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Background: Facebook represents a new dimension for global information sharing. Suicidal behaviours and attempts are increasingly reported on Facebook. This scoping review explores the various aspects of suicidal behaviours associated with Facebook, discussing the challenges and preventive measures. Methods: PubMed, Google Scholar, and Scopus were searched for related articles published in English up to October 2021, using different combinations of “Facebook” and “suicide”. A group of experts comprising consultant psychiatrists screened the records and read the full-text articles to extract relevant data. Twenty-eight articles were chosen as relevant and included in the review under four selected themes. Results: Facebook impacts on suicidal behaviours in different aspects. Announcing suicides through sharing notes or personal information may lead to the prediction of suicide but be harmful to the online audience. Live-streaming videos of suicide is another aspect that questions Facebook’s ability to monitor shared contents that can negatively affect the audience. A positive impact is helping bereaved families to share feelings and seek support online, commemorating the lost person by sharing their photos. Moreover, it can provide real-world details of everyday user behaviours, which help predict suicide risk, primarily through novel machine-learning techniques, and provide early warning and valuable help to prevent it. It can also provide a timeline of the user’s activities and state of mind before suicide. Conclusions: Social media can detect suicidal tendencies, support those seeking help, comfort family and friends with their grief, and provide insights via timelining the users’ activities leading to their suicide. One of the limitations was the lack of quantitative studies evaluating preventative efforts on Facebook. The creators’ commitment and the users’ social responsibility will be required to create a mentally healthy Facebook environment.

Fountoulakis K.N., Karakatsoulis G.N., Abraham S., Adorjan K., Ahmed H.U., Alarcón R.D., Arai K., Auwal S.S., Berk M., Bjedov S., Bobes J., Bobes-Bascaran T., Bourgin-Duchesnay J., Bredicean C.A., Bukelskis L., Burkadze A., Abud I.I.C., Castilla-Puentes R., Cetkovich M., Colon-Rivera H., Corral R., Cortez-Vergara C., Crepin P., De Berardis D., Delgado S.Z., De Lucena D., De Sousa A., Stefano R.D., Dodd S., Elek L.P., Elissa A., Erdelyi-Hamza B., Erzin G., Etchevers M.J., Falkai P., Farcas A., Fedotov I., Filatova V., Fountoulakis N.K., Frankova I., Franza F., Frias P., Galako T., Garay C.J., Garcia-Álvarez L., García-Portilla M.P., Gonda X., Gondek T.M., González D.M., Gould H., Grandinetti P., Grau A., Groudeva V., Hagin M., Harada T., Hasan T.M., Hashim N.A., Hilbig J., Hossain S., Iakimova R., Ibrahim M., Iftene F., Ignatenko Y., Irarrazaval M., Ismail Z., Ismayilova J., Jacobs A., Jakovljević M., Jakšić N., Javed A., Kafali H.Y., Karia S., Kazakova O., Khalifa D., Khaustova O., Koh S., Kopishinskaia S., Kosenko K., Koupidis S.A., Kovacs I., Kulig B., Lalljee A., Liewig J., Majid A., Malashonkova E., Malik K., Malik N.I., Mammadzada G., Mandalia B., Marazziti D., Marčinko D., Martinez S., Matiekus E., Mejia G., Memon R.S., Martínez X.E.M., Mickevičiūtė D., Milev R., Mohammed M., Molina-López A., Morozov P., Muhammad N.S., Mustač F., Naor M.S., Nassieb A., Navickas A., Okasha T., Pandova M., Panfil A.-L., Panteleeva L., Papava I., Patsali M.E., Pavlichenko A., Pejuskovic B., Da Costa M.P., Popkov M., Popovic D., Raduan N.J.N., Ramírez F.V., Rancans E., Razali S., Rebok F., Rewekant A., Flores E.N.R., Rivera-Encinas M.T., Saiz P., de Carmona M.S., Martínez D.S., Saw J.A., Saygili G., Schneidereit P., Shah B., Shirasaka T., Silagadze K., Sitanggang S., Skugarevsky O., Spikina A., Mahalingappa S.S., Stoyanova M., Szczegielniak A., Tamasan S.C., Tavormina G., Tavormina M.G.M., Theodorakis P.N., Tohen M., Tsapakis E.M., Tukhvatullina D., Ullah I., Vaidya R., Vega-Dienstmaier J.M., Vrublevska J., Vukovic O., Vysotska O., Widiasih N., Yashikhina A., Prezerakos P.E., Smirnova D.

The attention deficit hyperactivity disorder (ADHD) in women has recently received considerable attention, as research has shown an underestimation of the disorder in females, due to a difference in presentation compared to males: females have a higher risk of having ADHD, without those "disruptive" symptoms that determine the request for help. The purpose of the present narrative review is to identify the neglected clinical problems in the diagnostic and therapeutic intervention of women with ADHD and to analyze the associated comorbid problems. The conducted PubMed search and the relevant literature review on the topic show that the impairment of ADHD in women is underestimated due to the different ways the phenomenon manifests compared to traditional male's symptoms. This underestimation consequently leads to an inadequate treatment and has negative repercussions on the social context in which women are involved in.

Background: The current COVID-19 pandemic is affecting mental health of global population and, particularly, of people suffering from preexisting mental disorders. Aims: This study aims to report on findings from a phone-based clinical follow-up conducted in two large catchment areas in Italy and Paraguay, during the COVID-19 lockdown, in order to provide psychiatric assessments and measure the level of stress related to the quarantine in a large sample of psychiatric outpatients. Methods: A clinical phone-based follow-up has been conducted in two large catchment areas in the province of Chieti (Vasto, Italy) and City of Asunción (Paraguay), during the COVID-19 national lockdown. The following rating scales have been employed: Hamilton Anxiety Rating Scale (HAM-A); Hamilton Depression Rating Scale (HAM-D); 18-items Brief Psychiatric Rating Scale (BPRS-18). The psychological distress related to the outbreak has been assessed employing the Impact of Event Scale – Revised (IES-R). Results: A total of 110 outpatients were consecutively included and followed among those reporting a stable phase of illness before the COVID-19 lockdown. Findings confirmed a significant increase of general psychopathology, anxiety and fear as well as mild levels of stress related to the quarantine. Also, significant weight gain during the lockdown was detected among patients. Conclusions: This study confirmed the impact of COVID-19 lockdown on mental health of people suffering from psychiatric disorders and may also add evidence on the employment of digital psychiatry in the current pandemic.

