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The Endocannabinoid System (ECBs) may have a crucial role in bipolar disorder (BD). Previous reports have not detected abnormalities in the expression of the cannabinoid receptor gene CNR1, encoding for CBWe recruited 44 subjects with BD type I (BD-I), in mania (n = 22) and depression (n = 22) and 25 Healthy Controls (HC). CNR1 gene expression was analyzed using a quantitative real-time polymerase chain reaction from peripheral blood mononuclear cells. Data were analyzed using frequentist non-parametric and Bayesian approaches (generalized location-scale model based on lognormal and gamma distributions).Using the frequentist non-parametric approach, the depression group had lower CNR1 expression compared to the mania group (p = 0.004). In addition, there was a negative correlation between CNR1 expression and Hamilton Depression Scale score (rho = -0.37; p = 0.007). Bayesian analyses further revealed that CNR1 expression in the mania group was higher and less variable than among HC (95% probability), while CNR1 expression in the depression group was lower and more variable than among HC (100% probability).Lack of participants with bipolar disorder in the euthymic phase, lack of toxicology screening and evaluation of CNR1 variants.CNR1 expression is higher and less variable in mania than in depression. It is highly probable that these differences also distinguish individuals in different illness phases from healthy controls. Future studies are needed to clarify the role of the endocannabinoid system in bipolar disorder.

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, regulating metabolic homeostasis as well as leptin and ghrelin, and it could be considered as a potential plasmatic marker. The aim of this study was to assess whether circulating SIRT1 varies consistently with leptin, ghrelin, body mass index (BMI), and IgG reactive to hypothalamic antigens in anorexia nervosa (AN). Fifty-four subjects were evaluated: 32 with AN and 22 normal-weight control subjects. Serum levels of SIRT1, leptin, ghrelin, and IgG reactive to hypothalamic antigens were evaluated by ELISA. Results showed that serum SIRT1 is increased in patients with AN, and the amount is decreased in relation to the duration of the illness. SIRT1 concentration approaches the values obtained for the control group, although the difference is still statistically significant. A negative correlation between serum SIRT1 values and leptin or BMI values has been found. On the contrary, a positive correlation between SIRT1 and ghrelin or IgG specific for hypothalamic antigens is reported. These findings suggest that a peripheral evaluation of SIRT1 could be a possible clinical/biochemical parameter related to AN. In addition, we can assume that SIRT1 is related to autoantibody production and may correlate with the intensity/severity of AN. Thus, reducing the production of autoantibodies specific for hypothalamic cells could be a sign of improvement of the clinical condition.

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 p 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.

Background: Physical symptoms play an important role in late-life depression and may contribute to residual symptomatology after antidepressant treatment. In this exploratory study, we examined the role of specific bodily dimensions including movement, respiratory functions, fear of falling, cognition, and physical weakness in older people with depression.Methods: Clinically stable older patients with major depression within a Psychiatric Consultation-Liaison program for Primary Care underwent comprehensive assessment of depressive symptoms, instrumental movement analysis, dyspnea, weakness, activity limitations, cognitive function, and fear of falling. Network analysis was performed to explore the unique adjusted associations between clinical dimensions.Results: Sadness was associated with worse turning and walking ability and movement transitions from walking to sitting, as well as with worse general cognitive abilities. Sadness was also connected with dyspnea, while neurovegetative depressive burden was connected with activity limitations.Discussion: Limitations of motor and cognitive function, dyspnea, and weakness may contribute to the persistence of residual symptoms of late-life depression.

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.

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-attribution is 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 Regulation techniques 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.

