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Introduction Bipolar disorder (BD) is a recurrent disorder, causing functional impairment and raised mortality, particularly due to suicide. However, the difficulty in predicting suicidal behaviors relies in the lack of clear biomarkers. Machine learning (ML) has emerged as a promising tool to enhance suicidal prediction. However, most ML studies focused on lifetime attempts, without having a predictive time window, and did not employ time-dependent variables. Moreover, most studies lie on cross-sectional databases, without including more than one time-point. Objectives First, we aimed to predict 12-months suicide attempts in a naturalistic sample of BD patients, using clinical and demographic data. Second, we aimed to improve the prediction by including information from intermediate visits (1, 3, and 6 months), mimicking more closely the clinician’s way of thinking and the multiple observations a patient receives. Methods A sample of 163 BD patients (53% females, mean age 44.7, SD 15.3) were recruited. Based on EHR, 56 clinical and demographic features were extracted, including hospitalizations, suicidal behaviors lifetime and in the last 12 months, along with comorbidity, family history, work, and therapies. Patients were followed up for 12 months. Support Vector Machine (SVM) was used to differentiate subjects who attempted suicide versus those who did not in a 12-month time window, within a repeated nested Cross-Validation. The SVM was optimized weighting the hyperplane for uneven group sizes. Then, we repeated the analysis including information from intermediate visits (1, 3, 6 months after the first contact). For each visit, we created a composite score based on current therapy, new admissions, and ER presentations. To avoid circularity, all the information (ER, admission etc.) related to a suicide attempt were not included. Results During the 12-months follow-up, 9.8% of patients attempted suicide. The results from the 12-months suicide prediction model obtained an Area Under the Curve of 0.71(with a Balanced Accuracy (BAC) of 68%). After incorporating the composite scores based on intermediate visits in the model, the prediction raised to an Area Under the Curve of 0.78 (BAC 73%), suggesting that including intermediate visits is a valid method to improve prediction. The features that contributed the most to the prediction were the composite score at 6-month visit, lifetime number of suicide attempts, suicide attempts in the last 12 months, substance of abuse (other than cannabis), and antipsychotics. Conclusions ML proved a good prediction accuracy for suicide in a 12-months time window, and the prediction was improved by including data from intermediate visits. The model showed the importance of time-dependent features, such as attempts in the last 12 months. Our analysis might help in identifying early clinical risk factors and underlies the importance of multiple evaluations in populations at risk. Disclosure of Interest None Declared

Introduction: Cerebellar alterations, including both volumetric changes in the cerebellar vermis and dysfunctions of the corticocerebellar connections, have been documented in psychotic disorders. Starting from the clinical observation of a bipolar patient with cerebellar hypoplasia, the purpose of this review is to summarize the data in the literature about the association between hypoplasia of the cerebellar vermis and psychotic disorders [schizophrenia (SCZ) and bipolar disorder (BD)]., Methods: A bibliographic search on PubMed has been conducted, and 18 articles were finally included in the review: five used patients with BD, 12 patients with SCZ and one subject at psychotic risk., Results: For SCZ patients and subjects at psychotic risk, the results of most of the reviewed studies seem to suggest a gray matter volume reduction coupled with an increase in white matter volumes in the cerebellar vermis, compared to healthy controls. Instead, the results of the studies on BD patients are more heterogeneous with evidence showing a reduction, no difference or even an increase in cerebellar vermis volume compared to healthy controls., Conclusions: From the results of the reviewed studies, a possible correlation emerged between cerebellar vermis hypoplasia and psychotic disorders, especially SCZ, ultimately supporting the hypothesis of psychotic disorders as neurodevelopmental disorders., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Major Depressive Disorder (MDD) is a severe psychiatric disorder characterized by selective impairments in mood regulation, cognition and behavior. Although it is well-known that antidepressants can effectively treat moderate to severe depression, the biochemical effects of these medications on white matter (WM) integrity are still unclear. Therefore, the aim of the study is to review the main scientific evidence on the differences in WM integrity in responders and non-responders to antidepressant medications. A record search was performed on three datasets (PubMed, Scopus and Web of Science) and ten records matched our inclusion criteria. Overall, the reviewed studies highlighted a good efficacy of antidepressants in MDD treatment. Furthermore, there were differences in WM integrity between responders and non-responders, mainly localized in cingulate cortices, hippocampus and corpus callosum, where the former group showed higher fractional anisotropy and lower axial diffusivity values. Modifications in WM integrity might be partially explained by branching and proliferation as well as neurogenesis of axonal fibers mediated by antidepressants, which in turn may have positively affected brain metabolism and increase the quantity of the serotonergic neurotransmitter within synaptic clefts. However, the reviewed studies suffer from some limitations, including the heterogeneity in treatment duration, antidepressant administration, medical posology, and psychiatric comorbidities. Therefore, future studies are needed to reduce confounding effects of antidepressant medications and to adopt longitudinal and multimodal approaches in order to better characterize the differences in WM integrity between responders and non-responders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Videtta, Squarcina, Prunas, Brambilla and Delvecchio.)

