A 6-month follow-up study on response and relapse rates following an acute trial of repetitive transcranial magnetic stimulation in patients with major depression.

BACKGROUND: Little is known about the post-acute effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The present study focused on the 6-month follow-up of a sample of patients with major depression, after the completion of an acute 4 weeks rTMS trial, with the aim of evaluating response (in terms of sustained and late response) and relapse rates. METHODS: Following the completion of an acute trial of rTMS (T0-T4), 31 drug-resistant depressed patients (bipolar or unipolar) entered a naturalistic follow-up period of 6 months, with three timepoints (T5, T6, and T7) during which they were assessed with the Hamilton Depression Rating Scale and the Young Mania Rating Scale. RESULTS: Results showed that in the 6 months following an acute transcranial magnetic stimulation (TMS) trial, a higher rate of late responders was observed among previously acute TMS nonresponders (63.64%, 7 out of 11) compared to the rate of relapse among those who had acutely responded to TMS (10%, 2 out of 20). In addition, an overall high rate of maintained response (90%) was observed. CONCLUSION: Present findings seem to support the possibility of obtaining a clinical response also after the end of an acute TMS trial in patients with major depression. The concomitant low rate of relapse observed at the end of follow-up along with a high rate of maintained response provides further support to the post-acute efficacy of TMS. Nonetheless, further controlled studies, with larger samples and longer follow-up observation, are needed to confirm the reported results.

The metabolic basis of psychosis in bipolar disorder: A positron emission tomography study.

OBJECTIVES: Psychotic symptoms are a common feature in bipolar disorder (BD), especially during manic phases, and are associated with a more severe course of illness. However, not all bipolar subjects experience psychosis during the course of their illness, and this difference often guides assessment and pharmacological treatment. The aim of the present study is to elucidate, for the first time, the FDG uptake dysfunctions associated with psychosis in BD patients with and without a history of past psychotic symptoms, through a positron emission tomography (PET) approach. METHODS: Fifty BD patients with lifetime psychotic symptoms, 40 BD patients without lifetime psychotic symptoms and 27 healthy controls (HC) were recruited and underwent an 18F-FDG-PET session. RESULTS: Compared to HC, BD subjects shared common FDG uptake deficits in several brain areas, including insula, inferior temporal gyrus and middle occipital gyrus. Moreover, we found that BD patients with a history of past psychotic symptoms had a unique FDG uptake alteration in the right fusiform gyrus compared to both BD patients without lifetime psychotic symptoms and HC (all P < 0.01, cFWE corrected). CONCLUSIONS: Overall, our results suggest that FDG uptake alterations in brain regions involved in emotion regulation are a key feature of BD, regardless the presence of past psychosis. Finally, we demonstrated that the FDG uptake reduction in fusiform gyrus is associated with the presence of past psychotic symptoms in BD, ultimately leading towards the idea that the fusiform gyrus might be considered a putative biomarker of psychosis.

Exploring characteristics associated with first benzodiazepine prescription in patients with affective disorders and related diagnoses.

OBJECTIVE: In patients with affective disorders, benzodiazepines (BZDs) are frequently administered at the onset, sometimes inappropriately. We sought to identify clinical variables associated with first BZD prescription in a large sample of patients with affective disorders. METHODS: Four hundred sixty patients with mood or anxiety disorders attending different psychiatric services were assessed comparing those who received BZD as first treatment (BZD w/) and those who did not (BZD w/o). RESULTS: More than one third (35.7%) of the total sample had received BZDs as first prescription. In relation to mood disorders, BZD w/ subjects more frequently (a) had not a psychiatrist as first therapist, (b) had anxious symptoms at onset, (c) had adjustment disorder as first diagnosis, (d) were treated as outpatients. In relation to specific diagnoses, (a) personal decision of treatment for major depressive disorder, (b) outpatient status for bipolar disorder and (c) longer duration of untreated illness for adjustment disorder were more frequently associated with first BZD prescription. For anxiety disorders, the presence of stressful life events and the diagnoses of panic disorder or specific phobias were more frequently observed in BZD w/ patients. CONCLUSION: Patients with affective disorders frequently received BZDs as first prescription with significant differences between and within mood and anxiety disorders.

