Using a generative model of affect to characterize affective variability and its response to treatment in bipolar disorder.

The affective variability of bipolar disorder (BD) is thought to qualitatively differ from that of borderline personality disorder (BPD), with changes in affect persisting longer in BD. However, quantitative studies have not been able to confirm this distinction. It has therefore not been possible to accurately quantify how treatments like lithium influence affective variability in BD. We assessed the affective variability associated with BD and BPD as well as the effect of lithium using a computational model that defines two subtypes of variability: affective changes that persist (volatility) and changes that do not (noise). We hypothesized that affective volatility would be raised in the BD group, noise would be raised in the BPD group, and that lithium would impact affective volatility. Daily affect ratings were prospectively collected for up to 3 y from patients with BD or BPD and nonclinical controls. In a separate experimental medicine study, patients with BD were randomized to receive lithium or placebo, with affect ratings collected from week -2 to +4. We found a diagnostically specific pattern of affective variability. Affective volatility was raised in patients with BD, whereas affective noise was raised in patients with BPD. Rather than suppressing affective variability, lithium increased the volatility of positive affect in both studies. These results provide a quantitative measure of the affective variability associated with BD and BPD. They suggest a mechanism of action for lithium, whereby periods of persistently low or high affect are avoided by increasing the volatility of affective responses.

Mental status changes during elexacaftor/tezacaftor / ivacaftor therapy.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA, Trikafta) is the newest Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator drug approved by the Food and Drug Administration. Post-marketing reports with earlier CFTR modulators suggest these medications can impact mood, and in clinical trials an adverse effect of headache was reported with all currently approved CFTR modulators. However, there are no other documented reports of mental status changes during clinical trials or in post-marketing reports with elexacaftor/tezacaftor/ivacaftor. In this case series, we describe 6 patients who reported "mental fogginess" or other mental status changes shortly after initiation of this drug. The mechanism of this patient-reported side effect is still unclear. All patients noticed a change within the first 3 months of therapy. The management differed in each case, with all four cystic fibrosis (CF) care teams utilizing a patient-centered decision-making approach to address this concern.

Assessing the effects of methodological differences on outcomes in the use of psychedelics in the treatment of anxiety and depressive disorders: A systematic review and meta-analysis.

BACKGROUND: Classical psychedelics are a group of drugs which act as agonists on the serotonin-2A (5-HT2A) receptor. Evidence suggests they may have a uniquely rapid and enduring positive effect on mood. However, marked heterogeneity between methodological designs in this emerging field remains a significant concern. AIMS: To determine how differences in the type of psychedelic agent used and the number of dosing sessions administered affect subjects' depression and anxiety outcomes and adverse drug reactions (ADR). METHODS: This review collected and screened 1591 records from the MEDLINE and Web of Science databases for clinical trials reporting objective data on mood for subjects with a known anxiety or depression. RESULTS: After screening, nine clinical trials met inclusion criteria. Meta-analysis of these studies showed significant, large positive effect sizes for measures of anxiety (Cohen's d = 1.26) and depression (Cohen's d = 1.38) overall. These positive effects were also significant at acute (⩽1 week) and extended (>1 week) time points. No significant differences were observed between trials using different psychedelic agents (psilocybin, ayahuasca or lysergic acid diethylamide (LSD)), however, a significant difference was observed in favour of trials with multiple dosing sessions. No serious ADR were reported. CONCLUSION: Psilocybin, ayahuasca and LSD all appear to be effective and relatively safe agents capable of producing rapid and sustained improvements in anxiety and depression. Moreover, the findings of the present analysis suggest that they may show a greater efficacy when given to patients over multiple sessions as compared to the more common single session used in many of the existing trials.

Tryptophan-enriched diet or 5-hydroxytryptophan supplementation given in a randomized controlled trial impacts social cognition on a neural and behavioral level.