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.

Clozapine-induced myocarditis and pericarditis are uncommon adverse effects of clozapine treatment. However, in most cases, they lead to clozapine discontinuation. Here, we describe a case of successful clozapine rechallenge after clozapine-induced myopericarditis. The patient, a 31-year-old male with treatment-resistant schizophrenia (TRS), developed dyspnea on exertion and chest pain on day 19 after the start of clozapine titration. An electrocardiogram (ECG) showed widespread, mild, convex ST interval elevation. While troponin levels were mildly elevated, the echocardiogram was unremarkable. A myopericarditis diagnosis was formulated, and clozapine was stopped, with a progressive resolution of clinical, laboratory and ECG abnormalities. After 6 months, a rechallenge with clozapine was attempted. A very slow titration scheme was adopted, along with close monitoring of clinical, laboratory and ECG parameters. Clozapine target dose was reached without the occurrence of any abnormality. Given the unique role of clozapine in the management of TRS, clozapine rechallenge may be considered after pericarditis, even with troponin levels elevation. Further studies are needed to update current clinical guidelines., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Borderline personality disorder (BPD) is a common mental disorder characterized by instability in interpersonal relationships, impaired self-image, impulsivity and aggressive behaviors that often requires pharmacological treatments. Neuroimaging alterations have been extensively reported in BPD, especially in regions within the fronto-limbic system. Although medications can be an important confounding factor in functional Magnetic Resonance Imaging (fMRI) studies, their role on brain function in BPD patients still remains uncertain. Therefore, this review aims to improve our understanding on the potential effect of the most commonly prescribed drugs for BPD on brain function during processing of emotional tasks., Methods: A search on PubMed, Scopus and Web of Science of fMRI studies exploring the effect of antipsychotics, antidepressants and mood stabilizers on brain activity during processing of emotional tasks on BPD was conducted., Results: Overall the studies showed small or no effect of pharmacological treatments on brain activity and connectivity in BPD patients during processing of emotional tasks., Limitations: The small sample size, the observational design, the elevated percentage of women, the concomitant use of psychostimulants, anticholinergics and opioids substitute treatments and the high rate of comorbidities limit the conclusion of this review., Conclusions: Pharmacological treatments seem to have minor role on brain activity/connectivity in BPD patients during emotional tasks, ultimately suggesting that in BPD patients brain deficits seem not be influenced by medications. This might be due to functional brain specificities of BPD and to the differences in pharmacological regimens and compliance to therapy between BPD and other common psychiatric disorders., (Copyright © 2021. Published by Elsevier B.V.)

