Diurnal cortisol profiles in autistic adolescents and young adults: Associations with social difficulties and internalizing mental health symptoms.

Several autism-related characteristics, such as social difficulties, may contribute to high perceived stress and increased exposure to stressful life events in some autistic individuals. Repeated exposure to stress might lead to the dysfunction of the hypothalamic-pituitary-adrenocortical-axis and be a vulnerability factor for developing mental health difficulties. Previous studies show contradictory findings on salivary cortisol in autism. In the current study, we investigated diurnal cortisol profiles in autistic adolescents and young adults, as well as their associations with social difficulties, stress exposure, and mental health symptoms. Autistic (n = 48, Mage = 17.6) and nonautistic (n = 51, Mage = 18.4) participants collected salivary cortisol at home six times a day for 2 days. Social difficulties, exposure to stressful life events/bullying, and mental health symptoms were assessed with questionnaires and clinical interviews. Similar diurnal cortisol slopes (DCS) and cortisol awakening responses were observed between the groups, but autistic participants showed higher total cortisol output (AUCG, area under the curve with respect to ground) during the day (b = 19.09, p = 0.009). In the autistic group, more severe social difficulties were associated with flatter DCS (b = 0.01, p = 0.007). Finally, cortisol alterations were associated with self-reported mental health symptoms, especially in autistic females in analyses uncorrected for multiple comparisons. In conclusion, our results do not indicate autism-related group-level alterations in most diurnal cortisol measures, but autistic youth showed higher total cortisol (AUCG) compared with nonautistic peers. More detailed investigation of interindividual variability in cortisol profiles within autistic people might give us important insights into vulnerability to developing stress-related mental health difficulties.

Longitudinal Analysis of Brain Function-Structure Dependencies in 22q11.2DS and Psychotic Symptoms.

BACKGROUND: Understanding how brain function and structure relate to one another, compared to conventional unimodal analysis, opens a new biologically-relevant assessment of neural mechanisms. However, how function-structure dependencies evolve throughout typical and abnormal neurodevelopment remains elusive. The 22q11.2 deletion syndrome (22q11.2DS) offers an important opportunity to study the development of function-structure dependencies and their specific association to the pathophysiology of psychosis. METHODS: Previously, we used graph signal processing to combine brain activity and structural connectivity measures in adults, quantifying functional-structural dependency (FSD). Here, we combined FSD with longitudinal multivariate partial least squares correlation (PLS-C) to evaluate FSD alterations across groups and among patients with and without mild to moderate positive psychotic symptoms (PPS). We assessed 391 longitudinally repeated resting-state functional and diffusion-weighted magnetic resonance imaging from 194 healthy controls and 197 deletion carriers (age span 7-34, data collected over a span of 12 years) RESULTS: Relative to controls, patients with 22q11.2DS showed a persistent developmental offset from childhood, with regions of hyper- and hypo-coupling across the brain. Additionally, a second deviating developmental pattern showed an exacerbation during adolescence, presenting hypo-coupling in frontal and cingulate cortex and hyper-coupling in temporal regions for patients with 22q11.2DS. Interestingly, the observed aggravation during adolescence was strongly driven by the PPS+ group. CONCLUSIONS: These results confirm a central role of altered FSD-maturation in the emergence of psychotic symptoms in 22q11.2DS during adolescence. The FSD deviations precede the onset of psychotic episodes and thus offer a potential early indication for behavioral interventions in individuals at risk.

Transdiagnostic markers across the psychosis continuum: a systematic review and meta-analysis of resting state fMRI studies.

Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar disorder. A pathophysiological understanding of intrinsic brain activity underlying psychosis is crucial to improve diagnosis and treatment. While a potential continuum along the psychotic spectrum has been recently described in neuroimaging studies, especially for what concerns absolute and relative amplitude of low-frequency fluctuations (ALFF and fALFF), these efforts have given heterogeneous results. A transdiagnostic meta-analysis of ALFF/fALFF in patients with psychosis compared to healthy controls is currently lacking. Therefore, in this pre-registered systematic review and meta-analysis PubMed, Scopus, and Embase were searched for articles comparing ALFF/fALFF between psychotic patients and healthy controls. A quantitative synthesis of differences in (f)ALFF between patients along the psychotic spectrum and healthy controls was performed with Seed-based d Mapping, adjusting for age, sex, duration of illness, clinical severity. All results were corrected for multiple comparisons by Family-Wise Error rates. While lower ALFF and fALFF were detected in patients with psychosis in comparison to controls, no specific finding survived correction for multiple comparisons. Lack of this correction might explain the discordant findings highlighted in previous literature. Other potential explanations include methodological issues, such as the lack of standardization in pre-processing or analytical procedures among studies. Future research on ALFF/fALFF differences for patients with psychosis should prioritize the replicability of individual studies. Systematic review registration: https://osf.io/, identifier (ycqpz).

