Face and emotion recognition in individuals diagnosed with schizophrenia, ultra-high risk for psychosis, unaffected siblings, and healthy controls in a sample from Turkey.

Face and emotion recognition are crucial components of social cognition. We aimed to compare them in patients diagnosed with schizophrenia (SCZ), ultra-high risk for psychosis (UHR), unaffected siblings of schizophrenia patients (SIB), and healthy controls (HC). METHODS: One hundred sixty-six participants (45 SCZ, 14 UHR, 45 SIB, and 62 HC) were interviewed with the Structured Clinical Interview for DSM-5 (SCID-5). Positive and Negative syndrome scale (PANSS), PennCNB Facial Memory (CPF), and Emotion Recognition Task (ER40) were applied. RESULTS: In CPF, SCZ performed significantly lower than SIB and HC. SIB was also significantly lower than HC for total correct responses. The sample size of the UHR group was small, and the statistical comparisons did not reach a significance, however, a trend towards decreased performance between the SCZ and SIB was found. In ER40, SCZ performed significantly lower than HC and SIB in all domains, except for the insignificant findings for angry ER between SIB and SCZ. SIB also performed significantly lower than HC for angry, negative, and total ER. UHR was similar to SCZ for happy and sad ER and performed significantly lower than HC for happy ER. The effect of SCZ diagnosis on the efficiency of CPF and ER40 was significant when corrected for age and education. For SCZ, PANSS also significantly affected the CPF and ER40. CONCLUSION: Our findings suggest varying levels of face and emotion recognition deficits in individuals with SCZ, UHR, and SIB. Face and emotion recognition deficits are promising schizophrenia endophenotypes related to social cognition.

Subjective cognitive assessments and N-back are not correlated, and they are differentially affected by anxiety and depression.

Cognitive function (CF) is a core feature related to all psychiatric disorders. However, self-report scales of CF (SRSC) may not always correlate with CF's objective measures and may have different mediators. Tools to select for evaluating CF in diverse psychiatric populations and their determinants need to be studied. In this study, we aimed to assess the association of SRSC (Perceived Deficit Questionnaire-Depression (PDQ-D), and World Health Organization's Adult Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS) and its inattentiveness subscale) with Letter-N-back as an objective measure of CF, and to analyze their association with psychopathology. Two hundred nine (131 nonclinical, and 78 clinical with a psychiatric diagnosis of ICD10 F31-39 [mood disorders excluding Bipolar I] or F40-F49 [neurotic, stress-related or psychosomatic disorder] categories) participants were evaluated with PDQ-D, ASRS, Beck Depression Inventory (BDI), and Beck's Anxiety Inventory (BAI), and N-back. Both groups' data were included in the analysis. PDQ-D showed a small correlation with N-back scores, whereas ASRS showed no correlation. PDQ-D and ASRS showed a large correlation. Age and BAI scores significantly predicted both PDQ-D and ASRS, whereas the cognitive subscale of BDI predicted PDQ-D, but not ASRS. Only BAI scores predicted N-back results. The mediation model revealed that 2-back scores of N-back task directly affects PDQ-D scores, independent of BDI scores. However, the cognitive subscale of BDI moderated 2-back and PDQ-D association. On the contrary, BAI scores significantly mediated the association of 2-back scores with PDQ-D. The direct effect of 2-back scores in PDQ-D was insignificant in the mediation of BAI scores. Our study validates the discordance between SRSC and an objective measurement of CF. Anxiety may affect both self-report and objective measurement of CF, whereas depressive thought content may lead to higher cognitive dysfunction reports in nondemented participants.

Clinical Impact of Glucagon-Like Peptide-1 Receptor Analogs on the Complications of Obesity.

