•A history of psychotic features affects the course of Bipolar Disorder type I (BDI).•A deficit in sustained attention has been proposed as a cognitive trait marker for BDI.•Euthymic psychotic BDI differ from non-psychotic BDI in terms of brain activations during a sustained attention task.•Psychotic BDI patients showed altered activations of left-sided regions.•Non-psychotic BDI patients showed right-sided functional alterations.

Objectives: Bipolar disorder (BD) patients with a comorbid substance use disorder (SUD) are notoriously difficult to treat. Atypical antipsychotics (AAPs) are widely prescribed in BD, but their efficacy in patients with comorbid SUD is still debated. The aim of the present article is to systematically review the literature findings on the efficacy and safety of AAPs in BD patients with comorbid SUD. Methods: We searched PubMed to identify original studies focused on the treatment of dual diagnosed BD with AAPs. Results: Ten articles met our inclusion/exclusion criteria, involving a total of 969 subjects, 906 affected by BD and 793 with comorbid SUD: 4 were randomized controlled trials, 4 were open label trials and 2 were observational studies, published between 2002 and 2017. The most commonly abused substances were alcohol and cocaine. The AAPs used to treat patients were quetiapine (n = 337), asenapine (n = 119), olanzapine (n = 80), risperidone (n = 62), and aripiprazole (n = 48). In terms of safety, AAPs were usually well tolerated. Atypical antipsychotics were usually efficacious on acute mood symptoms, whereas their impact on substance-related issues was reported only in those studies without a placebo comparison. Conclusions: According to our results, even though AAPs are widely used and efficacious in treating the clinical symptoms of BD, there are not enough data to suggest their adjunctive benefit on craving and substance consumption.

In recent years, neuroscientific research into the brain bases of the self and its socio-relational nature has been conducted by experimental models of functional neuroimaging. In this editorial are explored the correspondence between the semantic anthropo-phenomenology of the German psychiatrist Jurg Zutt (1893-1980), and recent neuroscientific theories about different, but complementary, perspectives on the self and self-other relationship. In particular, we discuss the theoretical correlation between the Zutt’s concept of “Internal Attitude” and aberrant functioning of brain networks involved in self-related processing including the default mode network, the salience network and sensorimotor networks in patients with schizophrenia when solicited by socio-relational stimuli. The aim of this editorial is not only to propose a synthesis between the anthropological and neuroscientific perspectives, but, above all, to invoke a language that takes into account the human being in unison with the complexity of

The encoding of the space close to the body, named peri-personal space (PPS), is thought to play a crucial role in the unusual experiences of the self observed in schizophrenia (SCZ). However, it is unclear why SCZ patients and high schizotypal (H-SPQ) individuals present a narrower PPS and why the boundaries of the PPS are more sharply defined in patients. We hypothesise that the unusual PPS representation observed in SCZ is caused by an imbalance of excitation and inhibition (E/I) in recurrent synapses of unisensory neurons or an impairment of bottom-up and top-down connectivity between unisensory and multisensory neurons. These hypotheses were tested computationally by manipulating the effects of E/I imbalance, feedback weights and synaptic density in the network. Using simulations we explored the effects of such impairments in the PPS representation generated by the network and fitted the model to behavioural data. We found that increased excitation of sensory neurons could account for the smaller PPS observed in SCZ and H-SPQ, whereas a decrease of synaptic density caused the sharp definition of the PPS observed in SCZ. We propose a novel conceptual model of PPS representation in the SCZ spectrum that can account for alterations in self-world demarcation, failures in tactile discrimination and symptoms observed in patients.