Balance measures of mini and brief balance evaluation system tests for Iranian population.

Introduction: Falling is a serious problem for all ages. There are several tests to assess balance. Mini-BESTest and brief-BESTest are balance tests for which there are no normative values for Iranian people. We aimed to provide the normative values of mini-BESTest and brief-BESTest among healthy Iranian adults. Methods: A cross-sectional study was designed. Three hundred healthy adults (150 males and 150 females) in six age groups (18-29, 30-39, 40-49, 50-59, 60-69, +70 years) completed the tests using Persian mini-BESTest and brief-BESTest. Normative values were calculated for age groups. Results: Normative values of mini-BESTest and brief- BESTest decreased significantly with age (from 27 to 21.9 for mini-BESTest and from 22.9 to 15.4 for brief BESTest). There were no significant differences between genders except for females in 30-39 and 40-49 years age groups which scored better on brief-BESTest and mini-BESTest, respectively. Males had significantly scored better in brief- BESTest in 60-69 and ≥ 70 age groups. Conclusions: The normative values of the mini-BESTest and brief-BESTest provided for healthy Iranian adults can help clinicians when assessing subjects with balance dysfunction.

Thalamic contributions to psychosis susceptibility: Evidence from co-activation patterns accounting for intra-seed spatial variability (µCAPs).

The temporal variability of the thalamus in functional networks may provide valuable insights into the pathophysiology of schizophrenia. To address the complexity of the role of the thalamic nuclei in psychosis, we introduced micro-co-activation patterns (µCAPs) and employed this method on the human genetic model of schizophrenia 22q11.2 deletion syndrome (22q11.2DS). Participants underwent resting-state functional MRI and a data-driven iterative process resulting in the identification of six whole-brain µCAPs with specific activity patterns within the thalamus. Unlike conventional methods, µCAPs extract dynamic spatial patterns that reveal partially overlapping and non-mutually exclusive functional subparts. Thus, the µCAPs method detects finer foci of activity within the initial seed region, retaining valuable and clinically relevant temporal and spatial information. We found that a µCAP showing co-activation of the mediodorsal thalamus with brain-wide cortical regions was expressed significantly less frequently in patients with 22q11.2DS, and its occurrence negatively correlated with the severity of positive psychotic symptoms. Additionally, activity within the auditory-visual cortex and their respective geniculate nuclei was expressed in two different µCAPs. One of these auditory-visual µCAPs co-activated with salience areas, while the other co-activated with the default mode network (DMN). A significant shift of occurrence from the salience+visuo-auditory-thalamus to the DMN + visuo-auditory-thalamus µCAP was observed in patients with 22q11.2DS. Thus, our findings support existing research on the gatekeeping role of the thalamus for sensory information in the pathophysiology of psychosis and revisit the evidence of geniculate nuclei hyperconnectivity with the audio-visual cortex in 22q11.2DS in the context of dynamic functional connectivity, seen here as the specific hyper-occurrence of these circuits with the task-negative brain networks.

The Cerebellum and Cognitive Function: Anatomical Evidence from a Transdiagnostic Sample.

Multiple lines of evidence across human functional, lesion, and animal data point to a cerebellar role, in particular of crus I, crus II, and lobule VIIB, in cognitive function. However, a mapping of distinct facets of cognitive function to cerebellar structure is missing. We analyzed structural neuroimaging data from the Healthy Brain Network (HBN). Cerebellar parcellation was performed with a validated automated segmentation pipeline (CERES) and stringent visual quality check (n = 662 subjects retained from initial n = 1452). Canonical correlation analyses (CCA) examined regional gray matter volumetric (GMV) differences in association to cognitive function (quantified with NIH Toolbox Cognition domain, NIH-TB), accounting for psychopathology severity, age, sex, scan location, and intracranial volume. Multivariate CCA uncovered a significant correlation between two components entailing a latent cognitive canonical (NIH-TB subscales) and a brain canonical variate (cerebellar GMV and intracranial volume, ICV), surviving bootstrapping and permutation procedures. The components correspond to partly shared cerebellar-cognitive function relationship with a first map encompassing cognitive flexibility (r = 0.89), speed of processing (r = 0.65), and working memory (r = 0.52) associated with regional GMV in crus II (r = 0.57) and lobule X (r = 0.59) and a second map including the crus I (r = 0.49) and lobule VI (r = 0.49) associated with working memory (r = 0.51). We show evidence for a structural subspecialization of the cerebellum topography for cognitive function in a transdiagnostic sample.