Italian patients with more recent onset of Major Depressive Disorder have a shorter duration of untreated illness.

BACKGROUND: Previous investigation on the duration of untreated illness (DUI) in patients with Major Depressive Disorder (MDD) revealed a different latency to first antidepressant treatment, with adverse consequences in terms of outcome for individuals with a longer DUI. Recent reports, moreover, documented a reduced DUI, as observed with the passage of time, in patients with different psychiatric disorders. Hence, the present study was aimed to assess DUI and related variables in a sample of Italian patients with MDD as well as to investigate potential differences in subjects with onset before and after 2000. METHODS: An overall sample of 188 patients with MDD was assessed through a specific questionnaire investigating DUI and other variables related to the psychopathological onset and latency to first antidepressant treatment, after dividing them in two different subgroups on the basis of their epoch of onset. RESULTS: The whole sample showed a mean DUI of approximately 4.5 years, with patients with more recent onset showing a significantly shorter latency to treatment compared with the other group (27.1±42.6 vs 75.8±105.2 months, P<.05). Other significant differences emerged between the two subgroups, in terms of rates of onset-related stressful events and benzodiazepine prescription, respectively, higher and lower in patients with more recent onset. CONCLUSIONS: Our findings indicate a significant DUI reduction in MDD patients whose onset occurred after vs before 2000, along with other relevant differences in terms of onset-related correlates and first pharmacotherapy. Further studies with larger samples are warranted to confirm the present findings in Italy and other countries.

Access and latency to first antipsychotic treatment in Italian patients with schizophrenia and other schizophrenic spectrum disorders across different epochs.

BACKGROUND: The duration of untreated illness (DUI) is a measure to express the latency to first psychopharmacological treatment: it differs among psychiatric disorders, being influenced by several illness-intrinsic and environmental factors. The present study aimed to assess differences in DUI and related variables in patients with schizophrenia (SKZ) versus other schizophrenic spectrum disorders (SSDs) across different epochs. METHODS: 101 SKZ or SSD patients were assessed with respect to DUI and related variables through clinical interview and questionnaire. RESULTS: Patients with SKZ showed earlier ages of onset, first diagnosis and first antipsychotic treatment compared with patients with other SSDs (F = 11.02, p < 0.001; F = 12.68, p < 0.001; F = 13.74, p < 0.001, respectively) who showed an earlier access to benzodiazepines than SKZ patients (F = 6.547; p < 0.05). Dividing the total sample by the epoch of onset (before 1978; between 1978-2000; after 2000) showed a significantly later age of onset in patients with onset within the two most recent epochs (F = 7.46; p < 0.001) and a reduced DUI across epochs (from 144 to 41 to 20 months, on average; F = 11.78, p < 0.001). CONCLUSION: Schizophrenic patients showed earlier onset and longer DUI compared with patients with other SSDs. Data on the total sample showed a later age of onset and a reduced DUI across epochs.

S-adenosyl methionine (SAMe) for depression in adults.

