EEG-Meta-Microstates: Towards a More Objective Use of Resting-State EEG Microstate Findings Across Studies.

Over the last decade, EEG resting-state microstate analysis has evolved from a niche existence to a widely used and well-accepted methodology. The rapidly increasing body of empirical findings started to yield overarching patterns of associations of biological and psychological states and traits with specific microstate classes. However, currently, this cross-referencing among apparently similar microstate classes of different studies is typically done by "eyeballing" of printed template maps by the individual authors, lacking a systematic procedure. To improve the reliability and validity of future findings, we present a tool to systematically collect the actual data of template maps from as many published studies as possible and present them in their entirety as a matrix of spatial similarity. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps from ongoing or published studies. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps in the literature. The analysis of 40 included sets of template maps indicated that: (i) there is a high degree of similarity of template maps across studies, (ii) similar template maps were associated with converging empirical findings, and (iii) representative meta-microstates can be extracted from the individual studies. We hope that this tool will be useful in coming to a more comprehensive, objective, and overarching representation of microstate findings.

Telepsychiatry and other cutting-edge technologies in COVID-19 pandemic: Bridging the distance in mental health assistance.

BACKGROUND: At the end of 2019, a novel coronavirus (COVID-19) was identified in China. The high potential of human-to-human transmission led to subsequent COVID-19 global pandemic. Public health strategies including reduced social contact and lockdown have been adopted in many countries. Nonetheless, social distancing and isolation could also represent risk factors for mental disorders, resulting in loneliness, reduced social support and under-detection of mental health needs. Along with this, social distancing determines a relevant obstacle for direct access to psychiatric care services. The pandemic generates the urgent need for integrating technology into innovative models of mental healthcare. AIMS: In this paper, we discuss the potential role of telepsychiatry (TP) and other cutting-edge technologies in the management of mental health assistance. We narratively review the literature to examine the advantages and risks related to the extensive application of these new therapeutic settings, along with the possible limitations and ethical concerns. RESULTS: Telemental health services may be particularly feasible and appropriate for the support of patients, family members and healthcare providers during this COVID-19 pandemic. The integration of TP with other technological innovations (eg, mobile apps, virtual reality, big data and artificial intelligence (AI)) opens up interesting future perspectives for the improvement of mental health assistance. CONCLUSION: Telepsychiatry is a promising and growing way to deliver mental health services but is still underused. The COVID-19 pandemic may serve as an opportunity to introduce and promote, among numerous mental health professionals, the knowledge of the possibilities offered by the digital era.

Role and Perspectives of Inflammation and C-Reactive Protein (CRP) in Psychosis: An Economic and Widespread Tool for Assessing the Disease.

Schizophrenia is a major psychotic disorder affecting nearly 23.6 million people globally and greatly impacting the cognitive and social functioning of individuals. Multiple risk factors, including genetic, environmental, and epigenetic factors have been identified. However, the exact mechanism by which some factors aid in the development of schizophrenia is still uncertain. Acute and/or long-standing inflammation has been implicated as both a cause and effect of schizophrenia. Heightened immune responses have been documented in large cohorts of individuals with schizophrenia. While not completely known, multiple hypotheses, such as disruption of the blood-brain barrier, alterations in the kynurenine/tryptophan pathway, and increased microglial activation, have been presented to correlate inflammation with schizophrenic symptoms. Measurement of C-reactive protein (CRP) is a commonly performed and inexpensive test on patients' serum to determine levels of systemic inflammation in the body. Multiple studies have reported an elevated CRP level in different stages of schizophrenia, indicating its potential to be used as a viable biomarker in the diagnosis and monitoring of schizophrenia along with assessing treatment response to conventional and non-conventional treatment regimens. This review aims to evaluate the role of inflammation, in general, and CRP, in particular, in the pathogenesis of schizophrenia and its potential significance in diagnostic, therapeutic, and preventative approaches towards schizophrenia and psychosis.

Gut Microbiota and Bipolar Disorder: An Overview on a Novel Biomarker for Diagnosis and Treatment.

