Sleep and sleep disorders during pregnancy and postpartum: The Life-ON study.

OBJECTIVE: to prospectively assess sleep and sleep disorders during pregnancy and postpartum in a large cohort of women. METHODS: multicenter prospective Life-ON study, recruiting consecutive pregnant women at a gestational age between 10 and 15 weeks, from the local gynecological departments. The study included home polysomnography performed between the 23rd and 25th week of pregnancy and sleep-related questionnaires at 9 points in time during pregnancy and 6 months postpartum. RESULTS: 439 pregnant women (mean age 33.7 ± 4.2 yrs) were enrolled. Poor quality of sleep was reported by 34% of women in the first trimester of pregnancy, by 46% of women in the third trimester, and by as many as 71% of women in the first month after delivery. A similar trend was seen for insomnia. Excessive daytime sleepiness peaked in the first trimester (30% of women), and decreased in the third trimester, to 22% of women. Prevalence of restless legs syndrome was 25%, with a peak in the third trimester of pregnancy. Polysomnographic data, available for 353 women, revealed that 24% of women slept less than 6 h, and 30.6% of women had a sleep efficiency below 80%. Sleep-disordered breathing (RDI≥5) had a prevalence of 4.2% and correlated positively with BMI. CONCLUSIONS: The Life-ON study provides the largest polysomnographic dataset coupled with longitudinal subjective assessments of sleep quality in pregnant women to date. Sleep disorders are highly frequent and distributed differently during pregnancy and postpartum. Routine assessment of sleep disturbances in the perinatal period is necessary to improve early detection and clinical management.

Dimensional structure of first episode psychosis.

AIM: Current diagnostic systems, DSM-5 and ICD-10, still adopt a categorical approach to classify psychotic disorders. The present study was aimed at investigating the structure of psychotic symptomatology in both affective and non-affective psychosis from a dimensional approach. METHODS: Participants with a first episode psychosis (FEP) were recruited from a cluster-randomized controlled trial (GET-UP PIANO TRIAL), offered to all Community Mental Health Centres (CMHCs) located across two northern Italian regions. After clinical stabilization, patients were assessed with a comprehensive set of psychopathological measures including the Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale and the Bech-Rafaelsen Mania Rating Scale. A two-step cluster analysis was performed. RESULTS: Overall, 257 FEP patients (male, n = 171, 66.5%; mean age = 24.96 ± 4.56) were included in the study. The cluster analysis revealed a robust four-cluster solution: delusional-persecutory (n = 82; 31.9%), depressed (n = 95; 37%), excited (n = 26; 10.1%) and negative-disorganized (n = 54; 21%), thus suggesting a quadripartite structure with both affective and non-affective dimensions. Among non-affective dimensions, negative and disorganization symptoms constituted a unique construct apart from positive symptoms. CONCLUSIONS: Symptom dimensions may represent a useful tool for dissecting the indistinct and non-specific psychopathology of FEP in order to better target specific interventions.

Insight and Dissociation in Lucid Dreaming and Psychosis.

Dreams and psychosis share several important features regarding symptoms and underlying neurobiology, which is helpful in constructing a testable model of, for example, schizophrenia and delirium. The purpose of the present communication is to discuss two major concepts in dreaming and psychosis that have received much attention in the recent literature: insight and dissociation. Both phenomena are considered functions of higher order consciousness because they involve metacognition in the form of reflective thought and attempted control of negative emotional impact. Insight in dreams is a core criterion for lucid dreams. Lucid dreams are usually accompanied by attempts to control the dream plot and dissociative elements akin to depersonalization and derealization. These concepts are also relevant in psychotic illness. Whereas insightfulness can be considered innocuous in lucid dreaming and even advantageous in psychosis, the concept of dissociation is still unresolved. The present review compares correlates and functions of insight and dissociation in lucid dreaming and psychosis. This is helpful in understanding the two concepts with regard to psychological function as well as neurophysiology.

Microbiota in anorexia nervosa: The triangle between bacterial species, metabolites and psychological tests.

