COVID-19 and catatonia: Prevalence, challenges, pathophysiology, and treatment.

BACKGROUND: Emerging literature supports the association between acute COVID-19 infection and neuropsychiatric complications. This article reviews the evidence for catatonia as a potential neuropsychiatric sequela of COVID-19 infection. METHODS: PubMed was searched using the terms catatonia, severe acute respiratory syndrome coronavirus 2, and COVID-19. Articles were limited to those published in the English language between 2020 and 2022. Forty-five articles that specifically studied catatonia associated with acute COVID-19 infection were screened. RESULTS: Overall, 30% of patients with severe COVID-19 infection developed psychiatric symptoms. We found 41 cases of COVID-19 and catatonia, with clinical presentations that varied in onset, duration, and severity. One death was reported in a case of catatonia. Cases were reported in patients with and without a known psychiatric history. Lorazepam was successfully used, along with electroconvulsive therapy, antipsychotics, and other treatments. CONCLUSIONS: Greater recognition and treatment of catatonia in individuals with COVID-19 infection is warranted. Clinicians should be familiar with recognizing catatonia as a potential outcome of COVID-19 infection. Early detection and appropriate treatment are likely to lead to better outcomes.

Possible Role of Parvalbumin Interneurons in Meditation and Psychiatric Illness.

Parvalbumin (PV) interneurons are present in multiple brain regions and produce complex influences on brain functioning. An increasing number of research findings indicate that the function of these interneurons is more complex than solely to inhibit pyramidal neurons in the cortex. They generate feedback and feedforward inhibition of cortical neurons, and they are critically involved in the generation of neuronal network oscillation. These oscillations, generated by various brain regions, are linked to perceptions, thought processes, and cognitive functions, all of which, in turn, influence human emotions and behavior. Both animal and human studies consistently have found that meditation practice results in enhancement in the effects of alpha-, theta-, and gamma-frequency oscillations, which may correspond to positive changes in cognition, emotion, conscious awareness, and, subsequently, behavior. Although the study of meditation has moved into mainstream neuroscience research, the link between PV interneurons and any role they might play in meditative states remains elusive. This article is focused primarily on gamma-frequency oscillation, which is generated by PV interneurons, to develop insight and perspective into the role of PV interneurons in meditation. This article also points to new and emerging directions that address whether this role of PV interneurons in meditation extends to a beneficial, and potentially therapeutic, role in the treatment of common psychiatric disorders, including schizophrenia.

Use of selective serotonin and norepinephrine reuptake inhibitors (SNRIs) in the treatment of autism spectrum disorder (ASD), comorbid psychiatric disorders and ASD-associated symptoms: a clinical review.

It is challenging to treat symptoms of autism spectrum disorder (ASD), comorbid psychiatric disorders and ASD-associated symptoms. Some of the commonly used medications to treat these can, and frequently do have serious adverse side effects. Therefore, it is important to identify medications that are effective and with fewer side effects and negative outcomes. In this review, we looked at current evidence available for using the serotonin and norepinephrine reuptake inhibitors (SNRIs) class of medications in treating some of these often difficult to treat symptoms and behaviors. An extensive literature search was conducted using EBSCO.host. Our search algorithm identified 130 articles, 6 of which were deemed to meet criteria for the purpose of this review. Each of these six articles was independently reviewed and critically appraised. As a prototype of the SNRIs family, venlafaxine was found to be a useful adjuvant in children and adults with ASD for the treatment of self-injurious behaviors, aggression, and ADHD symptoms when used in doses lower than its antidepressant dosage. However, duloxetine was not found to show any added benefit in treatment of any of the comorbid symptoms and behaviors in ASD when compared to other antidepressants. On the other hand, milnacipran was reported to produce improvements in impulsivity, hyperactivity symptoms, and social functioning through reduction of inattention of ADHD when comorbid with ASD. Overall, SNRIs were shown variable effectiveness in treatment of these comorbid symptoms and behaviors in ASD.

Common neurofunctional dysregulations characterize obsessive-compulsive, substance use, and gaming disorders-An activation likelihood meta-analysis of functional imaging studies.