The ongoing Corona Virus Disease 2019 (COVID-19) pandemic appears to increase risk for mental illness, either directly due to inflammation caused by the virus or indirectly due to related psychosocial stress, resulting in the development of both anxious-depressive and psychotic symptoms. The purpose of the present study was to assess the frequency and characteristics of all patients with First Episodes Psychosis (FEP) without COVID-19 infection hospitalized in the first four months since lockdown in Milan. We recruited sixty-two patients hospitalized between March 8 to July 8, 2020 versus those first  hospitalized in the same period in 2019. The two subgroups were compared for sociodemographic variables and clinical characteristics of the episodes. Patients with FEP in 2020 were significantly older than patients with FEP in 2021, and presented with significantly less substances abuse. Interestingly, patients presenting with FEP in 2020 were significantly older than patients with FEP in 2019. These data are compatible with the greater vulnerability to stressful factors during the pandemic, as well as with the greater concern regarding a possible COVID-19 infection producing brain damage causing the FEP., (Copyright © 2021. Published by Elsevier B.V.)

Background: Given the strong relationship between circadian rhythm disruption and mood regulation, combined chronotherapeutic approaches have been proposed for mood disorders. However, a comprehensive review of the available evidence on the efficacy of such interventions for depression is lacking., Aim: To systematically review available literature on Triple Chronotherapy (Sleep Deprivation - Sleep Phase Advance - Bright Light Therapy) for depressive symptoms in Major Depression and Bipolar Depression., Methods: We followed the PRISMA statement for systematic reviews to conduct a web-based search on PubMed, Scopus and Embase using a list of selected keywords relevant to depression and chronotherapy., Results: After title and abstract screening of the 321 records retrieved, 25 potentially eligible studies were assessed at full-text screening. Nineteen studies were excluded for failure to match inclusion criteria. Six records of Triple Chronotherapy in addition to conventional treatment, published between 2009 and 2019, were included in the revision. All studies reported significant improvements on HAM-D scores at the end of treatment, with 50% to 84% response rates. Efficacy of treatment was confirmed on follow-up by three studies, with 58% to 61% response rates. Remission rates varied from 33,3% to 77%. Reported side effects were negligible across studies., Limitations: Available trials are very few and only one included a control group treated with a daily exercise program., Conclusions: The limited literature suggests that Triple chronotherapy might be a safe and effective addition to conventional antidepressant interventions, although well-designed, randomized controlled trials are needed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Affective psychosis is a common mental disorder characterized by structural/functional brain abnormalities, which seem to occur also at the early stages of the disease. However, the role of psychotropic medications on brain structure and function in affective first episode psychosis (A-FEP) still remains uncertain. Therefore, with this review we aim to gain more robust understanding regarding the potential effect of pharmacological treatments on the brain in A-FEP patients also experiencing a first manic episode., Methods: A search on PuBMed and Web of Science of longitudinal structural and functional Magnetic Resonance Imaging (MRI) as well as Diffusion Tensor Imaging (DTI) studies, exploring the effect of medications on the brain in A-FEP, was conducted. We selected nine studies, three randomized or pseudo-randomized controlled trials and six observational studies., Results: Overall the studies showed that a) mood stabilizers (MS) have no effect on gray matter (GM) volumes and a protective role on white matter (WM) volumes, b) antipsychotics (AP) have an unclear effect on GM volumes and a less potent effect on WM volumes compared to MS and c) both MS and AP tend to normalize brain activation and connectivity., Limitations: The small sample size, the observational design of the majority of the studies and the different methodological approaches limit the conclusion of this review., Conclusions: Medications seem to have a minor role on structural changes occurring in A-FEP patients during the early stages of the disease, while their effect on brain activation and connectivity seems more pronounced, but far to be conclusive., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Post-Traumatic Stress Disorder (PTSD) is often associated with impairments in emotional and cognitive domains. Contrarily to the emotional sphere, neural basis underpinnings to cognitive impairments are still not well known., Methods: We performed a bibliographic search on PUBMED of all the studies investigating the cognitive impairments in PTSD individuals. We considered only studies that applied cognitive tasks using a functional Magnetic Resonance Imaging technique. The inclusion criteria were met by nine studies., Results: Overall, PTSD individuals reported significant impairments in the dorsolateral prefrontal cortex, anterior cingulate cortex, inferior frontal gyrus, insula, inferior temporal cortex, supplement motor area, and Default Mode Network (DMN). Moreover, abnormal activity was reported in subcortical structures (e.g. hippocampus, amygdala, thalamus) and in the cerebellum., Limitations: Cognitive functioning was assessed using different cognitive tasks. Potential confounding factors such as age, sex, symptoms intensity, and comorbidities might have influenced the results., Conclusion: So far, the evidence reported that PTSD is characterized by cognitive impairments in several domains, such as attention, memory and autonomic arousal, which may be due to selective dysfunctions in brain regions that are part of cortical networks, the limbic system and DMN. However, further studies are needed in order to better assess the role of cognitive impairments in PTSD and to develop more targeted therapeutic approaches., (Copyright © 2020 Dossi, Delvecchio, Prunas, Soares and Brambilla.)