Anorexia nervosa (AN) is a psychiatric disease with devastating physical consequences, with a pathophysiological mechanism still to be elucidated. Metagenomic studies on anorexia nervosa have revealed profound gut microbiome perturbations as a possible environmental factor involved in the disease. In this study we performed a comprehensive analysis integrating data on gut microbiota with clinical, anthropometric and psychological traits to gain new insight in the pathophysiology of AN. Fifteen AN women were compared with fifteen age-, sex- and ethnicity-matched healthy controls. AN diet was characterized by a significant lower energy intake, but macronutrient analysis highlighted a restriction only in fats and carbohydrates consumption. Next generation sequencing showed that AN intestinal microbiota was significantly affected at every taxonomic level, showing a significant increase of Enterobacteriaceae, and of the archeon Methanobrevibacter smithii compared with healthy controls. On the contrary, the genera Roseburia, Ruminococcus and Clostridium, were depleted, in line with the observed reduction in AN of total short chain fatty acids, butyrate, and propionate. Butyrate concentrations inversely correlated with anxiety levels, whereas propionate directly correlated with insulin levels and with the relative abundance of Roseburia inulinivorans, a known propionate producer. BMI represented the best predictive value for gut dysbiosis and metabolic alterations, showing a negative correlation with Bacteroides uniformis (microbiota), with alanine aminotransferase (liver function), and with psychopathological scores (obsession-compulsion, anxiety, and depression), and a positive correlation with white blood cells count. In conclusion, our findings corroborate the hypothesis that the gut dysbiosis could take part in the AN neurobiology, in particular in sustaining the persistence of alterations that eventually result in relapses after renourishment and psychological therapy, but causality still needs to be proven.

Family Burden, Emotional Distress and Service Satisfaction in First Episode Psychosis. Data from the GET UP Trial.

Background: Literature has documented the role of family in the outcome of chronic schizophrenia. In the light of this, family interventions (FIs) are becoming an integral component of treatment for psychosis. The First Episode of Psychosis (FEP) is the period when most of the changes in family atmosphere are observed; unfortunately, few studies on the relatives are available. Objective: To explore burden of care and emotional distress at baseline and at 9-month follow-up and the levels of service satisfaction at follow-up in the two groups of relatives (experimental treatment EXP vs. treatment as usual TAU) recruited in the cluster-randomized controlled GET UP PIANO trial. Methods: The experimental treatment was provided by routine public Community Mental Health Centers (Italian National Health Service) and consisted of Treatment as Usual plus evidence-based additional treatment (Cognitive Behavioral Therapy for psychosis for patients, Family Intervention for psychosis, and Case Management). TAU consisted of personalized outpatient psychopharmacological treatment, combined with non-specific supportive clinical management and informal support/educational sessions for families. The outcomes on relatives were assessed by the Involvement Evaluation Questionnaire (IEQ-EU), the General Health Questionnaire (GHQ-12), and the Verona Service Satisfaction Scale (VSSS-EU). Differences within and between groups were evaluated. Results: At baseline, 75 TAU and 185 EXP caregivers were assessed. In the experimental group 92% of relatives participated in at least 1 family session. At follow-up both groups experienced improvement in all IEQ and GHQ items, but caregivers belonging to the EXP arm experienced a significantly greater change in 10 IEQ items (mainly pertaining to the "Tension" dimension) and in GHQ items. Due to the low sample size, a significant effectiveness was only observed for 2 IEQ items and 1 GHQ-12 item. With respect to VSSS data at follow-up, caregivers in the EXP arm experienced significantly greater satisfaction in 8 items, almost all pertaining to the dimensions "Relatives' Involvement" and "Professionals' Skills and Behavior." Conclusions: The Family intervention for psychosis delivered in the GET UP PIANO trial reduced family burden of illness and improved emotional distress and satisfaction with services. These results should encourage to promote FIs on caregivers of first-episode psychosis patients.