Objective: To discuss the impact of depression on work and how depression-related sick leave duration could be a potential indicator and outcome for measuring functionality in depression. Methods: Our review was based on a literature search and expert opinion that emerged during a virtual meeting of European psychiatrists that was convened to discuss this topic. Results: Current evidence demonstrates that depression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditions. A wide variety of pharmacological and non-pharmacological treatments and work-based interventions are effective in reducing depression-related sick leave duration and/or facilitating return to work. Recent real-world evidence showed that patients treated with antidepressant monotherapy appear to recover their working life faster than those receiving combination therapy. Although depression-related sick leave duration was found to correlate with severity of depressive symptoms, it cannot be used alone as a viable marker for disease severity. Conclusions: Given its multifactorial nature, depression-related sick leave duration is not on its own a viable outcome measure of depression severity but could be used as a secondary outcome alongside more formal severity measures and may also represent a useful measure of functionality in depression. Key points Depression in the working population and depression-related sick leave have a profound economic impact on society Depression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditions A wide variety of pharmacological and non-pharmacological treatments and work-based interventions have been shown to be effective in reducing depression-related sick leave duration and/or facilitating return to work In terms of pharmacological intervention, recent real-world evidence has shown that patients treated with antidepressant monotherapy are able to recover their working life faster than those treated with combination therapy Although depression-related sick leave duration has been shown to correlate with severity of depressive symptoms, it is not a viable outcome measure of depression severity on its own, but could be used as secondary outcome alongside more formal clinician- and patient-rated severity measures Depression-related sick leave duration may, however, represent a viable outcome for measuring functionality in depression.

Background: A growing number of neuroimaging studies have revealed spatial abnormalities of resting-state functional brain network activity in bipolar disorder (BD). Conversely, abnormalities of resting state temporal dynamics have been scarcely investigated so far. The aim of this study was to characterize the EEG microstates activity in BD patients with a history of manic predominant polarity. Patients were euthymic and pharmacologically stabilized. Methods: Nineteen BD patients (mean age 34.4 ± 11.0, 7 female) and 19 healthy controls (HC; mean age 38.2 ± 9.9, 7 female) were recruited. The psychometric evaluation included the Hamilton Depression Scale (HAMD), the Young Mania Rating Scale (YMRS), the Dissociative Experience Scale (DES), and the State-Trait Anxiety Inventory (STAI). Two runs of 2 minutes of EEG activity by a 128-channel system were acquired at rest and analyzed through microstate analysis. Results: We found a reduced presence of microstate B in BD patients compared to HC, since BD patients have a tendency to transit from the microstate B to the microstates C and D significantly more than HC. Furthermore, microstate B features were correlated with DES, state STAI and trait STAI scores. Conclusion: The reduced presence of microstate B might be associated with episodic autobiographic memory deficit, exaggerated self-focusing and states of dissociations characteristic of BD. Strong correlations of microstate B metrics and dynamics with symptoms of dissociation and anxiety across the two groups supported this interpretation.

Aim The present study is aimed at revaluating alexithymia, somatic sensations, resilience and their relationships with suicide ideation in drug naive adult outpatients suffering from first episode major depression (MD). Methods Data of 103 adult outpatients (49 men, 56 women) with a diagnostic and statistical manual of mental disorders, 4th edition, text revision (DSM-IV-TR) diagnosis of MD were analysed. Alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS-20) and resilience with the 25 items Connor-Davidson Resilience Scale (CD-RISC) whereas depression was evaluated using the 17-item Hamilton Depression Rating Scale, somatic sensations with the Body Sensations Questionnaire and suicide ideation with Scale of Suicide Ideation (SSI). Results Gender comparisons between all demographic and clinical variables showed no significant differences in all variables. Subjects who were found positive for alexithymia showed higher scores on all clinical variables controlling for age, gender and duration of the current episode. In a linear regression model, lower scores on CD-RISC and Difficulty in Identifying Feelings dimension of TAS-20 were significantly predictive of higher scores on SSI. Conclusions Alexithymia and low resilience were significant predictors of increased suicide ideation in a first MD episode. However, study limitations must be considered and future research needs are being discussed.

Capgras and Fregoli syndromes are two psychotic and complex conditions also known as Delusional Misidentification Syndromes (DMSs). Their description dates back to the beginning of XX century, and many explanatory models have been formulated through myths, psychoanalytical and psychological hypotheses, as well as neurobiological proposals. Even if DMSs are not fully considered in the modern diagnostic manuals, they still remain intriguing phenomena to be clinically observed and explained. Also, the employment of psychotropics and physical techniques in the treatment of such conditions is not supported by robust evidences and this may encourage further studies. We conclude that it would be of great interest to brush up the neglected MDSs in order to improve our knowledge on the underlying mechanisms of delusion and brain functioning.

Background: A research on mood disorder pathophysiology has hypothesized abnormalities in glutamatergic neurotransmission, by suggesting further investigation on glutamatergic N-methyl-Daspartate (NMDA) receptor modulators in treating Major Depressive Disorder (MDD). Esketamine (ESK), an NMDA receptor antagonist able to modulate glutamatergic neurotransmission has been recently developed as an intranasal formulation for treatment-resistant depression (TRD) and for rapid reduction of depressive symptomatology, including suicidal ideation in MDD patients at imminent risk for suicide. Objective: The present study aims at investigating recent clinical findings on research on the role of the glutamatergic system and ESK in treating suicidal depression in MDD and TRD. Methods: A systematic review was here carried out on PubMed/Medline, Scopus and the database on U.S. N.I.H. Clinical Trials (https://clinicaltrials.gov) and the European Medical Agency (EMA) (https://clinicaltrialsregister.eu) from inception until October 2019. Results: Intravenous infusion of ESK is reported to elicit rapid-acting and sustained antidepressant activity in refractory patients with MDD and TRD. In phase II studies, intranasal ESK demonstrated a rapid onset and a persistent efficacy in patients with TRD as well as in MDD patients at imminent risk for suicide. However, some data discrepancies have emerged in phase III studies. Conclusion: The U.S. Food and Drug Administration (FDA) granted fast track and Breakthrough Therapy Designation to Janssen Pharmaceuticals®, Inc. for intranasal ESK in 2013 for treatment-resistant depression (TRD) and in 2016 for the treatment of MDD with an imminent risk of suicide. However, further studies should be implemented to investigate the long-term efficacy and safety of intranasal ESK.

