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ABSTRACTIntroductionThe coronavirus (COVID-19) pandemic has led to as well as exacerbated mental health disorders, leading to increased use of psychotropic medications. Co-administration of COVID-19 and psychotropic medications may result in drug-drug interactions (DDIs), that may compromise both the safety and efficacy of both medications.Areas coveredThis review provides an update of the current evidence on DDIs between COVID-19 and psychotropic medications. The interactions are categorized into pharmacokinetic, pharmacodynamic, and other relevant types. A thorough literature search was conducted using electronic databases to identify relevant studies, and extract data to highlight potential DDIs, clinical implications, and management strategies.Expert opinionUnderstanding and managing potential DDIs between COVID-19 and psychotropic medications is paramount to ensuring safe and effective treatment of patients with COVID-19 and mental illness. Awareness of the diverse spectrum of DDIs, vigilant monitoring, and judicious dose modifications, while choosing pharmacotherapeutic options with low risk of interaction whenever possible, are necessary. Ongoing and future investigations should continue to review the dynamic landscape of COVID-19 therapeutic modalities and their interactions with psychotropic medications.

Background: People who reach old age enjoying good physical and mental health can be defined as (health) “superheroes”, given their relatively low impact on healthcare expenditure and the desirable model they represent. Aim: To evaluate prevalence and possible determinants of being “physical superheroes” (i.e., free from the ten major chronic conditions, plus obesity), “mental superheroes” (i.e., free from major mental symptoms), and “superheroes” (i.e., both mental and physical superheroes). Methods: A telephone-based cross-sectional study (LOST in Lombardia) was conducted in November 2020 (i.e., during the COVID-19 pandemic) on a representative sample of 4,400 adults aged ≥ 65 years from Lombardy region, northern Italy. All participants provided both current data and data referring to one year before. Results: Mental and physical superheroes were 59.0% and 17.6%, respectively. Superheroes were 12.8% overall, 15.1% among men, and 11.1% among women; 20.2% among individuals aged 65–69 years, 11.3% among 70–74, 10.0% among 75–79, and 8.3% among ≥ 80 years. Multivariable analysis showed that female sex, higher age, disadvantaged socio-economic status, and physical inactivity (pfor trend < 0.001) were inversely related to being superheroes. People not smoking (adjusted odds ratio, aOR = 1.40), alcohol abstainers (aOR = 1.30), and those free from feelings of hopelessness (aOR = 5.92) more frequently met the definition of superheroes. During COVID-19 pandemic, the proportion of superheroes decreased by 16.3%. Conclusions: Differences in the older adults’ health status are largely attributable to their lifestyles but are also likely due to gender, educational, and socio-economic disparities, which should be properly addressed by public health policies.

Cognitive-behavioral therapy (CBT) is a form of psychological treatment that is based on the underlying assumption that mental disorders and psychological distress are maintained by cognitive factors, that is, that general beliefs about the world, the self, and the future contribute to the maintenance of emotional distress and behavioral problems. The overall goal of CBT is to replace dysfunctional constructs with more flexible and adaptive cognitions. The most relevant cognitive-behavioral techniques in clinical practice are: i. Cognitive Restructuring(also known as the ABCDE method) is indicated to support patients dealing with negative beliefs or thoughts. The different steps in the cognitive restructuring process are summarized by the letters in the ABCDE acronym that describe the different stages of this coaching model: Activating event or situation associated with the negative thoughts, Beliefs and belief structures held by the individual that explain how they perceive the world which can facilitate negative thoughts, Consequences or feelings related to the activating event, Disputation of beliefs to allow individuals to challenge their belief system, and Effective new approach or effort to deal with the problem by facilitating individuals to replace unhelpful beliefs with more helpful ones. ii. Problem-Solving(also known as SOLVE) to raise awareness for specific triggers, and evaluate and choose more effective options. Each letter of the SOLVE acronym identifies different steps of the problem-solving process: Select a problem, generate Options, rate the Likely outcome of each option, choose the Very best option, and Evaluate how well each option worked. For example, a suicide attempt is reconceptualized as a failure in problem-solving. This treatment approach attempts to provide patients with a better sense of control over future emerging problems. iii. Re-attributionis a technique that enables patients to replace negative self-statements (eg, “it is all my fault”) with different statements where responsibility is attributed more appropriately. Furthermore, decatastrophizing may help subjects, especially adolescents decide whether they may be overestimating the catastrophic nature of the precipitating event, and by allowing them to scale the event severity they learn to evaluate situations along a continuum rather than seeing them in black and white. iv. Affect Regulationtechniques are often used with suicidal adolescents to teach them how to recognize stimuli that provoke negative emotions and how to mitigate the resulting emotional arousal through self-talk and relaxation.