Background: Despite several attempts, the etiopathogenesis of anorexia nervosa (AN) is still unknown. However, the activation of the immune response in neuropsychiatric diseases, including AN, is increasingly evident. We aimed to explore immune response parameters in patients with AN and identify the link between the presence of specific autoantibodies for hypothalamic antigens and the inflammatory response. The relationship between inflammatory markers and the duration of the disease has been also investigated. Methods: Twenty-two patients with AN were included, and none were under psychopharmacological treatment or suffering from autoimmune conditions. Serum concentrations of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and IL-21 were determined by ELISA kits. In addition, autoantibodies against hypothalamic antigens are quantitatively evaluated. Results: IL-6, IL-1 β, TNF-α, and TGF-β are significantly increased in patients with AN. A positive correlation with body mass index and with the amount of autoantibody specific for hypothalamic antigens exists. Notably, a progressive reduction of cytokines correlates with the progression of AN. In addition, IL-21 is increased in the blood of patients with AN and negatively correlates with autoantibody concentrations. Conclusions: This study shows that the increased pro-inflammatory phenotype in patients affected by AN correlates with the concentration of autoantibody specific for hypothalamic antigens. Of interest, the pro-inflammatory state seems to be reduced with duration of AN. In addition, IL-21 could work as a stimulant of the immune response, thus possibly increasing the autoreactivity.

Background: The ability to process sensory information is an essential adaptive function, and hyper- or hypo-sensitive maladaptive profiles of repones to environmental stimuli generate sensory processing disorders linked to cognitive, affective, and behavioural alterations. The research on neuroradiological correlates of the sensory processing profiles is still in its infancy and is mainly limited to the young-age population or neurodevelopmental disorders. So, the knowledge concerning the impact of the different sensory profiles on the structural and functional characteristics of the typically developed adult brain remains largely obscure. In this framework, this study aims to examine the structural and functional MRI correlates of sensory profiles in a sample of healthy adults. Method: We investigated structural T1, Diffusion Tensor Imaging (DTI), and resting-state functional MRI (rs-fMRI) correlates of Adolescent/Adult Sensory Profile (AASP) questionnaire subscales in 57 typical developing subjects (34 females; mean age: 32.7±9.3). Results: Only the AASP sensation seeking subscale provided significant results. Positive and negative correlations emerged with FA and RD in arcuate fasciculus (AF), anterior thalamic radiation (ATR), optic radiation (OR), superior longitudinal fasciculus (SLF), corpus callosum (CC), and the dorsal part of the cingulum bundle (dCB). In addition, we found a positive correlation between sensation seeking and grey matter volume in the parahippocampal cortex (PHC), precentral gyrus (PG), inferior temporal gyrus (IFG) and cuneus regions, and with cortical thickness in the IFG and postcentral gyrus (PCG). We did not find any correlation between rs-fMRI parameters and AASP subscales. Conclusion: Overall, our results suggest a positive correlation between sensation seeking and higher structural integrity in critical regions mainly involved in visuospatial and decision-making processing. We speculate that the better structural integrity associated with sensation seeking might at least partially reflect a possible neurobiological substrate of this sensory profile, characterized by active research of sensory stimuli and impulsive decision-making tendency. Further studies are needed to investigate the neuroradiological correlates of sensory profiles and their impact on behaviour, cognition, and affectivity in different developmental stages and psychiatric disorders.

Neurological diseases expose individuals to a higher risk of suicidal ideation and suicidal behavior, including completed suicides and suicide attempts. They also represent a paradigmatic arena to study the etiopathogenic mechanisms underlying suicidality because they are emblematic of the heterogeneity and complexity of mutual interrelationships characterizing this issue. On the one hand, neurological diseases imply strictly biological impairments that are postulated to be the basis of vulnerability to suicide or result in the need for treatments for which a suicidal risk has been hypothesized. On the other hand, they question some subjective experiences of neurological patients, up to near existential positions. Often, in fact, they are accompanied by severe hopelessness. The latter may originate in, particularly for the most severe neurological diseases, the absence of curative treatments, unpredictable disease progression that leads to acute relapses or chronicity, a decrease in autonomy or selfidentity, progressive social isolation, a sense of becoming useless, and perception of feeling stigmatized. This may ultimately cause a slip into experiencing an absurd condition. At the confluence of neurobiology and hopelessness, frequent psychiatric comorbidities may play a primary role. To conclude, neurological patients require special attention from clinicians in form of openly verbalizing and exploring the suicidal thematic, inquiring about protective and risk factors, and promptly initiating both a psychopharmacological treatment and, where possible, psychological support.