BACKGROUND: Obesity is a chronic disease associated with increased morbidity and mortality due to its complications. The aims of obesity treatment are primarily to accomplish weight loss, and prevention or treatment of its complications. Lifestyle changes along with behavioral therapy constitute the first-line treatment of obesity followed by pharmacotherapy. Glucagon-like peptide receptor analogs (GLP-1 RAs) are among the approved pharmacotherapy options. Their central effect on suppressing appetite results in considerable weight loss. However, their effect on the complications of obesity has not been very well recognized. This review aims to analyze the effects of GLP-1 RAs on the complications of obesity, as diabetes mellitus, hypertension, nonalcoholic steatohepatitis (NASH), cardiovascular diseases, polycystic ovary syndrome, infertility, obstructive sleep apnea (OSA), osteoarthritis, cancer and central nervous system problems. SUMMARY: Data from preclinical studies and clinical trials have been thoroughly evaluated. Effects regarding the complications as far as the scope of this review have covered can be summarized as blood glucose lowering, blood pressure lowering, resolution of NASH, improving major cardiovascular events, improving fertility and sex hormone levels, and improvement in OSA symptoms and in cognitive scores. Although the mechanisms are not fully elucidated, it is clear that the effects are not solely due to weight loss, but some pleiotropic effects like decreased inflammation, oxidative stress, and fibrosis also play a role in some of the complications. KEY MESSAGES: Treating obesity is not only enabling weight loss but ameliorating complications related to obesity. Thus, any antiobesity medication has to have some favorable effects on the complications. As far as the GLP-RA's analogs are concerned, there seems to be an improvement in many of the complications regardless of the weight loss effect of these medications.

Hyperglycemia with or without insulin resistance triggers different structural changes in brain microcirculation and perivascular matrix.

Both type-1 and type-2 DM are related to an increased risk of cognitive impairment, neurovascular complications, and dementia. The primary triggers for complications are hyperglycemia and concomitant insulin resistance in type-2 DM. However, the diverse mechanisms in the pathogenesis of diabetes-related neurovascular complications and extracellular matrix (ECM) remodeling in type-1 and 2 have not been elucidated yet. Here, we investigated the high fat-high sucrose (HFHS) feeding model and streptozotocin-induced type-1 DM model to study the early effects of hyperglycemia with or without insulin resistance to demonstrate the brain microcirculatory changes, perivascular ECM alterations in histological sections and 3D-reconstructed cleared brain tissues. One of the main findings of this study was robust rarefaction in brain microvessels in both models. Interestingly, the HFHS model leads to widespread non-functional angiogenesis, but the type-1 DM model predominantly in the rostral brain. Rarefaction was accompanied by basement membrane thickening and perivascular collagen accumulation in type-1 DM; more severe blood-brain barrier leakage, and disruption of perivascular ECM organization, mainly of elastin and collagen fibers' structural integrity in the HFHS model. Our results point out that the downstream mechanisms of the long-term vascular complications of hyperglycemia models are structurally distinctive and may have implications for appropriate treatment options.

Population-Based Psychiatric Comorbidity in Children and Adolescents With Autism Spectrum Disorder: A Meta-Analysis.

Psychiatric comorbidity in autism spectrum disorder (ASD) is a subject of critical scientific importance, affecting the quality of life, prognosis, and functional outcomes. The prevalence of psychiatric disorders vary considerably according to variables such as index subject characteristics, study setting, sampling frame, diagnostic methods used, as well as country of geographic origin. To date, most studies comprise clinical or treatment referral samples in tertiary care or subjects enrolled in clinical trials and genetic cohort collections. Such samples carry the potential for overestimation of both the frequency and severity of psychiatric comorbidity. A systematic literature search was performed using PubMed and Web of Science databases restricted to population-based study publications in the English between May 1, 2015, and May 31, 2020. A comprehensive keyword list was generated to investigate co-occurrence of psychiatric disorders in children and adolescents with ASD. A wide range of DSM-5 based disorders such as anxiety, mood, ADHD, intellectual disability/intellectual developmental disorder, eating/feeding, gender dysphoria and sleep-wake disorders were assessed. Initial search revealed a total of 1674 articles after removal of duplicates. Two independent researchers conducted a parallel-blinded screening process to identify the eligible studies based on titles and abstracts; 39 studies were analyzed in the current review. The main findings show prevalence estimates of 22.9% (95% CI: 17.7- 29.2) for intellectual disability; 26.2% (22-31) for attention-deficit hyperactivity disorder; 11.1% (8.6-14.1) for anxiety disorders; 19.7% (11.9-30.7) for sleep disorders; 7% (5.2- 9.3) for disruptive disorders; 2% (1.3- 3.1) for bipolar disorders; 2.7% (1.8- 4.2) for depression; 1.8% (0.4-8.7) for obsessive-compulsive disorder; and 0.6% (0.3-1.1) for psychosis. Psychiatric comorbidity in population-based studies is lower than in clinical and referred samples. However, our results also indicate that the frequency of psychiatric comorbidity in children and adolescents with ASD in the population context is considerable, without the influence of referral bias implicit in clinical and treatment samples. There is a need for better targeted diagnostic tools to detect psychiatric comorbidity in children and youth in future population-based studies, as an essential component in providing care as well as new insights into the nature and mechanisms of its underlying associations. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021234464].