BACKGROUND:Compulsive buying disorder (CBD) is a condition characterized by excessive preoccupations, impulses, and behaviors regarding buying, resulting in serious psychological, social, and financial problems. Even though it has not been included in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, "behavioral addictions" section, CBD is a hot topic in current clinical psychiatry, because of its relevant prevalence (at least 5% in adult populations) and severe effect on quality of life.The CBD shares some clinical features with substance-related and behavioral addictions, impulse control disorders, and obsessive compulsive disorder, and it is often comorbid with other psychiatric illnesses (especially depressive and anxiety disorders). The treatment of CBD is therefore difficult, and clear therapeutic guidelines are not yet available. Treating the comorbid disorders as the first-line approach, or combining drugs with different pharmacodynamic profiles, has been suggested to address this challenging condition.CASE:A 60-year-old woman affected by a severe form of CBD with comorbid major depressive disorder, resistant/intolerant to previous selective serotonin reuptake inhibitor treatments and only partially responder to mirtazapine, achieved a good clinical improvement adding bupropion.CONCLUSIONS:Combining 2 agents with different pharmacological profiles and mechanisms of action, such as bupropion and mirtazapine, could be a useful strategy in the management of complex CBD cases.

Schizophrenia has been described as a self-disorder, whereas social deficits are key features of the illness. Changes in "resting state" activity of brain networks involved in self-related processing have been consistently reported in schizophrenia, but their meaning for social perception deficits remains poorly understood. Here, we applied a novel approach investigating the relationship between task-evoked neural activity during social perception and functional organization of self-related brain networks during a "resting state". "Resting state" functional MRI was combined with task-related functional MRI using a social perception experiment. Twenty-one healthy control participants (HC) and 21 out-patients with a diagnosis of schizophrenia (SCH) were included. There were no significant differences concerning age, IQ, education and gender between the groups. Results showed reduced "resting state" functional connectivity between ventromedial prefrontal cortex and dorsal posterior cingulate cortex in SCH, compared to HC. During social perception, neural activity in dorsal posterior cingulate cortex and behavioral data indicated impaired congruence coding of social stimuli in SCH. Task-evoked activity during social perception in dorsal posterior cingulate cortex co-varied with dorsal posterior cingulate cortex-ventromedial prefrontal cortex functional connectivity during a "resting state" in HC, but not in SCH. Task-evoked activity also correlated with negative symptoms in SCH. These preliminary findings, showing disrupted prediction of social perception measures by "resting state" functioning of self-related brain networks in schizophrenia, provide important insight in the hypothesized link between self and social deficits. They also shed light on the meaning of "resting state" changes for tasks such as social perception.

The risk for psychosys at the most urban environment was estimated to be 2.37 times higher than in the most rural environment. In 1903 the sociologist Georg Simmel in a little essay titled “The Metropolis and Mental Life” suggested urban conditions necessitate the creation of a “protective organ” against the intensification of external and internal sensual stimuli in the city as compared to a rural setting. In 2006 Hetrick and Erickson proposed that symptoms of psychosis indicate a primary deficit in mechanisms of attention related to selection and inhibition stimuli. We argue that Simmel’s “protective organ” could be linked to the “Sensory Gating” theory for psychosys by Hetrick and Erickson.

BACKGROUND:Treatment-resistant schizophrenia (TRS) is a condition characterized by intense symptom severity and poor response to different antipsychotic agents. The first therapeutic option in TRS is clozapine, but often high/medium doses are not tolerated. Adding an oral antipsychotic to low doses of clozapine is a promising strategy in the management of TRS. On the contrary, there are few data on combined clozapine/long-acting injectable (LAI) medications, and none on clozapine/LAI-aripiprazole.CASE:A 21-year-old male schizophrenic patient, resistant to several oral and LAI medications, partially improved after clozapine 300 mg/d treatment. Unfortunately, he also reported excessive sedation and an episode of myoclonus, so clozapine was reduced to 150 mg/d, but no additional benefits were observed. Subsequently, LAI-aripiprazole (first 200 mg/mo, then 400 mg/mo) was added, and the patient's conditions dramatically improved over time. After 1 year of observation, symptoms reduction was 50% or greater, without significant adverse events.CONCLUSIONS:Clozapine use in TRS is often reduced or delayed due to the fear of serious adverse effects. Adding LAI-aripiprazole to low doses of clozapine may be a useful therapeutic option to obtain a good efficacy/tolerability balance.