Understanding of emotions and intentions are key processes in social cognition at which serotonin is an important neuromodulator. Its precursor is the essential amino acid tryptophan (TRP). Reduced TRP availability leads to weaker impulse control ability and higher aggression, while TRP supplementation promotes confidence. In a double-blind placebo-controlled fMRI study with 77 healthy adults, we investigated the influence of a 4 week TRP enriched diet and an acute 5-hydroxytryptophan (5-HTP) intake on two social-cognitive tasks, a moral evaluation and an emotion recognition task. With 5-HTP, immoral behavior without negative consequences was rated as more reprehensible. Additionally, during story reading, activation in insula and supramarginal gyrus was increased after TRP intake. No significant effects of TRP on emotion recognition were identified for the whole sample. Importantly, emotion recognition ability decreased with age which was for positive emotions compensated by TRP. Since the supramarginal gyrus is associated with empathy, pain and related information integration results could be interpreted as reflecting stricter evaluation of negative behavior due to better integration of information. Improved recognition of positive emotions with TRP in older participants supports the use of a TRP-rich diet to compensate for age related decline in social-cognitive processes.

The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations.

The development of neuropathy and of mood alterations is frequent after chemotherapy. These complications, independent from the antitumoral mechanism, are interconnected due to an overlapping in their processing pathways and a common neuroinflammatory condition. This study aims to verify whether in mice the treatment with the proteasome inhibitor bortezomib (BTZ), at a protocol capable of inducing painful neuropathy, is associated with anxiety, depression and supraspinal neuroinflammation. We also verify if the therapeutic treatment with the antagonist of the prokineticin (PK) system PC1, which is known to contrast pain and neuroinflammation, can prevent mood alterations. Mice were treated with BTZ (0.4 mg/kg three times/week for 4 weeks); mechanical allodynia and locomotor activity were evaluated over time while anxiety (dark light and marble burying test), depression (sucrose preference and swimming test) and supraspinal neuroinflammation were checked at the end of the protocol. BTZ treated neuropathic mice develop anxiety and depression. The presence of mood alterations is related to the presence of neuroinflammation and PK system activation in prefrontal cortex, hippocampus and hypothalamus with high levels of PK2 and PKR2 receptor, IL-6 and TNF-α, TLR4 and an upregulation of glial markers. PC1 treatment, counteracting pain, prevented the development of supraspinal inflammation and depression-like behavior in BTZ mice.

Adverse Side Effects Associated with Corticosteroid Therapy: A Study in 39 Patients with Generalized Myasthenia Gravis.

BACKGROUND The tolerability of high-dose oral corticosteroids in patients with generalized myasthenia gravis (gMG) has not been systematically assessed. We evaluated adverse side effects (ASEs) of corticosteroid treatment in patients with gMG. MATERIAL AND METHODS Retrospective analysis was conducted of ASEs reported as being related to corticosteroid treatment in 39 patients with gMG who were treated with oral corticosteroids for ≥1 year. RESULTS Median (interquartile range [IQR]) age was 60 (21) years, 53.8% of patients were women, and 66.7% were aged ≤65 years. Median (IQR) prednisone treatment duration was 14 (2) months; median (IQR) daily dose was 40 (15) mg. The median number of ASEs reported as corticosteroid-related was 2/patient (IQR, 1). Pre-diabetes and weight gain were most common (each 43.6% of patients). Bruising, insomnia, and osteoporosis were more prevalent in patients aged >65 years, while irritability, osteopenia, and pre-diabetes were more common in patients aged £65 years, although differences were not statistically significant. Irritability and weight gain were more prevalent in women (P=0.010 for irritability); osteoporosis and pre-diabetes more common in men (P=0.015 for osteoporosis). ASEs were generally more common in the high-dose prednisone group (>30 mg/day), but were only statistically significant for irritability (P=0.001). CONCLUSIONS Corticosteroid-related ASEs were common in patients with gMG. Some of these ASEs can have serious medical consequences, and certain ASEs appeared to be associated with specific patient characteristics. Demographics and comorbidities of patients with gMG must be carefully considered before corticosteroid initiation. Potential ASEs, such as unanticipated osteoporosis in men, require extra vigilance.