BACKGROUND: Depression is a recurrent illness with high rates of chronicity, treatment-resistance and significant economic impact. There is evidence in the literature that S-adenosyl methionine (SAMe), a naturally occurring compound in the human body, has antidepressant efficacy. This product may be an important addition to the armamentarium of antidepressant agents. OBJECTIVES: To assess the effects of SAMe in comparison with placebo or antidepressants for the treatment of depression in adults. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Group's Specialised Register (CCMDCTR Studies and Reference Register), MEDLINE, EMBASE, PsycINFO, international trial registers ClinicalTrials.gov and the World Health Organization trials portal (ICTRP). We checked reference lists, performed handsearching and contacted experts in the field. The CCMDCTR literature search was last updated on 5 February 2016. SELECTION CRITERIA: Randomised controlled trials comparing SAMe with placebo or antidepressants in adults with a diagnosis of major depression. DATA COLLECTION AND ANALYSIS: Two authors independently performed extraction of data and assessment of risk of bias. We contacted trialists of included studies for additional information. MAIN RESULTS: This systematic review included eight trials comparing SAMe with either placebo, imipramine, desipramine or escitalopram. We accepted trials that used SAMe as monotherapy or as add-on therapy to selective serotonin reuptake inhibitors (SSRIs), and we accepted both oral and parenteral administration. The review involved 934 adults, of both sexes, from inpatient and outpatient settings.The trials were at low risk of reporting bias. We judged the risk of selection, performance, detection and attrition bias as unclear or low, and one study was at high risk of attrition bias.There was no strong evidence of a difference in terms of change in depressive symptoms from baseline to end of treatment between SAMe and placebo as monotherapy (standardised mean difference (SMD) -0.54, 95% confidence interval (CI) -1.54 to 0.46; P = 0.29; 142 participants; 2 studies; very low quality evidence). There was also no strong evidence of a difference in terms of drop-out rates due to any reason between SAMe and placebo, when used as monotherapy (risk ratio (RR) 0.88, 95% CI 0.61 to 1.29; P = 0.52; 142 participants; 2 studies; low quality evidence).Low quality evidence showed that the change in depressive symptoms from baseline to end of treatment was similar between SAMe and imipramine, both as monotherapy (SMD -0.04, 95% CI -0.34 to 0.27; P = 0.82; 619 participants; 4 studies). There was also no strong evidence of a difference between SAMe and a tricyclic antidepressant in terms of drop-outs due to any reason (RR 0.61, 95% CI 0.28 to 1.31; P = 0.2; 78 participants; 3 studies; very low quality evidence).There was little evidence of a difference in terms of change in depressive symptoms from baseline to end of treatment between SAMe and escitalopram, both as monotherapy (MD 0.12, 95% CI -2.75 to 2.99; P = 0.93; 129 participants; 1 study; low quality evidence). There was no strong evidence of a difference between SAMe and escitalopram in terms of drop-outs due to any reason (RR 0.81, 95% CI 0.57 to 1.16; P = 0.26; 129 participants; 1 study; low quality evidence).There was low quality evidence that SAMe is superior to placebo as add-on to SSRIs in terms of change in depressive symptoms from baseline to end of treatment (MD -3.90, 95% CI -6.93 to -0.87; P = 0.01; 73 participants; 1 study). There was no strong evidence of a difference between SAMe and placebo as adjunctive therapy to an SSRI in terms of drop-outs due to any reason (RR 0.70, 95% CI 0.31 to 1.56; P = 0.38; 73 participants; 1 study; very low quality evidence).For all comparisons, secondary outcome measures of response and remission rates were consistent with these primary outcome measures.With regard to all extractable measures of the acceptability of SAMe, the quality of the evidence was low to very low. SAMe was not different from placebo and established antidepressants. The exception was that compared to imipramine, fewer participants experienced troublesome adverse effects when treated with parenteral SAMe.The specific adverse effects were not detailed in most of the included studies. There were two reports of mania/hypomania recorded for 441 participants in the SAMe arm. AUTHORS' CONCLUSIONS: Given the absence of high quality evidence and the inability to draw firm conclusions based on that evidence, the use of SAMe for the treatment of depression in adults should be investigated further. Future trials should be in the form of large randomised controlled clinical trials of high methodological quality, with particular attention given to randomisation, allocation concealment, blinding and the handling of missing data. Comparator antidepressants from all classes should be used. Adverse events should be detailed for each participant, bearing in mind that induction of mania is of particular interest.

Reduced duration of untreated illness over time in patients with schizophrenia spectrum, mood and anxiety disorders.