The gut microbiota is the set of microorganisms that colonize the gastrointestinal tract of living creatures, establishing a bidirectional symbiotic relationship that is essential for maintaining homeostasis, for their growth and digestive processes. Growing evidence supports its involvement in the intercommunication system between the gut and the brain, so that it is called the gut-brain-microbiota axis. It is involved in the regulation of the functions of the Central Nervous System (CNS), behavior, mood and anxiety and, therefore, its implication in the pathogenesis of neuropsychiatric disorders. In this paper, we focused on the possible correlations between the gut microbiota and Bipolar Disorder (BD), in order to determine its role in the pathogenesis and in the clinical management of BD. Current literature supports a possible relationship between the compositional alterations of the intestinal microbiota and BD. Moreover, due to its impact on psychopharmacological treatment absorption, by acting on the composition of the microbiota beneficial effects can be obtained on BD symptoms. Finally, we discussed the potential of correcting gut microbiota alteration as a novel augmentation strategy in BD. Future studies are necessary to better clarify the relevance of gut microbiota alterations as state and disease biomarkers of BD.

How does ayahuasca work from a psychiatric perspective? Pros and cons of the entheogenic therapy.

OBJECTIVE: Ayahuasca is a hallucinogenic plant preparation, traditionally consumed in sacred ceremonies by indigenous North-Westerner Amazonian countries like Colombia, Peru, Brazil, and Ecuador. It is fundamental to carefully balance benefits/risks related to the ayahuasca intake, both during ceremonies and experimental settings. The aim is at evaluating and comparing the potential therapeutic benefits versus health risks related to ayahuasca intake (both acutely and chronically), focusing on its application in psychedelic psychiatry. DESIGN: A comprehensive mini overview focusing on psychiatric outcomes following ayahuasca intake both in healthy volunteers and in clinical samples. RESULTS: Preclinical, observational, and experimental studies in healthy volunteers as well as in clinical samples suggest that ayahuasca may be beneficial as an antidepressant, emotional regulator, anxiolytic, and antiaddictive drug, by exerting fast-acting and enduring clinical effects. Ayahuasca appears to be safe and well tolerated, nausea and emesis being the most reported and transient side effects. Some findings suggest not to use ayahuasca in bipolar or psychotic patients because of an increased risk of manic switch and/or psychotic onset. CONCLUSIONS: Further research should be carried out in randomized, double-blind, placebo-controlled trials, by implementing neuroimaging studies, in order to better evaluate therapeutic potential of ayahuasca in mental disorders.

The 'dead man walking' disorder: an update on Cotard's syndrome.

In 1880, Jules Cotard described a peculiar syndrome after observing the case of a 43-year-old woman, which was characterized by melancholic anxiety, delusions of damnation or possession, a higher propensity to suicide ideation and deliberate self-harm, analgesia, hypochondriac thoughts of non-existence or ruin of several organs, of the whole body, of the soul, of divinity, and the idea of immortality or inability to die. Several expansions and reinterpretations have been made of the so-called Cotard's syndrome, which is often encompassed in different neurological and psychiatric disorders, complicating and worsening their symptomatic frameworks and making more difficult their treatments. However, the nosographic characterization of Cotard's syndrome remains elusive and is not now classified as a separate disorder in both ICD and DSM-5. Here, we try to give an update, as well as a putative systematization, of current views and opinions about this nosological entity in the light of the recent progress in the clinic, psychopathology and psycho-neurobiology.

Alexithymia, suicide ideation, affective temperaments and homocysteine levels in drug naïve patients with post-traumatic stress disorder: an exploratory study in the everyday 'real world' clinical practice.

Objective: The present exploratory study aimed to investigate relationships between alexithymia, suicide ideation, affective temperaments and homocysteine levels among drug-naïve adult outpatients with Post-Traumatic Stress Disorder (PTSD) in an everyday 'real world' clinical setting.Method: Sixty-four adult outpatients with PTSD were evaluated using the Davidson Trauma Scale (DTS), the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI), the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego-Autoquestionnaire. As well, homocysteine levels were measured.Results: Alexithymic subjects showed higher values on all scales but not homocysteine levels. Partial correlations showed that almost all studied variables were correlated with each other, except homocysteine levels. Regression analysis showed that higher disorder severity as measured by DTS and TAS-20 'Difficulty in Identifying Feelings' dimension was associated with higher SSI scores.Conclusions: In conclusion, alexithymic PTSD outpatients may be characterised by higher disorder severity and difficulty in identifying feelings that may be linked to increased suicide ideation, regardless of affective temperaments or homocysteine levels. Homocysteine levels were not related to any studied variable. However, study limitations are discussed and must be considered. KeypointsPatients with alexithymia showed increased PTSD severity, a higher score on TEMPS-A subscales, and more severe suicide ideation.The Difficulty in Identifying Feelings (DIF) dimension of TAS-20 was associated with suicide ideation in patients with PTSD.Homocysteine did not correlate with any studied variables.This study was exploratory and cross-sectional: further larger and prospective studies are needed.

