Showing papers in "Cns Spectrums in 2020"

A framework for understanding the pathophysiology of functional neurological disorder.

Abstract: The symptoms of functional neurological disorder (FND) are a product of its pathophysiology. The pathophysiology of FND is reflective of dysfunction within and across different brain circuits that, in turn, affects specific constructs. In this perspective article, we briefly review five constructs that are affected in FND: emotion processing (including salience), agency, attention, interoception, and predictive processing/inference. Examples of underlying neural circuits include salience, multimodal integration, and attention networks. The symptoms of each patient can be described as a combination of dysfunction in several of these networks and related processes. While we have gained a considerable understanding of FND, there is more work to be done, including determining how pathophysiological abnormalities arise as a consequence of etiologic biopsychosocial factors. To facilitate advances in this underserved and important area, we propose a pathophysiology-focused research agenda to engage government-sponsored funding agencies and foundations.

The effect of caloric restriction on working memory in healthy non-obese adults.

Abstract: Objective.We aim to evaluate the effect of caloric restriction (CR) in cognition by comparing performance in neuropsychological tests for working memory between a group of non-obese healthy subjects doing CR for 2 years with another consuming ad libitum diet (AL).Methods.This study was part of a larger multicenter trial called CALERIE that consisted of a randomized clinical trial with parallel-group comparing 2 years of 25% CR and AL in 220 volunteers with a BMI between 22 and 28 kg/m2, across 3 sites. The cognitive tests used were the Cambridge Neuropsychological Tests Automated Battery (CANTAB) for Spatial Working Memory (SWM) including the total number of errors (SWMTE) and strategy (SWMS). Included as possible moderators were sleep quality, mood states, perceived stress, and energy expenditure. Analyses were performed at baseline and months 12 and 24.Results.After adjustments, there was a significantly greater improvement in working memory assessed by the SWM for CR individuals, compared to AL. At month 24, it was related mostly to lower protein intake, compared to other macronutrients. Changes in SWM were moderated by changes in sleep quality, physical activity, and energy expenditure.Conclusion.On the long term, CR in healthy individuals seems to have a slightly positive effect on working memory. The study of brain CR targets opens new possibilities to prevent and treat cognitive deficits.

The broad autism phenotype in real-life: clinical and functional correlates of autism spectrum symptoms and rumination among parents of patients with autism spectrum disorder.

Abstract: Objective Increasing literature reported higher rates of psychiatric disorders in parents of children with autism spectrum disorder (ASD), as well as of autistic-like features in social and cognitive functioning. However, little attention has been paid to the association between autistic traits (AT) and global functioning in this population. The aim of the present work was to investigate clinical and functional correlates of AT among parents of ASD children, with a specific focus on ruminative thinking. Methods One hundred and twenty parents of ASD children were assessed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the Adult Autism Subthreshold Spectrum (AdAS Spectrum), the Ruminative Response Scale (RRS), the Social and Occupational Functioning Assessment Scale (SOFAS). Results Subjects with at least 1 psychiatric disorder (39.2%) showed significantly higher AdAS Spectrum and RRS scores. Subjects with a history of school difficulties and with language development alterations scored significantly higher on specific AdAS Spectrum domains. A significant negative correlation was found between SOFAS and AdAS Spectrum scores, as well as between SOFAS and RRS scores. AdAS Spectrum nonverbal communication domain score was identified has a statistically predictive variable for the presence of psychiatric disorders and lower SOFAS scores. Finally, we found a significant indirect effect of AdAS total score on SOFAS score, which was fully mediated by RRS total score. Conclusions AT in parents of ASD children seem to be associated with a higher vulnerability toward psychopathology and with a lower global functioning. Ruminative thinking may play a role in the relationship between AT and functional outcome.

The role of dopamine D3 receptors in the mechanism of action of cariprazine.

Abstract: Cariprazine is a new atypical antipsychotic drug (APD) with a unique pharmacodynamic profile, different from both typical and atypical APDs. Specifically, cariprazine acts as a partial agonist at the dopamine (DA) D2 and D3 receptors and serotonin 5-HT1A receptors, and as an antagonist at the 5-HT2B receptors. Moreover, it shows moderate affinities for adrenergic, histaminergic, and cholinergic receptors that are involved in mediating the side effects characteristic of typical APDs. In this review, we discuss the contribution of DA D3 receptors (D3Rs) in the etiology and pathophysiology of schizophrenia and the potential benefits that may be associated with a more selective targeting of D3R by APDs, as compared to other dopaminergic and non-dopaminergic receptor subtypes. Cariprazine, by acting on D3Rs, ameliorates anhedonia and cognitive deficits in animal models based on environmental or pharmacological manipulation. The reviewed results support the potential benefits of cariprazine in treating negative symptoms and cognitive deficits of schizophrenia, and therefore representing a promising approach in addressing the unmet clinical needs for the improved treatment of this serious neuropsychiatric disorder.