AIMS: Psychiatric disorders represent highly impairing conditions, often underdiagnosed and undertreated, with a conspicuous duration of untreated illness (DUI). Given that social and cultural factors influence the DUI and assuming that progress in diagnosis and treatment determines a reduced latency to pharmacotherapy, we assessed and compared DUI and related variables in a large sample of psychiatric patients (n = 562) whose onset occurred within three different a priori-defined epochs. METHODS: Two temporal cut-offs were established - the year 1978, when Law 180 (redefining standards for mental care) was introduced in Italy, and the year 2000 - in order to divide patients into three subgroups: onset before 1978, onset 1978-2000 and onset after 2000. RESULTS: A significant difference in terms of age at onset, age at first diagnosis and age at first treatment was observed in patients with onset 1978-2000 and in those with onset after 2000. In addition, a significant reduction of the DUI was found across epochs (onset before 1978: 192.25 ± 184.52 months; onset 1978-2000: 77.00 ± 96.63 months; and onset after 2000: 19.00 ± 31.67 months; P < 0.001). Furthermore, the proportion of patients with onset-related stressful events, use of benzodiazepines and neurological referral was found to be significantly different between the three epochs (χ(2) = 23.4, P < 0.001; χ(2) = 9.92, P = 0.007; χ(2) = 16.50, P = 0.011). CONCLUSIONS: Present data indicate a progressive, statistically significant reduction of latency to treatment and other related changes across subsequent epochs of onset in patients with different psychiatric disorders. Future studies will assess specific changes within homogeneous diagnostic subgroups.

Differences in duration of untreated illness, duration, and severity of illness among clinical phenotypes of obsessive-compulsive disorder.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a prevalent, disabling, and comorbid condition that is frequently under-recognized and poorly treated. OCD phenotypes may differ in terms of clinical presentation and severity. However, few studies have investigated whether clinical phenotypes differ in terms of latency to treatment (ie, duration of untreated illness[DUI]), duration, and severity of illness. The present study was aimed to quantify the aforementioned variables in a sample of OCD patients. METHODS: One hundred fourteen outpatients with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnosis of OCD were recruited, and their main clinical features were collected. Severity of illness was assessed through the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and the main phenotypes were identified through the Y-BOCS Symptom Checklist. A one-way analysis of variance (ANOVA) test, followed by a Bonferroni post-hoc test, were performed to compare DUI, duration, and severity of illness across subgroups. RESULTS: In the whole sample, the mean DUI exceeded 7 years (87.35±11.75 months), accounting for approximately half of the mean duration of illness (172.2±13.36 months). When subjects were categorized into 4 main clinical phenotypes, respectively, aggressive/checking (n=31), contamination/cleaning (n=37), symmetry/ordering (n=32), and multiple phenotypes (n=14), DUI, duration, and severity of illness resulted significantly higher in the aggressive/checking subgroup, compared to other subgroups (F=3.58, p<0.01; F=3.07, p<0.01; F=4.390, p<0.01). DISCUSSION: In a sample of OCD patients, along with a mean latency to treatment of approximately 7 years, regardless of the phenotype, patients had spent half of their duration of illness (DI) without being treated. DUI, duration, and severity of illness resulted significantly higher in the aggressive/checking subgroup.

Prevalence and disability of comorbid social phobia and obsessive-compulsive disorder in patients with panic disorder and generalized anxiety disorder.

OBJECTIVE: Generalized anxiety disorder (GAD) and panic disorder (PD) are disabling conditions, often comorbid with other anxiety disorders. The present study was aimed to assess prevalence and related disability of comorbid social phobia (SP) and obsessive-compulsive disorder (OCD) in 115 patients with GAD (57) or PD (58). METHODS: Patients were classified as having threshold, subthreshold, or no comorbidity, and related prevalence rates, as well as disability (Sheehan Disability Scale, SDS), were compared across diagnostic subgroups. RESULTS: SP and OCD comorbidities were present in 30.4% of the sample, with subthreshold comorbidities present at twice the rate of threshold ones (22.6% vs. 11.3%). Compared with GAD patients, PD patients showed significantly higher subthreshold and threshold comorbidity rates (27.6% and 13.8% vs. 17.5% and 8.8%, respectively). Comorbid PD patients had higher SDS scores than the comorbid and non-comorbid GAD subjects. The presence of threshold SP comorbidity was associated with the highest SDS scores. CONCLUSIONS: SP and OCD comorbidities were found to be prevalent and disabling among GAD and PD patients, with higher subthreshold than threshold rates, and a negative impact on quality of life. Present findings stress the importance of a dimensional approach to anxiety disorders, the presence of threshold and subthreshold comorbidity being the rule rather than the exception.

Vagus nerve stimulation in treatment-resistant depression: acute and follow-up results of an italian case series.