Bipolar disorder (BD) is a severe mental disorder with a wide range of cognitive deficits, both in the euthymic and acute phase of the disease. Interestingly, in recent years, there has been a growing interest in investigating the impact of ω-3 polyunsaturated fatty acids on cognition in BD. In this context, the aim of this study is to evaluate the effect of docosahexaenoic acid (C22:6 ω-3, DHA) supplementation on cognitive performances in euthymic BD patients. This is an exploratory, single-centre, double-blind randomized controlled trial evaluating 12 weeks DHA supplementation (1250 mg daily) vs. a placebo (corn oil) in 31 euthymic BD patients compared to 15 healthy controls (HCs) on cognitive functions, assessed by the Brief Assessment of Cognition in Affective Disorder (BAC-A). Plasma levels of DHA were measured. After 12 weeks of treatment, no significant group differences were observed in all neuropsychological tests between the four groups, except for the emotion inhibition test, where HCs with DHA had higher scores compared to either BD with DHA ( z = 3.9, p = 0.003) or BD with placebo ( t = 3.7, p = 0.005). Although our results showed that DHA could be effective for ameliorating cognition in healthy subjects, future studies are still needed to clarify the impact of DHA on cognition in BD., Competing Interests: The authors declare no conflict of interest.

Eveningness and sleep disturbances are considered as markers of Bipolar Disorder (BD) and influence mood and emotional or behavioral states. This study investigates the associations between circadian markers and sleep quality on residual depressive symptoms and inhibition/activation dimensions during the euthymic phase. A sample of 89 euthymic adult individuals with BD was assessed for circadian preference and typology using the Composite Scale of Morningness (CSM) and the Circadian Type Inventory (CTI) and for sleep quality using the Pittsburgh Sleep Quality Index (PSQI). The Montgomery and Asberg Depression Rating Scale (MADRS) and the Multidimensional Assessment of Thymic States (MAThyS) were used to measure residual depressive symptoms and the inhibition/activation dimensions. We examined any associations between these parameters using correlations and path analyses. We identified significant associations between eveningness and poorer sleep quality that correlated to higher depressive residual symptoms and a global inhibition. The use of path analyses led us to conclude that poor sleep quality mediated the relationship between eveningness and either residual mood symptoms or behavioral inhibition (motivation, sensory perception, interpersonal interaction, and cognition). These factors should be considered in the clinical evaluation of individuals with BD, with a specific attention during the euthymic phase, in order to achieve the best functional outcome possible.