Predictors and moderators of treatment outcome in patients receiving multi-element psychosocial intervention for early psychosis: results from the GET UP pragmatic cluster randomised controlled trial.

BackgroundThe GET UP multi-element psychosocial intervention proved to be superior to treatment as usual in improving outcomes in patients with first-episode psychosis (FEP). However, to guide treatment decisions, information on which patients may benefit more from the intervention is warranted.AimsTo identify patients' characteristics associated with (a) a better treatment response regardless of treatment type (non-specific predictors), and (b) a better response to the specific treatment provided (moderators).MethodSome demographic and clinical variables were selected a priori as potential predictors/moderators of outcomes at 9 months. Outcomes were analysed in mixed-effects random regression models. (Trial registration: ClinicalTrials.gov, NCT01436331)ResultsAnalyses were performed on 444 patients. Education, duration of untreated psychosis, premorbid adjustment and insight predicted outcomes regardless of treatment. Only age at first contact with the services proved to be a moderator of treatment outcome (patients aged ⩾35 years had greater improvement in psychopathology), thus suggesting that the intervention is beneficial to a broad array of patients with FEP.ConclusionsExcept for patients aged over 35 years, no specific subgroups benefit more from the multi-element psychosocial intervention, suggesting that this intervention should be recommended to all those with FEP seeking treatment in mental health services.

Establishment of an induced pluripotent stem cell (iPSC) line from a patient with Clozapine-responder Schizophrenia.

Peripheral blood mononuclear cells (PBMCs) were collected from a patient with treatment-refractory Schizophrenia who presented an exceptional clinical response to Clozapine. iPSC lines were established with a non-integrating reprogramming system based on Sendai virus. A footprint-free hiPSC line was characterized to confirm the expression of the main endogenous pluripotency markers and have a regular karyotype. Pluripotency was confirmed by differentiation into cells belonging to the three germ layers. This hiPSC line represents a valuable tool to study the molecular, biochemical and electrophysiological properties of mature neuronal populations belonging to Clozapine responder patients with a severe form of Schizophrenia.

Generation and characterization of an induced pluripotent stem cell (iPSC) line from a patient with clozapine-resistant Schizophrenia.

Peripheral Blood Mononuclear Cells (PBMCs) were collected from a patient with clozapine-resistant (also known as "super-refractory") Schizophrenia. iPSCs were established with a non-integrating Sendai virus-based reprogramming system. A footprint-free hiPSC line was characterized to express the main endogenous pluripotency markers and to retain a normal karyotype. Cells showed pluripotency competency by giving rise to progeny of differentiated cells belonging to the three germ layers. This hiPSC line represents a valuable tool to obtain mature, pathology-relevant neuronal populations in vitro that are suitable to investigate the molecular background of the schizophrenic disorder and the resultant patients' response to treatments.

[Factors affecting the choice of a family psychosocial intervention. A retrospective study from an experience of 8 years]. / Fattori che influenzano la scelta di un intervento familiare psicosociale. Studio retrospettivo da un'esperienza di 8 anni.

INTRODUCTION: Systematic studies have shown that the integration of pharmacological with psychosocial family treatments produces an improvement in clinical outcome with reduction of relapses, number and duration of hospitalizations. AIM: In the present study we wanted to investigate the presence of a possible association between household characteristics and the choice of joining a particular type of family intervention. MATERIALS AND METHODS: For this purpose, we performed a retrospective reconstruction of the therapy of a sample of 82 families treated with psychosocial family interventions for a period of 8 years. This sample was divided into 3 subgroups according to the type of family intervention performed (sporadic consulting, psychoeducation to term, continuous psychoeducation). Socio-demographic and clinical variables, motivations for the access to treatment and the relationship with the service of the families were investigated by reading the medical records, the use of PSICHE and the administration of a questionnaire that we created for this purpose. RESULTS: Type of pathology and clinical severity of the patients were not related to the choice of the type of psychosocial intervention performed by the family. On the contrary, considerable importance in choosing the type of psychosocial family intervention--in terms of personal involvement, duration of the same and shared objectives--have both the presence of comorbidity for substance use disorder between patients, and the role of the operator sending, who cannot disregard the objectives to be pursued and their consistency with the overall purposes of the intervention.