Stigma and functional neurological disorder: a research agenda targeting the clinical encounter.

Abstract: Stigma against patients with functional neurological disorder (FND) presents obstacles to diagnosis, treatment, and research. The lack of biomarkers and the potential for symptoms to be misunderstood, invalidated, or dismissed can leave patients, families, and healthcare professionals at a loss. Stigma exacerbates suffering and unmet needs of patients and families, and can result in poor clinical management and prolonged, repetitive use of healthcare resources. Our current understanding of stigma in FND comes from surveys documenting frustration experienced by providers and distressing healthcare interactions experienced by patients. However, little is known about the origins of FND stigma, its prevalence across different healthcare contexts, its impact on patient health outcomes, and optimal methods for reduction. In this paper, we set forth a research agenda directed at better understanding the prevalence and context of stigma, clarifying its impact on patients and providers, and promoting best practices for stigma reduction.

Risk factors for recidivism in individuals receiving community sentences: a systematic review and meta-analysis

Abstract: Objective. We aimed to systematically review risk factors for criminal recidivism in individuals given community sentences. Methods. We searched seven bibliographic databases and additionally conducted targeted searches for studies that investigated risk factors for any repeat offending in individuals who had received community (non-custodial) sentences. We included investigations that reported data on at least one risk factor and allowed calculations of odds ratios (ORs). If a similar risk factor was reported in three or more primary studies, they were grouped into domains, and pooled ORs were calculated. Results. We identified 15 studies from 5 countries, which reported data on 14 independent samples and 246,608 individuals. We found that several dynamic (modifiable) risk factors were associated with criminal recidivism in community-sentenced populations, including mental health needs (OR = 1.4, 95% confidence interval (CI): 1.2–1.6), substance misuse (OR = 2.3, 95% CI: 1.1–4.9), association with antisocial peers (OR = 2.2, 95% CI: 1.3–3.7), employment problems (OR = 1.8, 95% CI: 1.3–2.5), marital status (OR = 1.6, 95%: 1.4–1.8), and low income (OR = 2.0, 95% CI: 1.1–3.4). The strength of these associations was comparable to that of static (non-modifiable) risk factors, such as age, gender, and criminal history. Conclusion. Assessing dynamic (modifiable) risk factors should be considered in all individuals given community sentences. The further integration of mental health, substance misuse, and criminal justice services may reduce reoffending risk in community-sentenced populations.

Forensic patients in state psychiatric hospitals: 1999-2016.

Abstract: Introduction. In recent years mental health officials have reported a rise in the number of forensic patients present within their state psychiatric hospitals and the adverse impacts that these trends had on their hospitals. To date there have been no large-scale national studies conducted to determine if these trends are specific only to a few states or representative of a more global trend. The purpose of this study was to investigate these reported trends and their national prevalence. Methods. The forensic directors of each state behavioral health agency (including the District of Columbia) were sent an Excel spreadsheet that had two components: a questionnaire and data tables with information collected between 1996 and 2014 from the State Profiling System maintained by the National Association of State Mental Health Program Directors Research Institute. They were asked to verify and update these data and respond to the questionnaire. Results. Responses showed a 76% increase nationally in the number of forensic patients in state psychiatric hospitals between 1999 and 2014. The largest increase was for individuals who were court-committed after being found incompetent to stand trial and in need of inpatient restoration services. Discussion. The data reviewed here indicate that increases in forensic referrals to state psychiatric hospitals, while not uniform across all states, are nonetheless substantial. Conclusion. More research is needed to determine whether this multi-state trend is merely a coincidence of differing local factors occurring in many states, or a product of larger systemic factors affecting mental health agencies and the courts.

Compulsivity is measurable across distinct psychiatric symptom domains and is associated with familial risk and reward-related attentional capture.

Abstract: Background.Compulsivity can be seen across various mental health conditions and refers to a tendency toward repetitive habitual acts that are persistent and functionally impairing. Compulsivity involves dysfunctional reward-related circuitry and is thought to be significantly heritable. Despite this, its measurement from a transdiagnostic perspective has received only scant research attention. Here we examine both the psychometric properties of a recently developed compulsivity scale, as well as its relationship with compulsive symptoms, familial risk, and reward-related attentional capture.Methods. Two-hundred and sixty individuals participated in the study (mean age = 36.0 [SD = 10.8] years; 60.0% male) and completed the Cambridge-Chicago Compulsivity Trait Scale (CHI-T), along with measures of psychiatric symptoms and family history thereof. Participants also completed a task designed to measure reward-related attentional capture (n = 177).Results.CHI-T total scores had a normal distribution and acceptable Cronbach’s alpha (0.84). CHI-T total scores correlated significantly and positively (all p < 0.05, Bonferroni corrected) with Problematic Usage of the Internet, disordered gambling, obsessive-compulsive symptoms, alcohol misuse, and disordered eating. The scale was correlated significantly with history of addiction and obsessive-compulsive related disorders in first-degree relatives of participants and greater reward-related attentional capture.Conclusions. These findings suggest that the CHI-T is suitable for use in online studies and constitutes a transdiagnostic marker for a range of compulsive symptoms, their familial loading, and related cognitive markers. Future work should more extensively investigate the scale in normative and clinical cohorts, and the role of value-modulated attentional capture across compulsive disorders.