Can We Benefit from the Preoperative Psychometric Test with Symptom Checklist-90-Revised (SCL-90-R) to Predict Weight Loss After Sleeve Gastrectomy?

BACKGROUND: The psychological assessment is crucial before bariatric surgery. Derogatis' Symptom Checklist-90-Revised (SCL-90-R) is one of the most widely used measures of psychological symptoms and distress in both clinical and research settings. We aimed to investigate the predictive value of SCL-90-R subscale scores on postoperative excess weight loss percentage (EWLP) after laparoscopic sleeve gastrectomy (LSG). METHODS: Patients who underwent primary LSG for morbid obesity and fully completed preoperative SCL-90-R between January 2016 and July 2019 were retrospectively examined. A multiple linear regression analysis was performed to investigate the relationship between descriptive and psychological variables associated with EWLP percentage at the 12th-month. RESULTS: One hundred six patients who met the inclusion criteria were analyzed. The adequate weight loss (EWLP ˃ 50%) was achieved in 90% of patients after 12 months. The multiple linear regression analysis indicated that younger patients (ß = - 0.695; 95% CI - 1.056, - 0.333; p < 0.001), and patients with preoperative lower BMI (ß = - 1.524; 95% CI - 1.974, - 1.075; p < 0.001) achieved higher EWLP at 12th-month. High somatization score (ß = 11.975; 95% CI 3.653, 20.296; p = 0.005) and a low Global Severity Index (GSI) score (ß = - 24.276; 95% CI - 41.457, - 7.095; p = 0.006) had a positive effect on EWLP at 12th-month. CONCLUSIONS: Preoperative psychological testing can help predict surgical outcomes in the bariatric population. More intense lifestyle and behavioral support can be applied by targeting patients who are expected to lose less weight after surgery, and patients' weight loss potential can be increased.

Test-retest reliability of the Turkish translation of the Penn Computerized Neurocognitive Battery.

Psychiatric disorders are associated with cognitive dysfunction (CD), and reliable screening and follow-up of CD is essential both for research and clinical practice globally; yet, most assessments are in Western languages. We aimed to evaluate the test-retest reliability of the Turkish version of the Penn Computerized Neurocognitive Battery (PennCNB) to guide confident interpretation of results. Fifty-eight healthy individuals completed the PennCNB Turkish version in two sessions. After quality control, reliability analysis was conducted using Intraclass Correlation Coefficients (ICC), corrected for practice effects. Most measures were not significantly different between the sessions and had acceptable ICC values, with several exceptions. Scores were improved considerably for some memory measures, including immediate Facial Memory and Spatial Memory, and for incorrect responses in abstraction and mental flexibility, with correspondingly acceptable ICCs. Test-retest assessment of the Turkish version of the PennCNB shows that it can be used as a reliable real-time measurement of cognitive function in snapshot cross-sectional or longitudinal determinations. Preliminary validity assessment in this normative sample showed expected positive correlations with education level and negative correlations with age. Thus, the Turkish version of the PennCNB can be considered a reliable neuropsychological testing tool in research and clinical practice. Practice effects should be considered, especially when applied in short intervals. Significantly better performances in the retest, beyond practice effect, likely reflect nonlinear improvements in some participants who "learned how to learn" the memory tests or had insight on solving the abstraction and mental flexibility test.

Decreased psychiatric symptomatology after the onset of COVID-19 in a longitudinal college mental health study.

The COVID-19 pandemic brings significant challenges for college students. This study aims to investigate changes in psychiatric symptomatology among them compared to the pre-pandemic period alongside their determinants. Data are collected before and 3 months after the onset of the pandemic from 168 students who applied to a college mental health center. Psychiatric symptomatology is assessed by the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Adult Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS). Possible vulnerability factors are screened by a survey on COVID-19-related health and social isolation status, Fear of COVID-19 Scale, Social Media Use Disorder Scale (SMDS), Distress Thermometer, Scoff Eating Questionnaire, and International Physical Activity Questionnaire Short-Form (IPAQ). Results show decreased PHQ-9, GAD-7, and ASRS scores at follow-up. Even though the screen time increases, SMDS scores significantly decline. SMDS have a direct effect on PHQ-9 and ASRS levels, in addition to an indirect effect through the Distress Thermometer. Higher SMDS scores predict higher anxious and depressive symptomatology in repeated assessments. Fear of COVID-19 scores have a direct effect on GAD-7 scores only. This study suggests that the stress level and psychiatric symptomatology of the students decreased significantly in the early phases of the pandemic. The level of social media use disorder should be taken into account while following college students with mental health symptoms.