Compulsivity and loss of behavioral control represent core symptoms in obsessive-compulsive disorder (OCD), substance use disorder (SUD), and internet gaming disorder (IGD). Despite elaborated animal models suggesting that compulsivity is mediated by cortico-striatal circuits and a growing number of neuroimaging case-control studies, common neurofunctional alterations in these disorders have not been systematically examined. The present activation likelihood estimation (ALE) meta-analysis capitalized on previous functional magnetic resonance imaging (fMRI) studies to determine shared neurofunctional alterations among the three disorders. Task-based fMRI studies of individuals with SUD, OCD, or IGD were obtained. ALE was performed within each disorder. Next, contrast and conjunction meta-analyses were performed to determine differential and common alterations. Task-paradigm classes were group according to Research Domain Criteria (RDoC) domains to determine contributions of underlying behavioral domains. One hundred forty-four articles were included representing data from n = 6897 individuals (SUD = 2418, controls = 2332; IGD = 361, controls = 360; OCD = 715, controls = 711) from case-control studies. Conjunction meta-analyses revealed shared alterations in the anterior insular cortex between OCD and SUDs. SUD exhibited additionally pronounced dorsal-striatal alterations compared with both, OCD and IGD. IGD shared frontal, particularly cingulate alterations with all SUDs, while IGD demonstrated pronounced temporal alterations compared with both, SUD and OCD. No robust overlap between IGD and OCD was observed. Across the disorders, neurofunctional alterations were mainly contributed by cognitive systems and positive valence RDoC domains. The present findings indicate that neurofunctional dysregulations in prefrontal regions engaged in regulatory-control represent shared neurofunctional alterations across substance and behavioral addictions, while shared neurofunctional dysregulations in the anterior insula may mediate compulsivity in substance addiction and OCD.

Ketamine in the Past, Present, and Future: Mechanisms, Metabolites, and Toxicity.

PURPOSE OF REVIEW: While ketamine's analgesia has mostly been attributed to antagonism of N-methyl-D-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine's role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine's neurotoxicity have unclear human translatability and findings from key rodent and human studies are presented. RECENT FINDINGS: Ketamine's metabolites, and (2R,6R)-hydroxynorketamine in particular, may play a greater role in its clinical activity than previously believed. The activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and the mammalian target of rapamycin by ketamine are mechanisms that are still being elucidated. Ketamine might work best in nociplastic pain, which involves altered pain processing. While much is known about ketamine, new studies will continue to define its role in clinical medicine. Evidence supporting ketamine's neurotoxicity in humans is lacking and should not impede future ketamine clinical trials.

d-Serine is a potential biomarker for clinical response in treatment of post-traumatic stress disorder using (R,S)-ketamine infusion and TIMBER psychotherapy: A pilot study.

Post-traumatic stress disorder (PTSD) is a chronic and debilitating condition that is often refractory to standard frontline antidepressant therapy. A promising new approach to PTSD therapy is administration of a single sub-anesthetic dose of (R,S)-ketamine (Ket). The treatment produces rapid and significant therapeutic response, which lasts for only 4-7 days. In one of our studies, the mean duration of response was increased to 33 days when Ket administration was combined with a mindfulness-based cognitive therapy, Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER). We now report the results from a 20-patient study, which examined the duration of sustained response with combined TIMBER-Ket therapy, TIMBER-K arm, relative to the response observed in a placebo-controlled arm, TIMBER-P. A significant difference in the duration of response was observed between TIMBER-K and TIMBER-P arms: 34.44 ±â€¯19.12 days and 16.50 ±â€¯11.39 days, respectively (p = 0.022). Previous studies identified a negative correlation between antidepressant response to Ket and basal plasma concentrations of d-serine (DSR). In this study, the basal DSR levels positively correlated with the pre-treatment severity of PTSD symptoms (Pearson's r = 0.42, p = 0.07) and patients with basal DSR level ≥ 3.5 µM displayed not only higher PTSD severity but also shorter duration of response. The data indicate that basal DSR levels may serve as a biomarker of the severity of PTSD symptoms and as a predictor of clinical response. This article is part of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca.

Nonconventional interventions for chronic post-traumatic stress disorder: Ketamine, repetitive trans-cranial magnetic stimulation (rTMS), and alternative approaches.

It is alarming that only 59% of those who have post-traumatic stress disorder (PTSD) respond to selective serotonin reuptake inhibitors. Many existing treatments, both pharmacological and nonpharmacological, do not directly target trauma memories that lay at the core of the PTSD pathogenesis. Notable exceptions are medications like ketamine and propranolol and trauma-focused psychotherapies like eye-movement desensitization and reprocessing therapy (developed by Shapiro) and Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) for trauma memories (developed by Pradhan). Although the antidepressant effects of ketamine are no longer news, ketamine's effects on treatment refractory PTSD (TR-PTSD) is a recent concept. As TR-PTSD has a marked public health burden and significant limitations in terms of treatment interventions, a thorough assessment of current strategies is required. Research to bring clarity to the underlying pathophysiology and neurobiology of TR-PTSD delineating the chemical, structural, and circuitry abnormalities will take time. In the interim, in the absence of a 1-size-fits-all therapeutic approach, pragmatically parallel lines of research can be pursued using the pharmacological and nonpharmacological treatments that have a strong theoretical rationale for efficacy. This article aims to review the current literature on interventions for PTSD, most notably ketamine, trans-cranial magnetic stimulation treatment, yoga and mindfulness interventions, and TIMBER. We present an outline for their future use, alone as well as in combination, with a hope of providing additional insights as well as advocating for developing more effective therapeutic intervention for this treatment-resistant and debilitating condition.

