Autistic symptoms in unaffected first-degree relatives of people with schizophrenia: results from the Italian Network for Research on Psychoses multicenter study.

BACKGROUND: Autistic symptoms represent a frequent feature in schizophrenia spectrum disorders (SSD). However, the prevalence and the cognitive and functional correlates of autistic symptoms in unaffected first-degree relatives of people with SSD remain to be assessed. METHODS: A total of 342 unaffected first-degree relatives related to 247 outpatients with schizophrenia were recruited as part of the multicenter study of the Italian Network for Research on Psychoses (NIRP). Autistic features were measured with the PANSS Autism Severity Scale. Three groups of participants, defined on the presence and severity of autistic symptoms, were compared on a wide array of cognitive and functional measures. RESULTS: Of the total sample, 44.9% presented autistic symptoms; 22.8% showed moderate levels of autistic symptoms, which can be observed in the majority of people with SSD. Participants with higher levels of autistic symptoms showed worse performance on Working Memory (p = 0.014) and Social Cognition (p = 0.025) domains and in the Global Cognition composite score (p = 0.008), as well as worse on functional capacity (p = 0.001), global psychosocial functioning (p < 0.001), real-world interpersonal relationships (p < 0.001), participation in community activities (p = 0.017), and work skills (p = 0.006). CONCLUSIONS: A high prevalence of autistic symptoms was observed in first-degree relatives of people with SSD. Autistic symptoms severity showed a negative correlation with cognitive performance and functional outcomes also in this population and may represent a diagnostic and treatment target of considerable scientific and clinical interest in both patients and their first-degree relatives.

Does social cognition change? Evidence after 4 years from the Italian Network for Research on Psychoses.

BACKGROUND: Deficits in social cognition (SC) are significantly related to community functioning in schizophrenia (SZ). Few studies investigated longitudinal changes in SC and its impact on recovery. In the present study, we aimed: (a) to estimate the magnitude and clinical significance of SC change in outpatients with stable SZ who were assessed at baseline and after 4 years, (b) to identify predictors of reliable and clinically significant change (RCSC), and (c) to determine whether changes in SC over 4 years predicted patient recovery at follow-up. METHODS: The reliable change index was used to estimate the proportion of true change in SC, not attributable to measurement error. Stepwise multiple logistic regression models were used to identify the predictors of RCSC in a SC domain (The Awareness of Social Inference Test [TASIT]) and the effect of change in TASIT on recovery at follow-up. RESULTS: In 548 participants, statistically significant improvements were found for the simple and paradoxical sarcasm of TASIT scale, and for the total score of section 2. The reliable change index was 9.8. A cut-off of 45 identified patients showing clinically significant change. Reliable change was achieved by 12.6% and RCSC by 8% of participants. Lower baseline TASIT sect. 2 score predicted reliable improvement on TASIT sect. 2. Improvement in TASIT sect. 2 scores predicted functional recovery, with a 10-point change predicting 40% increase in the probability of recovery. CONCLUSIONS: The RCSC index provides a conservative way to assess the improvement in the ability to grasp sarcasm in SZ, and is associated with recovery.

Aggressiveness and violence in psychiatric patients: a clinical or social paradigm?

OBJECTIVE: Psychiatric disorders are often considered the leading cause of violence. This may be due to a stereotype created by media and general opinion. METHOD: The Modified Overt Aggression Scale (MOAS) was used to evaluate the severity of aggressive and violent behaviors in 400 patients who attended a post-acute psychiatric service in Milan from 2014 to 2016 and suffered from different psychiatric disorders. The psychopathological clinical picture was evaluated by Clinical Global Impression (CGI). The study also assessed the possible correlation between epidemiologic and sociodemographic factors, clinical variables, and aggression and violence. RESULTS: Of the total number of subjects, 21.50% showed a MOAS score >0, 11.50% presented mild aggression (0-10 MOAS weighted score), 9% moderate aggression (11-20), and 1% severe aggression (MOAS >20). With respect to violent behaviors, 16% of patients showed a score >0 in one MOAS subscale other than verbal aggression according to violence definition. The severity of clinical picture seemed to be related to higher weighted MOAS score. Multivariate testing of different sociodemographic and clinical variables showed that violence was related to unemployment status, and significantly correlated to compulsory admission (TSO), suicide attempts (TS), and personality disorders, while the severity of clinical psychiatric picture seemed to play a secondary role. CONCLUSION: Results have shown that personality disorders and sociodemographic factors, including economic factors, seem to be major determinants of violence among patients diagnosed with mental disorders.

The Role of Omega-3 Fatty Acids in Developmental Psychopathology: A Systematic Review on Early Psychosis, Autism, and ADHD.

In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of ω-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far.

Similar white matter changes in schizophrenia and bipolar disorder: A tract-based spatial statistics study.