Depression and suicidal behavior are 2 complex psychiatric conditions of significant public health concerns due to their debilitating nature. The need to enhance contemporary treatments and preventative approaches for these illnesses not only calls for distillation of current views on their pathogenesis but also provides an impetus for further elucidation of their novel etiological determinants. In this regard, inflammation has recently been recognized as a potentially important contributor to the development of depression and suicidal behavior. This review highlights key evidence that supports the presence of dysregulated neurometabolic and immunologic signaling and abnormal interaction with microbial species as putative etiological hallmarks of inflammation in depression as well as their contribution to the development of suicidal behavior. Furthermore, therapeutic insights addressing candidate mechanisms of pathological inflammation in these disorders are proposed.

AbstractBackgroundHighlighting the relationship between obsessive–compulsive disorder (OCD) and tic disorder (TD), two highly disabling, comorbid, and difficult-to-treat conditions, Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) acknowledged a new “tic-related” specifier for OCD, ie, obsessive–compulsive tic-related disorder (OCTD). As patients with OCTD may frequently show poor treatment response, the aim of this multicenter study was to investigate rates and clinical correlates of response, remission, and treatment resistance in a large multicenter sample of OCD patients with versus without tics.MethodsA sample of 398 patients with a DSM-5 diagnosis of OCD with and without comorbid TD was assessed from 10 different psychiatric departments across Italy. For the purpose of the study, treatment response profiles in the whole sample were analyzed comparing the rates of response, remission, and treatment-resistance as well as related clinical features. Multivariate logistic regressions were performed to identify possible factors associated with treatment response.ResultsThe remission group was associated with later ages of onset of TD and OCD. Moreover, significantly higher rates of psychiatric comorbidities, TD, and lifetime suicidal ideation and attempts emerged in the treatment-resistant group, with larger degrees of perceived worsened quality of life and family involvement.ConclusionsAlthough remission was associated with later ages of OCD and TD onset, specific clinical factors, such as early onset and presence of psychiatric comorbidities and concomitant TD, predicted a worse treatment response with a significant impairment in quality of life for both patients and their caregivers, suggesting a worse profile of treatment response for patients with OCTD.

Purpose: Anorexia nervosa (AN) is a serious and complex mental disorder affecting mainly young adult women. AN patients are characterized by low body weight in combination with self-induced starvation, intense fear of gaining weight, and distortion of body image. AN is a multifactorial disease, linked by recent evidence to a dysregulation of the immune system. Methods: In this pilot study, 22 blood serums from AN patients were tested for the presence of autoantibodies against primate hypothalamic periventricular neurons by immunofluorescence and by a home-made ELISA assay. Cellular fluorescence suggests the presence of autoantibodies which are able to recognize these neurons (both to body cell and fiber levels). By means of ELISA, these autoantibodies are quantitatively evaluated. In addition, orexigenic and anorexigenic molecules were measured by ELISA. As control, 18 blood serums from healthy age matched woman were analysed. Results: All AN patients showed a reactivity against hypothalamic neurons both by immunofluorescence and ELISA. In addition, ghrelin, pro-opiomelanocortin (POMC), and agouti-related peptide (AGRP) were significantly higher than in control serums (p< 0.0001). In contrast, leptin was significantly lower in AN patients than controls (p< 0.0001). Conclusions: Immunoreaction and ELISA assays on AN blood serum suggest the presence of autoantibodies AN related. However, it is not easy to determine the action of these antibodies in vivo: they could interact with specific ligands expressed by hypothalamic cells preventing their physiological role, however, it is also possible that they could induce an aspecific stimulation in the target cells leading to an increased secretion of anorexigenic molecules. Further studies are needed to fully understand the involvement of the immune system in AN pathogenesis. Level of evidence: V, descriptive study.

ObjectivesItaly is one of the first countries that imposed a nationwide stay-at-home order during the COVID-19 outbreak, inevitably resulting in changes in lifestyles and addictive behaviours. The aim of this work is to investigate the impact of lockdown restrictions on smoking habits using data collected within the Lost in Italy project.MethodsA web-based cross-sectional study was conducted on a representative sample of 6003 Italian adults aged 18–74 years. Study subjects were recruited from 27 April to 3 May 2020 and were asked to report changes in smoking habits before the lockdown and at the time of interview.ResultsDuring the lockdown, 5.5% of the overall sample quit or reduced smoking, but 9.0% of the sample started, relapsed smoking or increased their smoking intensity. In total, the lockdown increased cigarette consumption by 9.1%. An improvement in smoking habits was associated with younger age, occasional smoking and unemployment, whereas a worsening was mainly associated with mental distress. In particular, an increase in cigarette consumption during lockdown was more frequently reported among those with worsening quality of life (OR: 2.05; 95% CI: 1.49 to 2.80), reduction in sleep quantity (OR: 2.29; 95% CI: 1.71 to 3.07) and increased anxiety (OR: 1.83; 95% CI: 1.38 to 2.43) and depressive symptoms (OR: 2.04; 95% CI: 1.54 to 2.71).ConclusionsCOVID-19 lockdown had a huge impact on smoking consumption of the Italian general population. The main concern is for smokers who increase their cigarette consumption due to an increased mental distress. Providing greater resources for cessation services capable of reducing mental health symptoms in smokers is urgently needed.