Childhood attention-deficit hyperactivity disorder (ADHD) is a common precursor of adult bipolar disorders (BD). Furthermore, actigraphy studies demonstrate that each disorder may be associated with abnormalities in sleep and activity patterns. This study investigates whether the presence or absence of self-reported childhood experiences of ADHD symptoms is associated with different sleep and activity patterns in adults with BD. A sample of 115 euthymic adult patients with BD was assessed for childhood ADHD symptoms using the Wender Utah Rating Scale (WURS) and then completed 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and variability and daytime activity were compared between BD groups classified as ADHD+ ( n  = 24) or ADHD- ( n  = 91), defined according to established cutoff scores for the WURS; then we examined any associations between sleep-wake cycle parameters and ADHD dimensions (using the continuous score on the WURS). Neither approach revealed any statistically significant associations between actigraphy parameters and childhood ADHD categories or dimensions. We conclude that the sleep and activity patterns of adult patients with BD do not differ according to their self-reported history of ADHD symptoms. We discuss the implications of these findings and suggest how future studies might confirm or refute our findings.

Background: Elderly bipolar disorder (BD) and behavioural variant of frontotemporal dementia (bvFTD) may exhibit similar symptoms and both disorders are characterized by selective abnormalities in cortical and subcortical regions that are associated with cognitive and emotional impairments. We aimed to investigate common and distinct neural substrates of BD and bvFTD by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques., Methods: 3-Tesla MRI and 18 fluorodeoxyglucose-PET scans were acquired for 16 elderly BD patients, 23 bvFTD patients with mild cognitive impairments and 68 healthy controls (48 for PET and 20 for MRI analyses)., Results: BD and bvFTD patients exhibit a different localization of grey matter reductions in the lateral prefrontal cortex, with the first group showing grey matter decrease in the ventrolateral prefrontal cortex and the latter group showing grey matter reductions in the dorsolateral prefrontal cortex as well as unique grey matter and metabolic alterations within the orbitofrontal cortex. The bvFTD group also displayed unique volumetric shrinkage in regions within the temporo-parietal network together with greater metabolic impairments within the temporal cortex and more extensive volumetric and metabolic abnormalities within the limbic lobe. Finally, while the BD group showed greater grey matter volumes in caudate nucleus, bvFTD subjects displayed lower metabolism., Conclusion: This MRI-PET study explored, for the first time to the best of our knowledge, structural and functional abnormalities in bvFTD and elderly BD patients, with the final aim of identifying the specific biological signature of these disorders, which might have important implications not only in prevention but also in differential diagnosis and treatment.

Background: Social cognition (SC) and Theory of Mind (ToM) are compromised in patients with Schizophrenia (SKZ) and Bipolar Disorder (BD) and an increased frequency of metabolic abnormalities is reported in both disorders. Obesity seems associated with cognitive impairments The aim of our study is thus to assess the relationship between obesity and ToM in SKZ and BD., Methods: 36 stabilized outpatients (18 SKZ and 18 BD) were recruited and completed Reading the Mind in the Eyes Test, Italian version and Faux Pas Recognition Test, adult version. BMI was calculated from self-reported height and weight. Two different Generalized Linear Models were created including performance in Eyes test and in Faux Pas test as outcomes and BMI as covariate., Results: After stratifying for sex, we found a significant relationship between BMI and Faux Pas performance for male patients (p = 0.017), without significant interactions between sex and diagnosis. These results suggest a BMI effect on both affective and cognitive ToM in male patients., Limitations: Major confounders need to be considered: the greater number of subjects with SKZ in male subsample, a possible influence of neurocognitive performance, small sample size and self-reported BMI., Conclusions: There could be a relationship between ToM and metabolic dysfunctions, at least in male patients. The exact nature of this relationship has yet to be determined; an interesting theoretical framework is based on a combination of increased brain energy request and inefficient peripheral compensatory mechanisms, resulting in inefficient energy allocation to the brain., (Published by Elsevier B.V.)