Chinese herbal medicines for mild cognitive impairment: A protocol for meta-analysis and trial sequential analysis.

BACKGROUND: Mild cognitive impairment (MCI), as a common neurodegenerative aging disease representing an intermediate stage between normal cognitive functioning and dementia, poses an excessive burden on health care. The clinical benefit of Chinese herbal medicines (CHMs) for MCI remains inconclusive. This study is aimed at evaluating the efficacy and acceptability of CHMs through meta-analysis and trial sequential analysis (TSA). METHODS: We applied extensive strategies on preliminary literature screening to identify relevant randomized controlled trials which meticulously compare any of CHMs interventions with placebo groups as monotherapy for MCI. The primary outcome of this study is the change of global cognitive function, and the secondary outcomes include assessments of activities of daily living, mood, and adverse events. Data synthesis, risk of bias assessment, sensitivity and subgroup analyses, and TSA will be conducted with application of Review Manager, Stata, and TSA software. The quality of the evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation instrument. INPLASY registration number: INPLASY202190006 (https://inplasy.com/inplasy-2021-9-0006/). RESULTS: This study will confirm the clinical efficacy and safety of CHMs when used in the treatment of patients with MCI. CONCLUSION: This study will provide reliable evidence and references for the selection of CHMs in therapy and future clinical research of MCI.

The connection of 5-alpha reductase inhibitors to the development of depression.

Recent literature connects 5-alpha reductase inhibitors (5-ARIs) with neuropsychiatric adverse effects. Several clinical studies have indicated that former 5-ARIs users had a higher incidence of depressive symptoms and neuropsychiatric side effects than non-users. However, the underlying mechanisms involved in the depression in former 5-ARIs patients, a condition known as "post finasteride syndrome (PFS)", are not thoroughly understood. This review aims to summarize and discuss the association between 5-ARIs and depression as well as possible mechanisms. We used PubMed search terms including "depression", "depressive symptoms", "MDD", "anxiety", or "suicidal idea", and "5-alpha reductase inhibitors", "finasteride", "dutasteride", "5-ARIs". All relevant articles from in vivo and clinical studies from 2002 to 2021 were carefully reviewed. Any contradictory findings were included and debated. The potential mechanisms that link 5-ARIs and depression include alteration in neuroactive steroids, dopaminergic dysfunction, reduced hippocampal neurogenesis, increased neuroinflammation, alteration of the HPA axis, and epigenetic modifications. From this review, we hope to provide information for future studies based on animal experiments, and potential therapeutic strategies for depressive patients with PFS.

Psychological and Antibacterial Effects of Footbath Using the Lindera umbellata Essential Oil.

Lindera umbellata (Lu) essential oil primarily contains linalool and has relaxation properties. We investigated the psychological and antibacterial effects of footbath with Lu essential oil. The participants included 20 women without medical history and received two intervention plans: footbath without any essential oil and footbath using Lu essential oil. Next, questionnaires regarding impressions and mood states were provided for them to answer. In addition, their autonomic nervous system activity was measured, and the aerobic viable of count on the feet was determined. The high-frequency value reflecting the parasympathetic nervous system activity significantly increased after footbath using Lu essential oil. In the questionnaire about the mood states, the subscale scores of tension-anxiety, depression, fatigue, and confusion after intervention were lower than those before intervention regardless of the use of the essential oil. Conversely, the anger-hostility score decreased only in the group using Lu essential oil. Furthermore, the decrease in aerobic viable count after intervention was not significantly different between the two groups. Footbath using Lu essential oil increased the parasympathetic nervous system activity and relieved anger. Taken together, we suggest that footbath using Lu essential oil has a relaxation effect.