The present study evaluated short- and long-term efficacy and tolerability of augmentative vagus nerve stimulation (VNS) in a group of patients with treatment-resistant depression (N = 6). A statistically significant improvement in the Hamilton Depression Rating Scale (HDRS21) and Montgomery-Asberg Depression Rating Scale after 3 months (P = 0.039 and P = 0.05, respectively) was found in comparison with baseline (VNS implant). After 12 months, a statistically significant improvement was observed in the Hamilton Depression Rating Scale (HDRS21), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impression (P = 0.01, P = 0.005, and P = 0.001, respectively). Patients showed an overall favorable tolerability. Present data support VNS short- and long-term efficacy and tolerability in a small group of patients with treatment-resistant depression. Further controlled investigation is necessary to confirm the present open findings.

Zinc as a Neuroprotective Nutrient for COVID-19-Related Neuropsychiatric Manifestations: A Literature Review.

The outbreak of the pandemic associated with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) led researchers to find new potential treatments, including nonpharmacological molecules such as zinc (Zn2+). Specifically, the use of Zn2+ as a therapy for SARS-CoV-2 infection is based on several findings: 1) the possible role of the anti-inflammatory activity of Zn2+ on the aberrant inflammatory response triggered by COronaVIrus Disease 19 (COVID-19), 2) properties of Zn2+ in modulating the competitive balance between the host and the invading pathogens, and 3) the antiviral activity of Zn2+ on a number of pathogens, including coronaviruses. Furthermore, Zn2+ has been found to play a central role in regulating brain functioning and many disorders have been associated with Zn2+ deficiency, including neurodegenerative diseases, psychiatric disorders, and brain injuries. Within this context, we carried out a narrative review to provide an overview of the evidence relating to the effects of Zn2+ on the immune and nervous systems, and the therapeutic use of such micronutrients in both neurological and infective disorders, with the final goal of elucidating the possible use of Zn2+ as a preventive or therapeutic intervention in COVID-19. Overall, the results from the available evidence showed that, owing to its neuroprotective properties, Zn2+ supplementation could be effective not only on COVID-19-related symptoms but also on virus replication, as well as on COVID-19-related inflammation and neurological damage. However, further clinical trials evaluating the efficacy of Zn2+ as a nonpharmacological treatment of COVID-19 are required to achieve an overall improvement in outcome and prognosis.

Relationships between global functioning and neuropsychological predictors in subjects at high risk of psychosis or with a recent onset of depression.

OBJECTIVE: Psychotic disorders are frequently associated with decline in functioning and cognitive difficulties are observed in subjects at clinical high risk (CHR) for psychosis. In this work, we applied automatic approaches to neurocognitive and functioning measures, with the aim of investigating the link between global, social and occupational functioning, and cognition. METHODS: 102 CHR subjects and 110 patients with recent onset depression (ROD) were recruited. Global assessment of functioning (GAF) related to symptoms (GAF-S) and disability (GAF-D). and global functioning social (GF-S) and role (GF-R), at baseline and of the previous month and year, and a set of neurocognitive measures, were used for classification and regression. RESULTS: Neurocognitive measures related to GF-R at baseline (r = 0.20, p = 0.004), GF-S at present (r = 0.14, p = 0.042) and of the past year (r = 0.19, p = 0.005), for GAF-F of the past month (r = 0.24, p < 0.001) and GAF-D of the past year (r = 0.28, p = 0.002). Classification reached values of balanced accuracy of 61% for GF-R and GAF-D. CONCLUSION: We found that neurocognition was related to psychosocial functioning. More specifically, a deficit in executive functions was associated to poor social and occupational functioning.

Genome-wide association study detected novel susceptibility genes for social cognition impairment in people with schizophrenia.