Rapid urbanization worldwide is associated to an increase of population in the urban settings and this is leading to new emerging mental health issues. This narrative mini-review is based on a literature search conducted through PubMed and EMBASE. A total of 113 articles published on the issue of urban mental health have been selected, cited, reviewed, and summarized. There are emerging evidences about the association between urbanization and mental health issues. Urbanization affects mental health throughsocial, economic, andenvironmentalfactors. It has been shown that common mental syndromes report higher prevalence in the cities. Social disparities, social insecurity, pollution, and the lack of contact with nature are some of recognized factors affecting urban mental health. Further reserach studies and specific guidelines should be encouraged to help policy makers and urban designers to improve mental health and mental health care facilities in the cities; additional strategies to prevent and reduce mental illness in the urban settings should be also adopted globally.

Obsessive-compulsive disorder is often associated with schizophrenia and may represent a significant challenge in the treatment as this comorbidity may not respond properly to antipsychotic medication and usually require a pharmacological and psychotherapeutic add-on. In the present case report, we present the case of a 26-year-old male blue-collar subject who developed obsessive-compulsive disorder after a year of complete remission of schizophrenia symptoms under paliperidone long-acting injection that rapidly resolved after low-dosage cariprazine add-on. No adverse effects were reported due to cariprazine- paliperidone long-acting injection combination.

BackgroundHighlighting 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.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300–600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

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.

Background: The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself or more severe clinical levels of AUD. Objectives: Given the high association between alcohol metabolizing enzymes (AME) and the outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. Methods: We carried out a 12-week longitudinal clinical trial based on the treatment of AUD patients with naltrexone (N = 101), stratified by different alcohol metabolization genotypes. Genotyping was performed after the inclusion of the patients in the study, based on the individual presence of single nucleotide polymorphisms (SNPs) in the ADH (alcohol dehydrogenase)1B (ADH1B*2 and ADH1B*3), ADH1C (ADHC*1) and ALDH (aldehyde dehydrogenase) 2 (ALDH2*2) genes. The outcome of alcohol use has been monitored employing the timeline follow-back during the treatment. Results: The ADH1C*1 (Ile350Val, rs698) and ALDH2*2 (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the ADH1B*3 (Arg370Cys, rs2066702) allelic variant showed a negative outcome. Conclusions: The present study explores a genomic setting for the treatment of AUD with naltrexone. According to our findings, the association between ADH1C*1 and ALDH2*2 variants and better outcomes suggests a successful treatment, whereas the ADH1B*3 mutated allele might lead to an unsuccessful treatment. Further studies should be performed to investigate the relationship between alcohol metabolizing genotypes, the family history of alcohol use disorders and the effect of naltrexone on the outcomes. Genotyping may be a valuable tool for precision-medicine and individualized approach, especially in the context of alcohol use disorders. The small number of subjects was the main limitation of the present study.

Background: The pharmacological treatment of schizophrenia is currently based on the employment of antipsychotic medications showing an antagonism of dopaminergic and serotoninergic inhibitors. 20-40% of patients are drug-resistant or residually symptomatic in the long-term antipsychotic treatment, and new strategies are needed for improving their functional and cognitive impairment. Methods: This systematic review has summarized evidences from the literature regarding the newer pharmacological targets proposed for the treatment of psychosis. We included 128 peer-reviewed articles and 5 other relevant sources published from 2002 to 2020 on PubMed EMBASE, The Cochrane Library, and Google Scholar. Results: The possible role of glutamate and its receptors as targets of the antipsychotic mechanism of action has been described. Glutamatergic neurotransmission and NMDA receptors hypofunction are involved in the neurobiological explanatory model of psychosis and possibly targeted for the successful treatment of cognitive and residual symptoms. Results show an efficacy of D-cycloserine (antagonist at the Glycine site of the NMDA-R) in the treatment of negative symptoms of schizophrenia as well as Memantine (NMDA- Receptor antagonist) for cognition and psychopathology. The putative antipsychotic effect of cannabidiol on positive symptoms and cognition will also be discussed. The action on serotoninergic and GABAergic receptors will be considered as a new pharmacological target, with a possible efficacy of Vabicaserin on symptoms of psychosis. Mynocicline has shown to induce improvements in cognitive symptoms in schizophrenia, as well as Erythropoietin. Oxytocin has been reported to have an antipsychotic-like effect; moreover, COX-2 inhibitors lead to a reduction in positive symptoms of psychosis, specifically in the first episode of illness. Conclusion: This narrative report suggests a promising role of new agents in the treatment of Schizophrenia; however, more research is needed to approve their clinical employment.

Major depressive disorder carries a significant burden and a high risk for suicide. The need for more effective, safer, and faster-acting drugs is, therefore, compelling. The present chapter briefly assesses the most promising agents, focusing on non-monoamine-targeting compounds, namely, the glutamate antagonist ketamine and its enantiomer esketamine. A critical overview of the evidence and the pitfalls associated with current antidepressant drug development is likewise provided in the following text.

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.

