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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.

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.

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 2018, 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.

BackgroundBipolar 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).MethodsTwenty-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.ResultsGray 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.ConclusionsThese 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.

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 &omega, 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 &omega, 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.

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.

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.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).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).This finding confirms previous results on depression with concomitant anxiety symptoms: focusing on trazodone prolonged-release formulation, available data documented its efficacy in MDD.

Bipolar disorder (BD) and borderline personality disorder (BPD) are two disabling psychiatric conditions that are associated with a high rate of comorbidity and mortality (approximately 10% of BPD patients suffer from BD I disorder and another 10% show a comorbid BD II disorder). Up to date, the relationship between BD and BPD is controversial, and the debate on whether or not BPD should be considered within a broader bipolar spectrum is still ongoing. According to the literature, the underestimation of comorbidity rates between these disorders could lead to a significant delay in diagnosis and planning of appropriate treatments. In addition, this would lead to an increased risk of exposure to improper medications, a poorer outcome and a higher risk of complications. In this chapter we present a clinical case of a patient who suffers from BD and BPD. The discussion of this case report draws attention to the challenges associated with the diagnosis and treatment of a wide population of psychiatric patients, whose symptoms and clinical history appear to be somehow overlapping between BD and BPD, considered as distinct disorders according to the current nosography.

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.

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.

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 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.

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.

Background The clinical manifestations of Huntington’s disease (HD) also include psychiatric disturbances, as well as motor and cognitive disorders. Estimated rates for lifetime prevalence of psychiatric disorders among HD patients vary between 33% and 76%. Tetrabenazine is considered the first line treatment for motor disturbances in absences of some psychiatric contraindication (suicide risk). The current literature on the psychopharmacological treatment lack of a large randomised controlled trial, however many small case series are available. Aims We present a review of the literature describing treatments of psychiatric manifestation in HD, focusing on specific disturbances and the role of polytherapy. Methods A search in the main database sources (Medline, Isi Web of Knowledge and Medscape) has been performed in order to obtain a comprehensive evaluation of available psychopharmacological treatment in HD. Results Antidepressants like selective serotonin and serotonin norepinephrine reuptake inhibitors improve depression and are also used in obsessive-compulsive symptoms in HD patients. Mood stabiliser (Valproic Acid or Lamotrigine), alone or in combination with other drugs, are used in pathological mood swings and irritability. Atypical antipsychotics (Risperdidone, Olanzapine and Aripiprazole) were used in psychotic symptoms, and for managing agitation also in place of Tetrabenazine, with reduction of pathological movement. Conclusions Psychiatric symptoms in HD seem to respond well to psychopharmacological treatment. It is important to recognise psychiatric aspects and tailoring specific treatment, not only for psychopathology treatment with improvement of mood, ideation and quality of life of patients and prevention of serious complications how suicidality, but even for better managing neurological symptoms in HD.

Background The clinical manifestations of Huntington Disease include motor, cognitive and psychiatric disturbances. There is a wide spectrum of symptoms and the presence of disorders in psychiatric field worsens autonomy and quality of life of the patients. Main psychiatric syndromes may appear during progression of Huntington Disease, often in a non-typical way. Some authors have noticed even 20 years before onset of chorea or dementia symptoms of Huntington Disease. Aims We present a review of literature describing the main psychopathological pictures in Huntington Disease, whose prevalence is estimated between 33% and 76%. Results It is possible to make diagnosis of major depression in a percentage between 9% and 63%, and the suicide rate in patients is 4 to 6 times higher than normal population, with greater prevalence among patients over 50 years old. Hypomania and mania have been estimated in 4,8% to 10% of patients. Anxiety has been less studied however some studies report that it also occurs frequently (34–61%). Prevalence of irritability varies between 38% and 73%, whereas obsessive and compulsive symptoms are comprised between 5% and 52%. A picture of psychosis has prevalence estimated at 4% to 12%. Delirium, apathy and neuropsychological impairments are strictly correlated with the progression of the disease. Conclusions It is important to recognise psychiatric facets in HD, in order to tailor the psychopharmacological therapy and reduce the burden for the caregiver.

Introduction Experimental evidence indicates that patients with severe mental illness such as schizophrenia or mood disorders have a higher incidence of overweight and obesity (Daumit et al., 2003). Objectives This review describes the neuropsychological functioning and therapeutical approaches (psychotherapeutic, pharmacological, surgical) in obese patients with psychiatric disorders. Aims To provide suggestions for good clinical practice in obese subjects with psychopathology, based on data found in the literature. Methods MEDLINE and PubMed databases (1962-2012) were searched for English-language articles. Results Most of the literature says that the best treatment for these patients should use an integrated approach, starting from an assessment of the psychological and cognitive resources to set up a more effective and personalized therapeutic path. Conclusions Obese patients who have psychiatric disorders represent a population that requires specific treatment measures; in fact, the development, the maintenance and the outcome of the problem of weight are influenced not only by physical and life style factors, but also by specific factors related to psychopathology, neuropsycology, and side effects of certain drugs.