Several strands of evidence reported a significant overlapping, in terms of clinical symptoms, epidemiology and treatment response, between the two major psychotic disorders-Schizophrenia (SCZ) and Bipolar Disorder (BD). Nevertheless, the shared neurobiological correlates of these two disorders are far from conclusive. This study aims toward a better understanding of possible common microstructural brain alterations in SCZ and BD. Magnetic Resonance Diffusion data of 33 patients with BD, 19 with SCZ and 35 healthy controls were acquired. Diffusion indexes were calculated, then analyzed using Tract-Based Spatial Statistics (TBSS). We tested correlations with clinical and psychological variables. In both patient groups mean diffusion (MD), volume ratio (VR) and radial diffusivity (RD) showed a significant increase, while fractional anisotropy (FA) and mode (MO) decreased compared to the healthy group. Changes in diffusion were located, for both diseases, in the fronto-temporal and callosal networks. Finally, no significant differences were identified between patient groups, and a significant correlations between length of disease and FA and VR within the corpus callosum, corona radiata and thalamic radiation were observed in bipolar disorder. To our knowledge, this is the first study applying TBSS on all the DTI indexes at the same time in both patient groups showing that they share similar impairments in microstructural connectivity, with particular regards to fronto-temporal and callosal communication, which are likely to worsen over time. Such features may represent neural common underpinnings characterizing major psychoses and confirm the central role of white matter pathology in schizophrenia and bipolar disorder.

The first model of keeping energy balance and optimal psycho affective development: Breastfed infants.

BACKGROUND: Breastfed infants follow a peculiar growth fashion characterized by a rapid weight gain in the first weeks of life, then followed by a fast decrease in growth rates, a capacity to self-regulate the sense of hungry and satiety, and a minor propensity towards overweight and obesity later on, in parallel with a better neurodevelopmental performance. METHODS: We searched studies investigating the relationship between the feeding mode in infancy and the energy balance, so the possible associations with total energy expenditure and intake regulation. We focused the research on the interaction with the neuropsychological development and the possible role of microbiome in determinating the normal generation and regular functioning of the brain through the so named "gut-brain axis". RESULTS: Total energy expenditure (TEE) is different for breast-fed and formula-fed infants, in particular the feeding mode seems to affect the sleep organisation. Long-term breastfeeding, is one of the most studied factors of neurodevelopment, several studies reporting beneficial effects on child neuropsychological development. Probably this effect is modulated by genetic variations in fatty acid metabolism. Increasing data also showed that the intestinal microbiome exerts several functions which are able to influence neurodevelopment. LIMITATIONS: There is considerable controversy over whether nutrition in early life has a long-term influence on neurodevelopment. Other studies are needed to confirm the association between breastfeeding and brain development. CONCLUSIONS: The key points of energy disposal, the role and effects of the instestinal flora represent promising fields of investigation possibly leading to indications for the wide area of preventive medicine.

The combination of pharmacogenetic and pharmacokinetic analyses to optimize clomipramine dosing in major depression: a case report.

WHAT IS KNOWN AND OBJECTIVE: Polymorphisms in cytochrome P450 2D6 and 2C19 can lead to interindividual differences in drug plasma concentrations, affecting clomipramine efficacy. Pharmacokinetic and pharmacogenetic analyses may improve drug therapy. CASE SUMMARY: We report the case of a depressed woman requiring higher doses than standard of clomipramine. Identification of low plasma drug levels led to extensive pharmacogenetic analyses of all genes and major functional polymorphisms reported to affect clomipramine metabolism. WHAT IS NEW AND CONCLUSION: Therapeutic drug monitoring and pharmacogenetic analyses may be useful in the investigation and optimization of clomipramine in standard-dose non-responders.

"Long-acting" olanzapine in maintenance therapy of schizophrenia: A study with plasma levels.

INTRODUCTION: This prospective study was performed to evaluate clinical efficacy and tolerability of olanzapine long-acting injection (OLZ-LAI) and the relation between OLZ plasma level (PL) and the clinical outcome in maintenance therapy of schizophrenia. MATERIAL AND METHODS: Twenty-five chronic schizophrenic outpatients with age ranging from 18 to 65 years were included in this 9-month study. Patients were given a dosage of either 210 or 300 or 405 mg of OLZ-LAI every 28 days. Patients were evaluated at baseline and every four weeks by Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Scale (PANSS); at the same time, PL of OLZ was determined. The metabolic profile (aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein, low-density lipoprotein, total cholesterol, and glucose levels) was analyzed every two months. RESULTS: BPRS and total PANSS showed a statistically significant improvement from T2 with a clinical stabilization of psychopathological picture. PL ranged from 4.0 to 78.9 ng/ml (mean 20.59 ng/ml ± 14.66 standard deviation). The coefficient of variation of PLs was related to clinical stabilization. No post-injection delirium sedation syndrome occurred. CONCLUSIONS: Our data reveal the efficacy of OLZ-LAI in maintenance treatment of schizophrenia at lower dosages also in comparison with that of oral therapy. OLZ-LAI seems to be useful for guaranteeing constant PL of the drug. A lesser variation of PL was the most predictable factor associated with maintenance of clinical benefit.

Substance-induced psychoses: a critical review of the literature.