An exploratory metabolomic comparison of participants with fast or absent functional progression from 2CARE, a randomized, double-blind clinical trial in Huntington's disease.

Huntington's disease (HD) is increasingly recognized for diverse pathology outside of the nervous system. To describe the biology of HD in relation to functional progression, we previously analyzed the plasma and CSF metabolome in a cross-sectional study of participants who had various degrees of functional impairment. Here, we carried out an exploratory study in plasma from HD individuals over a 3-year time frame to assess whether differences exist between those with fast or absent clinical progression. There were more differences in circulating metabolite levels for fast progressors compared to absent progressors (111 vs 20, nominal p < 0.05). All metabolite changes in faster progressors were decreases, whereas some metabolite concentrations increased in absent progressors. Many of the metabolite levels that decreased in the fast progressors were higher at Screening compared to absent progressors but ended up lower by Year 3. Changes in faster progression suggest greater oxidative stress and inflammation (kynurenine, diacylglycerides, cysteine), disturbances in nitric oxide and urea metabolism (arginine, citrulline, ornithine, GABR), lower polyamines (putrescine and spermine), elevated glucose, and deficient AMPK signaling. Metabolomic differences between fast and absent progressors suggest the possibility of predicting functional decline in HD, and possibly delaying it with interventions to augment arginine, polyamines, and glucose regulation.

Utility of outdoor central site monitoring in assessing exposure of school children to ultrafine particles.

Epidemiological studies investigating the association between daily particle exposure and health effects are frequently based on a single monitoring site located in an urban background. Using a central site in epidemiological time-series studies has been established based on the premises of low spatial variability of particles within the areas of interest and hence the adequacy of the central sites to monitor the exposure. This is true to a large extent in relation to larger particles (PM2.5, PM10) that are typically monitored and regulated. However, the distribution of ultrafine particles (UFP), which in cities predominantly originate from traffic, is heterogeneous. With increasing pressure to improve the epidemiology of UFP, an important question to ask is, whether central site monitoring is representative of community exposure to this size fraction of particulate matter; addressing this question is the aim of this paper. To achieve this aim, we measured personal exposure to UFP, expressed as particle number concentration (PNC), using Philips Aerasense Nanotracers (NT) carried by the participants of the study, and condensation particle counters (CPC) or scanning mobility particle sizers (SMPS) at central fixed-site monitoring stations. The measurements were conducted at three locations in Brisbane (Australia), Cassino (Italy) and Accra (Ghana). We then used paired t-tests to compare the average personal and average fixed-site PNC measured over the same 24-h, and hourly, periods. We found that, at all three locations, the 24-h average fixed-site PNC was no different to the personal PNC, when averaged over the study period and all the participants. However, the corresponding hourly averages were significantly different at certain times of the day. These were generally times spent commuting and during cooking and eating at home. Our analysis of the data obtained in Brisbane, showed that maximum personal exposure occurred in the home microenvironment during morning breakfast and evening dinner time. The main source of PNC for personal exposure was from the home-microenvironment. We conclude that the 24-h average PNC from the central-site can be used to estimate the 24-h average personal exposure for a community. However, the hourly average PNC from the central site cannot consistently be used to estimate hourly average personal exposure, mainly because they are affected by very different sources.

The potential positive epigenetic effects of various mind-body therapies (MBTs): a narrative review.

Mind-body therapies (MBTs), such as mindfulness, meditation, yoga, and tai-chi, are said to improve quality of life by contributing to positive thinking and reducing overall distress. MBTs not only play a role in reducing stress and anxiety, but they are also found to epigenetically affect genes and other areas in our genomes that are implicated in inflammation, stress, and distress. This review analyzes the role of MBTs in reducing the epigenetic changes as reported in five previously conducted controlled studies found in the NCBI PubMed database. The methylation of the tumor necrosis factor gene, implicated in psychological distress, was shown to significantly decrease for the women who performed yoga. For people who took part in mindfulness meditation, there was a significant alteration in a variety of modifications of histone deacetylase enzymes as well as their expression patterns when compared to the control group. Other studies found that long-term meditators had slower biomarkers of aging, known as epigenetic clocks, and methylation in genes associated with immune cell metabolism and inflammation. Different genomic regions known as CpG dinucleotide sites ("CpG islands") were also found to be epigenetically altered in participants of tai-chi. These controlled studies were promising evidence on the potential of MBTs to affect the epigenetics of an individual. This information will be useful in diagnostic, therapeutic, and preventative measures, and can be an addition to western medicine, in a way that is more holistic and beneficial to the individual.