Feasibility and Effectiveness of a Multi-Element Psychosocial Intervention for First-Episode Psychosis: Results From the Cluster-Randomized Controlled GET UP PIANO Trial in a Catchment Area of 10 Million Inhabitants.

Integrated multi-element psychosocial interventions have been suggested to improve the outcomes of first-episode psychosis (FEP) patients, but they have been studied primarily in experimental settings and in nonepidemiologically representative samples. Thus, we performed a cluster-randomized controlled trial, comparing an integrated multi-element psychosocial intervention, comprising cognitive behavioral therapy, family intervention, and case management, with treatment as usual (TAU) for FEP patients in 117 community mental health centers (CMHCs) in a large area of northern Italy (10 million inhabitants). The randomized units (clusters) were the CMHCs, and the units of observation the patients (and, when available, their family members). The primary hypotheses were that add-on multicomponent intervention: (1) results in greater improvements in symptoms, as assessed with positive and negative syndrome scale and (2) reduces in-hospital stay, based on days of hospitalization over the 9-month follow-up. Four hundred and forty-four FEP patients received the intervention or TAU and were assessed at baseline and 9 months. Based on the retention rates of patients (and families) in the experimental arm, multi-element psychosocial interventions can be implemented in routine mental health services. Regarding primary outcomes, patients in the experimental arm showed greater reductions in overall symptom severity, while no difference could be found for days of hospitalization. Among the secondary outcomes, greater improvements were detected in the experimental arm for global functioning, emotional well-being, and subjective burden of delusions. No difference could be found for service disengagement and subjective burden of auditory hallucinations. These findings support feasibility and effectiveness of early interventions for psychosis in generalist mental health services.

Capgras delusion for animals and inanimate objects in Parkinson's Disease: a case report.

BACKGROUND: Capgras delusion is a delusional misidentification syndrome, in which the patient is convinced that someone that is well known to them, usually a close relative, has been replaced by an impostor or double. Although it has been frequently described in psychotic syndromes, including paranoid schizophrenia, over a third of the documented cases of Capgras delusion are observed in patients with organic brain lesions or neurodegenerative disease, including Parkinson's Disease. Variants of Capgras involving animals or inanimate objects have also been described. The etiology of Capgras in Parkinson's remains unclear, but may arise from a combination of factors, such as frontal lobe dysfunction and dopaminergic medication. CASE PRESENTATION: We present the case of a 53-year old right-handed female with Parkinson's disease who developed Capgras delusion during treatment with dopamine agonists and Levodopa/Carbidopa. She became convinced that her pet dogs and the plants in her garden had been substituted by identically looking ones. Our patient was initially treated with Quetiapine, with no improvement, and subsequently treated with Clozapine, which lead to partial regression of her symptoms. Neuropsychological Evaluation showed Mild Cognitive Impairment in Executive Functions. CONCLUSIONS: Given the clinical history, onset and evolution of symptoms we believe our patient's delusion resulted from the overlap of dopaminergic medication and Mild Cognitive Impairment in executive functions. Zoocentric Capgras, the variant we describe, has been rarely described in scientific literature, and we believe it is of interest due to its unusual characteristics.

Right hemisphere neural activations in the recall of waking fantasies and of dreams.

