Clinical Implications of Autistic Features in Patients With a First Episode of Psychosis.

Social cognitive impairments in first episode psychosis

BackgroundDebate continues about how long maintenance treatment should be continued following a first episode of psychosis (FEP). Resolving this question requires an understanding of the risk of recurrence which would be expected to vary as a function of the underlying cause of the psychosis. The range of diagnoses that may present as a FEP include schizophrenia and related schizophrenia spectrum disorders, bipolar mania, bipolar and unipolar depression, substance-induced psychosis, and unspecified psychotic disorders. The majority of FEP patients will receive the diagnosis of schizophrenia or bipolar disorder for which the 1- year risk of illness recurrence is estimated at 77% and 41%, respectively. We reviewed the literature in order to estimate the risk of relapse and the risk of developing a primary psychotic disorder following a FEP due to other diagnoses.MethodsWe conducted a primary literature review using Medline and PubMed. We included the following search terms: first episode, relapse, recurrence, depression with psychosis, psychotic depression, mania with psychosis, substance induced psychosis and psychosis. We included prospective and retrospective studies including those that involved medication discontinuation or naturalistic follow-up to determine the risk of recurrence following a FEP. We also reviewed the literature to determine the likelihood that FEP with these diagnoses would transition to a primary psychotic disorder (schizophrenia spectrum disorder or major mood disorder) for which published rates of recurrence would apply.ResultsTwo studies were identified which reported on the recurrence rate following a first episode of psychotic depression. Recurrence rates ranged from 27% at eight months to 80.6% at a mean of 32 months. An additional study found that following a first episode of psychotic depression, 29.9% and 14.3% of patients were diagnosed with schizophrenia and bipolar disorder, respectively, at 10-year follow-up. The risk of developing a primary psychotic disorder following a first episode of substance-induced psychosis has been investigated in three studies which reported rates of conversion to a primary psychotic disorder of 25% at one year, 25% at 10 years and 32% at 20 years. The risk of developing a primary psychotic disorder following a cannabis-induced psychosis has been investigated in three studies which reported rates of conversion of 44.5% at three years, 46% at eight years, and 47.4% at 20 years. Patients with a first episode of unspecified psychosis have been reported in a single study to have a 73.7% risk of developing a primary psychotic disorder at 10 year follow-up.DiscussionThe risk of illness recurrence following a FEP not initially diagnosed as a schizophrenia spectrum or bipolar disorder was found to vary by both initial diagnosis and by follow-up duration. Psychotic depression, substance-induced psychosis and other unspecified psychoses were all associated with either substantial risks of illness recurrence or development of a primary psychotic disorder. The risk of illness recurrence following medication discontinuation has not been established for these disorders as many of these studies included patients whether they were on or off of their prescribed medications. Clinical recommendation should be informed by future research on recurrence rates with and without maintenance medication for the different causes of FEP. In the meantime, patients with a FEP and their family members should be fully informed about the risk of illness recurrence and development of a primary psychotic disorder when considering any trial of medication discontinuation.

392 – Do neurocognition, theory of mind and psychiatric symptoms predict social outcome in schizophrenic disorders?

Background:Mood disorders and psychosis has been reported among the patients with macrocytosis; however, its prevalence among the first episode of psychosis and depression is unknown. The purpose of the study was to establish the prevalence of macrocytosis among the patients with the first episode of depression and psychosis.Materials and Methods:In this cross-sectional study, three groups comprising patients with first episode of depression (n = 100), patients with the first episode of psychosis (n = 100), and healthy controls (n = 100) were included. Blood samples were collected from each participant and analyzed using the automated coulter counter. The hematological variables (e.g., macrocytosis, anemia) in the three groups were compared using the Chi-square and analysis of variance tests.Results:The prevalence of macrocytosis among patients with depression and psychosis was 2.6 (8%) and 3.3 times (11%) higher, respectively than that among the healthy controls (3%). In addition, the hemoglobin concentration, mean corpuscular volume and mean platelet volume in patients with first episodes of psychosis and depression significantly differed from those in healthy controls P < 0.001.Conclusion:This study showed that the prevalence of macrocytosis among the first episode of depression and psychosis was higher than healthy controls. Macrocytosis may have etiological and prognostic significance among these patients. Prospective studies are needed to explore the clinical significance of macrocytosis among the patients with depression and psychosis in the clinical practice.