Backgrounds: Up to date, no studies in literature assessed the efficacy of a treatment schedule including i.v. trazodone followed by its oral administration. In light of this lack of evidence, the aim of the present study was to evaluate the efficacy and tolerability of trazodone, administered first i.v. and then orally in a sample of Major Depressive Disorder (MDD) patients., Methods: Thirty four patients underwent i.v. administration of trazodone (75-100 mg in 250 mL of saline) for 1 week. During the second week, oral extended-release formulation (150-300 mg per day) was added to the i.v. administration. Finally, extended-release trazodone was orally administration at doses of 150-300 mg per day. Psychometric scales were performed at baseline (T0), after 2 weeks (T1), 6 weeks (T2), after 3 months (T3), and 6 months (T4)., Results: The total sample included 34 subjects (14 males and 20 females). There was a statistically significant decrease in Hamilton Depression Rating Scale total scores from T0 to T1 (t=9.06; df=33), from T1 to T2 (t=4.96; df=29), from T2 to T3 (t=4.08; df=19), and from T3 to T4 (t=2.25; df=19); in Hamilton Anxiety Rating Scale total scores from T0 to T1 (t=8.79; df=33) and from T1 to T2 (t=5.61; df=29); in Montgomery-Asberg Depression Rating Scale total scores from T0 to T1 (t=9.30; df=33), from T1 to T2 (t=5.69; df=29), and from T2 to T3 (t=3.16; df=19)., Conclusions: This finding confirms previous results on depression with concomitant anxiety symptoms: focusing on trazodone prolonged-release formulation, available data documented its efficacy in MDD.

Background: Bipolar disorder (BD) is a major psychiatric illness characterized by heterogeneous symptoms including psychotic features. Up until now, neuroimaging studies investigating cerebral morphology in patients with BD have underestimated the potential impact of psychosis on brain anatomy in BD patients. In this regard, psychotic and non-psychotic BD may represent biologically different subtypes of the disorder, being possibly associated with specific cerebral features., Methods: In the present study, magnetic resonance imaging (MRI) at 3T was used to identify the neuroanatomical correlates of psychosis in an International sample of BD patients. A large sample of structural MRI data from healthy subjects (HC) and BD patients was collected across two research centers. Voxel based morphometry was used to compare gray matter (GM) volume among psychotic and non-psychotic BD patients and HC., Results: We found specific structural alterations in the two patient groups, more extended in the psychotic sample. Psychotic patients showed GM volume deficits in left frontal cortex compared to HC, and in right temporo-parietal cortex compared to both HC and non-psychotic patients (p < 0.001, > 100 voxels). Psychotic patients also exhibited enhanced age-related GM volume deficits in a set of subcortical and cortical regions., Limitations: The integration of multiple datasets may have affected the results., Conclusions: Overall, our results confirm the importance of classifying BD based on psychosis. The knowledge of the neuronal bases of psychotic symptomatology in BD can provide a more comprehensive picture of the determinants of BD, in the light of the continuum characteristic of major psychoses., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Structural and diffusion imaging studies have provided some evidence of abnormal organization of Corpus Callosum (CC) in Bipolar Disorder (BD). Therefore, by using Diffusion Weighted Imaging (DWI), which allows to build subtle prediction models of fiber integrity for white matter (WM) tracts, this study aims to further explore the microstructure integrity of CC in BD patients compared to matched healthy controls. Twenty-four chronic patients with BD and 35 healthy controls were included in the study. Circular regions of interest were placed, on diffusion images, in the left and right side of callosal regions (i.e. rostrum/genu, anterior body, posterior body, splenium) and the Apparent Diffusion Coefficient (ADC) was then calculated. Significantly increased ADC values were found in right anterior body and in right splenium in BD patients compared to healthy controls (all p < 0.05, Bonferroni corrected). In this study, we found abnormally increased ADC callosal values in BD suggesting microstructural anomalies specifically in the right hemisphere. Interestingly, this finding further supports the presence of an altered inter-hemispheric communication between frontal and temporo-parietal association areas in patients with BD, which may ultimately result in clinical symptoms and cognitive deficits., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Huntington's disease is a disorder that results in motor, cognitive, and psychiatric problems. The symptoms often take different forms and the presence of disturbances of the psychic sphere reduces patients' autonomy and quality of life, also impacting patients' social life. It is estimated that a prevalence between 33% and 76% of the main psychiatric syndromes may arise in different phases of the disease, often in atypical form, even 20 years before the onset of chorea and dementia. We present a narrative review of the literature describing the main psychopathological patterns that may be found in Huntington's disease, searching for a related article in the main database sources (Medline, ISI Web of Knowledge, Scopus, and Medscape). Psychiatric conditions were classified into two main categories: affective and nonaffective disorders/symptoms; and anxiety and neuropsychiatric features such as apathy and irritability. Though the literature is extensive, it is not always convergent, probably due to the high heterogeneity of methods used. We summarize main papers for pathology and sample size, in order to present a synoptic vision of the argument. Since the association between Huntington's disease and psychiatric symptoms was demonstrated, we argue that the prevalent and more invalidating psychiatric components should be recognized as early as possible during the disease course in order to best address psychopharmacological therapy, improve quality of life, and also reduce burden on caregivers., Competing Interests: The authors declare no conflict of interest.