The story-like organization of dreams is characterized by a pervasive bizarreness of events and actions that resembles psychotic thought, and largely exceeds that observed in normal waking fantasies. Little is known about the neural correlates of the confabulatory narrative construction of dreams. In this study, dreams, fantasies elicited by ambiguous pictorial stimuli, and non-imaginative first- and third-person narratives from healthy participants were recorded, and were then studied for brain blood oxygen level-dependent functional magnetic resonance imaging on a 3.0-Tesla scanner while listening to their own narrative reports and attempting a retrieval of the corresponding experience. In respect to non-bizarre reports of daytime activities, the script-driven recall of dreams and fantasies differentially activated a right hemisphere network including areas in the inferior frontal gyrus, and superior and middle temporal gyrus. Neural responses were significantly greater for fantasies than for dreams in all regions, and inversely proportional to the degree of bizarreness observed in narrative reports. The inferior frontal gyrus, superior and middle temporal gyrus have been implicated in the semantic activation, integration and selection needed to build a coherent story representation and to resolve semantic ambiguities; in deductive and inferential reasoning; in self- and other-perspective taking, theory of mind, moral and autobiographical reasoning. Their degree of activation could parallel the level of logical robustness or inconsistency experienced when integrating information and mental representations in the process of building fantasy and dream narratives.

Deep brain stimulation of the nucleus accumbens and bed nucleus of stria terminalis for obsessive-compulsive disorder: a case series.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a psychiatric condition defined by the presence of obsessions, compulsions, or both. It has a lifetime prevalence of 2%-3% and causes significant impairment in social and work functioning, as well as a reduced quality of life. Treatment includes pharmacotherapy and psychotherapy, but a significant number of patients fail to respond to treatment. Deep brain stimulation has shown to be a safe and effective procedure for severe, chronic, treatment-resistant OCD, and several surgical targets have been proposed for treatment, including the nucleus accumbens, the anterior limb of the internal capsule, the subthalamic nucleus, the globus pallidus, and the bed nucleus of stria terminalis. OBJECTIVES: To report the first Italian case series of patients who underwent DBS of 2 distinct targets for OCD: nulceus accumbens and bed nulceus of stria terminalis. METHODS: Four patients underwent DBS of the nulceus accumbens, and 4 patients underwent DBS of the bed nucleus of stria terminalis. RESULTS: Six patients showed a significant improvement in OCD symptoms. CONCLUSIONS: DBS of these 2 structures is a safe and effective procedure for the treatment of severe, refractory OCD.

Obsessive-compulsive disorder presenting with musical obsessions in otosclerosis: a case report.

INTRODUCTION: Musical obsessions consist of intrusive recollections of music fragments that are experienced as unwanted. Otosclerosis is caused by an abnormal bone homeostasis of the otic capsule and represents a frequent cause of hearing impairment. Many conditions causing hearing loss have been associated with musical hallucinations, but the association between musical obsessions and hearing loss is frequently overlooked. CASE PRESENTATION: We present the case of a 51-year-old Caucasian woman with a history of obsessive-compulsive disorder who developed musical obsessions soon after being diagnosed with otosclerosis. She was referred to our obsessive-compulsive disorder outpatient unit by her general psychiatrist. At the time of our first evaluation, she had severe musical obsessions that interfered with her social functioning and made her unable to follow conversations. She was started on 40mg of paroxetine and 2.5mg of aripiprazole, which led to significant improvement of her symptoms and of her social and work functioning. CONCLUSIONS: To the best of our knowledge, this is the first report of musical obsessions in a patient with hearing loss due to otosclerosis and a history of obsessive-compulsive disorder. This case suggests that a differential diagnosis of obsessive-compulsive disorder should be carefully considered in patients with hearing impairment who complain of involuntary musical imagery, especially in those patients who have a previous history of obsessive-compulsive disorder.

Depressive symptoms and major depressive disorder in patients affected by subclinical hypothyroidism: a cross-sectional study.