Amygdala subdivisions exhibit aberrant whole-brain functional connectivity in relation to stress intolerance and psychotic symptoms in 22q11.2DS.

The amygdala is a key region in emotional regulation, which is often impaired in psychosis. However, it is unclear if amygdala dysfunction directly contributes to psychosis, or whether it contributes to psychosis through symptoms of emotional dysregulation. We studied the functional connectivity of amygdala subdivisions in patients with 22q11.2DS, a known genetic model for psychosis susceptibility. We investigated how dysmaturation of each subdivision's connectivity contributes to positive psychotic symptoms and impaired tolerance to stress in deletion carriers. Longitudinally-repeated MRI scans from 105 patients with 22q11.2DS (64 at high-risk for psychosis and 37 with impaired tolerance to stress) and 120 healthy controls between the ages of 5 to 30 years were included. We calculated seed-based whole-brain functional connectivity for amygdalar subdivisions and employed a longitudinal multivariate approach to evaluate the developmental trajectory of functional connectivity across groups. Patients with 22q11.2DS presented a multivariate pattern of decreased basolateral amygdala (BLA)-frontal connectivity alongside increased BLA-hippocampal connectivity. Moreover, associations between developmental drops in centro-medial amygdala (CMA)-frontal connectivity to both impaired tolerance to stress and positive psychotic symptoms in deletion carriers were detected. Superficial amygdala hyperconnectivity to the striatum was revealed as a specific pattern arising in patients who develop mild to moderate positive psychotic symptoms. Overall, CMA-frontal dysconnectivity was found as a mutual neurobiological substrate in both impaired tolerance to stress and psychosis, suggesting a role in prodromal dysregulation of emotions in psychosis. While BLA dysconnectivity was found to be an early finding in patients with 22q11.2DS, which contributes to impaired tolerance to stress.

Multivariate patterns of disrupted sleep longitudinally predict affective vulnerability to psychosis in 22q11.2 Deletion Syndrome.

22q11.2 deletion syndrome (22q11DS) contributes dramatically to increased genetic risk for psychopathology, and in particular schizophrenia. Sleep disorders, including obstructive sleep apnea (OSA), are also highly prevalent, making 22q11DS a unique model to explore their impact on psychosis vulnerability. Still, the contribution of sleep disturbances to psychosis vulnerability remains unclear. We characterized the sleep phenotype of 69 individuals with 22q11DS and 38 healthy controls with actigraphy and sleep questionnaires. Psychiatric symptoms were measured concomitantly with the baseline sleep assessment and at longitudinal follow-up, 3.58±0.85 years later. We used a novel multivariate partial-least-square-correlation (PLSC) approach to identify sleep patterns combining objective and subjective variables, which correlated with psychiatric symptoms. We dissected longitudinal pathways linking sleep disturbances to psychosis, using multi-layer-network-analysis. 22q11DS was characterized by a non-restorative sleep pattern, combining increased daytime fatigue despite longer sleep duration. Non-restorative sleep combined with OSA symptoms correlated with both emotional and psychotic symptoms. Moreover, a sleep pattern evocative of OSA predicted longitudinal worsening of positive and negative symptoms, by accentuating the effects of emotional dysregulation. These results suggest that sleep disturbances could significantly increase psychosis risk, along an affective pathway. If confirmed, this suggests that systematic screening of sleep quality could mitigate psychosis vulnerability in 22q11DS.

Excitatory/Inhibitory Imbalance Underlies Hippocampal Atrophy in Individuals With 22q11.2 Deletion Syndrome With Psychotic Symptoms.