Lurasidone is a novel azapirone derivative and atypical antipsychotic agent with a high binding affinity for dopaminergic (D2), serotoninergic (5-HT2A), and 5-HT7 receptors (antagonist), a moderate affinity for 5- HT1A receptors (partial agonist), and no appreciable affinity for histaminergic (H1) and muscarinic (M1) receptors. It was recently included by the European Medication Agency among the in-label pharmacological treatments for children and adolescents affected by early onset schizophrenia. As a dopamine and serotonin antagonist, lurasidone acted on a variety of receptors and showed its efficacy both as an antipsychotic and an activating compound. Administered with food or within 30 minutes from a meal, it presents sufficient bioavailability and does not interact with most of the other drugs during metabolism. With little effects on hormones and weight gain, potential procognitive profile due to its 5-HT7 antagonism, and reduced extrapyramidal side effects, lurasidone could be a good choice in terms of both effectiveness and tolerability, particularly for patients headed towards a long-term treatment. This article aims to summarize the available scientific evidence from the literature on the use of lurasidone in children and adolescents and to provide recommendations for clinical management and future research.

AbstractBackgroundObsessive-compulsive disorder (OCD) and tic disorder (TD) represent highly disabling, chronic and often comorbid psychiatric conditions. While recent studies showed a high risk of suicide for patients with OCD, little is known about those patients with comorbid TD (OCTD). Aim of this study was to characterize suicidal behaviors among patients with OCD and OCTD.MethodsThree hundred and thirteen outpatients with OCD (n = 157) and OCTD (n = 156) were recruited from nine different psychiatric Italian departments and assessed using an ad-hoc developed questionnaire investigating, among other domains, suicide attempt (SA) and ideation (SI). The sample was divided into four subgroups: OCD with SA (OCD-SA), OCD without SA (OCD-noSA), OCTD with SA (OCTD-SA), and OCTD without SA (OCTD-noSA).ResultsNo differences between groups were found in terms of SI, while SA rates were significantly higher in patients with OCTD compared to patients with OCD. OCTD-SA group showed a significant male prevalence and higher unemployment rates compared to OCD-SA and OCD-noSA sample. Both OCTD-groups showed an earlier age of psychiatric comorbidity onset (other than TD) compared to the OCD-SA sample. Moreover, patients with OCTD-SA showed higher rates of other psychiatric comorbidities and positive psychiatric family history compared to the OCD-SA group and to the OCD-noSA groups. OCTD-SA and OCD-SA samples showed higher rates of antipsychotics therapies and treatment resistance compared to OCD-noSA groups.ConclusionsPatients with OCTD vs with OCD showed a significantly higher rate of SA with no differences in SI. In particular, OCTD-SA group showed different unfavorable epidemiological and clinical features which need to be confirmed in future prospective studies.

Transient receptor potential vanilloid 1 (TRPV1) is a polymodal cation channel gated by a large array of chemical and physical stimuli and distributed across different brain regions on neuronal and glial cells. Preclinical studies indicate that TRPV1 might be a target for the treatment of anxiety, depression and addictive disorders. The aim of this narrative review is to focus on studies examining the effects of TRPV1 antagonism on neuroinflammation, neuroprotection and epigenetic regulation. Results suggest that TRPV1 modulation leads to pro- or anti-inflammatory effects depending on the cytokine environment and that the TRPV1 antagonism can switch the microglia towards an anti-inflammatory phenotype. Moreover, TRPV1 inhibitors have neuroprotective properties through the regulation of calcium levels. Finally, TRPV1 antagonism exerts regulatory effects on genes involved in synaptic and cognitive functions through histone deacetylase 2 inhibition. These findings highlight different mechanisms that may underlie the efficacy of TRPV1 antagonists in animal models of severe psychiatric disorders.

Major affective disorder are common and disabling conditions linked to significant psychosocial impairment as well as negative outcome (e.g., suicidal behaviors) . According to a molecular perspective, major depressive disorder and suicidal behavior have been associated with structural and synaptic plasticity disturbances. Small non-coding RNAs, such as microRNAs (miRNAs), may play a significant role in the translational regulation of the synapse. This comprehensive overview is aimed to carefully review the preclinical and clinical literature results regarding the involvement of miRNAs in the pathophysiology and pharmacotherapy of major psychiatric conditions . MiRNAs may act as gene expression regulators critically affecting brain development. The alteration of some intracellular mechanisms together with impaired assembly, localization, and translational regulation of specific RNA binding proteins may affect important functions such as learning and memory contributing to the pathophysiology of major depressive disorder and suicidal behavior. Based on the main findings, most of the miRNAs which have been identified to date are expressed in human brain, where they regulate prominent neurobiological processes, such as neurogenesis and neuroplasticity. The main implications of the present findings are critically discussed.