A brief history of the criminalization of mental illness.

Abstract: This article traces the history of the way in which mental disorders were viewed and treated, from before the birth of Christ to the present day. Special attention is paid to the process of deinstitutionalization in the United States and the failure to create an adequately robust community mental health system to care for the people who, in a previous era, might have experienced lifelong hospitalization. As a result, far too many people with serious mental illnesses are living in jails and prisons that are ill-suited and unprepared to meet their needs.

Clinical implications of directly switching antidepressants in well-treated depressed patients with treatment-emergent sexual dysfunction: a comparison between vortioxetine and escitalopram

Abstract: Objective The objective of this work was to describe treatment-emergent sexual dysfunction (TESD) and tolerability following a switch from selective serotonin reuptake inhibitor (SSRI: citalopram, paroxetine, or sertraline) monotherapy to vortioxetine or escitalopram monotherapy in adults with well-treated major depressive disorder (MDD) and SSRI-induced sexual dysfunction. Methods Data were analyzed from the primary study, an 8-week, randomized, double-blind, head-to-head study in which participants with well-treated depressive symptoms but experiencing TESD with SSRIs were directly switched to flexible doses (10/20 mg) of vortioxetine or escitalopram. Sexual functioning was assessed by the Changes in Sexual Functioning Questionnaire-14 (CSFQ-14), efficacy by the Montgomery-Asberg Depression Rating Scale scores (MADRS) and Clinicians Global Impression of Severity/Improvement (CGI-S/CGI-I), and tolerability by adverse events. Efficacy and tolerability were assessed by pre-switch SSRI therapy where possible, and by participant characteristics. Results Greater improvements in TESD were seen in the vortioxetine compared with escitalopram groups based on: participant demographics (≤45 years, women; P = 0.045), prior SSRI treatment (P = 0.044), number of prior major depressive episodes (MDEs) (1-3; P = 0.001), and duration of prior SSRI therapy (>1 year; P = 0.001). Prior SSRI treatment did not appear to influence the incidence or severity of TEAEs, except for nausea. Regardless of prior SSRI, both treatments maintained antidepressant efficacy after 8 weeks. Conclusion Results suggest that vortioxetine is a safe and effective switch therapy for treating SSRI-induced sexual dysfunction in adults with well-treated MDD. Also, improvement in sexual dysfunction with vortioxetine or escitalopram may be influenced by prior SSRI usage, sex, age, and history of MDEs.

A 6-month follow-up study on response and relapse rates following an acute trial of repetitive transcranial magnetic stimulation in patients with major depression.

Abstract: BACKGROUND Little is known about the post-acute effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The present study focused on the 6-month follow-up of a sample of patients with major depression, after the completion of an acute 4 weeks rTMS trial, with the aim of evaluating response (in terms of sustained and late response) and relapse rates. METHODS Following the completion of an acute trial of rTMS (T0-T4), 31 drug-resistant depressed patients (bipolar or unipolar) entered a naturalistic follow-up period of 6 months, with three timepoints (T5, T6, and T7) during which they were assessed with the Hamilton Depression Rating Scale and the Young Mania Rating Scale. RESULTS Results showed that in the 6 months following an acute transcranial magnetic stimulation (TMS) trial, a higher rate of late responders was observed among previously acute TMS nonresponders (63.64%, 7 out of 11) compared to the rate of relapse among those who had acutely responded to TMS (10%, 2 out of 20). In addition, an overall high rate of maintained response (90%) was observed. CONCLUSION Present findings seem to support the possibility of obtaining a clinical response also after the end of an acute TMS trial in patients with major depression. The concomitant low rate of relapse observed at the end of follow-up along with a high rate of maintained response provides further support to the post-acute efficacy of TMS. Nonetheless, further controlled studies, with larger samples and longer follow-up observation, are needed to confirm the reported results.

Efficacy and safety of ketamine in the management of anxiety and anxiety spectrum disorders: a review of the literature.

Abstract: Anxiety disorders are among the most prevalent psychiatric conditions. Despite many proven pharmacological and non-pharmacological treatments available, high rates of partial response and low rates of long-term remission remain. Ketamine has been receiving increasing attention as an interventional treatment modality in psychiatry, especially among refractory conditions, including major depressive disorder. There is limited yet growing evidence to support the use of ketamine in anxiety disorders. In this review of the literature, we present case reports, case series, and controlled trials demonstrating proof-of-concept for its potential role in the treatment of anxiety and anxiety spectrum disorders. Its unique mechanism of action, rapid onset, and high rate of response have driven its use in clinical practice. Ketamine is generally well tolerated by patients and has a limited side effect profile; however, the effects of long-term use are unknown. While there is a growing body of research and increasing clinical experience to suggest ketamine may have clinical applications in the treatment of refractory anxiety disorders, further research to determine long-term safety and tolerability is indicated.