Aberrant social cognition is a core feature of schizophrenia, persisting from clinical high-risk and genetic high-risk states to the first episode of psychosis. This study aimed to identify shared and distinct social cognition-related functional alterations across clinical high-risk, genetic high-risk, and first episode of psychosis groups, shedding light on varying risk levels for first episode of psychosis development. Meta-analyses were performed on 38 whole-brain task-based functional magnetic resonance imaging studies (12 clinical high risk, 15 genetic high risk, 11 first episode of psychosis) using Seed-based d Mapping. Function abnormalities were assessed within each patient group, with quantitative comparisons made against controls. Clinical high-risk and genetic high-risk individuals showed neither shared nor distinct abnormal brain activation during social cognition tasks. A shared cluster of increased activation in the right anterior cingulate cortex was observed between genetic high-risk and first episode of psychosis groups. However, no conjunction or disjunction results were found between clinical high-risk and first episode of psychosis groups. Meta-regression analyses revealed accelerated age-related greater activation decline in the left insula in individuals with clinical high risk. In conclusion, the absence of shared social cognition-related brain activation between clinical high risk and genetic high risk may signify differences in neural correlates underlying social cognition deficits between these groups and they follow distinct neural pathways toward first episode of psychosis. The shared abnormal anterior cingulate cortex activation in genetic high risk and first episode of psychosis may represent an endophenotype of schizophrenia.

The PANSS Autism Severity Score (PAUSS) is a popular measure of autistic features in First Episode Psychosis (FEP) samples. However, evidence on its longitudinal stability, course and treatment response is poor. Therefore, the main aim of this research was to compare clinical outcomes between FEP individuals with or without "autistic features" enrolled within an "Early Intervention in Psychosis" (EIP) service across 2years of follow-up, as well as any significant association with EIP treatment components. FEP subjects completed the Positive And Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF), and the Health of the Nation Outcome Scale (HoNOS) at entry and across the follow-up. Statistical tests included Kaplan-Meyer survival analysis, mixed-design ANOVA, and multiple linear logistic regression analysis. 301 FEP subjects were enrolled (85 [28.0%] scored above the PAUSS cut-off score). Across the follow-up, the PAUSS + subgroup showed lower incidence rates of both symptomatic and functional remission. No PAUSS long-term stability was observed, but a statistically significant reduction in its values. This longitudinal change was mainly predicted by the total number of case management sessions offered within the EIP program. Our results suggest that the PAUSS could not represent a valid instrument to assess "trait-like" autistic features in FEP subjects. On contrary, it seems to capture a FEP subgroup characterized by higher severity levels in psychopathology and poorer outcomes and prognosis.

To determine the baseline individual characteristics that predicted symptom recovery and functional recovery at 10-years following the first episode of psychosis. AESOP-10 is a 10-year follow up of an epidemiological, naturalistic population-based cohort of individuals recruited at the time of their first episode of psychosis in two areas in the UK (South East London and Nottingham). Detailed information on demographic, clinical, and social factors was examined to identify which factors predicted symptom and functional remission and recovery over 10-year follow-up. The study included 557 individuals with a first episode psychosis. The main study outcomes were symptom recovery and functional recovery at 10-year follow-up. At 10 years, 46.2% (n = 140 of 303) of patients achieved symptom recovery and 40.9% (n = 117) achieved functional recovery. The strongest predictor of symptom recovery at 10 years was symptom remission at 12 weeks (adj OR 4.47; CI 2.60-7.67); followed by a diagnosis of depression with psychotic symptoms (adj OR 2.68; CI 1.02-7.05). Symptom remission at 12 weeks was also a strong predictor of functional recovery at 10 years (adj OR 2.75; CI 1.23-6.11), together with being from Nottingham study centre (adj OR 3.23; CI 1.25-8.30) and having a diagnosis of mania (adj OR 8.17; CI 1.61-41.42). Symptom remission at 12 weeks is an important predictor of both symptom and functional recovery at 10 years, with implications for illness management. The concepts of clinical and functional recovery overlap but should be considered separately.