BACKGROUND: Abnormal neurotransmitter levels have been reported in individuals at high risk for schizophrenia, leading to a shift in the excitatory/inhibitory balance. However, it is unclear whether these alterations predate the onset of clinically relevant symptoms. Our aim was to explore in vivo measures of excitatory/inhibitory balance in 22q11.2 deletion carriers, a population at genetic risk for psychosis. METHODS: Glx (glutamate+glutamine) and GABA+ (gamma-aminobutyric acid with macromolecules and homocarnosine) concentrations were estimated in the anterior cingulate cortex, superior temporal cortex, and hippocampus using the Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence and the Gannet toolbox in 52 deletion carriers and 42 control participants. T1-weighted images were acquired longitudinally and processed with FreeSurfer version 6 to extract hippocampal volume. Subgroup analyses were conducted in deletion carriers with psychotic symptoms. RESULTS: While no differences were found in the anterior cingulate cortex, deletion carriers had higher levels of Glx in the hippocampus and superior temporal cortex and lower levels of GABA+ in the hippocampus than control participants. We additionally found a higher Glx concentration in the hippocampus of deletion carriers with psychotic symptoms. Finally, more pronounced hippocampal atrophy was significantly associated with increased Glx levels in deletion carriers. CONCLUSIONS: We provide evidence for an excitatory/inhibitory imbalance in temporal brain structures of deletion carriers, with a further hippocampal Glx increase in individuals with psychotic symptoms that was associated with hippocampal atrophy. These results are in line with theories proposing abnormally enhanced glutamate levels as a mechanistic explanation for hippocampal atrophy via excitotoxicity. Our results highlight a central role of glutamate in the hippocampus of individuals at genetic risk for schizophrenia.

The continuum of attention dysfunction: Evidence from dynamic functional network connectivity analysis in neurotypical adolescents.

The question of whether attention-related disorders such as attention-deficit/hyperactivity disorder (ADHD) are best understood as clinical categories or as extreme ends of a spectrum is an ongoing debate. Assessing individuals with varying degrees of attention problems and utilizing novel methodologies to assess relationships between attention and brain activity may provide key information to support the spectrum hypothesis. We scanned 91 neurotypical adolescents during rest using functional magnetic resonance imaging. We conducted static and dynamic functional network connectivity (FNC) analysis and correlated findings to behavioral metrics of ADHD, attention problems, and impulsivity. We found that dynamic FNC analysis detects significant differences in large-scale neural connectivity as a function of individual differences in attention and impulsivity that are obscured in static analysis. We show ADHD manifestations and attention problems are associated with diminished Salience Network-centered FNC and that ADHD manifestations and impulsivity are associated with prolonged periods of dynamically hyperconnected states. Importantly, our meta-state analysis results reveal a relationship between ADHD manifestations and exhibiting variable and volatile dynamic behavior such as changing meta-states more often and traveling over a greater dynamic range. These findings in non-clinical adolescents provide support for the continuum model of attention disorders.

Neural Basis of Internal Attention in Adults with Pure and Comorbid ADHD.

OBJECTIVE: To examine whether putatively atypical neuronal activity during internal attention in ADHD yields insights into processes underlying emotion dysregulation. METHODS: We used a word processing paradigm to assess neural activations in adults with ADHD (N = 46) compared to controls (N = 43). We measured effects of valence, applied partial-least squares correlation analysis to assess multivariate brainbehavior relationships and ran subgroup analyses to isolate results driven by pure ADHD (N = 18). RESULTS: During internal attention, ADHD, compared to controls, have (1) increased activation in the right angular gyrus (rAG), which appears driven by pure, not comorbid, ADHD and (2) diminished activation in the insula and fronto-striatal circuitry. Diminished activations were driven by negatively-valenced internal attention and negatively correlated with increased affective lability within the ADHD group. CONCLUSION: Internal attention in ADHD is associated with increased rAG activation, possibly reflecting difficulty converging external and internal information, and diminished activation within emotion regulation circuitry.

Is elevated ALT associated with lifestyle risk factors? A population-based survey.