IntroductionLanguage is usually considered the social vehicle of thought in intersubjective communications. However, the relationship between language and high-order cognition seems to evade this canonical and unidirectional description (ie, the notion of language as a simple means of thought communication). In recent years, clinical high at-risk mental state (CHARMS) criteria (evolved from the Ultra-High-Risk paradigm) and the introduction of the Clinical Staging system have been proposed to address the dynamicity of early psychopathology. At the same time, natural language processing (NLP) techniques have greatly evolved and have been successfully applied to investigate different neuropsychiatric conditions. The combination of at-risk mental state paradigm, clinical staging system and automated NLP methods, the latter applied on spoken language transcripts, could represent a useful and convenient approach to the problem of early psychopathological distress within a transdiagnostic risk paradigm.Methods and analysisHelp-seeking young people presenting psychological distress (CHARMS+/− and Clinical Stage 1a or 1b; target sample size for both groups n=90) will be assessed through several psychometric tools and multiple speech analyses during an observational period of 1-year, in the context of an Italian multicentric study. Subjects will be enrolled in different contexts: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa—IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Mental Health Department—territorial mental services (ASL 3—Genoa), Genoa, Italy; and Mental Health Department—territorial mental services (AUSL—Piacenza), Piacenza, Italy. The conversion rate to full-blown psychopathology (CS 2) will be evaluated over 2 years of clinical observation, to further confirm the predictive and discriminative value of CHARMS criteria and to verify the possibility of enriching them with several linguistic features, derived from a fine-grained automated linguistic analysis of speech.Ethics and disseminationThe methodology described in this study adheres to ethical principles as formulated in the Declaration of Helsinki and is compatible with International Conference on Harmonization (ICH)-good clinical practice. The research protocol was reviewed and approved by two different ethics committees (CER Liguria approval code: 591/2020—id.10993; Comitato Etico dell’Area Vasta Emilia Nord approval code: 2022/0071963). Participants will provide their written informed consent prior to study enrolment and parental consent will be needed in the case of participants aged less than 18 years old. Experimental results will be carefully shared through publication in peer-reviewed journals, to ensure proper data reproducibility.Trial registration numberDOI:10.17605/OSF.IO/BQZTN.

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.

The SARS-CoV-2 pandemic has led significant social repercussions and forced people to wear face masks. Recent research has demonstrated that the human ability to infer emotions from facial configurations is significantly reduced when face masks are worn. Since the mouth region is specifically crucial for deaf people who speak sign language, the current study assessed the impact of face masks on inferring emotional facial expressions in a population of adult deaf signers. A group of 34 congenitally deaf individuals and 34 normal-hearing individuals were asked to identify happiness, sadness, fear, anger, and neutral expression on static human pictures with and without facial masks presented through smartphones. For each emotion, the percentage of correct responses with and without face masks was calculated and compared between groups. Results indicated that face masks, such as those worn due to the SARS-CoV-2 pandemic, limit the ability of people to infer emotions from facial expressions. The negative impact of face masks is significantly pronounced when deaf people have to recognize low-intensity expressions of happiness. These findings are of essential importance because difficulties in recognizing emotions from facial expressions due to mask wearing may contribute to the communication challenges experienced by the deaf community during the SARS-CoV-2 pandemic, generating feelings of frustration and exclusion.

It has been widely demonstrated that time processing is altered in patients with schizophrenia. This perspective review delves into such temporal deficit and highlights its link to low-level sensory alterations, which are often overlooked in rehabilitation protocols for psychosis. However, if temporal impairment at the sensory level is inherent to the disease, new interventions should focus on this dimension. Beyond more traditional types of intervention, here we review the most recent digital technologies for rehabilitation and the most promising ones for sensory training. The overall aim is to synthesise existing literature on time in schizophrenia linking psychopathology, psychophysics, and technology to help future developments.