Background:In the past few decades, increasing evidence in the literature has appeared describing the role of the antioxidant defense system and redox signaling in the multifactorial pathophysiology of psychosis. It is of interest to clinicians and researchers alike that abnormalities of the antioxidant defense system are associated with alterations of cellular membranes, immune functions and neurotransmission, all of which have some clinical implications.Methods:This narrative review summarizes the evidence regarding oxidative stress in the early stages of psychosis. We included 136 peer-reviewed articles published from 2007 to 2020 on PubMed EMBASE, The Cochrane Library and Google Scholar.Results:Patients affected by psychotic disorders show a decreased level of non-enzymatic antioxidants, an increased level of lipid peroxides, nitric oxides, and a homeostatic imbalance of purine catabolism. In particular, a significantly reduced antioxidant defense has been described in the early onset first episode of psychosis, including reduced levels of glutathione. Also, it has been shown that a decreased basal low-antioxidant capacity correlates with cognitive deficits and negative symptoms, mostly related to glutamate-receptor hypofunction. In addition, atypical antipsychotic drugs seem to show significant antioxidant activity. These factors are critical in order to treat cases of first-onset psychosis effectively.Conclusion:This systematic review indicates the importance that must be given to anti-oxidant defense systems.

Adverse childhood experiences are significant risk factors in the development of adolescent borderline personality disorder symptoms (BPDs). Theorists have posited that two personality vulnerabilities factors, self-criticism and dependency, may inform our understanding of this relationship. However, no research has examined the associations between early negative experiences, personality vulnerabilities, and adolescent BPDs. The current study aimed to identify profiles of dependency and self-criticism to examine the associations of these profiles with cumulative forms of childhood maltreatment (CM) and BPDs as well as to explore the mediating and moderating role of vulnerable personality profiles in the relationship between cumulative CM and BPDs. Two hundred and forty-one nonclinical and clinical adolescents participated in the study (Mage= 16.37,SD= 1.84). The findings indicated three different profiles: average dependent profile, dependent and self-critical profile, and self-critical profile. Individuals in the average dependent profile presented lower levels of CM and BPDs. Mediation analyses showed that relative to the average dependent profile, a higher cumulative CM history predicted a higher probability of belonging in the dependent and self-critical profile or the self-critical profile and, in turn, this was associated with higher levels of BPDs. No moderating effects of profiles of dependency and self-criticism were found.

BackgroundThe emergence of the COVID-19 pandemic has affected the lives of many people, including medical students. The present study explored internet addiction and changes in sleep patterns among medical students during the pandemic and assessed the relationship between them.MethodsA cross-sectional study was carried out in seven countries, the Dominican Republic, Egypt, Guyana, India, Mexico, Pakistan, and Sudan, using a convenience sampling technique, an online survey comprising demographic details, information regarding COVID-19, the Pittsburgh Sleep Quality Index (PSQI), and the Internet Addiction Test (IAT).ResultsIn total, 2749 participants completed the questionnaire. Of the total, 67.6% scored above 30 in the IAT, suggesting the presence of an Internet addiction, and 73.5% scored equal and above 5 in the PSQI, suggesting poor sleep quality. Internet addiction was found to be significant predictors of poor sleep quality, causing 13.2% of the variance in poor sleep quality. Participants who reported COVID-19 related symptoms had disturbed sleep and higher internet addiction levels when compared with those who did not. Participants who reported a diagnosis of COVID-19 reported poor sleep quality. Those living with a COVID-19 diagnosed patient reported higher internet addiction and worse sleep quality compared with those who did not have any COVID-19 patients in their surroundings.ConclusionThe results of this study suggest that internet addiction and poor sleep quality are two issues that require addressing amongst medical students. Medical training institutions should do their best to minimize their negative impact, particularly during the current COVID-19 pandemic.

Homophobia is still a scourge in the modern era. Despite a greater acceptance of sexual variations and same-sex marriage in many countries, homophobia is widely sustained by religious, political and cultural values and beliefs at individual and social level. Most of homophobic attitudes are based on the principle of heteronormativity according to which heterosexuality is the standard for legitimating social and sexual relationships and homosexuality is considered as an abnormal variant. Homophobia may be also recognised at institutional level (state-sponsored homophobia, social homophobia) and supported by laws or religious beliefs. Moreover, internalised homophobia (IH) is defined as the inward direction of societal homophobic behaviours at individual level and refers to the subjective psychological impact of these negative attitudes. In fact, IH is significantly associated with a high prevalence of internalising mental disorders such as depression, anxiety, stress/trauma-related disorders, etc. We believe that a set of immediate actions are needed in order to contrast homophobia and its impact on mental health, in particular political initiatives, educational trainings and scientific research should be promoted with a specific focus on mental health needs of people target of homophobia.

Background: The Duration of Untreated Psychosis (DUP) is the time between the first-episode psychosis (FEP) and the initiation of antipsychotic treatment. It is an important predictor of several disease-related outcomes in psychotic disorders. The aim of this manuscript is investigating the influence of cannabis on the DUP and its clinical correlates. Methods: During years 2014–2019, sixty-two FEP patients with and without cannabis use disorder (CUD) were recruited from several Italian psychiatric hospitals. The subjects were then divided into two groups based on the duration of the DUP and assessed at the beginning of the antipsychotic treatment and after 3 and 6 months, using the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF) scale, and the Dissociative Experiences Scale (DES-II). Results: As expected, a longer DUP was associated with worse symptoms and cannabis use did not seem to affect the DUP, but both were related with more dissociative symptoms at onset and over time. Discussion: According to our study, cannabis use can be a predictor of FEP and DUP, and of disease outcome. However, several factors might influence the relationship between cannabis use and DUP. Preventing cannabis use and early diagnosis of psychotic disorders might impact the disease by reducing the persistence of symptoms and limiting dissociative experiences.