OBJECTIVES: People with schizophrenia (SCZ) present serious and generalised deficits in social cognition (SC), which affect negatively patients' functioning and treatment outcomes. The genetic background of SC has been investigated in disorders other than SCZ providing weak and sparse results. Thus, our aim was to explore possible genetic correlates of SC dysfunctions in SCZ patients with a genome-wide study (GWAS) approach. METHODS: We performed a GWAS meta-analysis of data coming from two cohorts made of 242 and 160 SCZ patients, respectively. SC was assessed with different tools in order to cover its different domains. RESULTS: We found GWAS significant association between the TMEM74 gene and the patients' ability in social inference as assessed by The Awareness of Social Inference Test; this association was confirmed by both SNP-based analysis (lead SNP rs3019332 p-value = 5.24 × 10-9) and gene-based analysis (p-value = 1.09 × 10-7). Moreover, suggestive associations of other genes with different dimensions of SC were also found. CONCLUSIONS: Our study shows for the first time GWAS significant or suggestive associations of some gene variants with SC domains in people with SCZ. These findings should stimulate further studies to characterise the genetic underpinning of SC dysfunctions in SCZ.

A case of treatment-resistant bipolar depression and comorbid OCD treated with deep brain stimulation of the medial forebrain bundle: 5 years follow-up results.

Limited though promising evidence exists on the efficacy of Deep Brain Stimulation (DBS) of the Medial Forebrain Bundle (MFB) in otherwise intractable patients with Major Depression and Obsessive-Compulsive Disorder (OCD). Herein, we present acute and follow-up results (up to 5 years) of a 42 year old man with a diagnosis of treatment-resistant Bipolar Depression (BD) and comorbid OCD, successfully treated with DBS of the MFB. Regular follow-up visits with psychometric evaluations highlighted a considerable improvement of patient's depressive and OC symptoms at 5 years from implant. According to the limited, reported experience, we support the efficacy and tolerability of DBS of the MFB as a promising intervention in patients with treatment-resistant BD and comorbid OCD, with specific emphasis on the long-term outcome.

Substance-Induced Psychoses: An Updated Literature Review.

Background: On the current psychopharmacological panorama, the variety of substances able to provoke an episode of acute psychosis is rapidly increasing. Such psychotic episodes are classified according to the major category of symptoms: positive, negative, or cognitive psychotic episodes. On one hand, the abuse of methamphetamines, cannabis, and cocaine plays a big role in increasing the incidence of episodes resembling a psychotic disorder. On the other hand, the progress in terms of pharmacodynamics knowledge has led to the synthesis of new drugs, such as cannabinoids and cathinone's, which have rapidly entered into the common pool of abusers' habits. Regarding these newly synthesized substances of abuse, further clinical studies are needed to understand their psychogenic properties. The topic of this review is complicated due to the frequent abuse of psychotomimetic drugs by patients affected by psychotic disorders, a fact that makes it extremely difficult to distinguish between an induced psychosis and a re-exacerbation of a previously diagnosed disorder. Methods: The present narrative review summarizes results from clinical studies, thus investigating the psychotogenic properties of abused substances and the psychotic symptoms they can give rise to. It also discusses the association between substance abuse and psychosis, especially with regards to the differential diagnosis between a primary vs. a substance-induced psychotic disorder. Findings: Our findings support the theory that psychosis due to substance abuse is commonly observed in clinical practice. The propensity to develop psychosis seems to be a function of the severity of use and addiction. Of note, from a phenomenological point of view, it is possible to identify some elements that may help clinicians involved in differential diagnoses between primary and substance-induced psychoses. There remains a striking paucity of information on the outcomes, treatments, and best practices of substance-induced psychotic episodes.

Case Report: The Association Between Chromosomal Anomalies and Cluster A Personality Disorders: The Case of Two Siblings With 16p11.2 Deletion and a Review of the Literature.

Although several studies have shown the correlation between chromosomal rearrangements and the risk of developing psychotic disorders, such as schizophrenia, little attention has been given to identifying the genetic basis of pre-disposing personality so far. In this regard, a limited but significant number of studies seem to indicate an association between chromosomal anomalies and cluster A personality disorders (CAPD). Starting from the clinical description of two brothers affected by familial 16p11 deletion syndrome (OMIM #611913), both sharing cluster A and C personality traits, the aim of the present study is to critically review the literature regarding the correlation between chromosomal rearrangements and CAPD. A bibliographic search on PubMed has been conducted, and eight studies were finally included in our review. Most of the studies highlight the presence of schizotypal personality disorder in the 22q11.2 deletion syndrome, whose evolutionary course toward psychotic pictures is well-known. One study also identified a paranoid personality disorder in a patient with a deletion on chromosome 7q21.3. No studies have so far identified the presence of paranoid personality disorder in 16p11 deletion, as in the case of the two siblings we report, while its association with psychosis and autism is already known. Although further epidemiologic studies on broader populations are indicated, our observations might pave the way for the definition of new diagnostic subgroups of CAPD and psychotic disorders, in order to implement the clinical management of such complex conditions.