Effects of ß-Phenylethylamine on Psychomotor, Rewarding, and Reinforcing Behaviors and Affective State: The Role of Dopamine D1 Receptors.

Beta-phenylethylamine (ß-PEA) is a well-known and widespread endogenous neuroactive trace amine found throughout the central nervous system in humans. In this study, we demonstrated the effects of ß-PEA on psychomotor, rewarding, and reinforcing behaviors and affective state using the open-field test, conditioned place preference (CPP), self-administration, and ultrasonic vocalizations (USVs) paradigms. We also investigated the role of the dopamine (DA) D1 receptor in the behavioral effects of ß-PEA in rodents. Using enzyme-linked immunosorbent assay (ELISA) and Western immunoblotting, we also determined the DA concentration and the DA-related protein levels in the dorsal striatum of mice administered with acute ß-PEA. The results showed that acute ß-PEA increased stereotypic behaviors such as circling and head-twitching responses in mice. In the CPP experiment, ß-PEA increased place preference in mice. In the self-administration test, ß-PEA significantly enhanced self-administration during a 2 h session under fixed ratio (FR) schedules (FR1 and FR3) and produced a higher breakpoint during a 6 h session under progressive ratio schedules of reinforcement in rats. In addition, acute ß-PEA increased 50-kHz USV calls in rats. Furthermore, acute ß-PEA administration increased DA concentration and p-DAT and TH expression in the dorsal striatum of mice. Finally, pretreatment with SCH23390, a DA D1 receptor antagonist, attenuated ß-PEA-induced circling behavior and ß-PEA-taking behavior in rodents. Taken together, these findings suggest that ß-PEA has rewarding and reinforcing effects and psychoactive properties, which induce psychomotor behaviors and a positive affective state by activating the DA D1 receptor in the dorsal striatum.

Mental Health in New Mothers: A Randomised Controlled Study into the Effects of Dietary Flavonoids on Mood and Perceived Quality of Life.

The postnatal period is a significant period of physical, physiological and psychological change for mothers, rendering them particularly vulnerable to changes in mood or disorders such as postnatal depression (PND). Previous interventions with foods high in flavonoids have demonstrated beneficial acute and chronic mood effects in healthy child, adolescent and adult populations. It is unclear whether mood effects persist in populations who are potentially at-risk of developing mood disorders, such as postnatal mothers. This exploratory study investigated the effects of a 2-week daily dietary flavonoid intervention on mood (PANAS-NOW), anxiety (STAI), depressive symptoms (PHQ-8) and perceived quality of life (WHOQOL-BREF) in forty-one new mothers in the 0-12-month postnatal period, before and after flavonoid intervention. Mothers either added high flavonoid foods to their daily diet, or did not include additions following a randomised, between-groups, controlled design. Significant effects were observed in the flavonoid group with mothers reporting lower state anxiety and higher perceived quality of physical health at the 2-week timepoint. These findings suggest that regular dietary consumption of flavonoids may benefit mothers' anxiety and perceived quality of life in the postnatal period. Replication of these results may indicate the potential for dietary flavonoids to promote healthy mood regulation in mothers or prevent the onset or severity of symptoms in postnatal psychological disorders, both of which would be beneficial for women's health services and public mental health.

Influence of Cannabinoid Receptor 1 Genetic Variants on the Subjective Effects of Smoked Cannabis.

As many jurisdictions consider relaxing cannabis legislation and usage is increasing in North America and other parts of the world, there is a need to explore the possible genetic differences underlying the subjective effects of cannabis. This pilot study investigated specific genetic variations within the cannabinoid receptor 1 (CNR1) gene for association with the subjective effects of smoked cannabis. Data were obtained from a double-blinded, placebo-controlled clinical trial studying the impact of cannabis intoxication on driving performance. Participants randomized to the active cannabis group who consented to secondary genetic analysis (n = 52) were genotyped at the CNR1 rs1049353 and rs2023239 polymorphic areas. Maximum value and area under the curve (AUC) analyses were performed on subjective measures data. Analysis of subjective effects by genotype uncovered a global trend towards greater subjective effects for rs1049353 T-allele- and rs2023239 C-allele-carrying subjects. However, significant differences attributed to allelic identity were only documented for a subset of subjective effects. Our findings suggest that rs1049353 and rs2023239 minor allele carriers experience augmented subjective effects during acute cannabis intoxication.