The impact of the prolonged COVID-19 pandemic on stress resilience and mental health: A critical review across waves.

The global public health crisis caused by COVID-19 has lasted longer than many of us would have hoped and expected. With its high uncertainty and limited control, the COVID-19 pandemic has undoubtedly asked a lot from all of us. One important central question is: how resilient have we proved in face of the unprecedented and prolonged coronavirus pandemic? There is a vast and rapidly growing literature that has examined the impact of the pandemic on mental health both on the shorter (2020) and longer (2021) term. This not only concerns pandemic-related effects on resilience in the general population, but also how the pandemic has challenged stress resilience and mental health outcomes across more specific vulnerable population groups: patients with a psychiatric disorder, COVID-19 diagnosed patients, health care workers, children and adolescents, pregnant women, and elderly people. It is challenging to keep up to date with, and interpret, this rapidly increasing scientific literature. In this review, we provide a critical overview on how the COVID-19 pandemic has impacted mental health and how human stress resilience has been shaped by the pandemic on the shorter and longer term. The vast literature is dominated by a wealth of data which are, however, not always of the highest quality and heavily depend on online and self-report surveys. Nevertheless, it appears that we have proven surprisingly resilient over time, with fast recovery from COVID-19 measures. Still, vulnerable groups such as adolescents and health care personnel that have been severely impacted by the COVID-19 pandemic do exist. Large interindividual differences exist, and for future pandemics there is a clear need to comprehensively and integratively assess resilience from the start to provide personalized help and interventions tailored to the specific needs for vulnerable groups.

Depression, But Not Dissociative Experiences, Predicts Overgeneral Memory: A Systematic Review and Meta-Regression Analysis.

Background: Reduced memory specificity (i.e., overgeneral memory) is a characteristic of autobiographical memories widely studied in clinical populations, and it is explained by rumination, functional avoidance, and executive dysfunction. Though the relationship of autobiographical memory specificity with mood and anxiety disorders has been shown, how it relates to dissociation is not well-established. Thus, we aimed to investigate whether dissociative experiences are related to overgeneral memory while considering concurrent depression as a possible confounding factor. Methods: We conducted a systematic review in compliance with The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and searched PubMed and Web of Science databases using autobiograph* and dissoc* as our keywords. Results: Of the 768 studies identified, 9 studies fulfilled the inclusion criteria. A meta-regression analysis was conducted to analyze the relationship between dissociative experiences and depression scores with autobiographical memory test scores. Our research revealed that depression scores, but not dissociative experiences, are significantly related to reduced memory specificity. Conclusion: While the possible overlap between dissociation and depression should be considered in the interpretation of the findings, dissociative experiences do not seem to pose vulnerability for reduced specificity of autobiographical memory. The number of studies on the topic is limited, and they do not have longitudinal follow-ups. The heterogeneous reporting of memory scores and low scores of dissociative experiences in the samples are also limitations of the existing studies.

Production and comprehension of co-speech gestures in Parkinson's disease.

This study examined how impairments in sensorimotor abilities of individuals with Parkinson's Disease (PD) can be related to the use and understanding of co-speech hand gestures involving literal and figurative actions. We tested individuals with PD (n = 18, 12 males, Mage = 56.5, SDage = 8.16, PD duration since onset: M = 5.36 years, SD = 3.51, Hoehn and Yahr Scale:MH&Y = 2.09, SDH&Y = 0.50) and age- and education-matched neurotypical controls (n = 18, 14 males, Mage = 56.61, SDage = 8.88) with two experimental tasks. In the gesture production task, participants retold the narratives presented to them in a written format. In the gesture comprehension task, participants were asked to match a gesture with a novel verb in literal and figurative sentence contexts. Results showed that patients with PD gestured significantly less than the neurotypical controls. No group differences were found for the type of gesture use. Individuals with PD performed worse than controls on matching gestures with novel verbs, particularly for figurative meanings. Individuals' severity in the disease negatively correlated with their performance for these figurative novel verb-gesture matches. The performances in the two tasks did not correlate. These findings suggest that problems in sensorimotor abilities resulting from PD can influence overall gesture production and gesture comprehension, providing further evidence on the relations between PD and the impaired use of multimodal language.