Montreal Cognitive Assessment (MoCA) as a screening tool for cognitive impairment in early stages of psychosis

Altered default network resting state functional connectivity in patients with a first episode of psychosis

BackgroundThe suffering people experience following a first episode of psychosis is great, and has been well-investigated. Conversely, potential positive outcomes following a first episode of psychosis have been under-investigated. One such outcome that may result from a first episode of psychosis is posttraumatic growth, or a positive aftermath following the trauma of a first psychotic episode. While posttraumatic growth has been described following other physical and mental illnesses, posttraumatic growth has received very little attention following a first episode of psychosis. To address this research gap, we will conduct a mixed methods study aimed at answering two research questions: 1) How do people experience posttraumatic growth following a first episode of psychosis? 2) What predicts, or facilitates, posttraumatic growth following a first episode of psychosis?Methods/designThe research questions will be investigated using a mixed methods convergent design. All participants will be service-users being offered treatment for a first episode of psychosis at a specialized early intervention service for young people with psychosis, as well as their case managers.. A qualitative descriptive methodology will guide data-collection through semi-structured interviews with service-users. Service-users and case managers will complete questionnaires related to posttraumatic growth and its potential predictors using quantitative methods. These predictors include the impact a first episode of psychosis on service-users’ lives, the coping strategies they use; the level of social support they enjoy; and their experiences of resilience and recovery. Qualitative data will be subject to thematic analysis, quantitative data will be subject to multiple regression analyses, and results from both methods will be combined to answer the research questions in a holistic way.DiscussionFindings from this study are expected to show that in addition to suffering, people with a first episode of psychosis may experience positive changes. This study will be one of few to have investigated posttraumatic growth following a first episode of psychosis, and will be the first to do so with a mixed methods approach.

Background: Clinical and functional outcome improvement in psychotic disorders is a challenge for the investigators. Recent advances offered opportunities for ameliorating the course of the illness during its early stages and for identifying treatment-resistant patients. Patients who had not response to two different antipsychotics, administered at correct doses for a sufficient period, can be operationally considered treatment-resistant. Available evidence suggested that the response's trajectory to the antipsychotic treatment revealed that a small proportion of subjects are poor responders (8.2%), the majority of patients have a moderate response (76.4%), and only 15.4% can be considered rapid responders with the greatest magnitude of response. Patients with first episode of psychosis generally obtain a more favorable response profile. Nevertheless, in around 25% of these patients symptoms of psychosis persist with a worse long-term course of illness.Objectives: The aim of this review is to report current evidences on the main predictors of treatment non-response in patients at early stage of psychosis.Methods: We used a specific string that guaranteed a high sensitive search in pubmed. We included the following types of publications: randomized-controlled trials, observational studies, longitudinal studies, retrospective studies, case-control studies, open-label investigations, cohort studies, and reviews. Publications must concern predictors of treatment resistance in early psychosis.Results: Forty-seven records were included: 5 reviews, 3 meta-analyses, 22 longitudinal studies, 2 retrospective studies, 1 naturalistic study, 6 randomized controlled trials, 2 open-label studies, 2 case-control studies, 4 cohort studies, 2 retrospective studies. Several factors were identified as predictors of treatment resistance: lower premorbid functioning; lower level of education; negative symptoms from first psychotic episode; comorbid substance use; younger age at onset; lack of early response; non-adherence to treatment; and longer duration of untreated psychosis. The role of gender and marital status is still controversial. More evidences are needed about neurobiological, genetic, and neuroimaging factors.Conclusions: The identification of specific predictive factors of treatment resistance in patients with first episode of psychosis ameliorates the quality of clinical management of these patients in the critical early phase of schizophrenia.