Outcomes of elderly patients with organophosphate intoxication.

This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between 2008 and 2017. Patients were stratified into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors suffered higher rates of hypotension (P < 0.001), shock (P < 0.001) and kidney injury (P = 0.001) than survivors did. Kaplan-Meier analysis indicated that patients with shock suffered lower cumulative survival than did patients without shock (log-rank test, P < 0.001). In a multivariate-Cox-regression model, shock was a significant predictor of mortality after intoxication (odds ratio 18.182, 95% confidence interval 2.045-166.667, P = 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively.

Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers.

Electrophysiological studies show that nicotine enhances neural responses to characteristic frequency stimuli. Previous behavioral studies partially corroborate these findings in young adults, showing that nicotine selectively enhances auditory processing in difficult listening conditions. The present work extended previous work to include both young and older adults and assessed the nicotine effect on sound frequency and intensity discrimination. Hypotheses were that nicotine improves auditory performance and that the degree of improvement is inversely proportional to baseline performance. Young (19-23 years old) normal-hearing nonsmokers and elderly (61-80) nonsmokers with normal hearing between 500 and 2000 Hz received nicotine gum (6 mg) or placebo gum in a single-blind, randomized crossover design. Participants performed three experiments (frequency discrimination, frequency modulation identification, and intensity discrimination) before and after treatment. The perceptual differences were analyzed between pre- and post-treatment, as well as between post-treatment nicotine and placebo conditions as a function of pre-treatment baseline performance. Compared to pre-treatment performance, nicotine significantly improved frequency discrimination. Compared to placebo, nicotine significantly improved performance for intensity discrimination, and the improvement was more pronounced in the elderly with lower baseline performance. Nicotine had no effect on frequency modulation identification. Nicotine effects are task-dependent, reflecting possible interplays of subjects, tasks and neural mechanisms.

Effect of Oat ß-Glucan on Affective and Physical Feeling States in Healthy Adults: Evidence for Reduced Headache, Fatigue, Anxiety and Limb/Joint Pains.

The gastrointestinal (GI) side-effects of dietary fibers are recognized, but less is known about their effects on non-GI symptoms. We assessed non-GI symptoms in a trial of the LDL-cholesterol lowering effect of oat ß-glucan (OBG). Participants (n = 207) with borderline high LDL-cholesterol were randomized to an OBG (1 g OBG, n = 104, n = 96 analyzed) or Control (n = 103, n = 95 analyzed) beverage 3-times daily for 4 weeks. At screening, baseline, 2 weeks and 4 weeks participants rated the severity of 16 non-GI symptoms as none, mild, moderate or severe. The occurrence and severity (more or less severe than pre-treatment) were compared using chi-squared and Fisher's exact test, respectively. During OBG treatment, the occurrence of exhaustion and fatigue decreased versus baseline (p < 0.05). The severity of headache (2 weeks, p = 0.032), anxiety (2 weeks p = 0.059) and feeling cold (4 weeks, p = 0.040) were less on OBG than Control. The severity of fatigue and hot flashes at 4 weeks, limb/joint pain at 2 weeks and difficulty concentrating at both times decreased on OBG versus baseline. High serum c-reactive-protein and changes in c-reactive-protein, oxidized-LDL, and GI-symptom severity were associated with the occurrence and severity of several non-GI symptoms. These data provide preliminary, hypothesis-generating evidence that OBG may reduce several non-GI symptoms in healthy adults.