Schizophrenia is frequently complicated by the occurrence of depressive symptoms, anhedonia, obsessions and compulsions, suicidal ideation, and substance abuse, that causes exacerbations and remissions and, in several cases, sustained morbidity and disability.The present study aimed to evaluate the effect of paliperidone palmitate once-monthly long-acting injection (PP-LAI) mainly on "non-core" symptoms in persons with recent diagnosis schizophrenia, during a follow-up period of almost 12 months (T1) in the context of the "real world" everyday clinical practice.Concerning core symptoms of schizophrenia, PP-LAI was effective in reducing all symptoms at T1 as measured by Positive and Negative Syndrome Scale (PANSS), including depressive symptoms, and increased the functioning. Moreover, concerning the non-core symptoms of schizophrenia, PP-LAI treatment was effective in reducing scores of anhedonia, suicidal ideation and obsessive-compulsive symptoms at T1. However, the levels of alexithymia remained relatively stable, even if reduced.The present retrospective, multicenter, non-sponsored, collaborative study showed that early PP-LAI treatment was effective in improving almost all the core dimensions and "non-core" symptoms of schizophrenia, and this may have positive repercussions on both functioning and quality of life.PP-LAI treatment should be offered earlier as possible and was effective on "non-core" symptoms of schizophrenia at follow-up, but had a little effect on alexithymia. However, study' limitations must be considered and future researches are needed to confirm these interesting findings.

Introduction: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study. ----- Material and methods: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively. ----- Statistical analysis: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables. ----- Results: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed. ----- Conclusions: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them.

Background: Suicide is a major public health problem on a global scale, with about 800.000 deaths every year. In particular, it represents one of the main causes of death among adolescents and young adults aged between 15 and 29 years. The World Health Organization (WHO) describes suicide as “an act of deliberate killing” and that is placed at the extreme end of the continuous spectrum of suicidal behaviors (SBs). These include suicidal ideation, attempted suicide and suicide itself. Objective: The aim of the present review was to better clarify the suicide vulnerability genetic biomarkers and genetic variants correlated with the response to lithium and clozapine and to evaluate some correspondences. Methods: We reviewed the current literature, focusing our attention on genetic molecular studies about neurobiological systems involved in SBs and pharmacogenetic studies about antisuicidal drugs (lithium and clozapine). Results: The studies that we have reviewed have shown mixed results. Interestingly, rs1800532 polymorphism of the SLC6A4 gene, encoding for the serotonin transporter, is potentially correlated with both suicide vulnerability and a poor response to lithium and clozapine. Conclusion: Due to the impact of suicide on public health, more studies are needed to open a promising route to prevent suicide in personalized and precise psychiatry.

Lithium is considered the gold standard in the treatment of bipolar disorder (BD) and is used as first-line therapy in prophylaxis and in the treatment of acute mania and depression. However, although lithium is universally accepted as a reference standard in the treatment of BD, its diffusion in clinical practice is still limited. In order to test awareness of the indications for the use of lithium, its methods of clinical use and the monitoring of the main side effects, a survey was carried out among young Italian psychiatrists (less than 40 years old). This survey was followed by an expert meeting in which the results of the survey were analyzed and discussed in order to identify the main critical issues regarding drug management and possible solutions. This work highlights how young Italian psychiatrists have presented a good awareness of the use of lithium in clinical practice. In particular, knowledge of the guidelines regarding safety and attention to strategies that can improve long-term adherence is adequate.

Childhood maltreatment (CM) is a predictor of poor outcome across treatments for major depressive disorder (MDD), while its potential role as a predictor of differential responses to specific antidepressants has received little attention. The present systematic review examined pharmacological studies (published up to June 30th, 2020) that included head-to-head comparisons of antidepressant treatments among adult MDD patients with a reported history of CM or no history to evaluate if CM may help clinicians choose antidepressants with greatest likelihood of successful outcome. Only three studies were included, providing limited and provisional results. These preliminary findings suggest that sustained-release bupropion (alone or in combination) or aripiprazole-augmentation as next-step intervention did not demonstrate differential outcome among MDD patients with or without a history of childhood adversity. Further, sertraline and the group of antidepressants with low affinity for the serotonin transporter may be less suitable for MDD patients with childhood abuse history than escitalopram, venlafaxine-XR, or antidepressants with high affinity for the serotonin transporter. The critical question of the most potentially efficacious treatment regimens for adult MDD with CM history requires further large-sample studies involving a greater number of medications, specifically designed to analyse the moderating effects of different types of CM, and possibly including objective biomarkers.

Introduction There are several new and emerging antipsychotic medication strategies recently marketed or under clinical development for the treatment of several mental disorders. There is the need to provide an up-to-date overview on the safety of this new generation of antipsychotic medications, which includes also the third-generation antipsychotics (TGA). Areas covered The authors aimed at providing a synthesis of the most current evidence about the safety profile of the recently developed and/or marketed antipsychotics. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO, and the Cochrane Library from inception until March 2020, combining free terms and MESH headings for the topics of TGA and recently developed and/or marketed antipsychotics as following: ((safety OR adverse events OR side effects) AND ((brexpiprazole OR cariprazine OR inhaled loxapine OR lumateperone (ITI-007) OR lurasidone OR pimavanserin OR roluperidone (MIN-101) OR transdermal patch asenapine)). Expert opinion Overall, newer antipsychotics display a good safety profile, with a well-demonstrated lower metabolic liability compared to second-generation antipsychotics. Furthermore, TGA appear to specifically target negative symptomatology and improving cognitive domains. Abbreviations Aps=Antipsychotic Drugs; AEs = Adverse Effects; EPS = Extrapyramidal Symptoms; NMS = Neuroleptic malignant syndrome; D = Dopamine; Ki = Inhibitory Constant; 5-HT = Serotonin; ECG = Electrocardiogram; H = Histamine; M = Muscarinic; BMI = Body Mass Index.