Association of Excessive Daytime Sleepiness with the Zung Self-Rated Depression Subscales in Adults with Coronary Artery Disease and Obstructive Sleep Apnea.

Excessive daytime sleepiness (EDS) is a factor associated with both obstructive sleep apnea (OSA) and depressive symptoms. Continuous positive airway pressure (CPAP) treatment may decrease EDS in adults with OSA; however, the modulatory role of depressive symptoms on the improvement of EDS is not known. We aimed to explore the association between subscales of the Zung Self-rated Depression Scale (SDS) and Epworth Sleepiness Scale (ESS) over a 2-year period in coronary artery disease (CAD) patients with OSA. This was a post-hoc analysis of the RICCADSA cohort, in which 399 adults with CAD (155 sleepy OSA [apnea-hypopnea index ≥ 15/h] and ESS score ≥ 10, who were offered CPAP; and 244 nonsleepy OSA [ESS < 10]), randomized to CPAP [n = 122] or no-CPAP [n = 122]) were included. Three factors were extracted from the Zung SDS, based on the principal component analysis: F1, cognitive symptoms and anhedonia; F2, negative mood; and F3, appetite. In a mixed model, the ESS score decreased by 3.4 points (p < 0.001) among the sleepy OSA phenotype, which was predicted by the decline in the F2, but not in the F1 and F3 scores. The fixed effects of time were not significant in the nonsleepy OSA groups, and thus, further analyses were not applicable. Additional within-group analyses showed a significant decrease in all subscales over time both in the sleepy and nonsleepy OSA patients on CPAP whereas there was a significant increase in the nonsleepy OSA group randomized to no-CPAP. We conclude that the improvement in negative mood symptoms of depression, but not changes in cognitive symptoms and anhedonia as well as appetite, was a significant predictor of decline in the ESS scores over a 2-year period in this CAD cohort with sleepy OSA on CPAP treatment.

Blood-brain barrier leakage and perivascular collagen accumulation precede microvessel rarefaction and memory impairment in a chronic hypertension animal model.

Hypertension (HT) is one of the main causes of vascular dementia, lead to cognitive decline. Here, we investigated the relationship between cerebral microvessels, pericytes, extracellular matrix (ECM) accumulation, blood-brain barrier (BBB) breakdown, and memory impairment at mid-life in a chronic hypertension animal model. Spontaneously hypertensive rats (SHRs) (n = 20) are chosen for the model and age matched Wistar rats (n = 16) as controls. Changes in brain microvasculature and in vitro experiments are shown with immunofluorescence studies and cognition with open field, novel object recognition, and Y maze tests. There was a significant reduction in pericyte coverage in SHRs (p = 0.021), while the quantitative parameters of the cerebral microvascular network were not different between groups. On the other hand, parenchymal albumin leakage, as a Blood-brain barrier (BBB) breakdown marker, was prominent in SHRs (p = 0.023). Extracellular matrix (ECM) components, collagen type 1, 3 and 4 were significantly increased (accumulated) around microvasculature in SHRs (p = 0.011, p = 0.013, p = 0.037, respectively). Furthermore, in vitro experiments demonstrated that human brain vascular pericytes but not astrocytes and endothelial cells secreted type I collagen upon TGFß1 exposure pointing out a possible role of pericytes in increased collagen accumulation around cerebral microvasculature due to HT. Furthermore, valsartan treatment decreased the amount of collagen type 1 secreted by pericytes after TGFß1 exposure. At the time of evaluation, SHRs did not demonstrate cognitive decline and memory impairments. Our results showed that chronic HT causes ECM accumulation and BBB leakage before leading to memory impairments and therefore, pericytes could be a novel target for preventing vascular dementia.

Effect of Exenatide Use on Cognitive and Affective Functioning in Obese Patients With Type 2 Diabetes Mellitus: Exenatide Use Mediates Depressive Scores Through Increased Perceived Stress Levels.