Defining effective strategies to prevent post-traumatic stress in healthcare emergency workers facing the COVID-19 pandemic in Italy.

Abstract: Italy, May 19th. As we write, the end of the COVID-19 outbreak is finally in view; however, its psychological impact on healthcare workers (HCWs) remains an urgent question. Italy was the first European Country to face the pandemic that started in Codogno (Lodi), declared “red zone” and isolated by February 20th 2020. To date, the number of confirmed COVID-19 cases exceeds 215 000, with a death toll exceeding 30 000, over 23 000 HCWs being infected and 161 of them— 130 physicians and 31 nurses—losing their life to complications of the infection. Because HCWs facing the COVID-19 outbreak were exposed to extreme and prolonged work-related stress with a high risk of exhaustion, burnout and post-traumatic stress reactions, the COVID-19 crisis was defined as the “9/11 of health care systems.” Since the introduction of the Diagnostic and Statistical Manual for Mental Disorders—5th edition (DSM-5), work-related repeated or extreme exposure to aversive details of traumatic eventsmay qualify for a trauma. In linewith this, recent literature on burnout and post-traumatic stress disorder (PTSD) among first responders and HCWs, highlighted specific risk factors such as the frequent unpredictability of daily work cases and perceived expectations from patients and their families in critical cases/situations. While the Italian health care systemwas weakened by years and years of budgetary cuts, the COVID-19 outbreak amplified the chronic difficulties, leading to increased risk for negative mental health outcomes among HCWs. First, typical pre-existing risk factors for PTSDwere frequently present among ItalianHCWs, including female gender and young to middle age with young children. Second, specific characteristics of COVID-19 added further burden: rapidly increased flow of critical patients forcing physicians to make extremely difficult decision tainted with pervasive helplessness; clinical presentation characterized by severe distress, rapidly worsening dyspnea with insidious and unpredictable course, requiring constant medical updating with worldwide emerging multiple clinical manifestations and treatment of the COVID-19 infection increasing distress at the time of patient’s death; constant need for complete isolation during patient care, both for the patient and the providers, given the extremely high contamination risk, and the shortage of protective personal equipment that lead to fear, anger, and resentment against the authorities. Third, the systemic impact of the disease and its social repercussions also included: rapid and sometimes chaotic reorganization of services and logistical challenges for recruiting new emergency departments and intensive care unit (ICU) personnel, both to managing the increasing number of patients and to substitute HCWs becoming ill; introducing unskilled HCWs in highly specialized units, leading to feelings of frustration, isolation, hopelessness, and irritability; lack of social support at work; the need to work with new colleagues or redeployed strangers; lack of social support at home with schools closures and children confined at home; fear of infecting family members leading to further isolation. Taken together, there was an urgent need to efficiently provide mental health support to firstline HCWs early in the outbreak, to promote resilience and mitigate long-term effects of exposure to multiple COVID-related stressors. Similarly, to Chinese hospital, Codogno Hospital (Lodi) rapidly delineated and deployed mental health support to first-line HCWs in collaboration with researchers at the Pisa University Hospital (Psychiatric Clinic), based on their expertise developed in most recent years, in particular during the L'Aquila earthquake. A psychological first management service for emergency personnel was set up in Codogno (Lodi), with a psychiatrist and a psychologist, to address HCW’s hyperarousal, irritability, trouble sleeping, psychological distress, and unwillingness to rest. As the pandemic spread across Italy, a nationwide “red zone” was declared on March 10th, and all hospitals reorganized to face the COVID-19 crisis leveraging the 2 weeks of experience of the northern regions. HCWs were however reluctant to access the psychological interventions, requiring instead support for patient management. They reported difficulties in facing the needs of their patients’who were in CNS Spectrums

Differentiating Tardive Dyskinesia: A Video-Based Review of Antipsychotic-Induced Movement Disorders in Clinical Practice

Abstract: Accurate diagnosis and appropriate treatment of tardive dyskinesia (TD) are imperative, as its symptoms can be highly disruptive to both patients and their caregivers. Misdiagnosis can lead to incorrect interventions with suboptimal or even deleterious results. To aid in the identification and differentiation of TD in the psychiatric practice setting, we review its clinical features and movement phenomenology, as well as those of other antipsychotic-induced movement disorders, with accompanying links to illustrative videos. Exposure to dopamine receptor blocking agents (DRBAs) such as antipsychotics or antiemetics is associated with a spectrum of movement disorders including TD. The differential diagnosis of TD is based on history of DRBA exposure, recent discontinuation or dose reduction of a DRBA, and movement phenomenology. Common diagnostic challenges are the abnormal behaviors and dyskinesias associated with advanced age or chronic mental illness, and other movement disorders associated with DRBA therapy, such as akathisia, parkinsonian tremor, and tremor related to use of mood stabilizing agents (eg, lithium, divalproex). Duration of exposure may help rule out acute drug-induced syndromes such as acute dystonia or acute/subacute akathisia. Another important consideration is the potential for TD to present together with other drug-induced movement disorders (eg, parkinsonism, parkinsonian tremor, and postural tremor from mood stabilizers) in the same patient, which can complicate both diagnosis and management. After documentation of the phenomenology, severity, and distribution of TD movements, treatment options should be reviewed with the patient and caregivers.