Background There are scarce and discrepant data about the prevalence and correlates of co-occurring eating disorders (EDs) among people with a primary diagnosis of bipolar disorder (BD), and vice-versa, compelling a systematic review and meta-analysis on the matter. Methods MEDLINE/PsycINFO databases were systematically searched for original studies documenting BD⇌ED comorbidity across the lifespan, from inception up until April 20th, 2020. Random-effects meta-analysis and meta-regression analyses were conducted, accounting for multiple moderators. Results Thirty-six studies involved 15,084 primary BD patients. Eleven studies encompassed 15,146 people with primary EDs. Binge eating disorder (BED) occurred in 12.5% (95%C.I.=9.4-16.6%, I2=93.48%) of BDs, while 9.1% (95%C.I.=3.3-22.6%) of BEDs endorsed BD. Bulimia Nervosa (BN) occurred in 7.4% (95%C.I.=6-10%) of people with BD, whereas 6.7% (95%C.I.=12-29.2%) of subjects with BN had a diagnosis of BD. Anorexia Nervosa (AN) occurred in 3.8% (95%C.I.=2-6%) of people with BDs; 2% (95%C.I.=1-2%) of BD patients had a diagnosis of AN. Overall, BD patients with EDs had higher odds of being female vs. non-ED controls. Several moderators yielded statistically significant differences both within- and between different types of BDs and EDs. Limitations Scant longitudinal studies, especially across different EDs and pediatric samples. High heterogeneity despite subgroup comparisons. Limited discrimination of the quality of the evidence. Conclusions The rates of BD⇌ED comorbidity vary across different diagnostic groups, more than they do according to the “direction” of BD⇌ED. Further primary studies should focus on the risks, chronology, clinical impact, and management of the onset of intertwined BD⇌ED across different ages, promoting a continuum approach.

Dysthymia is a psychopathological construct historically described and often reconsidered through the centuries. Its first description is dated back to 400 b.C., when Hippocrates proposed his theory about the ‘black bile’ and the melancholic temperament. The concept of dysthymia (dys-, ‘ill’, thymia-, ‘emotions’) has been largely elaborated in the XIX and XX centuries by Burton, Cullen, Schneider, Kretschmer, Akiskal and other authors, and recently re-formulated in the various editions of the modern Diagnostic and Statistical Manual of Mental Disorders under different diagnostic labels: neurotic depression, dysthymic disorder, persistent depressive disorder. Beyond the nosology, dysthymia issues some other challenges, including the need for further research to characterise the peculiar pathophysiological framework of this syndrome (compared with major depressive disorder) and to better define evidences about tailored-treatment options and their effectiveness.

Pollutant agents are exponentially increasing in modern society since industrialization processes and technology are being developed worldwide. Impact of pollution on public health is well known but little has been described on the association between environmental pollutants and mental health. A literature search on PubMed and EMBASE has been conducted and 134 articles published on the issue of pollution and mental health have been included, cited, reviewed, and summarized. Emerging evidences have been collected on association between major environmental pollutants (air pollutants, heavy metals, ionizing radiation [IR], organophosphate pesticides, light pollution, noise pollution, environmental catastrophes) and various mental health disorders including anxiety, mood, and psychotic syndromes. Underlying pathogenesis includes direct and indirect effects of these agents on brain, respectively, due to their biological effect on human Central Nervous System or related to some levels of stress generated by the exposure to the pollutant agents over the time. Most of emerging evidences are still nonconclusive. Further studies should clarify how industrial production, the exploitation of certain resources, the proximity to waste and energy residues, noise, and the change in lifestyles are connected with psychological distress and mental health problems for the affected populations.

BackgroundThe elderly population and numbers of nursing homes residents are growing at a rapid pace globally. Uncertainty exists regarding the actual rates of major depressive disorder (MDD), bipolar disorder and schizophrenia as previous evidence documenting high rates relies on suboptimal methodology.AimsTo carry out a systematic review and meta-analysis on the prevalence and correlates of MDD, bipolar disorder and schizophrenia spectrum disorder among nursing homes residents without dementia.MethodMajor electronic databases were systematically searched from 1980 to July 2017 for original studies reporting on the prevalence and correlates of MDD among nursing homes residents without dementia. The prevalence of MDD in this population was meta-analysed through random-effects modelling and potential sources of heterogeneity were examined through subgroup/meta-regression analyses.ResultsAcross 32 observational studies encompassing 13 394 nursing homes residents, 2110 people were diagnosed with MDD, resulting in a pooled prevalence rate of 18.9% (95% CI 14.8–23.8). Heterogeneity was high (I2 = 97%, P≤0.001); no evidence of publication bias was observed. Sensitivity analysis indicated the highest rates of MDD among North American residents (25.4%, 95% CI 18–34.5, P≤0.001). Prevalence of either bipolar disorder or schizophrenia spectrum disorder could not be reliably pooled because of the paucity of data.ConclusionsMDD is highly prevalent among nursing homes residents without dementia. Efforts towards prevention, early recognition and management of MDD in this population are warranted.

Objective: Selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of treatment of major depressive disorder (MDD). However, non-response is common, often necessitating combination strategies. The present study assessed the efficacy of vortioxetine as an add-on therapy in patients with SSRI-resistant MDD. Methods: The charts of 36 adult outpatients with DSM-IV-TR MDD who had not achieved a response after at least 8 weeks of treatment with an SSRI were reviewed retrospectively. Subjects were treated with vortioxetine (5-20 mg/day) for 8 weeks added to the current SSRI. The main outcome measures were change from baseline in total Hamilton Scale for Depression (HAM-D) score and the rate of response (a 50% or greater reduction in HAM-D score and a Clinical Global Impression ‐ Improvement module [CGI-I] score of 1 or 2 at endpoint). HAM-D scores ≤ 7 were considered as remission. Additional outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Scale for Suicide Ideation (SSI). Results: 32 patients completed the 8 weeks of treatment. At 8 weeks, a significant reduction in HAM-D score was observed (p ≤ 0.001), with response obtained by 41.7% and remission by 33.3% of patients. Significant reductions in SHAPS and SSI were also observed (p ≤ 0.001 for both scales). Conclusions: Adjunctive vortioxetine may be useful and well-tolerated in stage I treatment-resistant depression. However, the limitations of this study (such as small sample size, absence of randomization and control group, retrospective design, etc.) must be considered.

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. Keypoints Patients 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.

BackgroundObsessive-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.