PURPOSE/BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a molecule used to treat type 2 diabetes mellitus (T2DM). Given their widespread expression in the nervous system, GLP-1 receptors also play a role in regulating mood and cognitive function. Here, we aimed to compare obese patients with T2DM, with or without exenatide (a GLP-1R agonist) use on cognitive and affective functioning. METHODS/PROCEDURES: A total of 43 patients with T2DM (23 on exenatide and 20 without exenatide) were evaluated with the Snaith-Hamilton Pleasure Scale, Cognitive Failures Questionnaire, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7, Childhood Trauma Questionnaire, Perceived Stress Scale (PSS), and Chronic Stress Scale, in addition to laboratory-based measures of reward learning (the probabilistic reward task) and working memory (Letter-N-Back task). FINDINGS/RESULTS: Patients on exenatide had higher body mass index (BMI) (37.88 ± 5.44 vs 35.29 ± 6.30; P = 0.015), PHQ-9 (9.70 ± 4.92 vs 6.70 ± 4.66; P = 0.026), and PSS (29.39 ± 6.70 vs 23.35 ± 7.69; P = 0.015) scores. Other stress scales (Childhood Trauma Questionnaire and Chronic Stress Scale), Generalized Anxiety Disorder-7 scores, response bias, or discriminability as assessed by probabilistic reward task and self-report (Cognitive Failures Questionnaire) and laboratory-based (Letter-N-Back) cognitive measures were not significantly different between groups (both Ps > 0.05). Multivariate linear regression analyses adding BMI and PSS as covariates revealed that although BMI had no effect (P = 0.5), PSS significantly predicted PHQ-9 scores (P = 0.004). Mediation analysis showed that exenatide users reported higher PSS, with greater PSS associated with higher PHQ-9 levels (b = 0.236). There was no evidence on exenatide directly influencing PHQ-9 independent of PSS (c' = 1.573; P = 0.305; 95% bootstrap confidence interval, -1.487 to 4.634). IMPLICATIONS/CONCLUSIONS: Based on previous research and our findings, exenatide use might be mediating depression scores through disrupting stress responses.

Neuropsychiatric Symptoms of COVID-19 Explained by SARS-CoV-2 Proteins' Mimicry of Human Protein Interactions.

The first clinical symptoms focused on the presentation of coronavirus disease 2019 (COVID-19) have been respiratory failure, however, accumulating evidence also points to its presentation with neuropsychiatric symptoms, the exact mechanisms of which are not well known. By using a computational methodology, we aimed to explain the molecular paths of COVID-19 associated neuropsychiatric symptoms, based on the mimicry of the human protein interactions with SARS-CoV-2 proteins. Methods: Available 11 of the 29 SARS-CoV-2 proteins' structures have been extracted from Protein Data Bank. HMI-PRED (Host-Microbe Interaction PREDiction), a recently developed web server for structural PREDiction of protein-protein interactions (PPIs) between host and any microbial species, was used to find the "interface mimicry" through which the microbial proteins hijack host binding surfaces. Classification of the found interactions was conducted using the PANTHER Classification System. Results: Predicted Human-SARS-CoV-2 protein interactions have been extensively compared with the literature. Based on the analysis of the molecular functions, cellular localizations and pathways related to human proteins, SARS-CoV-2 proteins are found to possibly interact with human proteins linked to synaptic vesicle trafficking, endocytosis, axonal transport, neurotransmission, growth factors, mitochondrial and blood-brain barrier elements, in addition to its peripheral interactions with proteins linked to thrombosis, inflammation and metabolic control. Conclusion: SARS-CoV-2-human protein interactions may lead to the development of delirium, psychosis, seizures, encephalitis, stroke, sensory impairments, peripheral nerve diseases, and autoimmune disorders. Our findings are also supported by the previous in vivo and in vitro studies from other viruses. Further in vivo and in vitro studies using the proteins that are pointed here, could pave new targets both for avoiding and reversing neuropsychiatric presentations.

Intrinsic Auricular Muscle Zone Stimulation Improves Walking Parameters of Parkinson's Patients Faster Than Levodopa in the Motion Capture Analysis: A Pilot Study.

