13–16 years from the DRC who, suffer from PTSD, will be investigated. The participants are based at the Nakivale refugee settlement, an official refugee camp in Uganda, Africa, which is among the largest in the world. The participants will be randomized into an Exercise Training (ET) group with a maximum heart rate (HRmax) of > 60%, an Alternative Intervention (AI) group with low-level exercises, and a Waiting-list Control (WC) group. After the 8-week interventional phase, changes in cortisol awakening response (CAR) and DHEA in the ET group that correspond to an improvement in PTSD symptoms are expected that remain at follow-up after 3 months. Discussion To date, there is no controlled and reliable longitudinal study examining the effects of an ET program on symptom severity in individuals with PTSD that can be explained with a harmonization of cortisol secretion. The presented study design introduces an intervention that can be implemented with little expenditure. It aims to provide a promising low-threshold and cost-effective treatment approach for the application in resource-poor settings. Trial registration German Trials Register, ID: DRKS00014280. Registered prospectively on 15 March 2018.

Obesity is a disease characterized by an excessive accumulation of fat in the body and it has been linked the enhancement of inflammation-related endogenous molecules, such as adenosine (AD). Since blueberries may induce anti-obesity effects, we tested the hypothesis that blueberries consumption contained in hypocaloric diet would decrease weight, BMI as well as glucose, cholesterol, triglycerides and AD levels in obese subjects. The baseline conditions of obesity-related variables were collected for all subjects prior the implementation of blueberries intake. Later, participants received a hypocaloric diet that included the consumption of blueberries (50 g/day) during 30 days. We found that male obese subjects that consumed blueberries showed a decrease in weight, glucose, cholesterol, triglycerides and AD whereas female obese subjects that ate blueberries in hypocaloric diet showed no differences in weight, BMI, glucose and triglycerides but displayed a diminution in cholesterol and AD levels. Data suggest that intake of blueberries seems to decrease some of the obese-linked parameters in male or female subjects. Importantly, blueberry consumption decreased the inflammation-related compound AD in both sexes.

Histone methylation/demethylation plays an important modulatory role in chromatin restructuring, RNA transcription and is essential for controlling a plethora of biological processes. Due to many human diseases have been related to histone methylation/demethylation, several compounds such as 3-deazaneplanocin A (DZNep) or 3-((6-(4,5-Dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoic acid; N-[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-4-pyrimidinyl]-β-Alanine (GSK-J1), have been designed to inhibit histone methylase or suppress histone demethylase, respectively. In the present study, we investigated the effects on the sleep-wake cycle and sleep-related neurochemical levels after systemic injections of DZNep or GSK-J1 given during the light or dark phase in rats. DZNep dose-dependently (0.1, 1.0, or 10 mg/kg, i.p.) prolonged wakefulness (W) duration while decreased slow wave sleep (SWS) and rapid eye movement sleep (REMS) time spent during the lights-on period with no changes observed in dark phase. In opposite direction, GSK-J1 (0.1, 1.0, or 10 mg/kg, i.p.) injected at the beginning of the lights-on period induced no statistical changes in W, SWS, or REMS whereas if administered at darkness, we found a diminution in W and an enhancement in SWS and REMS. Finally, brain microdialysis experiments in freely moving animals were used to evaluate the effects of DZNep or GSK-J1 treatments on contents of sleep-related neurochemicals. The results showed that DZNep boosted extracellular levels of dopamine, norepinephrine, epinephrine, serotonin, adenosine, and acetylcholine if injected at the beginning of the lights-on period whereas GSK-J1 exerted similar outcomes but when administered at darkness. In summary, DZNep and GSK-J1 may control the sleep-wake cycle and sleep-related neurochemicals through histone methylation/demethylation activity.

An increasing body of experimental data have suggested that aberrant functional interactions between large-scale networks may be the most plausible explanation of psychopathology across multiple mental disorders, including substance-related and addictive disorders. In the current research, we have investigated the association between problematic cannabis use (PCU) and triple-network electroencephalographic (EEG) functional connectivity. Twelve participants with PCU and 24 non-PCU participants were included in the study. EEG recordings were performed during resting state (RS). The exact Low-Resolution Electromagnetic Tomography software (eLORETA) was used for all EEG analyses. Compared to non-PCU, PCU participants showed an increased delta connectivity between the salience network (SN) and central executive network (CEN), specifically, between the dorsal anterior cingulate cortex and right posterior parietal cortex. The strength of delta connectivity between the SN and CEN was positively and significantly correlated with higher problematic patterns of cannabis use after controlling for age, sex, educational level, tobacco use, problematic alcohol use, and general psychopathology (rp = 0.40, p = 0.030). Taken together, our results show that individuals with PCU could be characterized by a specific dysfunctional interaction between the SN and CEN during RS, which might reflect the neurophysiological underpinnings of attentional and emotional processes of cannabis-related thoughts, memories, and craving.

The endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)], receptors (CB1 and CB2), enzymes such as [fatty acid amide hydrolase (FAHH) and monoacylglycerol lipase (MAGL)], as well as the anandamide membrane transporter. Although the role of this complex neurobiological system in the sleep–wake cycle modulation has been studied, the contribution of the blocker of FAAH/transient receptor potential cation channel subfamily V member 1 (TRPV1), N-arachidonoyl-serotonin (AA-5-HT) in sleep has not been investigated. Thus, in the present study, varying doses of AA-5-HT (5, 10, or 20 mg/Kg, i.p.) injected at the beginning of the lights-on period of rats, caused no statistical changes in sleep patterns. However, similar pharmacological treatment given to animals at the beginning of the dark period decreased wakefulness (W) and increased slow wave sleep (SWS) as well as rapid eye movement sleep (REMS). Power spectra analysis of states of vigilance showed that injection of AA-5-HT during the lights-off period diminished alpha spectrum across alertness in a dose-dependent fashion. In opposition, delta power spectra was enhanced as well as theta spectrum, during SWS and REMS, respectively. Moreover, the highest dose of AA-5-HT decreased wake-related contents of neurotransmitters such as dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT) whereas the levels of adenosine (AD) were enhanced. In addition, the sleep-inducing properties of AA-5-HT were confirmed since this compound blocked the increase in W caused by stimulants such as cannabidiol (CBD) or modafinil (MOD) during the lights-on period. Additionally, administration of AA-5-HT also prevented the enhancement in contents of DA, NE, EP, 5-HT and AD after CBD of MOD injection. Lastly, the role of AA-5-HT in sleep homeostasis was tested in animals that received either CBD or MOD after total sleep deprivation (TSD). The injection of CBD or MOD increased alertness during sleep rebound period after TSD. However, AA-5-HT blocked this effect by allowing animals to display an enhancement in sleep across sleep rebound period. Overall, our findings provide evidence that AA-5-HT is an important modulator of sleep, sleep homeostasis and neurotransmitter contents.

The sleep disorder narcolepsy is now considered a neurodegenerative disease because there is a massive loss of neurons containing the neuropeptide hypocretin/orexin (HCRT). In consequence, narcoleptic patients have very low cerebrospinal fluid (CSF) levels of HCRT. Studies in animal models of narcolepsy have shown the neurophysiological role of the HCRT system in the development of this disease. For example, the injection of the neurotoxin named hypocretin-2-saporin (HCRT2/SAP) into the lateral hypothalamus (LH) destroys the HCRT neurons, therefore diminishes the contents of HCRT in the CSF and induces narcoleptic-like behavior in rats. Transplants of various cell types have been used to induce recovery in a variety of neurodegenerative animal models. In models such as Parkinson's disease, cell survival has been shown to be small but satisfactory. Similarly, cell transplantation could be employed to implant grafts of HCRT cells into the LH or even other brain regions to treat narcolepsy. Here, we report for the first time that transplantation of HCRT neurons into the LH of HCRT2/SAP-lesioned rats diminishes narcoleptic-like sleep behavior. Therefore, cell transplantation may provide an effective method to treat narcolepsy.

BACKGROUND:Oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) are amides of fatty acids and ethanolamine named N-acylethanolamines or acylethanolamides. The hydrolysis of OEA and PEA is catalyzed by the fatty acid amide hydrolase (FAAH). A number of FAAH inhibitors that increase the levels of OEA and PEA in the brain have been developed, including URB597. In the present report, we examined whether URB597, OEA or PEA injected into wake-related brain areas, such as lateral hypothalamus (LH) or dorsal raphe nuclei (DRN) would promote wakefulness (W) in rats. METHODOLOGY AND PRINCIPAL FINDINGS:Male Wistar rats (250-300 g) were implanted for sleep studies with electrodes to record the electroencephalogram and electromyogram as well as a cannulae aimed either into LH or into DRN. Sleep stages were scored to determine W, slow wave sleep (SWS) and rapid eye movement sleep (REMS). Power spectra bands underly neurophysiological mechanisms of the sleep-wake cycle and provide information about quality rather than quantity of sleep, thus fast Fourier transformation analysis was collected after the pharmacological trials for alpha (for W; α = 8-12 Hz), delta (for SWS; δ = 0.5-4.0 Hz) and theta (for REMS; θ = 6.0-12.0 Hz). Finally, microdialysis samples were collected from a cannula placed into the nucleus accumbens (AcbC) and the levels of dopamine (DA) were determined by HPLC means after the injection of URB597, OEA or PEA. We found that microinjection of compounds (10, 20, 30 µg/1 µL; each) into LH or DRN during the lights-on period increased W and decreased SWS as well as REMS and enhanced DA extracellular levels. CONCLUSIONS:URB597, OEA or PEA promoted waking and enhanced DA if injected into LH or DRN. The wake-promoting effects of these compounds could be linked with the enhancement in levels of DA and indirectly mediated by anandamide.