The report of the joint WPA/CINP workgroup on the use and usefulness of antipsychotic medication in the treatment of schizophrenia.

Abstract: This is a report of a joint World Psychiatric Association/International College of Neuropsychopharmacology (WPA/CINP) workgroup concerning the risk/benefit ratio of antipsychotics in the treatment of schizophrenia It utilized a selective but, within topic, comprehensive review of the literature, taking into consideration all the recently discussed arguments on the matter and avoiding taking sides when the results in the literature were equivocal The workgroup's conclusions suggested that antipsychotics are efficacious both during the acute and the maintenance phase, and that the current data do not support the existence of a supersensitivity rebound psychosis Long-term treated patients have better overall outcome and lower mortality than those not taking antipsychotics Longer duration of untreated psychosis and relapses are modestly related to worse outcome Loss of brain volume is evident already at first episode and concerns loss of neuropil volume rather than cell loss Progression of volume loss probably happens in a subgroup of patients with worse prognosis In humans, antipsychotic treatment neither causes nor worsens volume loss, while there are some data in favor for a protective effect Schizophrenia manifests 2 to 3 times higher mortality vs the general population, and treatment with antipsychotics includes a number of dangers, including tardive dyskinesia and metabolic syndrome; however, antipsychotic treatment is related to lower mortality, including cardiovascular mortality In conclusion, the literature strongly supports the use of antipsychotics both during the acute and the maintenance phase without suggesting that it is wise to discontinue antipsychotics after a certain period of time Antipsychotic treatment improves long-term outcomes and lowers overall and specific-cause mortality

Cariprazine efficacy in bipolar I depression with and without concurrent manic symptoms: post hoc analysis of 3 randomized, placebo-controlled studies.

Abstract: Objective. Mixed presentations, defined by simultaneous occurrence of depressive and manic symptoms, are difficult to treat. Antidepressants, although commonly used, have weak evidence of efficacy and may increase risk of mood destabilization. The aim of this pooled post hoc analysis was to evaluate the efficacy of cariprazine in the treatment of bipolar depression with or without concurrent manic symptoms. Methods. Patients from 3 randomized, double-blind, placebo-controlled studies who met DSM-IV-TR or DSM-5 criteria for bipolar I disorder with a current major depressive episode were identified to have concurrent manic symptoms by baseline Young Mania Rating Scale total score ≥4. Efficacy was assessed in cariprazine 1.5 and 3 mg/day dose groups versus placebo; analyses included the least squares mean change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. Results. Of 1383 patients randomized to treatment, 808 (58.4%) had concurrent manic symptoms. For patients with manic symptoms, mean reduction in MADRS total score from baseline to week 6 was significantly greater for both cariprazine 1.5 and 3 mg/day compared with placebo, with least squares mean differences (LSMDs) versus placebo of -2.5 (p = .0033) and -2.9 (p = .0010), respectively; for patients without manic symptoms, the LSMD was significant for 1.5 mg/day (-3.3; p = .0008), but not for 3 mg/day (-1.9; p = .0562). Conclusion. The results of this post hoc analysis suggest that cariprazine may be an appropriate treatment option for patients with bipolar I depression with or without manic symptoms, with higher doses potentially more effective in patients with manic symptoms.

Eating disorders and autism spectrum: links and risks.

Abstract: In the last decades, increasing attention has been provided to socio-cultural and neurobiological factors involved in the psychopathology of feeding and eating disorders (FED), encouraging a multifactorial approach. In this framework, several authors stressed an association between FED and other kinds of psychiatric disorders from both a psychopathological and a neurobiological point of view. In particular, many promising contributions are focusing on the possible link between FED and autism spectrum disorder (ASD). Growing interest about this association rose from the frequently reported evidence of ASD-like traits amongst FED patients and abnormal eating behaviors amongst patients with ASD. This narrative review overview aims to summarize the most relevant findings about the overlap between different kinds of FED and the autism spectrum, taking into account the most recent hypotheses about the psychopathology of both these conditions. While most of the studies focused on anorexia nervosa, both ASD and autistic traits seem to be detectable also in other kinds of FED. In addition, the recently increased interest toward a dimensional approach to psychopathology led to progressively broadening the concept of ASD, focusing on its subthreshold and gender-specific manifestations and on its link with other psychiatric conditions, including FED. Globally the studies summarized here provide further support to theoretical models featuring a neurodevelopmental approach for mental disorders. In particular, FED have been conceptualized as a possible psychopathological trajectory of a neurodevelopmental alteration, toward which female gender would act as one of many predisposing factors.