Purpose: Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) and the role of Alanine aminotransferase (ALT) in diagnosing liver injury along with the increasing prevalence of lifestyle risk factors, we aimed to evaluate the association between serum ALT level and lifestyle risk factors in a population-based survey. Methods: This was a population-based study conducted in rural and urban areas of Iran in 2016. Cluster sampling method was applied to enroll a total of 31,050 participants aged ≥ 18. Demographic data, anthropometric measures, and laboratory samples were gathered. Multivariate logistic regression analyses were performed using three different cut-off levels for elevated ALT to assess the relationship between elevated ALT and lifestyle risk factors. Results: The prevalence of elevated ALT was significantly higher in men with elevated body mass index (BMI), waist-to-hip ratio (WTH), hip circumference, and salt consumption, likewise, in women with higher BMI and WTH. In the multivariate logistic model adjusted for age and sex, high WTH (adjusted odds ratio: 1.73; 95% CI 1.52-1.96), BMI > 25 (1.51; 95% CI 1.29-1.76), hip circumference (1.26; 95% CI 1-1.58), and current smoking (0.67; 95% CI 0.56-0.8) were associated with elevated ALT levels using American cut-off (ALT > 33U/L for male and ALT > 25U/L for female). Only physical measurements (BMI, WTH) but not lifestyle risk factors were related to the increased ALT regardless of the selected cut-offs. Conclusion: As elevated ALT was associated with several lifestyle risk factors, stewardship programs should be established to modify lifestyle risk factors, such as abdominal obesity and physical inactivity. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01137-6.

Neural substrates of psychosis revealed by altered dependencies between brain activity and white-matter architecture in individuals with 22q11 deletion syndrome.

BACKGROUND: Dysconnectivity has been consistently proposed as a major key mechanism in psychosis. Indeed, disruptions in large-scale structural and functional brain networks have been associated with psychotic symptoms. However, brain activity is largely constrained by underlying white matter pathways and the study of function-structure dependency, compared to conventional unimodal analysis, allows a biologically relevant assessment of neural mechanisms. The 22q11.2 deletion syndrome (22q11DS) constitutes a remarkable opportunity to study the pathophysiological processes of psychosis. METHODS: 58 healthy controls and 57 deletion carriers, aged from 16 to 32 years old,underwent resting-state functional and diffusion-weighted magnetic resonance imaging. Deletion carriers were additionally fully assessed for psychotic symptoms. Firstly, we used a graph signal processing method to combine brain activity and structural connectivity measures to obtain regional structural decoupling indexes (SDIs). We use SDI to assess the differences of functional structural dependency (FSD) across the groups. Subsequently we investigated how alterations in FSDs are associated with the severity of positive psychotic symptoms in participants with 22q11DS. RESULTS: In line with previous findings, participants in both groups showed a spatial gradient of FSD ranging from sensory-motor regions (stronger FSD) to regions involved in higher-order function (weaker FSD). Compared to controls, in participants with 22q11DS, and further in deletion carriers with more severe positive psychotic symptoms, the functional activity was more strongly dependent on the structure in parahippocampal gyrus and subcortical dopaminergic regions, while it was less dependent within the cingulate cortex. This analysis revealed group differences not otherwise detected when assessing the structural and functional nodal measures separately. CONCLUSIONS: Our findings point toward a disrupted modulation of functional activity on the underlying structure, which was further associated to psychopathology for candidate critical regions in 22q11DS. This study provides the first evidence for the clinical relevance of function-structure dependency and its contribution to the emergence of psychosis.

Exploring associations between diurnal cortisol, stress, coping and psychopathology in adolescents and young adults with 22q11.2 deletion syndrome.

Background: 22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition associated to a high risk for psychiatric disorders, including psychosis. Individuals with 22q11DS are thought to experience increased levels of chronic stress, which could lead to alterations in hypothalamic-pituitary-adrenocortical (HPA)-axis functioning. In the current study, we investigated for the first time diurnal salivary cortisol profiles in adolescents and young adults with 22q11DS as well as their link with stress exposure, coping strategies and psychopathology, including psychotic symptoms. Methods: Salivary cortisol was collected from adolescents and young adults with 22q11DS (n = 30, age = 19.7) and matched healthy controls (HC; n = 36, age = 18.5) six times a day for two days. Exposure to stressful life events, including peer victimization, coping strategies and general psychopathology were assessed with questionnaires. Psychotic symptoms and psychiatric comorbidities were evaluated with clinical interviews. Results: We observed similar daily levels and diurnal profiles of salivary cortisol in adolescents and young adults with 22q11DS compared to HCs. However, participants with 22q11DS reported less frequent exposure to stress than HCs. In 22q11DS, we observed a significant association between the use of non-adaptive coping strategies and the severity of psychotics symptoms. Cortisol level was not associated to severity of psychotic symptoms, but elevated cortisol awakening response (CAR) was found in participants with 22q11DS with higher levels of general psychopathology. Conclusions: Our results do not support earlier propositions of altered HPA-axis functioning in 22q11DS but highlight the need to further investigate diurnal cortisol as an indicator of HPA-axis functioning and its link with (earlier) stress exposure and psychopathology in this population. Interventions should target the development of adaptive coping skills in preventing psychosis in 22q11DS.