Alterations in brain intrinsic activity-as organized in resting-state networks (RSNs) such as sensorimotor network (SMN), salience network (SN), and default-mode network (DMN)-and in neurotransmitters signaling-such as dopamine (DA) and serotonin (5-HT)-have been independently detected in psychiatric disorders like bipolar disorder and schizophrenia. Thus, the aim of this work was to investigate the relationship between such neurotransmitters and RSNs in healthy, by reviewing the relevant work on this topic and performing complementary analyses, in order to better understand their physiological link, as well as their alterations in psychiatric disorders. According to the reviewed data, neurotransmitters nuclei diffusively project to subcortical and cortical regions of RSNs. In particular, the dopaminergic substantia nigra (SNc)-related nigrostriatal pathway is structurally and functionally connected with core regions of the SMN, whereas the ventral tegmental area (VTA)-related mesocorticolimbic pathway with core regions of the SN. The serotonergic raphe nuclei (RNi) connections involve regions of the SMN and DMN. Coherently, changes in neurotransmitters activity impact the functional configuration and level of activity of RSNs, as measured by functional connectivity (FC) and amplitude of low-frequency fluctuations/temporal variability of BOLD signal. Specifically, DA signaling is associated with increase in FC and activity in the SMN (hypothetically via the SNc-related nigrostriatal pathway) and SN (hypothetically via the VTA-related mesocorticolimbic pathway), as well as concurrent decrease in FC and activity in the DMN. By contrast, 5-HT signaling (via the RNi-related pathways) is associated with decrease in SMN activity along with increase in DMN activity. Complementally, our empirical data showed a positive correlation between SNc-related FC and SMN activity, whereas a negative correlation between RNi-related FC and SMN activity (along with tilting of networks balance toward the DMN). According to these data, we hypothesize that the activity of neurotransmitter-related neurons synchronize the low-frequency oscillations within different RSNs regions, thus affecting the baseline level of RSNs activity and their balancing. In our model, DA signaling favors the predominance of SMN-SN activity, whereas 5-HT signaling favors the predominance of DMN activity, manifesting in distinct behavioral patterns. In turn, alterations in neurotransmitters signaling (or its disconnection) may favor a correspondent functional reorganization of RSNs, manifesting in distinct psychopathological states. The here suggested model carries important implications for psychiatric disorders, providing novel and well testable hypotheses especially on bipolar disorder and schizophrenia.

Despite the well-recognized effects of endogenous opioids on mood and behavior, research on its role in bipolar disorder (BD) is still limited to small or anecdotal reports. Considering that Beta-endorphins (β-END) and Mu-opioid receptors (MOR), in particular, have a crucial activity in affective modulation, we hypothesized their alteration in BD. A cross-sectional study was conducted. We compared: (1) BD type I (BD-I) patients (n = 50) vs healthy controls (n = 27), (2) two BD-I subject subgroups: manic (MAN; n = 25) vs depressed (DEP; n = 25) subjects. Plasma levels of β-END and MOR gene expression in peripheral blood mononuclear cells were analyzed using ELISA Immunoassay qRT-PCR. We found that subjects with BD exhibited a significant upregulation of MOR gene expression and a decrease of β-END (p0.0001 for both). MAN display higher MOR levels than DEP (p0.001) and HC (p0.0001). Plasma levels of β-END were lower in DEP compared to MAN (p0.05) and HC (p0.0001). The main limitations are the cross-sectional design and the lack of a group of euthymic subjects. Although preliminary, our results suggest a dysregulation of the endogenous opioid systems in BD. In particular, both MAN and DEP showed a reduction of β-END levels, whereas MAN was associated with MOR gene overexpression.

Background The increasing availability of high-potency cannabis-derived compounds and the use of synthetic cannabinoids may be responsible for severe side effects like cognitive impairment, psychosis or self-injurious behaviours (SIB). In particular, SIB like non-suicidal self-injury (NSSI) and deliberate self-harm (DSH) raise growing concern as a possible consequence of cannabis use. However, the research to date has not addressed the relationship between cannabinoid use and SIB systematically. Methods We conducted a systematic review on PubMed up to March 2020, using search terms related to cannabinoids and SIB. Results The search yielded a total of 440 abstracts. Of those, 37 studies published between 1995 and 2020 were eligible for inclusion. Cannabinoid use was significantly associated with SIB at the cross-sectional (OR=1.569, 95%CI [1.167–2.108]) and longitudinal (OR=2.569, 95%CI [2.207–3.256]) level. Chronic use, presence of mental disorders, depressive symptoms, emotional dysregulation and impulsive traits might further increase the likelihood of self-harm in cannabis users. Synthetic cannabinoids may trigger highly destructive SIB mainly through the psychotomimetic properties of these compounds. Conclusion Cannabinoid use was associated with an increased prevalence of self-injury and may act as a causative factor with a duration-dependent manner. Emotional regulation and behavioural impulsivity functions might crucially moderate this association. Future studies should further investigate the mechanisms underlying this association, while exploring potential therapeutic applications of substances modulating the endocannabinoid system.