Factors Associated With Real-Life Functioning in Persons With Schizophrenia in a 4-Year Follow-up Study of the Italian Network for Research on Psychoses.

Importance: The goal of schizophrenia treatment has shifted from symptom reduction and relapse prevention to functional recovery; however, recovery rates remain low. Prospective identification of variables associated with real-life functioning domains is essential for personalized and integrated treatment programs. Objective: To assess whether baseline illness-related variables, personal resources, and context-related factors are associated with work skills, interpersonal relationships, and everyday life skills at 4-year follow-up. Design, Setting, and Participants: This multicenter prospective cohort study was conducted across 24 Italian university psychiatric clinics or mental health departments in which 921 patients enrolled in a cross-sectional study were contacted after 4 years for reassessment. Recruitment of community-dwelling, clinically stable persons with schizophrenia was conducted from March 2016 to December 2017, and data were analyzed from January to May 2020. Main Outcomes and Measures: Psychopathology, social and nonsocial cognition, functional capacity, personal resources, and context-related factors were assessed, with real-life functioning as the main outcome. Structural equation modeling, multiple regression analyses, and latent change score modeling were used to identify variables that were associated with real-life functioning domains at follow-up and with changes from baseline in these domains. Results: In total, 618 participants (427 male [69.1%]; mean [SD] age, 45.1 [10.5] years) were included. Five baseline variables were directly associated with real-life functioning at follow-up: neurocognition with everyday life (ß, 0.274; 95% CI, 0.207-0.341; P < .001) and work (ß, 0.101; 95% CI, 0.005-0.196; P = .04) skills; avolition with interpersonal relationships (ß, -0.126; 95% CI, -0.190 to -0.062; P < .001); positive symptoms with work skills (ß, -0.059; 95% CI, -0.112 to -0.006; P = .03); and social cognition with work skills (ß, 0.185; 95% CI, 0.088-0.283; P < .001) and interpersonal functioning (ß, 0.194; 95% CI, 0.121-0.268; P < .001). Multiple regression analyses indicated that these variables accounted for the variability of functioning at follow-up after controlling for baseline functioning. In the latent change score model, higher neurocognitive abilities were associated with improvement of everyday life (ß, 0.370; 95% CI, 0.253-0.486; P < .001) and work (ß, 0.102; 95% CI, 0.016-0.188; P = .02) skills, social cognition (ß, 0.133; 95% CI, 0.015-0.250; P = .03), and functional capacity (ß, 1.138; 95% CI, 0.807-1.469; P < .001); better baseline social cognition with improvement of work skills (ß, 0.168; 95% CI, 0.075-0.261; P < .001) and interpersonal functioning (ß, 0.140; 95% CI, 0.069-0.212; P < .001); and better baseline everyday life skills with improvement of work skills (ß, 0.121; 95% CI, 0.077-0.166; P < .001). Conclusions and Relevance: Findings of this large prospective study suggested that baseline variables associated with functional outcome at follow-up included domains not routinely assessed and targeted by intervention programs in community mental health services. The key roles of social and nonsocial cognition and of baseline everyday life skills support the adoption in routine mental health care of cognitive training programs combined with personalized psychosocial interventions aimed to promote independent living.

Accuracy of self-assessment of real-life functioning in schizophrenia.