Alcohol consumption and related disorders in Iran: Results from the National Surveillance of Non-Communicable Diseases' Survey (STEPs) 2016.

BACKGROUND: Alcohol consumption is a public health concern which is illegal in Iran. Moreover, due to cultural and religious beliefs, the available population-based research findings on alcohol consumption are inadequate. We aimed to provide an estimate on alcohol consumption using a large-scale population-based survey in Iran. MATERIALS AND METHODS: The National Surveillance of Non-Communicable Risk Factors in Iran was a population-based survey conducted in 2016. The epidemiologic distribution of alcohol consumption and its related disorders were assessed using weighted survey methods and multiple logistic regression models. Age standardized rates were calculated using Iran's national population census in 2016. RESULTS: At the national level, the prevalence rates of lifetime and current alcohol consumption were 8.00% (95% CI: 7.67-8.32) and 4.04% (95% CI: 3.81-4.27), respectively. The highest prevalence was reported among 25 to 34 year-olds. Individuals of higher socioeconomic status consumed significantly greater levels of alcohol. At provincial level, the highest and lowest percentages of the current alcohol drinking rates in Iran's provinces were, 23.92% (95% CI: 17.56-30.28) and 0.4% (95% CI: 0-1.18) in males, 1.58% (95% CI: 0.22-2.94) and 0% in females, respectively. In urban regions, the highest alcohol consumption rate was more than 22 times greater than the lowest alcohol consumption rate. Current alcohol drinkers were 2 times more prone to injury as compared to nondrinkers (ORadj: 2.0, 95%CI: 1.7, 2.3). CONCLUSION: In Iran, the prevalence of alcohol consumption is low, although there is a considerable variation of alcohol consumption at provincial level as well as in different gender groups. Therefore, preventive WHO-recommended measures should be adopted more seriously by vulnerable groups.

Spatio-Temporal Analysis of the Hepatitis B Prevalence in Iranian Blood Donors from 2000 to 2016 at National and Provincial Level.

BACKGROUND: High risk blood transfusions can cause a lot of financial and psychological burden to the community. The prevalence of Hepatitis B is useful for evaluating the blood products' safety and donor selection methods. We aimed to predict the prevalence of hepatitis B in Iranian blood donors from 2000-2016. METHODS: Positive cases of hepatitis B from 2006 to 2014 were collected from Iranian Blood Transfusion Organization. This database was classified according to the age, provinces, and type of donation. Data was not existed in all subnational levels and all years, therefore, for predicting the hepatitis B prevalence, two separate, Spatio-temporal and mixed model (GLMM) were developed. RESULTS: At the national level, the hepatitis B prevalence declined from 0.69 (0.51 to 0.90) in 2000 to 0.27 (0.21 to 0.33) in 2016. In first-time, regular, and repeated donors, this prevalence declined from 2.31 (1.74 to 2.31), 0.26 (0.19 to 0.34), and 0.51 (0.38 to 0.68) in 2000 to 0.87 (0.69 to 1.09), 0.09 (0.07 to 0.12), and 0.19 (0.14 to 0.24) in 2016. At the provincial level, the highest and lowest prevalence in 2016 was observed in North Khorasan and Gilan. With increasing age, the average prevalence of hepatitis B, increased. CONCLUSION: Prevalence of hepatitis B in Iranian blood donors has been reduced significantly over 17 years, but still new cases of hepatitis B are reported. By precise monitoring the donor selection process and implementing more sensitive laboratory screening, we can reduce the risk of new infectious agents.

Brain microstructural abnormalities in 22q11.2 deletion syndrome: A systematic review of diffusion tensor imaging studies.