Distress due to lithium-induced polyuria: exploratory study.

Lithium-induced polyuria, although common, often goes unrecognized. The purpose of the present study was therefore to investigate the complaints of polyuria, and distress and functional impairment associated with polyuria, in 56 patients with bipolar disorder on long-term lithium treatment. All participants underwent 24-h urine collection, and renal function tests. Polyuria (24-h urine volume > 3 L) was found in 70% of subjects. Unless directly enquired about, polyuria was underreported. Impairment in work and daily routine due to increased urine output/frequency was associated with 24-h urine volumes. Polyuria is a highly prevalent, distressing and impairing side-effect of long-term lithium treatment, requiring due attention.

Hereditary pseudocholinesterase deficiency discovery after electroconvulsive therapy.

Inherited pseudocholinesterase deficiency refers to an uncommon defect in the butyrylcholinesterase enzyme which can result in prolonged muscle paralysis due to delayed breakdown of choline ester paralytic anaesthetic agents. We describe a 25-year-old woman receiving electroconvulsive therapy (ECT) for treatment of depression in whom motor function did not recover adequately after administration of succinylcholine. Investigated post-ECT, she was found to have severe pseudocholinesterase deficiency. Implications of pseudocholinesterase deficiency for ECT treatment and anaesthetic strategies are discussed.

Combining Ketamine, Brain Stimulation (rTMS) and Mindfulness Therapy (TIMBER) for Opioid Addiction.

Opioid addiction in the United States currently presents a national crisis despite availability of different treatments. Prior findings suggest that both repetitive transcranial magnetic stimulation (rTMS) and subanesthetic dose of ketamine are efficacious in patients with opioid use disorders (OUD) when administered in isolation. However, their therapeutic value may be undermined by varying clinical responses that tend to dissipate with treatment cessation. There has been no study to date that has used a combination of both for OUD, and there are still many unanswered questions with respect to both. TIMBER (Trauma Interventions using Mindfulness Based Extinction and Reconsolidation of memories) therapy attempts to alter the expression of emotionally charged memories such as traumatic memories, and has been successfully tried in chronic post-traumatic stress disorder (PTSD) and in combination with memory-altering pharmacotherapy like ketamine infusion. By a combination of extinction and reconsolidation of memory approaches, TIMBER works to not over-flood and/or retraumatize as is seen in other treatment approaches. TIMBER involves a balanced combination of both the memory extinction and memory reconsolidation approaches (rather than extinction-only approaches) which explains its superior efficacy in PTSD and benefit in substance use disorders.

Cross-sectional analysis of plasma and CSF metabolomic markers in Huntington's disease for participants of varying functional disability: a pilot study.

Huntington's Disease (HD) is a progressive, fatal neurodegenerative condition. While generally considered for its devastating neurological phenotype, disturbances in other organ systems and metabolic pathways outside the brain have attracted attention for possible relevance to HD pathology, potential as therapeutic targets, or use as biomarkers of progression. In addition, it is not established how metabolic changes in the HD brain correlate to progression across the full spectrum of early to late-stage disease. In this pilot study, we sought to explore the metabolic profile across manifest HD from early to advanced clinical staging through metabolomic analysis by mass spectrometry in plasma and cerebrospinal fluid (CSF). With disease progression, we observed nominally significant increases in plasma arginine, citrulline, and glycine, with decreases in total and D-serine, cholesterol esters, diacylglycerides, triacylglycerides, phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins. In CSF, worsening disease was associated with nominally significant increases in NAD+, arginine, saturated long chain free fatty acids, diacylglycerides, triacylglycerides, and sphingomyelins. Notably, diacylglycerides and triacylglyceride species associated with clinical progression were different between plasma and CSF, suggesting different metabolic preferences for these compartments. Increasing NAD+ levels strongly correlating with disease progression was an unexpected finding. Our data suggest that defects in the urea cycle, glycine, and serine metabolism may be underrecognized in the progression HD pathology, and merit further study for possible therapeutic relevance.

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead.

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data - emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.

Cognitive functions in bipolar affective disorder and schizophrenia: comparison.