In the last two decades the awareness of depression as a public health issue has increased and the literature has flourished towards its primary and secondary prevention. Whereas timely targeting of depression risk factors is a frontier towards reducing the incidence of the disorder, nowadays the early diagnosis is of primary importance. Screening depressive disorders is paramount, since there are several types of depression. Besides, early diagnosis would improve the outcome of treatment, reduce the frequency of relapses and generally lead to higher levels of quality of life. We highlight the feasibility of depression screening in primary care and the need of a comprehensive public health approach. (www.actabiomedica.it)

Abstract. Background: Climate factors may offer a stronger explanation of the variations in suicide rates compared with economic variables, even in the case of patients admitted involuntarily. Aims: We assessed the role of temperature as a determinant of the increased prevalence of suicide attempts (SA). Method: The sample comprised all cases of hospitalization for SA at the Psychiatric Clinic of the IRCCS Ospedale Policlinico San Martino between August 2013 and July 2018. For ambient temperature, data were provided by the Meteorological Observatory of the University of Genoa. Results: We noted a peak in suicides that was typically found in late spring and early summer due to global warming. Limitations: Other environmental/psychological factors contributing to the onset of an acute clinical event were not considered. The cross-sectional design of the study is another limitation. Conclusion: Further studies are needed to clarify the impact of climatic factors on suicide behavior and implement early intervention and preventive strategies for mental health.

The new 2019 coronavirus disease (COVID-19) outbreak forced mental health providers to overcome their general reluctance about telematic assistance, shifting from a face-to-face approach to online therapy to promote continuity of care for psychiatric patients.An ad-hoc web-based survey questionnaire assessing the impact of the COVID-19 pandemic on therapeutic setting in Mental Health Services was sent via email from March 15, 2021 to June 15, 2021 to mental health providers in Genova, Italy. The survey was anonymous and a free Google Forms® software was used.Two hundred nineteen mental health providers completed the survey, and the overall response rate (ORR) was 65%. During the COVID-19 pandemic period, the continuity of care was mainly guaranteed using electronic devices. Psychologists reported a higher availability of video call assistance service to guarantee continuity of care for psychiatric patients compared to psychiatrists and psychotherapists (p0,001). Psychiatrists reported the lowest degree of satisfaction about this new telematic approach (p0,01), while psychologists and to a lesser extent psychotherapists speculated to use it even in non-pandemic times (p=0,02).COVID-19 pandemic creates an opportunity to overcome normative, technological and cultural barriers to the use of online psychotherapy, showing the importance of adapting the therapeutic setting to both collective and individual needs. Despite initial concerns about its effectiveness and efficacy, a general degree of satisfaction was expressed by the majority of the mental health providers. Further efforts will be needed to enhance this new way of working and to train therapists with particular regard to those employed in the public health system.

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.

Background and aim of the work: Suicide is a worldwide phenomenon, with a relevant number of victims. Moreover, repercussions of suicidality-across its entire spectrum-involve not only the individual but also survivors and communities, in a profound and lasting way. As such, suicidality represents a crucial public mental health concern, in which risk/protection factors’ study represent a key issue. However, research primarily focused on suicidality risk factors. This study, moving from Frankl’s first observations on “Meaning in Life” (MiL) as protective against suicidality, aimed to identify the main themes that suicidal patients identified as MiL carriers, or potential carriers, in their existences. Methods: Qualitative study on 144 patients admitted to the Geneva University Hospital’s emergency department for suicidal ideation (SI) and suicide attempt (SA). Results: Interpersonal/affective relationships constituted the main theme (71.53%), with emphasis on family (39.80%), children/grandchildren (36.89%). Profession/education, intellectual/non-intellectual pleasures, and transcendental dimension also emerged. Conclusions: These aspects could be considered among a public health agenda’s points for suicide prevention programs taking into account also protective factors promotion/support, including community’s mental health resources. Reconnecting to introduction’s historical part, our findings are consistent with Frankl’s observations. Even if exposed to “absurd” and reluctant to deliberate on this, he seems approach Camus conceptualization who, confronted to the necessity of predictable and conform to recognizable personal patterns transcending chaos for a sense-giving perspective, invited to imagine that a meaning, even a “non-absolute meaning”, may lie in apparent smallest things and that Sisyphus can have “the possibility to revolt by trying to be happy”.