Dr. Guasp et al. assessed the performance of serum neurofilament light chain (NfL) testing in differentiating anti-NMDA receptor encephalitis (NMDARe) from psychiatric causes of a first episode of psychosis (pFEP) in an observational study of 118 patients with NMDARe (33 of whom had isolated psychosis at presentation), comparing them with 45 patients with pFEP, 36 patients with herpes simplex encephalitis (HSV), and 36 healthy controls. They found that young patients with first episode psychosis and serum NfL ≥15 pg/mL had a 120 times higher chance of having NMDARe than pFEP, with this cutoff correctly classifying 96% of patients with pFEP and 85% of patients with NMDARe and isolated psychosis. Notably, all patients with HSV also had serum NFL≥15 pg/mL. The authors concluded that patients with first episodes of psychosis of unclear etiology and serum NfL ≥15 pg/mL should undergo testing for NMDAR antibodies in the CSF. In response, Dr. Vale notes that the presence of NMDAR antibodies is not essential for diagnosing autoimmune encephalitis, given that other autoantibodies can cause psychotic presentations, and that elevations of NfL may reflect comorbidities causing central or peripheral neuroaxonal damage. Dr. Vale argues that given the severity of first episodes of psychosis, all such patients should be considered for CSF examinations, as was the historical practice for concerns of neurosyphilis. Responding to these comments, the authors agree that CSF studies should be reincorporated in the evaluation of patients with new onset psychosis, but note that they restricted their study to the identification of NMDARe, given that this condition can almost perfectly mimic psychiatric causes of first episodes of psychosis, in contrast to other autoimmune encephalitides, which typically have other concurrent neurologic features. They argue that the usefulness of serum NfL testing seen in their study is a relevant finding, regardless of any other underlying contributors to NfL elevation. This exchange highlights the importance of ongoing research into noninvasive markers of neurologic causes of psychosis. It is the editors' opinion that in practice, routine CSF testing for all patients with first episodes of psychosis is unlikely to be feasible in all psychiatric facilities, and as such, screening using serum markers will likely complement clinical examination-guided autoantibody testing in the future. Dr. Guasp et al. assessed the performance of serum neurofilament light chain (NfL) testing in differentiating anti-NMDA receptor encephalitis (NMDARe) from psychiatric causes of a first episode of psychosis (pFEP) in an observational study of 118 patients with NMDARe (33 of whom had isolated psychosis at presentation), comparing them with 45 patients with pFEP, 36 patients with herpes simplex encephalitis (HSV), and 36 healthy controls. They found that young patients with first episode psychosis and serum NfL ≥15 pg/mL had a 120 times higher chance of having NMDARe than pFEP, with this cutoff correctly classifying 96% of patients with pFEP and 85% of patients with NMDARe and isolated psychosis. Notably, all patients with HSV also had serum NFL≥15 pg/mL. The authors concluded that patients with first episodes of psychosis of unclear etiology and serum NfL ≥15 pg/mL should undergo testing for NMDAR antibodies in the CSF. In response, Dr. Vale notes that the presence of NMDAR antibodies is not essential for diagnosing autoimmune encephalitis, given that other autoantibodies can cause psychotic presentations, and that elevations of NfL may reflect comorbidities causing central or peripheral neuroaxonal damage. Dr. Vale argues that given the severity of first episodes of psychosis, all such patients should be considered for CSF examinations, as was the historical practice for concerns of neurosyphilis. Responding to these comments, the authors agree that CSF studies should be reincorporated in the evaluation of patients with new onset psychosis, but note that they restricted their study to the identification of NMDARe, given that this condition can almost perfectly mimic psychiatric causes of first episodes of psychosis, in contrast to other autoimmune encephalitides, which typically have other concurrent neurologic features. They argue that the usefulness of serum NfL testing seen in their study is a relevant finding, regardless of any other underlying contributors to NfL elevation. This exchange highlights the importance of ongoing research into noninvasive markers of neurologic causes of psychosis. It is the editors' opinion that in practice, routine CSF testing for all patients with first episodes of psychosis is unlikely to be feasible in all psychiatric facilities, and as such, screening using serum markers will likely complement clinical examination-guided autoantibody testing in the future.

Several studies have demonstrated that patients with schizophrenia show impairments in social cognition and current evidence indicate that this deficit is associated with abnormal activity in specific brain regions. In addition to functional imaging studies, we believe that the identification of structural correlates of social cognitive processes may help to better understand the neural underpinnings of these specific skills. The main objective of this study was to investigate the relationship between gray matter density and social cognitive deficits in first episode of schizophrenia spectrum psychosis, using a comprehensive assessment that we previously demonstrated to be a highly sensitive measure of social cognitive deficits in this population. Thirty-eight patients with a first episode of psychosis participated in this study, and the Four Factor Test of Social Intelligence was used as a measure of social cognition. Social cognitive impairments in first episode psychosis were significantly correlated with reduced gray-matter density in the left middle frontal gyrus other regions within the mirror neuron system network (MSN), namely the right supplementary motor cortex, the left superior temporal gyrus and the left inferior parietal lobule. We concluded that structural abnormalities within the MSN may account for the social cognitive deficits present in some psychiatric disorders, such as schizophrenia.

Antibodies to Surface Dopamine-2 Receptor and N-Methyl-D-Aspartate Receptor in the First Episode of Acute Psychosis in Children

Predictors of acute treatment response in patients with a first episode of non-affective psychosis: Sociodemographics, premorbid and clinical variables