The aim of the present study was to investigate the relationships between alexithymia, suicide ideation, C-Reactive Protein (CRP), and serum lipid levels in adult outpatients with a DSM-IV diagnosis of Generalized Anxiety Disorder (GAD). Seventy consecutive patients with GAD were recruited and evaluated. Measures were the Hamilton Anxiety Scale, the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI), and the Montgomery Åsberg Depression Rating Scale (MADRS). All patients were assessed for: CRP, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceridaemia (TG), and very-low-density lipoprotein cholesterol (VLDL-C). TC/HDL-C and LDL-C/HDL-C ratios were also evaluated. Alexithymic patients showed higher scores on almost all rating scales and altered serum CRP and lipid levels vs. non-alexithymics. In the hierarchical regression model, the presence of higher MADRS scores together with higher scores at the Difficulty in Identifying Feelings dimension of TAS-20 were associated with higher rates of suicide ideation. Although alexithymic subjects with GAD may show a CRP and cholesterol dysregulation, this latter seems independent on increased suicide ideation, rather to Difficulty in Identifying Feelings, and subthreshold depressive symptoms. Study limitations and future research implications are discussed.

Gambling disorder (GD) is a psychiatric condition associated with both social and family costs; DSM-5 currently includes GD among addictive disorders. Despite the high burden of this condition, to date there are no treatment guidelines approved by Food and Drug Administration (FDA). Purpose of this paper is to offer a qualitative overview about the different pharmacologic agents used for the treatment of GD. Our analysis, conducted on a final selection of 75 scientific papers, demonstrates that a variety of pharmaceutical classes have been utilised, with different results. Published data, although limited by brief duration of the studies and small number of enrolled subjects, shows mixed evidence for serotonergic antidepressants, opioid antagonists, and mood stabilizers. Other compounds, such as glutamatergic agents and psychostimulants, deserve further studies.

We investigated the efficacy of S-Adenosyl-L-Methionine (SAMe) augmentation in patients with treatment-resistant depressive disorder (TRD). Thirty-three outpatients with major depressive episode who failed to respond to at least 8 weeks of treatment with two adequate and stable doses of antidepressants were treated openly with fixed dose of SAMe (800 mg) for 8 weeks, added to existing medication. The primary outcome measure was the change from baseline in total score on Hamilton Rating Scale for Depression (HAM-D). The Clinical Global Impression of Improvement (CGI-I) was rated at the endpoint. Patients with a reduction of 50% or more on HAM-D total score and a CGI-I score of 1 or 2 at endpoint were considered responders; remission was defined as a HAM-D score ≤7. Secondary outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Sheehan Disability Scale (SDS). At 8 weeks, a significant decrease in HAM-D score was observed with response achieved by 60% of the patients and remission by 36%. Also a statistically significant reduction in SHAPS and SDS was observed. Our findings indicate that SAMe augmentation may be effective and well tolerated in stage II TRD. However, limitations of the present study must be considered and further placebo-controlled trials are needed.

Scopo. Questo studio ha inteso valutare: 1) i livelli di insicurezza percepita dai pazienti con disturbi mentali; 2) le caratteristiche socio-demografiche e cliniche dei pazienti che presentano livelli più elevati d’insicurezza percepita e le cause della loro insicurezza; 3) l’incidenza dei reati subiti. Metodi. I dati sono stati raccolti presso gli ambulatori di 24 centri di salute mentale italiani, reclutati attraverso la rete del Coordinamento Nazionale dei Giovani Psichiatri della Società Italiana di Psichiatria nel periodo febbraio-aprile 2011. I primi 20 pazienti che si sono recati presso il CSM nel periodo considerato sono stati invitati a partecipare e valutati con strumenti di misura standardizzati. Risultati. I 426 pazienti reclutati sono prevalentemente di sesso femminile (70,1%), con un’età media di 45 anni (±13,5) e un buon livello di scolarizzazione. Il 52% dei pazienti ha una diagnosi di disturbo dell’umore, il 37,8% di disturbo d’ansia. Il 43% del campione indica l’incertezza come sentimento prevalente. Il 93% del campione ritiene di avere delle paure, tra le quali più frequenti sono lutti o perdite (41,2%), difficoltà economiche (28,4%) e malattie fisiche o psichiche (26,5%). Discussione e conclusioni. I nostri risultati indicano un senso diffuso di incertezza percepita, come probabile conseguenza del periodo storico che stiamo vivendo. È verosimile che questo sentimento abbia un notevole impatto anche sul benessere psicofisico dei pazienti, contribuendo a un peggioramento dello stato psicopatologico. Studi futuri sono necessari per approfondire la relazione tra paure, insicurezza e disturbi mentali.