Pathophysiologic mechanisms, neuroimaging and treatment in wake-up stroke

Abstract: Wake-up stroke (WUS) or ischemic stroke occurring during sleep accounts for 14%-29.6% of all ischemic strokes. Management of WUS is complicated by its narrow therapeutic time window and attributable risk factors, which can affect the safety and efficacy of administering intravenous (IV) tissue plasminogen activator (t-PA). This manuscript will review risk factors of WUS, with a focus on obstructive sleep apnea, potential mechanisms of WUS, and evaluate studies assessing safety and efficacy of IV t-PA treatment in WUS patients guided by neuroimaging to estimate time of symptom onset. The authors used PubMed (1966 to March 2018) to search for the term "Wake-Up Stroke" cross-referenced with "pathophysiology," ''pathogenesis," "pathology," "magnetic resonance imaging," "obstructive sleep apnea," or "treatment." English language Papers were reviewed. Also reviewed were pertinent papers from the reference list of the above-matched manuscripts. Studies that focused only on acute Strokes with known-onset of symptoms were not reviewed. Literature showed several potential risk factors associated with increased risk of WUS. Although the onset of WUS is unknown, a few studies investigated the potential benefit of magnetic resonance imaging (MRI) in estimating the age of onset which encouraged conducting clinical trials assessing the efficacy of MRI-guided thrombolytic therapy in WUS.

Addicted to compulsion: assessing three core dimensions of addiction across obsessive-compulsive disorder and gambling disorder.

Abstract: ObjectiveSeveral studies suggested that obsessive-compulsive disorder (OCD) patients display increased impulsivity, impaired decision-making, and reward system dysfunction. In a Research Domain Criteria (RDoC) perspective, these findings are prototypical for addiction and have led some authors to view OCD as a behavioral addiction. Thus, the aim of this study was to investigate similarities and differences on impulsivity, decision-making, and reward system, as core dimensions of addiction, across OCD and gambling disorder (GD) patients.MethodsForty-four OCD patients, 26 GD patients, and 40 healthy controls (HCs) were included in the study. Impulsivity was assessed through the Barratt Impulsiveness Scale, decision-making through the Iowa Gambling Task, and reward system through a self-report clinical instrument (the Shaps-Hamilton Anhedonia Scale) assessing hedonic tone and through an olfactory test assessing hedonic appraisal to odors.ResultsBoth OCD and GD patients showed increased impulsivity when compared to HCs. More specifically, the OCD patients showed cognitive impulsivity, and the GD patients showed both increased cognitive and motor impulsivity. Furthermore, both OCD and GD patients showed impaired decision-making performances when compared to HCs. Finally, GD patients showed increased anhedonia and blunted hedonic response to pleasant odors unrelated to gambling or depression/anxiety symptoms, while OCD patients showed only increased anhedonia levels related to OC and depression/anxiety symptoms.ConclusionOCD patients showed several similarities and some differences with GD patients when compared to HCs on impulsivity, decision-making, and reward system, three core dimensions of addiction. These results could have relevant implications for the research of new treatment targets for OCD.

Antineuroinflammatory therapy: potential treatment for autism spectrum disorder by inhibiting glial activation and restoring synaptic function

Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by deficits in social interactions and perseverative and stereotypical behavior. Growing evidence points toward a critical role for synaptic dysfunction in the onset of ASD, and synaptic function is influenced by glial cells. Considering the evidence that neuroinflammation in ASD is mediated by glial cells, one hypothesis is that reactive glial cells, under inflammatory conditions, contribute to the loss of synaptic functions and trigger ASD. Ongoing pharmacological treatments for ASD, including oxytocin, vitamin D, sulforaphane, and resveratrol, are promising and are shown to lead to improvements in behavioral performance in ASD. More importantly, their pharmacological mechanisms are closely related to anti-inflammation and synaptic protection. We focus this review on the hypothesis that synaptic dysfunction caused by reactive glial cells would lead to ASD, and discuss the potentials of antineuroinflammatory therapy for ASD.

Treatment of functional neurological disorder: current state, future directions, and a research agenda.

Abstract: Functional neurological disorder (FND) encompasses a complex and heterogeneous group of neuropsychiatric syndromes commonly encountered in clinical practice. Patients with FND may present with a myriad of neurological symptoms and frequently have comorbid medical, neurological, and psychiatric disorders. Over the past decade, important advances have been made in understanding the pathophysiology of FND within a biopsychosocial framework. Many challenges remain in addressing the stigma associated with this diagnosis, refining diagnostic criteria, and providing access to evidence-based treatments. This paper outlines FND treatment approaches, emphasizing the importance of respectful communication and comprehensive explanation of the diagnosis to patients, as critical first step to enhance engagement, adherence, self-agency, and treatment outcomes. We then focus on a brief review of evidence-based treatments for psychogenic non-epileptic seizures and functional movement disorder, a guide for designing future treatment trials for FND, and a proposal for a treatment research agenda, in order to aid in advancing the field to develop and implement treatments for patients with FND.