The purpose of this study was to investigate the relationship between cognitive insight and cerebral metabolism in patients suffering from psychosis. The Beck Cognitive Insight Scale (BCIS) was administered to 63 patients with psychosis undergoing Positron Emission Tomography investigation. The sample was divided into two groups considering the BCIS score. Data were analyzed using Statistical Parametric Mapping., Results: patients with low insight, compared to those with high insight, showed decreased metabolism in the right fusiform gyrus, left precuneus, superior temporal gyrus and insula bilaterally, as well as increased metabolism in the left orbito-frontal gyrus (all p<0.005). Our results suggest that reduced posterior (occipito-temporo-insulo-parietal) and increased anterior (orbitofrontal) cerebral metabolism may sustain low cognitive insight in psychosis.

Background: Bipolar disorder (BD) may be characterized by the presence of psychotic symptoms and comorbid substance abuse. In this context, structural and metabolic dysfunctions have been reported in both BD with psychosis and addiction, separately. In this study, we aimed at identifying neural substrates differentiating psychotic BD, with or without substance abuse, versus substance-induced psychosis (SIP) by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET)., Methods: Twenty-seven BD type I psychotic patients with (n=10) or without (n=17) substance abuse, 16 SIP patients and 54 healthy controls were enrolled in this study. 3T MRI and 18-FDG-PET scanning were acquired., Results: Gray matter (GM) volume and cerebral metabolism reductions in temporal cortices were observed in all patients compared to healthy controls. Moreover, a distinct pattern of fronto-limbic alterations were found in patients with substance abuse. Specifically, BD patients with substance abuse showed volume reductions in ventrolateral prefrontal cortex, anterior cingulate, insula and thalamus, whereas SIP patients in dorsolateral prefrontal cortex and posterior cingulate. Common alterations in cerebellum, parahippocampus and posterior cingulate were found in both BD with substance abuse and SIP. Finally, a unique pattern of GM volumes reduction, with concomitant increased of striatal metabolism, were observed in SIP patients., Conclusions: These findings contribute to shed light on the identification of common and distinct neural markers associated with bipolar psychosis and substance abuse. Future longitudinal studies should explore the effect of single substances of abuse in patients at the first-episode of BD and substance-induced psychosis., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Neurocognitive and social cognition deficits have been largely reported in Schizophrenia (SKZ) but their association with psychopathology remains uncertain. Our purpose was to explore the relationship between symptom dimensions and neuropsychological performances. We enrolled 35 stabilized schizophrenic outpatients of the Department of Psychiatry of Policlinico Hospital, University of Milan, who completed psychiatric Rating Scales, the Brief Assessment of Cognition in Schizophrenia (BACS) and the Executive and Social Cognition Battery (ESCB). Disorganized dimension seems to have the most significant impact on cognition, being associated with performance in several BACS subtests (verbal memory, working memory, motor speed, symbol coding, Tower of London) and ESCB tasks (MET and Hotel task number of tasks attempted, number of broken MET rules, sum of deviations in Hotel Task). Positive dimension correlated with performance in verbal fluency, negative dimension with IOWA Test results, cognitive dimension with MET number of inefficiencies and Eyes test score. Impulsive-aggressive and depressive dimensions weakly correlated only with Faux Pas test. Our study supports the existence of a specific disorganized dimension in SKZ, separated from cognitive dimension evaluated through clinical instruments (e.g. PANSS), but capable of influencing cognitive abilities. Furthermore, it strengthens the validity of