Background: Following the characterization of the chemical structure of D9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, researchers have moved on with scientific valuable explorations. Objectives: The aim of this review is to highlight the role of endocannabinoid system in neurodegenerative diseases. Materials and Methods: The article is a critical analysis of the most recent data currently present in scientific literature on the subject; a qualitative synthesis of only the most significant articles has been performed. Results: In central nervous system, endocannabinoids show a neuromodulatory function, often of retrograde type. This way, they play an important role in synaptic plasticity and in cognitive, motor, sensory and affective processes. In addition, in some acute or chronic pathologies of central nervous system, such as neurodegenerative and neuroinflammatory diseases, endocannabinoids can perform a pro-homeostatic and neuroprotective function, through the activation of CB1 and CB2 receptors. Scientific evidence shows that an hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases. Conclusions: The important role played by endocannabinoid system promises interesting developments, in particular to evaluate the effectiveness of new drugs in both psychiatry and neurology.

Schizophrenic patients may report unusual perception of their own body. Studies using the rubber hand illusion (RHI) proposed that they exhibit a distorted sense of body ownership. However, since the RHI is mostly achieved with the contribution of visuo-tactile integration, the stronger RHI observed in schizophrenic patients could reflect either a general increase of the response to multisensory stimuli or a larger influence of visual cues on the tactile sensory experience. The purpose of the present study is to investigate patients' perception of their own body by means of a behavioral paradigm that measures their proneness to the RHI without relying on multisensory integration occurring during actual experience of touch. In a previous study we demonstrated in healthy participants that expectation of touch experience arising at the sight of a human hand approaching a rubber hand is enough to induce a sense of ownership over the same hand. Here we take advantage of the same paradigm to investigate body ownership in schizophrenia. Patients observed the experimenter's hand while approaching – without touching – either a rubber hand or a piece of wood placed in front of them. The seen object could be either aligned to participant's hand or rotated by 180°. Phenomenology of the illusion revealed that schizophrenic patients exhibited sense of ownership over the rubber hand, but more weakly than healthy controls. The present study sheds new light on the experience of body ownership in schizophrenic patients, corroborating the notion that alterations of bodily self-awareness play an important role in schizophrenia.

To elucidate the relationships between alexithymia, suicide ideation and serum lipid levels in drug-naïve adult outpatients with a DSM-IV diagnosis of Panic Disorder (PD), 72 patients were evaluated. Measures were the Panic Attack and Anticipatory Anxiety Scale, the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI) and the Montgomery Åsberg Depression Rating Scale (MADRS). Alexithymic patients showed higher scores on all rating scales and altered serum lipid levels than non-alexithymics. In the hierarchical regression model, the presence of lower HDL-C and higher VLDL-C levels and Difficulty in Identifying Feelings dimension of TAS-20 were associated with higher suicide ideation. In conclusion, alexithymic individuals with PD may show a cholesterol dysregulation that may be linked to suicide ideation. The authors discuss study limitations and future research needs.

AIMS:To assess in a sample of people with mental disorders: 1) fear of crime and perceived insecurity; 2) the association between fear of crime and insecurity; 3) the incidence of crimes.METHODS:Twenty-four Italian mental health centres have been invited to participate in the study from the network of the Early Career Psychiatrists' Committee of the Italian Psychiatric Association. In each participating centre, the first 20 patients consecutively accessing the mental health centre between February and April 2011 have been recruited. All patients have been assessed using validated assessment tools.RESULTS:The final sample consists of 426 patients. They are mostly female (70.1%), with a mean age of 45 years (± 13.5), and with a good level of education. Fifty-two percent of patients have a diagnosis of mood disorders, and 37.8% on anxiety spectrum disorders. About half of the sample declares that the most prominent feeling toward life is uncertainty. Almost all patients report to have at least one big fear, with the most frequently report being: 1) loss or death of a loved one (41.2%); 2) financial constraint (28.4%); 3) physical or mental health problems (26.5%).DISCUSSION AND CONCLUSIONS:Our results show the presence of a common sense of uncertainty among patients, probably as a result of the historical moment we are facing. It is reasonable that this attitude toward life can have a detrimental impact on patients' psychological and physical wellbeing, contributing to high levels of distress. Further studies are needed in order to clarify the possible relationship between fears, uncertainty and mental disorders.