AIMS: Earlier comparisons of cognitive impairment among patients with bipolar disorder and schizophrenia have found a largely similar profile of deficits, but results have varied between studies. This prompted the current attempt at another such comparison. METHODS: Executive functions, memory, IQ, attention-concentration and perceptuomotor function were assessed in 48 bipolar disorder patients with operationally defined euthymia, and compared with 32 schizophrenia patients in remission, and 23 normal controls. Comparisons were re-attempted after controlling for years of schooling and residual affective symptoms. RESULTS: Uncontrolled comparisons indicated that, compared to controls, both bipolar disorder and schizophrenia patients were significantly impaired on different tests of executive function, memory, IQ and perceptuomotor functions. Controlling for years of schooling and residual affective symptoms, however, served to remove most of the differences between patients and controls, apart from some aspects of executive function in schizophrenia and memory impairment in both schizophrenia and bipolar disorder. Patients with schizophrenia consistently performed worse than patients with bipolar disorder, but none of the differences between schizophrenia and bipolar disorder were significant. CONCLUSIONS: Patients with bipolar disorder exhibit cognitive difficulties that are very similar to schizophrenia in terms of their profile, although patients with schizophrenia may have more severe and widespread impairments. The resemblance in cognitive profiles has important implications for the etiology and treatment of both disorders.

Role of Repetitive Transcranial Magnetic Stimulation (rTMS) in Treatment of Addiction and Related Disorders: A Systematic Review.

BACKGROUND: Addiction and related disorders are devastating with their tremendous social, psychological, and physical consequences for which development of optimally effective treatments is long overdue. Repetitive Transcranial Magnetic Stimulation (rTMS) is relatively safe and is becoming an emerging therapeutic tool for these conditions. METHODS: This systematic review was conducted using PubMed, PsycINFO, PsychiatryOnline and Cochrane Library ranging from year 2001 to 2017. RESULTS: Our search selected 70 related articles of which, based on the Strength of Recommendation Taxonomy (SORT) guidelines, 11 indicated Level-1 study quality and class-B strength of recommendation for rTMS in nicotine addiction (effective in 218/289 subjects who received rTMS as found in 11 studies). Level-2/Class-B evidence was found for alcohol and cocaine addictions (Alcohol: effective in 126/193 subjects who received rTMS as found in 8 studies; Cocaine: effective in 86/128 subjects, as found in 5 studies). For food cravings, Level-3/Class-B evidence was noted (effective in 134/169, found in 7 studies). However, the evidence was limited to Level-3/Class-C for heroin (10/20 subjects received active rTMS, effective in 1 study), methamphetamine (33/48 subjects received active rTMS, effective in 2 studies), cannabis (18/18 subjects received active rTMS, effective in 1 study), and pathological gambling (31/31 subjects received active rTMS, effective in 2 studies). CONCLUSION: rTMS may serve as an emerging therapeutic option for addiction and related disorders. The major lacunae include important methodological limitations and dearth of knowledge about precise mechanism of action that need to be addressed in the future studies.

A clinical comparison between 0.5% levobupivacaine and 0.5% levobupivacaine with dexamethasone 8 mg combination in brachial plexus block by the supraclavicular approach.

BACKGROUND AND AIMS: Dexamethasone as an adjuvant to bupivacaine for supraclavicular brachial plexus (SCBP) block prolongs motor and sensory blockade. However, the effect of dexamethasone (8 mg) when added to levobupivacaine has not been well studied. This study was conducted to find out analgesic efficacy of dexamethasone as adjuvant to levobupivacaine in SCBP block. METHODS: Ultrasound- guided SCBP block was given to sixty patients, randomly assigned into two groups. Group S (thirty patients) received 2 mL normal saline with 25 mL levobupivacaine (0.5%) and Group D (thirty patients) received 2 mL of dexamethasone (8 mg) with 25 mL of levobupivacaine (0.5%), respectively. Time for the first rescue analgesia, number of rescue analgesics required in 24 h and different block characteristics was assessed. Chi-square test and Student's t-test were used for statistical analysis. RESULTS: Time for request of the first rescue analgesia was 396.13 ± 109.42 min in Group S and 705.80 ± 121.46 min in Group D (P < 0.001). The requirement for rescue analgesics was more in Group S when compared to Group D. The onset of sensory and motor block was faster in Group D when compared to Group S. The mean duration of sensory and motor block was significantly longer in Group D than Group S. CONCLUSION: The addition of dexamethasone to levobupivacaine in SCBP blockade prolonged time for first rescue analgesia and reduced the requirement of rescue analgesics with faster onset and prolonged duration of sensory and motor block.