Alexithymia is a disabling condition frequently linked to major depressive disorder (MDD) and able to enhance symptoms severity and suicide risk. This study aimed to clarify whether patients with and without alexithymia may differ concerning illness presentation and clinical course, which is a major gap in the scientific literature.The present sample included 381 euthymic outpatients with MDD recruited at the Department of Neuroscience (DINOGMI), University of Genoa. The Toronto Alexithymia Scale (TAS-20) and additional rating scales (Clinical Global Impression (CGI), Hamilton Anxiety Rating Scale (HAM-A), Intent Score Scale (ISS) were administered to all participants.Alexithymic patients were more likely to have lower educational level (11.6 ± 3.2 vs. 12.4 ± 3.4, p ≤ .05), have used previous psychiatric drugs (85.7% vs. 72.8%, p =.001), use current antidepressants (84.7% vs. 69.4%, p = .001), and have higher cardiological comorbid disorders (10.7% vs. 5.0%, p = ≤.05). After multivariate analyses, alexithymia was associated with lower educational level (OR=0.928, p = .05), and higher current antidepressants use (OR 2.302, p = .01); difficulties in identifying feelings were associated with lower educational level (p = ≤.005), higher psychiatric comorbidity (p = ≤.001), and previous psychiatric medications (p = .01). Furthermore, having a lower educational level remained the only factor associated with both difficulties in communicating feelings (p = ≤.001) and thoughts oriented to external context (p = ≤.005).The study is limited by the small sample size and its cross-sectional nature.Alexithymia appears a useful specifier of adverse outcomes, associated with distinct socio-demographic and clinical characteristics. Its identification would allow to provide a more personalized care.

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 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.

The prediction of acute and maintenance lithium treatment response carries major clinical and neurobiological implications, warranting systematic review. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant review searched major electronic databases from inception until December 2017 for studies documenting a clinical diagnosis of bipolar disorder (BD) made according to the mainstream diagnostic manuals and confirmed by a structured interview. Eligible studies allowed a quantitative comparison of endpoint vs baseline mean values of a given biomarker, regardless of the mood phase of patients with BD, and the disorder was assessed for severity using validated rating tool(s). Owing to the purposely applied stringent selection criteria, 16 acute and 12 maintenance studies could be included. The anticipated publication bias limited the chances of reportable generalizable findings, hindering a side-by-side comparison of different records across varying biomarkers and subsequent meta-analyses. The PRISMA approach was nonetheless preferred; it aimed at enhancing the homogeneity of the included results and minimizing the chances of “apples and oranges” with respect to the present research theme. The present critical review confirms the need for future research to specifically assess either pretreatment and/or posttreatment putative biomarkers of patients with BD and treated with lithium. © 2018 Elsevier B.V.

Background Hospitalization accounts for significant health care resource utilization for treatment-resistant Bipolar Disorder (BD), especially among frequent users of acute inpatient psychiatric units. Appraisal of the clinical features and predictive role of selected variables is therefore crucial in such population, representing the aim of the present research. Methods A hundred and nineteen BD inpatients with an established history of pharmacological treatment resistance for either mania or bipolar depression were classified as long hospitalization cases (LOS+) and their controls and compared against each other for a number of demographic, clinical, and psychopathological features. Results Overall, female sex, current second-generation atypical antipsychotic (SGA)/mood stabilizer other than lithium as well as antidepressant treatment at the admission occurred statistically more frequently among LOS+ cases, concordant with higher scores at the Hamilton scales for depression and anxiety. Lithium utilization at the time of hospitalization did not differ between cases and controls (LOS-, n = 81/119), as predominant affective temperament and other psychopathological rating did not. Overall, the time of admission, use of SGA, anticonvulsant (other than lithium), antidepressant, lifetime alcohol dependence, and BD Type (-I or -II), but not current mood polarity at the time of hospitalization, correctly predicted LOS+ grouping 68.2% of the times: Exp(B) = 3.151, p042. Limitations Post-hoc, cross-sectional study, relatively small sample size, recall and selection bias on some diagnoses. Conclusions Overall, LOS+ treatment-resistant BD inpatients characterize for higher severity and greater pharmaco-utilization use, which warrants replication studies to include additional predictors to shed further light on the matter.

Introduction: Bipolar disorder (BD) is a considerable burden to the affected individual. The need for novel drug targets and improved drug design (DD) in BD is therefore clear. Areas covered: The following article provides a brief, narrative, clinician-oriented overview of the most promising novel pharmacological targets for BD along with a concise overview regarding the general DD process and the unmet needs relevant to BD. Expert opinion: A number of novel potential drug targets have been investigated. With the notable exception of the kynurenine pathway, available evidence is too scarce to highlight a definitive roadmap for forthcoming DD in BD. BD itself may present with different facets, as it is a polymorphic clinical spectrum. Therefore, promoting clinical-case stratification should be based on precision medicine, rather than on novel biological targets. Furthermore, the full release of raw study data to the scientific community and the development of uniform clinical trial standards (including more realistic outcomes) should be promoted to facilitate the DD process in BD.

Background Schizophrenia is a complex illness in which genetic, environmental, and epigenetic components have been implicated. However, recently, psychiatric disorders appear to be related to a chronic inflammatory state, at the level of specific cerebral areas which have been found as well impaired and responsible for schizophrenia symptomatology. Hence, a role of inflammatory mediators and cytokines has been as well defined. Accordingly, the role of an acute inflammatory phase protein, the C-reactive protein (CRP) has been recently investigated. Objective The objective of the present study is to evaluate how PCR may represent a biomarker in schizophrenia, i.e. correlated with illness phases and/or clinical manifestation and/or psychopathological severity. Methods A systematic review was here carried out by searching the following keywords ((C-reactive protein AND ((schizophrenia) OR (psychotic disorder))) for the topics 'PCR' and 'Schizophrenia', by using MESH terms. Results An immune dysfunction and inflammation have been described amongst schizophrenic patients. Findings reported elevated CRP levels in schizophrenia, mainly correlated with the severity of illness and during the recrudescent phase. CRP levels are higher when catatonic features, negative symptomatology and aggressiveness are associated. CRP levels appeared not to be related to suicidal behaviour and ideation. Conclusion CRP and its blood levels have been reported higher amongst schizophrenic patients, by suggesting a role of inflammation in the pathogenesis of schizophrenia. Further studies are needed to better understand if CRP may be considered a biomarker in schizophrenia.

• Creativity may be proposed as a bridge between free association and psychiatric disorders in a perspective in which creativity could have neural biomarkers linked one side to free association and to psychiatric diseases too.