The relationship between subclinical hypothyroidism and depression is still controversial. Our objective was to compare the prevalence of depressive symptoms and major depressive disorder in a population of patients affected by subclinical hypothyroidism and a control group without thyroid disease. The authors enrolled 123 consecutive outpatients affected by subclinical hypothyroidism undergoing follow-up at the endocrinology department of San Paolo Hospital in Milan and 123 controls without thyroid disease under the charge of general physicians.All patients and controls underwent an evaluation by means of a psychiatric interview; Hamilton Rating Scale for Depression (HAM-D); Montgomery-Asberg Depression Rating Scale (MADRS); and serum thyroid stimulating hormone, free T4, and free T3 levels. Patients were also screened for thyroid peroxidase antibodies and thyroglobulin antibodies. Patients affected by subclinical hypothyroidism had a prevalence of depressive symptoms of 63.4% at HAM-D and 64.2% at MADRS; 22 patients (17.9%) had a diagnosis of depressive episode (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria). The control group had a prevalence of depressive symptoms of 27.6% at HAM-D and 29.3% at MADRS, and only seven controls had a diagnosis of depressive episode. The prevalence of depressive symptoms between these two groups was statistically different. This study underlines a strong association between subclinical hypothyroidism and depressive symptoms, which could have some important diagnostic and therapeutic implications in the clinical practice.

Such stuff as psychoses are made on?

In her target article, Sue Llewellyn concludes that an unconstrained form of consciousness is necessary for the elaboration of meaningful associations. Unlike the author's view that dedifferentiation of memory encoding processes across wakefulness and sleep determines schizophrenia, our proposal suggests this mechanism could reflect a common neurobiological substrate for psychosis across several different diagnostic domains.

Are delusional contents replayed during dreams?

The relationship between dream content and waking life experiences remains difficult to decipher. However, some neurobiological findings suggest that dreaming can, at least in part, be considered epiphenomenal to ongoing memory consolidation processes in sleep. Both abnormalities in sleep architecture and impairment in memory consolidation mechanisms are thought to be involved in the development of psychosis. The objective of this study was to assess the continuity between delusional contents and dreams in acutely psychotic patients. Ten patients with a single fixed and recurring delusional content were asked to report their dreams during an acute psychotic break. Sixteen judges with four different levels of acquaintance to the specific content of the patients' delusions were asked to group the dreams, expecting that fragments of the delusional thought would guide the task. A mathematical index (f,t) was developed in order to compare correct groupings between the four groups of judges. Most judges grouped the dreams slightly above chance level and no relevant differences could be found between the four groups [F(3,12)=1.297; p=n.s.]. Scoring of dreams for specific delusional themes suggested a continuity in terms of dream and waking mentation for two contents (Grandiosity and Religion). These findings seem to suggest that at least some delusional contents recur within patients' dreams. Future studies will need to determine whether such continuity reflects ongoing consolidation processes that are relevant to current theories of delusion formation and stabilization.

[Risk of hospitalization among patients with co-occurring psychotic and substance use disorders: a 12-year follow-up]. / Il rischio di ricovero in pazienti comorbili affetti da disturbi psicotici e da uso di sostanze: follow-up a 12 anni.

AIM: The study aims to analyze the impact of substance use disorders (SUD) on the risk of hospitalization among patients affected by psychotic disorders. METHODS: During 1995, the patients consecutively admitted to psychiatric hospitalization or to an outpatient visit, were included in the study. Patients were interviewed by a questionnaire with specific reference to Addiction Severity Index (ASI), in order to assess the presence of SUD. During 2008, for each patient, the retrospective assessment of the days and the number of hospitalizations, due to psychiatric cause between 1996 and 2007, was performed. RESULTS: During 1995, 102 patients were included in the study, 15 patients (14.7%) with a current SUD, 17 patients (16.7%) with a past SUD, and 70 patients (68.6% of the sample) without SUD. The follow-up analysis did not show any statistically significant difference among the three subgroups for what concerns the risk of receiving at least one hospitalization and the risk of involuntary treatment. By contrast, hospitalized patients with current SUD, if compared to hospitalized patients with past SUD or patients without SUD, appeared to have a significantly higher overall number of hospital admissions and days of hospitalization. DISCUSSION: The current SUD group showed, in terms of hospitalizations, worse prognostic profiles than the group without SUD and the group with past SUD. The prominent role of a comprehensive assessment and a therapeutic strategy taking into account the potential negative effect of substance use on the stabilization of psychotic symptoms is therefore confirmed.