Substances with psychotomimetic properties such as cocaine, amphetamines, hallucinogens and cannabis are widespread, and their use or abuse can provoke psychotic reactions resembling a primary psychotic disease. The recent escalating use of methamphetamine throughout the world and its association with psychotic symptoms in regular users has fuelled concerns. The use of cannabis and cocaine by young people has considerably increased over recent years, and age at first use has dramatically decreased. There is some evidence that cannabis is now on the market in a more potent form than in previous decades. Furthermore, a large number of studies have reported a link between adolescent cannabis use and the development of stable psychosis in early adulthood. The situation is further complicated by the high rates of concomitant substance use by subjects with a psychotic illness which, especially in young users with an early-phase psychotic disorder, can make diagnosis difficult. This paper reviews the literature concerning the properties of psychotogenic substances and the psychotic symptoms they can give rise to, and discusses the association between substance abuse and psychosis with particular emphasis on the differential diagnosis of a primary and substance-induced psychotic disorder. The findings of this review indicate 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 dependence. 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.

Depressive dimension, clinical outcome, and duration of hospitalization in acute schizophrenia.

In the present study we extract clusters of symptoms in acute hospitalized patients affected by Schizophrenia, using factor analysis of BPRS-E. We aim to explore the relationship between symptom dimensions, duration of hospitalization, and clinical outcome, in order to test if the depressive dimension might contribute significantly to predict the outcome. The data were drawn from a prospective, naturalistic, observational study of schizophrenic patients consecutively admitted to a psychiatric ward (SPDC, Ospedale Maggiore Policlinico of Milan), during a re-exacerbation phase. General symptomatology was measured through BPRS-E at baseline (T0) and at discharge (T1). We found symptoms of acute schizophrenia to cluster together in four distinct domains, labelled "Depression", "Excitement", "Positive symptoms", and "Negative symptoms". The "Depression" cluster is significantly associated to a good clinical outcome, as measured by percentage of improvement in BPRS score, but not to duration of hospitalization.

Validity and reliability of the Structured Clinical Interview for the Trauma and Loss Spectrum (SCI-TALS).

BACKGROUND: DSM-IV identifies three stress response disorders (acute stress (ASD), post-traumatic stress (PTSD) and adjustment disorders (AD)) that derive from specific life events. An additional condition of complicated grief (CG), well described in the literature, is triggered by bereavement. METHODS: This paper reports on the reliability and validity of the Structured Clinical Interview for Trauma and Loss Spectrum (SCI-TALS) developed to assess the spectrum of stress response. The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising clinical and subsyndromal manifestations. Study participants, enrolled at 6 Italian Departments of Psychiatry, included consecutive patients with PTSD (N = 48), CG (N = 44), and controls (N = 48). RESULTS: We showed good reliability and validity of the SCI-TALS. Domain scores were significantly higher in participants with PTSD or CG compared to controls. There were high correlations between specific SCI-TALS domains and corresponding scores on established measures of similar constructs. Participants endorsing grief and loss events reported similar scores on all instruments, except those with CG who scored significantly higher on the domain of grief reactions. CONCLUSION: These results support the existence of a specific grief-related condition and the proposal that different forms of stress response have similar manifestations.

Increased serum interleukin-8 and interleukin-10 in schizophrenic patients resistant to treatment with neuroleptics and the stimulatory effects of clozapine on serum leukemia inhibitory factor receptor.

There is now evidence that schizophrenia may be accompanied by an activation of the monocytic and T-helper-2 (Th-2) arms of cell-mediated immunity (CMI) and by various alterations in the Th-1 arm of CMI. There is also evidence that repeated administration of typical and atypical antipsychotics may result in negative immunomodulatory effects. This study was carried out to examine (1) the serum concentrations of interleukin-8 (IL-8), IL-10, the soluble CD8 (sCD8) and the leukemia inhibitory factor receptor (LIF-R) in nonresponders to treatment with typical neuroleptics as compared with normal volunteers and responders to treatment; and (2) the effects of atypical antipsychotics on the above immune variables. The latter were determined in 17 nonresponders to treatment with neuroleptics and in seven normal volunteers and 14 schizophrenic patients who had a good response to treatment with antipsychotic agents. The nonresponders had repeated measurements of the immune variables before, and 2 and 4 months after treatment with clozapine or risperidone. Serum IL-8 and IL-10 were significantly higher in schizophrenic patients than in normal controls. The serum concentrations of the sCD8 were significantly increased 2 months, but not 4 months, after starting treatment with atypical antipsychotics. Serum LIF-R concentrations were significantly increased 2 and 4 months after starting treatment with atypical antipsychotics. It is concluded that: (1) schizophrenia is characterized by an activation of both pro-inflammatory and anti-inflammatory aspects of cell-mediated immunity; (2) prolonged treatment with atypical antipsychotics may increase the anti-inflammatory capacity of the serum in schizophrenic patients by increasing serum LIF-R concentrations; and (3) short-term treatment with clozapine may induce signs of immune activation which disappear upon prolonged treatment.