22q11.2 deletion syndrome (22q11DS) is a severe genetic syndrome characterized by cognitive deficits and neuropsychiatric disorders, particularly schizophrenia. Neuroimaging alterations have been extensively reported in 22q11DS, both in gray and white matter structures. However, a considerable variability among the results affects the generalizability of the findings to date. Herein, we reviewed diffusion tensor imaging (DTI) findings in 22q11DS, their association with psychosis and cognition, and the implications of DTI studies on neurodevelopment in 22q11DS. We also investigated differences between 22q11DS and schizophrenic patients without 22q11DS. Using an online search of PubMed and Embase, we identified studies investigating DTI findings in 22q11DS. After selecting eligible studies in accordance with the preferred reporting items for systematic reviews and meta-analyses guideline, we included thirty-one studies. Overall, 22q11DS patients show altered structural connectivity and disrupted microstructural organization of most cortical and subcortical structures and white matter tracts. Moreover, despite a significant heterogeneity in the results, reduced diffusivity measures and elevated fractional anisotropy were observed. However controversial, compared to typically developing children, 22q11DS patients reached the peak of fractional anisotropy (FA) and the trough of radial diffusivity (RD) at an older age, which shows neurodevelopmental delay. DTI measures were also associated with psychotic symptoms and cognitive deficits. In conclusion, this study provides a comprehensive review of microstructural alterations in 22q11DS. Future larger investigations on this syndrome could potentially lead to the detection of early diagnostic imaging markers for genetically induced schizophrenia, thus improving the treatment and, ultimately, the outcome.

Neurologic Manifestations of COVID-19.

Neurological manifestations of novel coronavirus disease (COVID-19) are reported to occur in as much as 37% of the affected patients. These manifestations range from headache and dizziness to altered mental status and consciousness, anosmia, ageusia, sensory disturbances, and stroke. The mechanisms by which the neurological symptoms arise are not yet determined but may either proceed as an indirect consequence of systemic hyperinflammation or result from the direct invasion of the virus to neural and glial cells. The neural invasion can explain both the retrograde pathway of encephalitis and the early manifestation of anosmia by invading the olfactory bulb. Moreover, in the case of attacking the brain stem, it may take part in the early apnea manifestation reported by patients. Additionally, neurotropism of the virus could be the cause of acute hemorrhagic encephalitis. Hyperinflammation can have acute and prolonged effects in the nervous system, such as acute demyelination and predisposition to multiple sclerosis. Moreover, the pro-inflammatory state contributes to hypercoagulation, which in turn could result in cerebrovascular injuries in COVID-19 patients. This chapter would discuss that the neurologic manifestations of the COVID-19 are to be looked at as a multifactorial entangled phenomenon.

Interdisciplinary Approaches to COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has been a significant concern worldwide. The pandemic has demonstrated that public health issues are not merely a health concern but also affect society as a whole. In this chapter, we address the importance of bringing together the world's scientists to find appropriate solutions for controlling and managing the COVID-19 pandemic. Interdisciplinary cooperation, through modern scientific methods, could help to handle the consequences of the pandemic and to avoid the recurrence of future pandemics.

Dysmaturation Observed as Altered Hippocampal Functional Connectivity at Rest Is Associated With the Emergence of Positive Psychotic Symptoms in Patients With 22q11 Deletion Syndrome.

BACKGROUND: Hippocampal alterations are among the most replicated neuroimaging findings across the psychosis spectrum. Moreover, there is strong translational evidence that preserving the maturation of hippocampal networks in mice models prevents the progression of cognitive deficits. However, the developmental trajectory of hippocampal functional connectivity (HFC) and its contribution to psychosis is not well characterized in the human population. 22q11 deletion syndrome (22q11DS) offers a unique model for characterizing early neural correlates of schizophrenia. METHODS: We acquired resting-state functional magnetic resonance imaging in 242 longitudinally repeated scans from 84 patients with 22q11DS (30 with moderate to severe positive psychotic symptoms) and 94 healthy control subjects in the age span of 6 to 32 years. We obtained bilateral hippocampus to whole-brain functional connectivity and employed a novel longitudinal multivariate approach by means of partial least squares correlation to evaluate the developmental trajectory of HFC across groups. RESULTS: Relative to control subjects, patients with 22q11DS failed to increase HFC with frontal regions such as the dorsal part of the anterior cingulate cortex, prefrontal cortex, and supplementary motor area. Concurrently, carriers of the deletion had abnormally higher HFC with subcortical dopaminergic areas. Remarkably, this aberrant maturation of HFC was more prominent during midadolescence and was mainly driven by patients exhibiting subthreshold positive psychotic symptoms. CONCLUSIONS: Our findings suggest a critical period of prefrontal cortex-hippocampal-striatal circuit dysmaturation, particularly during late adolescence, which in light of current translation evidence could be a target for short-term interventions to potentially achieve long-lasting rescue of circuit dysfunctions associated with psychosis.