Effects of Thai Local Ingredient Odorants, Litsea cubeba and Garlic Essential Oils, on Brainwaves and Moods.

The functional food market is growing with a compound annual growth rate of 7.9%. Thai food recipes use several kinds of herbs. Lemongrass, garlic, and turmeric are ingredients used in Thai curry paste. Essential oils released in the preparation step create the flavor and fragrance of the famous tom yum and massaman dishes. While the biological activities of these ingredients have been investigated, including the antioxidant, anti-inflammatory, and antimicrobial activities, there is still a lack of understanding regarding the responses to the essential oils of these plants. To investigate the effects of essential oil inhalation on the brain and mood responses, electroencephalography was carried out during the non-task resting state, and self-assessment of the mood state was performed. The essential oils were prepared in several dilutions in the range of the supra-threshold level. The results show that Litsea cubeba oil inhalation showed a sedative effect, observed from alpha and beta wave power reductions. The frontal and temporal regions of the brain were involved in the wave alterations. Garlic oil increased the alpha wave power at lower concentrations; however, a sedative effect was also observed at higher concentrations. Lower dilution oil induced changes in the fast alpha activity in the frontal region. The alpha and beta wave powers were decreased with higher dilution oils, particularly in the temporal, parietal, and occipital regions. Both Litsea cubeba and turmeric oils resulted in better positive moods than garlic oil. Garlic oil caused more negative moods than the others. The psychophysiological activities and the related brain functions require further investigation. The knowledge obtained from this study may be used to design functional food products.

A meta-regression of methodological features that predict the effects of medications on the subjective response to alcohol.

BACKGROUND: Alcohol administration paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). There has been an ongoing debate about sample characteristics and methodological features that affect the likelihood of detecting an early efficacy signal for AUD medications. We conducted a meta-regression to test whether the drinking level of the study sample and the peak breath alcohol concentration (BrAC) in the alcohol administration study predict the efficacy of AUD pharmacotherapies on the subjective responses to alcohol. METHODS: We computed the effects of 21 medications on alcohol-induced stimulation, sedation, negative mood, and craving during alcohol administration in 49 studies. RESULTS: Meta-regression analyses indicated a significant and positive effect of pre-study drinks per month on alcohol-induced stimulation (ß = 0.142, p < 0.0001), such that as drinking increases, the benefit of medication over placebo decreases. There was an effect of drinks per month on negative mood (ß = -0.164, p = 0.0248), such that at higher levels of drinks per month, the effects of medications on negative mood are stronger. For sedation, there was an effect of peak BrAC (ß = 0.119, p = 0.0002), such that at low levels of peak BrAC, the effects of medication on sedation were null. For craving, there was a peak BrAC × drinks per month interaction such that at low levels of BrAC, a heavier drinking sample is required to detect the effects of medication on craving. Sensitivity analyses comparing naltrexone studies and non-naltrexone studies suggested that naltrexone was less sensitive to drinks per month across subjective response domains. CONCLUSIONS: These analyses show that design features are critical in studies that test the effects of medications on the subjective responses to alcohol. By specifying the significance and directionality of these effects, as well as the specific points in BrAC or drinks per month at which medication effects are detectable, the study offers recommendations for design features of alcohol administration studies that aim to inform AUD medication development.

The efficacy of systemic administration of lipopolysaccharide in modelling pre-motor Parkinson's disease in C57BL/6 mice.