A consensus has not yet been reached regarding the accuracy of people with schizophrenia in self-reporting their real-life functioning. In a large (n = 618) cohort of stable, community-dwelling schizophrenia patients we sought to: (1) examine the concordance of patients' reports of their real-life functioning with the reports of their key caregiver; (2) identify which patient characteristics are associated to the differences between patients and informants. Patient-caregiver concordance of the ratings in three Specific Level of Functioning Scale (SLOF) domains (interpersonal relationships, everyday life skills, work skills) was evaluated with matched-pair t tests, the Lin's concordance correlation, Somers' D, and Bland-Altman plots with limits of agreement (LOA). Predictors of the patient-caregiver differences in SLOF ratings were assessed with a linear regression with multivariable fractional polynomials. Patients' self-evaluation of functioning was higher than caregivers' in all the evaluated domains of the SLOF and 17.6% of the patients exceeded the LOA, thus providing a self-evaluation discordant from their key caregivers. The strongest predictors of patient-caregiver discrepancies were caregivers' ratings in each SLOF domain. In clinically stable outpatients with a moderate degree of functional impairment, self-evaluation with the SLOF scale can become a useful, informative and reliable clinical tool to design a tailored rehabilitation program.

Prevalence of antipsychotic-induced extrapyramidal symptoms and their association with neurocognition and social cognition in outpatients with schizophrenia in the "real-life".

First generation antipsychotics (FGAs) are more likely to induce extrapyramidal side-effects (EPS) than second generation antipsychotics (SGAs), and EPS have been shown associated to cognitive deficits in schizophrenia. So far, no study has explored the relationships between EPS and social cognition (SC) in people with schizophrenia. Therefore, we assessed the prevalence of EPS in a large sample of drug-treated community-dwelling persons with schizophrenia and explored their relationships with patients' neurocognitive and SC abilities. 875 patients underwent EPS, psychopathological, neurocognitive and SC assessments by means of standardized measures. Relationships between EPS, psychopathology and neurocognitive and SC measures were investigated by correlation tests. Moreover, a partial correlation network was computed by means of a network analysis. 256 patients were treated with FGAs alone or in combination with SGA and 619 with SGAs. EPS were significantly more frequent in FGA-treated group than in the SGA-treated one. Patients with EPS disclosed a more severe psychopathology and were more impaired in neurocognitive and SC measures compared to those without EPS. Disorganization, expressive deficit, and duration of illness were significantly associated to both neurocognitive and SC measures while EPS were associated to neurocognitive measures only. The network analysis showed that parkinsonism was the sole EPS directly connected to both psychopathological and neurocognitive indices whereas no direct connection emerged between EPS and SC measures. Present findings confirm that EPS are still present in the era of SGAs and contribute, together with other clinical variables, to the neurocognitive but not to the SC impairment of patients with schizophrenia.

Brain Morphology of Cannabis Users With or Without Psychosis: A Pilot MRI Study.

Cannabis is the illicit drug most commonly used worldwide, and its consumption can both induce psychiatric symptoms in otherwise healthy subjects and unmask a florid psychotic picture in patients with a prior psychotic risk. Previous studies suggest that chronic and long-term cannabis exposure may exert significant negative effects in brain areas enriched with cannabinoid receptors. However, whether brain alterations determined by cannabis dependency will lead to a clinically significant phenotype or to a psychotic outbreak at some point of an abuser's life remains unclear. The aim of this study was to investigate morphological brain differences between chronic cannabis users with cannabis-induced psychosis (CIP) and non-psychotic cannabis users (NPCU) without any psychiatric conditions and correlate brain deficits with selective socio-demographic, clinical and psychosocial variables. 3T magnetic resonance imaging (MRI) scans of 10 CIP patients and 12 NPCU were acquired. The type of drug, the frequency, and the duration, as well socio-demographic, clinical and psychosocial parameters of dependency were measured. CIP patients had extensive grey matter (GM) decreases in right superior frontal gyrus, right precentral, right superior temporal gyrus, insula bilaterally, right precuneus, right medial occipital gyrus, right fusiform gyrus, and left hippocampus in comparison to chronic cannabis users without psychosis. Finally, in CIP patients, the results showed a negative correlation between a domain of the Brief Psychiatric Rating Scale (BPRS), BPRS-Activity, and selective GM volumes. Overall, the results suggest that cannabis-induced psychosis is characterized by selective brain reductions that are not present in NPCU. Therefore, neuroimaging studies may provide a potential ground for identifying putative biomarkers associated with the risk of developing psychosis in cannabis users.