The primary aim of the present study was to compare the effects of agomelatine (AGO) and venlafaxine XR (VLX) on anhedonia in patients with major depressive disorder. Secondary end points were to test its antidepressant and anxiolytic efficacy.Sixty patients were enrolled and randomly assigned to two different treatments: AGO (25-50 mg/d; n = 30 subjects) or VLX (75-150 mg/d, n = 30 subjects). Psychopathological assessment was performed at baseline and after 8 weeks of treatment with the Snaith Hamilton Rating Scale (SHAPS), the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression for anhedonia, depression, anxiety, and global improvement, respectively.Both groups showed a significant reduction in time for the SHAPS, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. A significant between-group difference was observed for SHAPS scores: patients treated with AGO showed a more relevant reduction compared with that in VLX-treated patients. Moreover, only patients treated with AGO showed a statistically significant improvement in Clinical Global Impression scores.In this study, AGO showed significantly greater efficacy on anhedonia and similar antidepressant efficacy to the serotonin-norepinephrine reuptake inhibitor VLX in patients with major depressive disorder during an 8-week treatment period. Anhedonia has been considered a potential trait marker related to vulnerability for depression. Therefore, the efficacy of AGO on this dimension holds particular importance in the treatment of patients with anhedonic features.

Cannabis is among the most widely used illicit substances. Epidemiological and neuroscientific evidence, though poorly integrated, have established a strong association between cannabis use and increased risk of psychosis. Chronic cannabis use, especially of new synthetic varieties, may trigger psychosis and precipitate schizophrenia in vulnerable individuals. However, the specific pathways by which cannabis affects brain function are unclear. It seems likely that a complex genetic-environmental interaction may underlie the link between cannabis exposure and psychosis onset, with multiple genetic variations and several environmental factors (i.e., trauma or maltreatment during childhood) involved. Also, the possible role of basic symptoms in cannabis users is still not fully acknowledged. Basic symptoms may possibly be a marker for the development of full schizophrenia in cannabis users and their recognition may play a role in prevention strategies. Moreover, the differential impact of different types of cannabis has been generally overlooked and little is known about possible pharmacological treatment approaches (with antipsychotics, cannabis agonists, cannabis antagonists) for cannabis users at risk of psychosis. The aim of the present review is to open this issue with a broad introduction on the clinical and pathophysiological link between cannabis abuse and psychosis onset.

Introduction: Depression is a common disorder associated with significant disability and is a substantial burden on the individual, their relatives and friends, and on society as a whole. Sleep disturbances are key features of depressive symptomatology, with more than 80% of depressed patients complaining of poor quality sleep. Methods: The range of available antidepressants is here reviewed in relation to mechanisms of action and the evidence of sleep alteration in patients with depression. Results: The available treatments are largely effective but their use is compromised by poor tolerability and low adherence to treatment. It is also clear that currently used antidepressant agents tend to disrupt sleep architecture. Agomelatine, a novel antidepressant, has been found successful in treating depressed patients. Because of its dual mechanism of action on MT1 and MT2 melatonin receptors in the SCN and its 5-HT2c antagonist properties, agomelatine has been effective in improving both quality of sleep and mood in depressed patients. Conclusions: There is clinical and epidemiological evidence that sleep disturbances in depression constitute a risk factor for poor clinical outcomes. Specifically, insomnia complaints precede the onset and recurrence of depression. For this rea- son antidepressants with a faster onset of action, with less interferences on sleep architecture would be expected to bring larger numbers of depressed patients to full remission.