Emotional distress, brain functioning, and biobehavioral processes in cancer patients: a neuroimaging review and future directions.

Abstract: Despite emerging evidence that distress and adversity can contribute to negative health outcomes in cancer, little is known about the brain networks, regions, or circuits that can contribute to individual differences in affect/distress states and health outcomes in treated cancer patients. To understand the state-of-the-science in this regard, we reviewed neuroimaging studies with cancer patients that examined the associations between negative affect (distress) and changes in the metabolism or structure of brain regions. Cancer patients showed changes in function and/or structure of key brain regions such as the prefrontal cortex, thalamus, amygdala, hippocampus, cingulate cortex (mainly subgenual area), hypothalamus, basal ganglia (striatum and caudate), and insula, which are associated with greater anxiety, depression, posttraumatic stress disorder (PTSD) symptoms, and distress. These results provide insights for understanding the effects of these psychological and emotional factors on peripheral stress-related biobehavioral pathways known to contribute to cancer progression and long-term health outcomes. This line of work provides leads for understanding the brain-mediated mechanisms that may explain the health effects of psychosocial interventions in cancer patients and survivors. A multilevel and integrated model for distress management intervention effects on psychological adaptation, biobehavioral processes, cancer pathogenesis, and clinical outcomes is proposed for future research.

The use of lithium in mixed states.

Abstract: Lithium is a unique drug. In more than 60 years of observation, it showed its multiple important clinical properties in treating mania, stabilizing mood alterations, preventing suicide and protecting from neurodegeneration. It was also the most extensively studied drug in psychiatry. Nevertheless, it is generally underprescribed. Specifically, lithium is virtually not considered in the treatment of patients affected by mixed affective states. Lithium is not suggested for the acute treatment of mixed affective states and is considered to be less effective than other mood stabilizers in the long-term management of these patients. The main reason why lithium has no indication for mixed states is the "lack of evidence." Actually, there are several reasons to consider lithium as an effective treatment in patients with mixed affective states.

Using network analysis to explore cognitive domains in patients with unipolar versus bipolar depression: a prospective naturalistic study.

Abstract: Objective Despite growing evidence in the field of cognitive function in mood disorders, the neurocognitive profiles of patients with unipolar and bipolar depression still need further characterization. In this study, we applied network analysis, hypothesizing this approach could highlight differences between major depressive disorder (MDD) and bipolar disorder (BD) from a cognitive perspective. Methods The cognitive performance of 109 patients (72 unipolar and 37 bipolar depressed outpatients) was assessed through the Montreal Cognitive Assessment (MoCA), and a series of clinical variables were collected. Differences in cognitive performance between MDD and BD patients were tested using non-parametric tests. Moreover, a network graph representing MoCA domains as nodes and Spearman's rho correlation coefficients between the domains as edges was constructed for each group. Results The presence of mild cognitive impairment was observed in both MDD and BD patients during depression. No statistical significant difference was found between the two groups in terms of overall cognitive performance and across single domains. Nonetheless, network analytic metrics demonstrated different roles of memory and executive dysfunction in MDD versus BD patients: in particular, MDD network was more densely interconnected than BD network, and memory was the node with the highest betweenness and closeness centrality in MDD, while executive function was more central in BD. Conclusions From a network analytic perspective, memory impairment displays a central role in the cognitive impairment of patients with unipolar depression, whereas executive dysfunction appears to be more central in bipolar depression. Further research is warranted to confirm our results.

Decriminalizing LGBTQ+: Reproducing and resisting mental health inequities.

Abstract: Secure settings are not queer because lesbian, gay, bisexual, transgender, queer, questioning, Two Spirit, and asexual (LGBTQ+) people populate them, and neither are LGBTQ+ people inherently criminal because they are found in those spaces. Queer people bear disproportionate health, mental health, and social inequities that have had, historically and currently, the effect to criminalize them. This review discusses effective language and ideologies when working with LGBTQ+ people in secure settings. Major health, mental health, and social inequities are reviewed, along with the applied framework of minority stress. Then, the process of criminalization is diagrammed across the phases of predetainment, being in the system, and through re-entering the community. Finally, multilevel strategies are offered to decriminalize LGBTQ+ people ideologically and in practice.

Toward specific ways to combine ketamine and psychotherapy in treating depression.