A New Rating Scale (SAVE-9) to Demonstrate the Stress and Anxiety in the Healthcare Workers During the COVID-19 Viral Epidemic.

The COVID-19 epidemic has been a major global public health problem during past months in Italy and in several other Countries and on the date of publication of this article, is still a serious public health problem. The health staff, engaged in the care of the sick and in the prevention of the spread of the infection have been subjected to a further increase in psychological difficulties and work-related stress, related to the workload for the continuous influx of sick and intense and close working shifts for the viral emergency. The SAVE-9 (Stress and Anxiety to Viral Epidemics - 9 items) scale has been developed as a tool for assessing work anxiety and stress in response to the viral epidemic of health professionals working to prevent the spread of the virus and to treat infected people.

Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors.

Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization (WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is for healthcare professionals to predict. However, recent evidence in genomic studies has pointed out the essential role that genetics could play in influencing person's suicide risk. Combining genomic and clinical risk assessment approaches, some studies have identified a number of biomarkers for suicidal ideation, which are involved in neural connectivity, neural activity, mood, as well as in immune and inflammatory response, such as the mammalian target of rapamycin (mTOR) signaling. This interesting discovery provides the neurobiological bases for the use of drugs that impact these specific signaling pathways in the treatment of suicidality, such as ketamine. Ketamine, an N-methyl-d-aspartate glutamate (NMDA) antagonist agent, has recently hit the headlines because of its rapid antidepressant and concurrent anti-suicidal action. Here we review the preclinical and clinical evidence that lay the foundations of the efficacy of ketamine in the treatment of suicidal ideation in mood disorders, thereby also approaching the essential question of the understanding of neurobiological processes of suicide and the potential therapeutics.

Effect of agomelatine treatment on C-reactive protein levels in patients with major depressive disorder: an exploratory study in "real-world," everyday clinical practice.

OBJECTIVE: Agomelatine is a newer antidepressant but, to date, no studies have been carried out investigating its effects on C-reactive protein (CRP) levels in major depressive disorder (MDD) before and after treatment. The present study aimed (i) to investigate the effects of agomelatine treatment on CRP levels in a sample of patients with MDD and (ii) to investigate if CRP variations were correlated with clinical improvement in such patients. METHODS: 30 adult outpatients (12 males, 18 females) with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of MDD were recruited in "real-world," everyday clinical practice and treated with a flexible dose of agomelatine for 12 weeks. The Hamilton Rating Scale for Depression (HAM-D) and the Snaith-Hamilton Pleasure Scale (SHAPS) were used to evaluate depressive symptoms and anhedonia, respectively. Moreover, serum CRP was measured at baseline and after 12 weeks of treatment. RESULTS: Agomelatine was effective in the treatment of MDD, with a significant reduction in HAM-D and SHAPS scores from baseline to endpoint. CRP levels were reduced in the whole sample, with remitters showing a significant difference in CRP levels after 12 weeks of agomelatine. A multivariate stepwise linear regression analysis showed that higher CRP level variation was associated with higher baseline HAM-D scores, controlling for age, gender, smoking, BMI, and agomelatine dose. CONCLUSIONS: Agomelatine's antidepressant properties were associated with a reduction in circulating CRP levels in MDD patients who achieved remission after 12 weeks of treatment. Moreover, more prominent CRP level variation was associated with more severe depressive symptoms at baseline.

The Role of Inhaled Loxapine in the Treatment of Acute Agitation in Patients with Psychiatric Disorders: A Clinical Review.

Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders. The efficacy of inhaled loxapine has been evaluated in one Phase II trial on patients with schizophrenia, and in two Phase III trials in patients with schizophrenia and bipolar disorder. Moreover, there are two published case series on patients with borderline personality disorder and dual diagnosis patients. Inhaled loxapine has proven to be effective and generally well tolerated when administered to agitated patients with schizophrenia and bipolar disorder. Two case series have suggested that inhaled loxapine may also be useful to treat agitation in patients with borderline personality disorder and with dual diagnosis, but further studies are needed to clarify this point. However, the administration of inhaled loxapine requires at least some kind of patient collaboration, and is not recommended in the treatment of severe agitation in totally uncooperative patients. Moreover, the drug-related risk of bronchospasm must always be kept in mind when planning to use inhaled loxapine, leading to a careful patient assessment prior to, and after, administration. Also, the higher costs of inhaled loxapine, when compared to oral and intramuscular medications, should be taken into account when selecting it for the treatment of agitation.

Celecoxib Adjunctive Treatment to Antipsychotics in Schizophrenia: A Review of Randomized Clinical Add-On Trials.

Schizophrenia is a severe, chronic and debilitating mental disorder. Past literature has reported various hypotheses about the psychopathology of schizophrenia. Recently, a growing literature has been trying to explain the role of inflammation in the etiopathogenesis of schizophrenia. In the past, numerous immune modulation and anti-inflammatory treatment options have been proposed for schizophrenia, but sometimes the results were inconsistent. Electronic search was carried out in November 2015. PubMed and Scopus databases have been used to find studies to introduce in this review. Only randomized-placebo-controlled add-on trials were taken into account. In this way, six articles were obtained for the discussion. Celecoxib showed beneficial effects mostly in early stages of schizophrenia. In chronic schizophrenia, the data are controversial, possibly in part for methodological reasons.

BDNF serum levels in subjects developing or not post-traumatic stress disorder after trauma exposure.

Post-traumatic stress disorder (PTSD) is a syndrome resulting from exposure to a severe traumatic event that poses threatened death or injury and produces intense fear and helplessness. The neural structures implicated in PTSD development belong to the limbic system, an important region for emotional processing. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that serves as survival factor for selected populations of central nervous system (CNS) neurons and plays a role in the limbic system by regulating synaptic plasticity, memory processes and behavior. Impaired BDNF production in the brain can lead to a variety of CNS dysfunctions including symptoms associated with PTSD. However, so far fewer studies have investigated this neurotrophin in patients with PTSD. Furthermore, given the multiple role of BDNF in various CNS disorders, it cannot be excluded that traumatic events per se may influence neurotrophin levels, without a direct association to the PTSD syndrome. To elucidate these issues, in this study we analyzed BDNF serum levels in two groups of subjects: patients with trauma exposure who developed PTSD, and subjects with trauma exposure who did not develop PTSD. We found that BDNF serum levels were lower in PTSD patients as compared to related control subjects. Thus, these data suggest that BDNF might be involved in pathophysiology of PTSD and consequently therapeutic approaches aimed at restoring BDNF serum levels may be beneficial to this pathology.

Aberrant salience in cannabis-induced psychosis: a comparative study.