ecological tasks in evaluating cognition in SKZ., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Recent data have shown that genetic variability in the progranulin (GRN) gene may contribute to the susceptibility to developing bipolar disorder (BD). However, in regard to patients with BD, no information is available on the role of genetic variability and plasma progranulin levels in different types of this disorder., Methods: In this study, we performed an association analysis of GRN in an Italian population consisting of 134 patients with BD and 232 controls to evaluate progranulin plasma levels., Results: The presence of the polymorphic variant of the rs5848 single nucleotide polymorphism is protective for the development of bipolar I disorder (BD-I) (odds ratio = 0.55, 95% confidence interval: 0.33-0.93; p = 0.024) but not bipolar II disorder (BD-II) (p > 0.05). In addition, plasma progranulin levels are significantly decreased in BD [mean ± standard deviation (SD) 112 ± 35 versus 183 ± 93 ng/mL in controls; p < 0.001]., Conclusions: Regarding the influence of GRN variability on BD susceptibility, the predisposing genetic background differs between BD-I and BD-II, possibly implying that pathogenic mechanisms differ between the two subtypes of BD., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A hexanucleotide repeat expansions in the first intron of C9ORF72 has been shown to be responsible for a high number of familial cases of amyotrophic lateral sclerosis and/or frontotemporal lobar degeneration. The same mutation has been described in a patient with bipolar disorder, but up to now, not in patients suffering from schizophrenia. We determined the frequency of the C9ORF72 hexanucleotide repeat expansions in a population of 298 patients with schizophrenia or schizoaffective disorder. The pathogenic repeat expansion was detected in 2 patients (0.67%). Both of them presented with auditory hallucinations and had comorbid alcohol abuse. In addition, a positive family history for psychiatric and/or neurodegenerative diseases was present. The repeat expansion in the C9ORF72 gene is a rare, but possible, cause of schizophrenic spectrum disorders. We cannot rule out however whether the number of repeats influence the phenotype., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This study aimed to determine the extent of impairment in social and non-social cognitive domains in an ecological context comparing bipolar (BD), schizophrenic (SKZ) patients and healthy controls (HC). The sample was enrolled at the Department of Psychiatry of Policlinico Hospital, University of Milan; it includes stabilized SKZ patients (n = 30), euthymic bipolar patients (n = 18) and HC (n = 18). Patients and controls completed psychiatric assessment rating scales, the Brief Assessment of Cognition in Schizophrenia (BACS) and the Executive and Social Cognition Battery (ESCB) that contains both ecological tests of executive function and social cognition, in order to better detect cognitive deficits in patients with normal results in standard executive batteries. The three groups differed significantly for gender and substance abuse, however, the differences did not influence the results. BD patients showed less impairment on cognitive performance compared to SKZ patients, even in "ecological" tests that mimic real life scenarios. In particular, BD performed better than SKZ in verbal memory (p < 0.0038) and BACS symbol coding (p < 0.0043). Regarding the ESCB tests, in the Hotel task SKZ patients completed significantly less tasks (p < 0.001), showed a greater number of errors in Multiple Errands Test (MET-HV) (p < 0.0248) and a worse performance in Theory of Mind (ToM) tests (p < 0.001 for the Eyes test and Faux pas test). Both patients' groups performed significantly worse than HC. Finally, significant differences were found between the two groups in GAF scores, being greater among BD subjects (p < 0.001). GAF was correlated with BACS and ESCB scores showing the crucial role of cognitive and ecological performances in patients' global functioning.