Abstract: In major depression, remission rate in response to monoaminergic antidepressant is around 50%. The lack of strong synergies between classical antidepressants and psychotherapy may be due to the molecular effects of classical antidepressants. They modulate synapses but they do not substantially influence synaptogenesis. They also increase brain-derived neurotrophic factor (BDNF). However, for activity-dependent plasticity, BDNF release has to work in concert with activation of synaptogenesis. There has been considerable excitement about ketamine’s antidepressant effect. Ketamine leads to fast changes in synaptic function and plasticity that go well beyond effects of classical antidepressants. As a result, ketamine may turn out to have the capacity to considerably enhance the effects of psychotherapy. Such enhancing effects may become an important clinical indication for ketamine since its purely pharmacological effect is transient. This editorial outlines some mechanistic hypotheses, how Behavioral Activation, Trauma-Focused Psychotherapies and Humanistic Psychotherapy may specifically prolong ketamine’s antidepressant effects.

Early seizures after ischemic stroke: focus on thrombolysis.

Abstract: Introduction.Stroke is a significant underlying cause of epilepsy. Seizures due to ischemic stroke (IS) are generally categorized into early seizures (ESs) and late seizures (LSs). Seizures in thrombolysis situations may raise the possibility of other etiology than IS.Aim.We overtook a systematic review focusing on the pathogenesis, prevalence, risk factors, detection, management, and clinical outcome of ESs in IS and in stroke/thrombolysis situations. We also collected articles focusing on the association of recombinant tissue-type plasminogen activator (rt-PA) treatment and epileptic seizures.Results.We have identified 37 studies with 36,775 participants. ES rate was 3.8% overall in patients with IS with geographical differences. Cortical involvement, severe stroke, hemorrhagic transformation, age (<65 years), large lesion, and atrial fibrillation were the most important risk factors. Sixty-one percent of ESs were partial and 39% were general. Status epilepticus (SE) occurred in 16.3%. 73.6% had an onset within 24 h and 40% may present at the onset of stroke syndrome. Based on EEG findings seizure-like activity could be detected only in approximately 18% of ES patients. MRI diffusion-weighted imaging and multimodal brain imaging may help in the differentiation of ischemia vs. seizure. There are no specific recommendations with regard to the treatment of ES.Conclusion.ESs are rare complications of acute stroke with substantial burden. A significant proportion can be presented at the onset of stroke requiring an extensive diagnostic workup.

Pregabalin augmentation for resistant obsessive-compulsive disorder: a double-blind placebo-controlled clinical trial.

Abstract: BACKGROUND AND OBJECTIVE Glutamate dysfunction has been shown to be associated with pathophysiology of obsessive-compulsive disorder (OCD). Our objective is to survey the effects of pregabalin (a glutamate-modulating agent) as an augmenting treatment for resistant OCD. PATIENTS AND METHODS In this 12-week double-blind placebo-controlled clinical trial, 56 patients with resistant OCD were randomly allocated to receive either pregabalin or placebo plus their current medication (sertraline). Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to evaluate the outcomes. Adverse effects were also registered. RESULTS Of the 56 patients with resistant OCD who were randomly allocated in 2 groups of pregabalin (n = 28) and placebo group (n = 28), 42 patients (22 in pregabalin group and 20 in placebo group) completed the trial. Throughout the trial, the mean score decreased from 26.13± 7.03 to 8.81 ± 3.47 in the pregabalin group (p < 0) and from 26.85 ± 4.34 to 17.63 ± 4.22 in the placebo group (p < 0). At the end of trial, 16 (57.14%) patients in the pregabalin group and 2 (7.14%) patients in the placebo group showed more than 35% decline in YBOCS (p < .01). The pregabalin group showed good tolerability and safety. CONCLUSIONS Our study revealed that pregabalin, as an augmenting medication, is more effective than placebo in the treatment of patients with resistant OCD.

Fixated Threat Assessment Centers: preventing harm and facilitating care in public figure threat cases and those thought to be at risk of lone-actor grievance-fueled violence.

Abstract: The rediscovery of the importance of mental illness in the risk assessment and management of those who threaten, approach, and harm public figures has led to a new way of dealing with those that threaten public figures. This approach emphasises the role of "fixation" which may be defined as an intense preoccupation pursued to an abnormally intense degree. It integrates a threat assessment paradigm with the literature on stalking. The need for such an approach was highlighted in research on the prevalence of harassment of public figures. Psychiatry has a key role in this approach which sees mental health clinicians and Police work together in Fixated Threat Assessment Centres (FTACs). An FTAC functions by assessing the level of concern and sharing information to facilitate interventions that are often mental health based. The purpose is not the hopeless task of identifying those who will go on to perpetrate serious violence, rather to intervene in the group they emerge from, to prevent harm. As well as decreasing risk to the persons fixated upon, this approach improves care to the mentally disordered people who harass and threaten them and, in doing so, decreases the likelihood of their criminalization while enhancing their quality of life. As expertise in the area has grown, policing and security agencies in several countries have expanded the FTAC model to cover individuals thought at risk of lone-actor grievance-fueled violence, a term that captures both different forms of mass killing and lone actor terrorism.