Weather affects physical and mental health through several modalities which are not fully elucidated. The aim of the present study was to investigate the impact of meteorological variables and other indexes in a large sample of hospitalized patients, focusing on subjects who were involuntarily admitted. We hypothesized a direct relation between the amount of involuntary admissions and mean sunshine hours. Furthermore, we supposed that specific meteorological factors may significantly influence hospitalizations of patients affected by severe psychiatric conditions. All subjects were consecutively recruited from the Psychiatric Inpatient Unit of San Luigi Gonzaga Hospital, Orbassano (Turin, Italy) from September 2013 to August 2015. Socio-demographic and clinical characteristics were carefully collected. Meteorological data were derived by the Italian Meteorology's Climate Data Service of Physics Department of the University of Turin (Latitude: 45°03′07,15″ Nord, Longitude: 007°40′53,30″ Est, Altitude: 254 m above the sea level) ( http://www.meteo.dfg.unito.it/ ). Our data indicate significant differences regarding temperature (minimum, maximum, and medium), solar radiation, humidex and windchill index, and hours of sunshine in psychiatric patients who were involuntarily hospitalized. After logistic regression analyses, only maximum and medium temperature, and humidex index remained significantly associated with involuntary admission in an emergency psychiatric ward. The limitations of this study include the cross-sectional study design and the single hospital for patients' recruitment. Furthermore, results and seasonal patterns obtained by patients requiring hospitalization might significantly differ from those who were not hospitalized. Exploring in a more detailed manner those environmental factors associated with involuntary admissions could lead to early intervention and prevention strategies for such distressing hospitalizations.

Psychomotor symptoms of depression are understudied despite having a severe impact on patient outcomes. This review aims to summarize the evidence on motor features of depression assessed with instrumental procedures, and examine age-related differences. We included studies investigating posture, balance and gait ascertained with instrumental measurements among individuals with depressive symptoms or disorders. Studies on subjects with specific physical illnesses were excluded. Methodological quality was assessed with the Newcastle - Ottawa Scale (NOS) and PRISMA guidelines were followed. 33 studies (13 case-control, five cross-sectional, nine longitudinal and six intervention) with overall low-medium quality were included. Different instruments were employed to assess posture (e.g. digital cameras), balance (balance, stepping platform) or gait (e.g. Six-Minute-Walking Test, instrumented walkways). Results suggest that depression in adults is associated with significant impairments of posture, balance and gait. Motor abnormalities among depressed older adults may depend on the interplay of physical diseases, cognitive impairment and mood. Very few intervention studies measured motor symptoms as outcome. Available evidence suggests, however, that antidepressant drugs and physical exercise may be beneficial for motor abnormalities. Despite the lack of high-quality studies, instrumental assessments confirm the presence and importance of motor abnormalities in depression, with potential age-related differences in their pathophysiology.

Structural and functional abnormalities of the cerebellum have been observed in schizophrenia since the first neuroimaging studies. More recently, the functions of the cerebellum have been extended beyond sensorimotor control to include participation in higher-level cognition and affective regulation. Consistently, the "cognitive dysmetria" theory posits that dysfunctions of cortical-subcortical-cerebellar circuitry may be crucial for the pathogenesis of different clinical features of schizophrenia. This conceptual framework offers a set of testable hypotheses, now that various tools to exert direct modulation of cerebellar activity are available. We conducted a systematic review of studies examining the effects of cerebellar modulation in schizophrenia. Two independent authors conducted a search within PubMed for articles published up to April 2019 and identified 10 studies (three randomized controlled trials, two open-label studies, two case reports, one preclinical study) describing the effects of cerebellar circuitry modulation in patients with schizophrenia or animal models. The majority of interventions were uncontrolled and used stimulation of the cerebellar vermis, using transcranial magnetic stimulation or transcranial direct-current stimulation. Most studies detected improvements after cerebellar modulation. Clinical changes mostly pertained the domains of negative symptoms, depressive symptoms and cognitive functions. In conclusion, few studies examined the effects of cerebellar modulation in schizophrenia but yielded promising results. This approach may hold therapeutic potential, pending further methodologically robust replication.