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterised by the loss of dopaminergic neurons in the substantia nigra. Mounting evidence indicates a crucial role of inflammation and concomitant oxidative stress in the disease progression. Therefore, the aim of this study was to investigate the ability of systemically administered lipopolysaccharide (LPS) to induce motor and non-motor symptoms of PD, inflammation, oxidative stress and major neuropathological hallmarks of the disease in regions postulated to be affected, including the olfactory bulb, hippocampus, midbrain and cerebellum. Twenty-one male C57BL/6 mice, approximately 20 weeks old, received a dose of 0.3 mg/kg/day of LPS systemically on 4 consecutive days and behavioural testing was conducted on days 14-18 post-treatment, followed by tissue collection. Systemically administered LPS increased latency time in the buried food seeking test (indicative of olfactory impairment), and decreased time spent in central zone of the open field (anxiety-like behaviour). However, there was no change in latency time in the rotarod test or the expression of tyrosine hydroxylase (TH) in the midbrain. Systemically administered LPS induced increased glial markers GFAP and Iba-1 and oxidative stress marker 3-nitrotyrosine (3-NT) in the olfactory bulb, hippocampus, midbrain and cerebellum, and there were region specific changes in the expression of NFκB, IL-1ß, α-synuclein, TH and BDNF proteins. The model could be useful to further elucidate early non-motor aspects of PD and the possible mechanisms contributing to the non-motor deficits.

Minocycline alleviates Gulf War Illness rats via altering gut microbiome, attenuating neuroinflammation and enhancing hippocampal neurogenesis.

Accumulating evidences suggest that deficits in neurogenesis, chronic inflammation and gut microbiome dysregulation contribute to the pathophysiology of Gulf War Illness (GWI). Minocycline has been demonstrated to be a potent neuroprotective agent and could regulate neuroinflammation. The present study intends to investigate whether the treatment of minocycline maintains better cognition and mood function in a rat model of GWI and the potential mechanism. Rats received 28 days of GWI-related chemical exposure and restraint stress, along with daily minocycline or vehicle treatment. Cognitive and mood function, neuroinflammation, neurogenesis and gut microbiota were detected. We found that minocycline treatment induces better cognitive and mood function in the GWI rat model, as indicated by open-field test, elevated plus maze test, novel object recognition test and forced swim test. Moreover, minocycline treatment reversed the altered gut microbiome, neuroinflammation and the decreased hippocampal neurogenesis of rats with GWI. Taken together, our study indicated that minocycline treatment exerts better cognitive and mood function in GWI rat model, which is possibly related to gut microbiota remodeling, restrained inflammation and enhanced hippocampal neurogenesis. These results may establish minocycline as a potential prophylactic or therapeutic agent for the treatment of GWI.

Brain imaging of cannabinoid type I (CB1 ) receptors in women with cannabis use disorder and male and female healthy controls.

Cannabis effects are predominantly mediated by pharmacological actions on cannabinoid type 1 (CB1 ) receptors. Prior positron emission tomography (PET) studies in individuals who use cannabis included almost exclusively males. PET studies in females are needed because there are sex differences in cannabis effects, progression to cannabis use disorder (CUD), and withdrawal symptom severity. Females with CUD (N = 10) completed two double-blind cannabis smoking sessions (Session 1: placebo; Session 2: active), and acute cannabis effects were assessed. After Session 2, participants underwent 3 days of monitored cannabis abstinence; mood, craving, and withdrawal symptoms were assessed and a PET scan (radiotracer: [11 C]OMAR) followed. [11 C]OMAR Distribution volume (VT ) from these participants was compared with VT of age/BMI-similar female non-users of cannabis ("healthy controls"; N = 10). VT was also compared between female and male healthy controls (N = 7). Females with CUD displayed significantly lower VT than female healthy controls in specific brain regions (hippocampus, amygdala, cingulate, and insula). Amygdala VT was negatively correlated with mood changes (anger/hostility) during abstinence, but VT was not correlated with other withdrawal symptoms or cannabis effects. Among healthy controls, females had significantly higher VT than males in all brain regions examined. Chronic cannabis use appears to foster downregulation of CB1 receptors in women, as observed previously in men, and there are inherent sex differences in CB1 availability. Future studies should elucidate the time course of CB1 downregulation among females who use cannabis and examine the relation between CB1 availability and cannabis effects among other populations (e.g., infrequent users; medicinal users).