Background: Natural Cannabis (NC) and Synthetic Cannabinoids (SCs) use can increase the risk and exacerbate the course of psychotic disorders. These could be influenced by the Aberrant Salience (AS) construct. It refers to an excess of attribution of meaning to stimuli that are otherwise regarded as neutral, thereby transform them into adverse, dangerous, or mysterious entities. This leads the patient to engage in aberrant and consequently incorrect interpretative efforts concerning the normal perception of reality and its relationship with our analytical abilities. AS appears to play a significant role in the onset and perpetuation of psychotic disorders. The internal conflict arising from aberrant attributions of significance leads to delusional thoughts, ultimately culminating in the establishment of a self-sustaining psychosis. Aims: To examine the differences between psychoses course not associated with cannabis use and those associated with NC-use and SCs-use, in terms of psychotic and dissociative symptoms, AS, global functioning and suicidal ideation. Methods: A sample of 62 patients with First Episode Psychosis (FEP) was divided into 3 groups: non cannabis users (non-users, N = 20); NC-users or rather Delta-9-tetrahydrocannabinol (THC) users (THC-users, N = 21); SCs-users, commonly referred to as SPICE-users (SPICE-users, N = 20). Each group underwent assessments at the onset of psychotic symptoms, as well as at the 3 months and 6 months marks, utilizing a range of psychopathological scales. These included the Positive and Negative Syndrome Scale (PANSS) for investigating psychotic symptoms, the Global Assessment of Functioning (GAF) scale for assessing overall functioning, the Dissociative Experiences Scale (DES-II) for measuring dissociative symptoms, the Scale for Suicide Ideation (SSI) for evaluating suicidal ideation and the Aberrant Salience Inventory (ASI) scale for gauging AS. Results: SPICE-users showed more severe and persistent positive symptoms, while negative symptoms were mostly represented among non-users. Non-users showed better recovery than SPICE-users in global functioning. All groups showed a decrease in both ASI scores and subscale scores. SPICE-users exhibited higher global AS scores and less improvement in this aspect compared to other groups. Conclusion: This study may help understanding the role of AS in both non-substance-related and substance-induced psychosis. This knowledge may lead clinician to a better diagnosis and identify patient-tailored psychopharmacological treatment.

Relationship between Health-Anxiety and Cyberchondria: Role of Metacognitive Beliefs.

PURPOSE: The current study was designed to examine the relationship between health anxiety, cyberchondria (its constructs), and metacognitive beliefs. In addition, it also evaluated the moderating role of metacognitive beliefs in this relationship. DESIGN AND METHOD: The present study used the purposive sampling technique to acquire a sample of (N = 500) adults, among them (N = 256) women and (N = 244) men, and the age of the sample ranged from 20 to 50 years. Short Health Anxiety Inventory, Cyberchondria Severity Scale, and Metacognitions Questionnaire-Health Anxiety were used to operationalize the present study variables. FINDINGS: The descriptive statistics revealed that all instruments have good psychometric properties, as Cronbach's alpha coefficients for all scales are ≥0.70. In addition to this, the Pearson correlation showed that all variables of the present study have a significant positive correlation with each other. Furthermore, the regression analysis described that health anxiety and metacognitive beliefs (biased thinking and beliefs about uncontrollable thoughts) were the significant positive predictors of cyberchondria. Moreover, moderation analysis showed that metacognitive beliefs significantly strengthened the association between health anxiety and cyberchondria and its constructs. PRACTICAL IMPLICATIONS: The present study will help medical practitioners to understand how metacognitive beliefs and health anxiety can cause an increase in cyberchondria. This will help them to design better treatment plans for people with cyberchondria.

Trazodone Add-on in COVID-19-related Selective Serotonin Reuptake Inhibitor-resistant Post-traumatic Stress Disorder in Healthcare Workers: Two Case Reports.

COVID-19 represents a significant stress factor for all people worldwide due to several factors, including quarantine, lockdowns, fear of contagion, deaths, and other traumatic events. However, the healthcare workers (HCWs) have paid the higher price of this pandemic in terms of fatalities, contagions, and psychological well-being. Studies suggest that this particular population is at increased risk of developing a severe post-traumatic stress disorder (PTSD). The early diagnosis and timely treatment of PTSD in HCWs may restore well-being and significantly impact health services functioning, reducing burnout, days spent far from work, disrupted personal and team empowerment, and worse job performances. In the present article, we reported on two cases of HCWs directly involved in the treatment of COVID-19 patients who showed selective serotonin reuptake inhibitor-resistant PTSD, which was successfully treated with extended-release trazodone TRZ ContramidⓇ add-on.

Cariprazine Add-on in Inadequate Clozapine Response: A Report on Two Cases.

Cariprazine is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to the D3 receptor, antagonism of 5HT2B receptors, and partial agonism of 5HT1A. Currently, cariprazine has shown clinical efficacy in patients with schizophrenia and with bipolar disorder, as well as adjunctive treatment in patients with Major Depressive Disorder (MDD) and drug-resistant MDD. In the present case series, we report on two patients with treatment-resistant schizophrenia and partial response to clozapine who benefit from combination with cariprazine. The effects of cariprazine combination were remarkable also concerning the adverse metabolic effects of clozapine.