It has been demonstrated that intrinsic auricular muscles zone stimulation (IAMZS) can improve the motor symptoms of Parkinson's disease (PD) patients who are examined with the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. In the present pilot study, using motion capture technology, we aimed to investigate the efficacy of IAMZS compared to medication alone or in combination with medication. Ten PD patients (mean age: 54.8 ± 10.1 years) were enrolled. Each participant participated in three different sessions: sole medication, sole stimulation-20 min of IAMZS, and combined IAMZS (20 min) and medication. Each session was performed on different days but at the same time to be aligned with patients' drug intake. Motion capture recording sessions took place at baseline, 20, 40, and 60 min. Statistical analysis was conducted using one-way repeated measures ANOVA. Bonferroni correction was implemented for pairwise comparisons. The sole medication was ineffective to improve gait-related parameters of stride length, stride velocity, stance, swing, and turning speed. In the sole-stimulation group, pace-related gait parameters were significantly increased at 20 and 40 min. These improvements were observed in stride length at 20 (p = 0.0498) and 40 (p = 0.03) min, and also in the normalized stride velocity at 40 min (p-value = 0.02). Stride velocity also tended to be significant at 20 min (p = 0.06) in the sole-stimulation group. Combined IAMZS and medication demonstrated significant improvements in all the time segments for pace-related gait parameters [stride length: 20 min (p = 0.04), 40 min (p = 0.01), and 60 min (p < 0.01); stride velocity: 20 min (p < 0.01), 40 min (p = 0.01), and 60 min (p < 0.01)]. These findings demonstrated the fast action of the IAMZS on PD motor symptoms. Moreover, following the termination of IAMZS, a prolonged improvement in symptoms was observed at 40 min. The combined use of IAMZS with medication showed the most profound improvements. The IAMZS may be particularly useful during medication off periods and may also postpone the long-term side effects of high-dose levodopa. A large scale multicentric trial is required to validate the results obtained from this pilot study. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03907007.

Association between GLP-1 receptor gene polymorphisms with reward learning, anhedonia and depression diagnosis.

BACKGROUND: Glucagon-like peptide-1 receptors (GLP-1Rs) are widely expressed in the brain. Evidence suggests that they may play a role in reward responses and neuroprotection. However, the association of GLP-1R with anhedonia and depression diagnosis has not been studied. Here, we examined the association of GLP-1R polymorphisms with objective and subjective measures of anhedonia, as well as depression diagnosis. METHODS: Objective [response bias assessed by the probabilistic reward task (PRT)] and subjective [Snaith-Hamilton Pleasure Scale (SHAPS)] measures of anhedonia, clinical variables and DNA samples were collected from 100 controls and 164 patients at McLean Hospital. An independent sample genotyped as part of the Psychiatric Genomics Consortium (PGC) was used to study the effect of putative GLP-1R polymorphisms linked to response bias in PRT on depression diagnosis. RESULTS: The C allele in rs1042044 was significantly associated with increased PRT response bias, when controlling for age, sex, case-control status and PRT discriminability. AA genotype of rs1042044 showed higher anhedonia phenotype based on SHAPS scores. However, analysis of PGC major depressive disorder data showed no association between rs1042044 and depression diagnosis. CONCLUSION: Findings suggest a possible association of rs1042044 with anhedonia but no association with depression diagnosis.

Can GLP-1 Be a Target for Reward System Related Disorders? A Qualitative Synthesis and Systematic Review Analysis of Studies on Palatable Food, Drugs of Abuse, and Alcohol.

The role of glucagon-like peptide 1 (GLP-1) in insulin-dependent signaling is well-known; GLP-1 enhances glucose-dependent insulin secretion and lowers blood glucose in diabetes. GLP-1 receptors (GLP-1R) are also widely expressed in the brain, and in addition to its role in neuroprotection, it affects reward pathways. This systematic review aimed to analyze the studies on GLP-1 and reward pathways and its currently identified mechanisms. Methods: "Web of Science" and "Pubmed" were searched to identify relevant studies using GLP-1 as the keyword. Among the identified 26,539 studies, 30 clinical, and 71 preclinical studies were included. Data is presented by grouping rodent studies on palatable food intake, drugs of abuse, and studies on humans focusing on GLP-1 and reward systems. Results: GLP-1Rs are located in reward-related areas, and GLP-1, its agonists, and DPP-IV inhibitors are effective in decreasing palatable food intake, along with reducing cocaine, amphetamine, alcohol, and nicotine use in animals. GLP-1 modulates dopamine levels and glutamatergic neurotransmission, which results in observed behavioral changes. In humans, GLP-1 alters palatable food intake and improves activity deficits in the insula, hypothalamus, and orbitofrontal cortex (OFC). GLP-1 reduces food cravings partially by decreasing activity to the anticipation of food in the left insula of obese patients with diabetes and may inhibit overeating by increasing activity to the consumption of food in the right OFC of obese and left insula of obese with diabetes. Conclusion: Current preclinical studies support the view that GLP-1 can be a target for reward system related disorders. More translational research is needed to evaluate its efficacy on human reward system related disorders.