Environmental variables can regulate behavior in healthy subjects. Recently, some authors investigated the role of meteorological variables in bipolar patients with an impact on both the onset and course of bipolar disorder (BD). The aim of this study was to investigate the impact of meteorological variables and other indexes in bipolar hospitalized patients. We examined all patients admitted to the Psychiatric Inpatient Unit of San Luigi Gonzaga Hospital, Orbassano (Turin, Italy) from September 2013 to August 2015, collecting several socio-demographic and clinical characteristics. Seven hundred and thirty patients were included. Compared to the day of admission of control individuals, patients with BD were admitted on a day that presented higher minimum, medium, and maximum temperature, higher maximum humidity, higher solar radiation, and higher hours of sunshine. After logistic regression analysis, admissions to the emergency psychiatric ward due to a primary diagnosis of BD were associated with maximum temperature and solar radiation. The current study provides a novel perspective on the question surrounding seasonal mood patterns in patients with BD. A greater awareness of all possible precipitating factors is needed to inform self-management and psycho-educational programs as well as to improve resilience regarding affective recurrences in the clinical practice.

Depressive and manic phases in bipolar disorder show opposite constellations of affective, cognitive, and psychomotor symptoms. At a neural level, these may be related to topographical disbalance between large-scale networks, such as the default mode network (DMN) and sensorimotor network (SMN). We investigated topographical patterns of variability in the resting-state signal-measured by fractional SD (fSD) of the BOLD signal-of the DMN and SMN (and other networks) in two frequency bands (Slow5 and Slow4) with their ratio and clinical correlations in depressed (n = 20), manic (n = 20), euthymic (n = 20) patients, and healthy controls (n = 40). After controlling for global signal changes, the topographical balance between the DMN and SMN, specifically in the lowest frequency band, as calculated by the Slow5 fSD DMN/SMN ratio, was significantly increased in depression, whereas the same ratio was significantly decreased in mania. Additionally, Slow5 variability was increased in the DMN and decreased in the SMN in depressed patients, whereas the opposite topographical pattern was observed in mania. Finally, the Slow5 fSD DMN/SMN ratio correlated positively with clinical scores of depressive symptoms and negatively with those of mania. Results were replicated in a smaller independent bipolar disorder sample. We demonstrated topographical abnormalities in frequency-specific resting-state variability in the balance between DMN and SMN with opposing patterns in depression and mania. The Slow5 DMN/SMN ratio was tilted toward the DMN in depression but was shifted toward the SMN in mania. The Slow5 fSD DMN/SMN pattern could constitute a state-biomarker in diagnosis and therapy.

Transient Receptor Potential Vanilloid 1 (TRPV1) channels are non-selective cationic polymodal receptors gated by several different chemical and physical stimuli. TRPV1 receptors are distributed in several brain areas and interact with important neurotransmitter systems linked to mental disorders, such as endocannabinoid and opioid systems. The increasing number of results obtained in this field has recently attracted growing attention to these receptors as potential targets for the treatment of different psychiatric conditions. To review the available results on this topic, we searched on PubMed, Embase and Science Direct databases up to May 2020 using the following search string: "TRPV1", thus including a total of 48 studies. The results, still limited to preclinical studies, suggest that TRPV1 antagonism could represent a potential mechanism for the treatment of depression and anxiety, as well as for opioids, methamphetamine and cocaine addiction. Few available results consider schizophrenia-like behaviours, suggesting an intriguing role of TRPV1 receptors in the neurobiology of major psychoses. Single studies report the effectiveness of TRPV1 antagonists in animal models of obsessive-compulsive disorder and fibromyalgia. Future preclinical and clinical studies are required to shed further light on the feasibility of the use of TRPV1 modulators in psychopharmacology.