Background: Vortioxetine (VRX) is a multimodal antidepressant that acts as serotonin (5HT) transporter inhibitor as well as 5HT 3A and 5HT 7 receptors antagonist, 5HT 1A and 5HT 1B receptors partial agonist. It was recently approved in the US and the EU for the treatment of adult patients with Major Depressive Disorder (MDD). Objective: The present article aims at systematically reviewing findings of the published and unpublished research on the pharmacological properties, efficacy, safety and tolerability of oral VRX in the treatment of MDD. Method: A systematic review, in accordance with the Cochrane Collaboration and the PRISMA guidelines, was conducted searching the electronic databases MEDLINE, by combining the following keyterms: ((vortioxetine OR LU AA21004 OR brintellix) AND (antidepressant OR depression OR major depressive disorder), without language/time restrictions. Further studies were retrieved from reference listing of relevant articles or manual search. Preclinical and clinical studies (RCT and open label trials) were here retrieved. Results: Several placebo-controlled and active-treatment studies demonstrated the antidepressant efficacy and tolerability of VRX in adult patients affected with MDD. In addition, VRX seems to own procognitive activity. VRX seems generally well tolerated, without significant cardiovascular or weight gain effects. The most common adverse events reported included nausea, vomiting, hyperhidrosis, headache, dizziness, somnolence, diarrhoea and dry mouth. Conclusion: Overall, placebo controlled and active treatment trials support that VRX is effective and well tolerated in MDD. Its combined serotonin reuptake inhibition with agonism, partial agonism and antagonism of a number of receptors might provide a broader spectrum of antidepressant activity than currently available agents.

Background: NPS belonging to the benzodiazepine (BZD) class, e.g., ‘legal/designer BZDs’/‘research chemicals’, have recently emerged in the drug (mainly online/virtual) market. Objective: While certain NPS belonging to the BZD class possess pharmacological profiles similar to controlled pharmaceutical BZDs, clinical and pharmacological profiles of current emerging BZDs are still not well-described. Therefore, there is a need to increase clinicians’/public health knowledge/awareness, to incentive harm reduction strategies. Methods: A comprehensive overview was carried out by using the EMCDDA/EDND database regularly monitored by our research team, by specifically looking at the ‘new BZDs’ so far notified. Furthermore, given the limitation of peer-reviewed data published so far, a nonparticipant multilingual qualitative netnographic study was conducted to obtain further clinical/pharmacological/ toxicological data, including psychonauts’ online trip reports. Results: First designer BZDs appeared as NPS around 2007. So far, 29 designer BZDs have been notified to the EMCDDA, being some of them extremely powerful, also at lower dosages. They are sold as tablets/powder/pellets/capsules/blotters/liquids, at very affordable prices, and variably administered. Some are also sold on the illicit drugmarket as counterfeit forms of traditional BZDs or as either adulterants or diluents in heroin or other synthetic opioids/cannabinoids. Nowadays, there is no guarantee of the quality of designer BZDs composition/purification and, hence, most NPS consumers may be inadvertently exposed to unsafe and harmful compounds. Conclusions: Given the limited information on their pharmacology/toxicity, variations in dosage, onset of effects, combination of substances, potency, and general patient or individual variability, the concomitant use of these substances with other drugs entails several and unpredictable risks.

Background and Objectives: Post-traumatic stress disorder (PTSD) is a common psychiatric disorder resulting from a traumatic event, is manifested through hyperarousal, anxiety, depressive symptoms, and sleep disturbances. Despite several therapeutic approaches being available, both pharmacological and psychological, recently a growing interest has developed in using cannabis and synthetic cannabinoids stems from their consideration as more efficient and better tolerated alternatives for the treatment of this condition. The present paper aims to evaluate the clinical and therapeutic potentials of medical cannabis and synthetic cannabinoids in treating PTSD patients. Methods: A systematic electronic search was performed, including all papers published up to May 2019, using the following keywords (((cannabis[Title/Abstract]) OR (synthetic cannabinoids [Title/Abstract])) AND ((PTSD[Title/Abstract]) OR (Posttraumatic stress disorder[Title/Abstract]))) for the topics ‘Cannabis’, ‘Synthetic Cannabinoids’, ‘PTSD’, and MESH terms, on the PubMed, Cochrane Library, and Web of Science online databases. For data gathering purposes, PRISMA guidelines were followed. Results were organized into two groups, considering cannabis and synthetic cannabinoids as different therapeutic approaches for PTSD. Results: Present data show that cannabis and synthetic cannabinoids, both acting on the endocannabinoids system, may have a potential therapeutic use for improving PTSD symptoms, e.g., reducing anxiety, modulating memory-related processes, and improving sleep. Conclusions: Even though the current literature suggests that cannabis and synthetic cannabinoids may have a role in the treatment of PTSD, there is currently limited evidence regarding their safety and efficacy. Therefore, additional research is needed in order to better understand the effectiveness and therapeutic usage of these drug classes and monitor their safety.

Depressive disorders represent protean psychiatric illnesses with heterogeneous clinical manifestations and a multitude of comorbidities leading to severe disability. In spite of decades of research on the pathophysiogenesis of these disorders, the wide variety of pharmacotherapies currently used to treat them is based on the modulation of monoamines, whose alteration has been considered the neurobiological foundation of depression, and consequently of its treatment. However, approximately one third to a half of patients respond partially or become refractory to monoamine-based therapies, thereby jeopardizing the therapeutic effectiveness in the real world of clinical practice. Recent scientific evidence has been pointing out the essential role of other biological systems beyond monoamines in the pathophysiology of depressive disorders, in particular, the glutamatergic neurotransmission. In the present review, we will discuss the most advanced knowledge on the involvement of glutamatergic system in the molecular mechanisms at the basis of depression pathophysiology, as well as the glutamate-based therapeutic strategies currently suggested to optimize depression treatment (e.g., ketamine). Finally, we will mention further “neurobiological targeted” approaches, based on glutamate system, with the purpose of promoting new avenues of investigation aiming at developing interventions that overstep the monoaminergic boundaries to improve depressive disorders therapy.