Prevalence and Associated Features of Anxiety Disorder Comorbidity in Bipolar Disorder: A Meta-Analysis and Meta-Regression Study.

Objective: Bipolar disorder is highly comorbid with anxiety disorders, however current and lifetime comorbidity patterns of each anxiety disorder and their associated features are not well studied. Here, we aimed to conduct a meta-analysis and meta-regression study of current evidence. Method: We searched PubMed to access relevant articles published until September 2015, using the keywords "Bipolar disorder" or "Affective Psychosis" or "manic depressive" separately with "generalized anxiety," "panic disorder," "social phobia," "obsessive compulsive," and "anxiety." Variables for associated features and prevalence of anxiety disorders were carefully extracted. Results: Lifetime any anxiety disorder comorbidity in BD was 40.5%; panic disorder (PD) 18.1%, generalized anxiety disorder (GAD) 13.3%, social anxiety disorder (SAD) 13.5% and obsessive compulsive disorder (OCD) 9.7%. Current any anxiety disorder comorbidity in BD is 38.2%; GAD is 15.2%, PD 13.3%, SAD 11.7%, and OCD 9.9%. When studies reporting data about comorbidities in BDI or BDII were analyzed separately, lifetime any anxiety disorder comorbidity in BDI and BDII were 38% and 34%, PD was 15% and 15%, GAD was 14% and 16.6%, SAD was 8% and 13%, OCD was 8% and 10%, respectively. Current any DSM anxiety disorder comorbidity in BDI or BDII were 31% and 37%, PD was 9% and 13%, GAD was 8% and 12%, SAD was 7% and 11%, and OCD was 8% and 7%, respectively. The percentage of manic patients and age of onset of BD tended to have a significant impact on anxiety disorders. Percentage of BD I patients significantly decreased the prevalence of panic disorder and social anxiety disorder. A higher rate of substance use disorder was associated with greater BD-SAD comorbidity. History of psychotic features significantly affected current PD and GAD. Conclusions: Anxiety disorder comorbidity is high in BD with somewhat lower rates in BDI vs BDII. Age of onset, substance use disorders, and percentage of patients in a manic episode or with psychotic features influences anxiety disorder comorbidity.

Stress modulates cortical excitability via α-2 adrenergic and glucocorticoid receptors: As assessed by spreading depression.

An increase in cortical excitability may be one of the factors mediating stress-induced vulnerability to neuropsychiatric disorders. Since stress increases extracellular glutamate and predisposes to migraine with aura attacks, we aimed to study the effect of stress on cortical spreading depression (CSD), the biological substrate of migraine aura and a measure of cortical excitability. CSD was induced by increasing concentrations of KCl applied over the dura with 5-minute intervals and recorded from parieto-occipital cortex to assess the CSD-induction threshold in acutely-stressed, chronically-stressed and naive mice. To study the mechanisms of acute stress-induced decrease in CSD threshold, we systemically administered clonidine, yohimbine, propranolol, CRH1 receptor antagonist NBI27914, mifepristone and spironolactone at doses shown to be effective on stress as well as a central noradrenergic neurotoxin (DSP-4) before acute stress. CSD threshold was significantly lowered by acute and chronic stress as well as central noradrenergic denervation. Clonidine and mifepristone further decreased the CSD threshold below the acute stress-induced levels, whereas yohimbine reversed the acute stress-induced decrease in CSD threshold compared to the saline-injected and stressed control groups. Propranolol, NBI27914 and spironolactone did not modify the effect of acute stress on CSD threshold. Stress increases cortical excitability as illustrated by a decrease in CSD-induction threshold. This action of acute stress is mediated by α2-adrenergic and glucocorticoid receptors. The decrease in CSD threshold may account for the stress-induced susceptibility to migraine. CSD may be used as a tool to study the link between stress-related disorders and cortical excitability.