Affective temperaments have been described since the early 20th century and may play a central role in psychiatric illnesses, such as bipolar disorder (BD). However, the neuronal basis of temperament is still unclear. We investigated the relationship of temperament with neuronal variability in the resting state signal—measured by fractional standard deviation (fSD) of Blood‐Oxygen‐Level Dependent signal—of the different large‐scale networks, that is, sensorimotor network (SMN), along with default‐mode, salience and central executive networks, in standard frequency band (SFB) and its sub‐frequencies slow4 and slow5, in a large sample of healthy subject (HC, n = 109), as well as in the various temperamental subgroups (i.e., cyclothymic, hyperthymic, depressive, and irritable). A replication study on an independent dataset of 121 HC was then performed. SMN fSD positively correlated with cyclothymic z‐score and was significantly increased in the cyclothymic temperament compared to the depressive temperament subgroups, in both SFB and slow4. We replicated our findings in the independent dataset. A relationship between cyclothymic temperament and neuronal variability, an index of intrinsic neuronal activity, in the SMN was found. Cyclothymic and depressive temperaments were associated with opposite changes in the SMN variability, resembling changes previously described in manic and depressive phases of BD. These findings shed a novel light on the neural basis of affective temperament and also carry important implications for the understanding of a potential dimensional continuum between affective temperaments and BD, on both psychological and neuronal levels.

Summary Backgrounds Nerve growth factor (NGF) is involved in the modulation of the neuro–endocrine–immune (NEI) system, whereas alterations in neuroplasticity and NEI homeostasis seem to play a role in the pathophysiology of major depressive disorder (MDD). Objective of the study was to investigate NGF levels variations in MDD patients during antidepressant treatment with duloxetine, a relatively newer SNRI. Methods 30 MDD patients and 32 healthy controls were assessed using Hamilton depression scale (HAM-D) and monitored for NGF serum levels at baseline, week 6 and week 12 of duloxetine treatment (60 mg/day) and at baseline, respectively. Results According to early clinical response to duloxetine (defined at week 6 by reduction >50% of baseline HAM-D score), MDD patients were distinguished in early responders (ER) and early non-responders (ENR), who overall reached clinical response at week 12. Laboratory analysis showed overall significant lower baseline NGF levels among depressed patients compared to healthy controls, not significantly in ER and significantly in ENR. During duloxetine treatment NGF levels further decreased in association with clinical response, reaching significantly lower values in ER at W6 compared to controls, and in ENR at W12 compared to baseline. Conclusions A decrease in NGF levels during duloxetine treatment in association to clinical response could be indicative of a relative restoring of NEI stress-adaptation system, since stressors, inducing neuronal instability due to neurotrophins activity changes, permits circuitry remodeling as background in the selection of alternative adaptive behaviors. However, the lower baseline NGF levels found in MDD patients that further decrease during the treatment could represent a lower neurotrophin set point, possibly reflecting a functional impairment in stress-adaptive neuroplasticity in depressive disorders.

Neurotransmitters and hormones regulate major immune functions, including the selection of T helper (Th)1 or Th2 cytokine responses, related to cell-mediated and humoral immunity, respectively. A role of imbalance and dynamic switching of Th1/Th2 system has been proposed, with relative displacement of the immune reserve in relation to complex interaction between Th1/Th2 and neuro-hormonal balance fluctuations, in the pathogenesis of various chronic human diseases, probably also including psychiatric disorders. Components of the stress system such as norepinephrine (NE) and glucocorticoids appear to mediate a Th2 shift, while serotonin (5-HT) and melatonin might mediate a Th1 shift. Some antidepressants would occur affecting these systems, acting on neurotransmitter balance (especially the 5-HT/NE balance) and expression levels of receptor subtypes, which in turn affect cytokine production and relative Th1/Th2 balance. It could be therefore hypothesized that the antidepressant-related increase in NE tone enhances the Th2 response, while the decrease in NE tone or the increase in 5-HT tone enhances the Th1 response. However, the neurotransmitter and Th1/Th2 balance modulation could be relative, aiming to restore physiological levels a previous imbalance in receptor sensitivity and cytokine production. The considerations on neuro-immunomodulation could represent an additional aid in the study of pathophysiology of psychiatric disorders and in the choice of specific antidepressants in specific clusters of symptoms, especially in comorbidity with internal pathologies. Furthermore limited data, reviewed here, have shown the effectiveness of some antidepressants as pure immunomodulators. However, these considerations are tentative and require experimental confirmation or refutation by future studies.