Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis

AbstractPatients with autoimmune encephalitides, especially those with antibodies to the N-methyl-d-aspartate receptor (NMDAR), often present with prominent psychosis and respond well to immunotherapies. Although most patients progress to develop various neurological symptoms, it has been hypothesised that a subgroup of patients with first-episode psychosis (FEP) suffer from a forme fruste of autoimmune encephalitis. Without accurate identification, this immunotherapy-responsive subgroup may be denied disease-modifying treatments. Thirty studies addressing aspects of this hypothesis were identified in a systematic review. Amongst other shortcomings, 15/30 reported no control group and only 6/30 determined cerebrospinal fluid (CSF) autoantibodies. To ourselves address these—and other—limitations, we investigated a prospectively ascertained clinically well-characterised cohort of 71 FEP patients without traditional neurological features, and 48 healthy controls. Serum and CSF were tested for autoantibodies against seven neuronal surface autoantigens using live cell-based assays. These identified 3/71 (4%) patient sera with weak binding to either contactin-associated protein-like 2, the NMDAR or glycine receptor versus no binding from 48 control samples (p = 0.28, Fisher’s test). The three seropositive individuals showed no CSF autoantibodies and no differences from the autoantibody-negative patients in their clinical phenotypes, or across multiple parameters of peripheral and central inflammation. All individuals were negative for CSF NMDAR antibodies. In conclusion, formes frustes of autoimmune encephalitis are not prevalent among FEP patients admitted to psychiatric care. Our findings do not support screening for neuronal surface autoantibodies in unselected psychotic patients.

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Time for a change of practice: the real-world value of testing for neuronal autoantibodies in acute first-episode psychosis

BJPsych Open ◽

10.1192/bjo.2018.27 ◽

2018 ◽

Vol 4 (4) ◽

pp. 262-264 ◽

Cited By ~ 6

Author(s):

Thomas A. Pollak ◽

Belinda R. Lennox

Keyword(s):

Lumbar Puncture ◽

Real World ◽

Culture Change ◽

Autoimmune Encephalitis ◽

First Episode Psychosis ◽

Acute Onset ◽

First Episode ◽

The Real ◽

Episode Psychosis ◽

Neuronal Autoantibodies

SummaryIt is time that all patients with acute-onset psychosis are screened for autoimmune encephalitis, that lumbar puncture becomes a routine psychiatric investigation and that immunotherapy is available in indicated cases. We call for a culture change in the management of psychosis by psychiatry.Declaration of interestNone.

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Brief psycho-education for caregivers of persons with first episode psychosis

Indian Journal of Positive Psychology ◽

10.15614/ijpp.v9i01.11741 ◽

2018 ◽

Vol 9 (01) ◽

Author(s):

Praful Prabhuappa Kapse ◽

Manisha Kiran

Keyword(s):

First Episode Psychosis ◽

First Episode ◽

Control Group ◽

Episode Psychosis ◽

Study Results ◽

Before And After ◽

Quasi Experimental ◽

Expressed Emotions ◽

Experimental Group ◽

Group Family

Caring for the persons with first episode psychosis is challenging and demanding. It may lead to the increased burden, expressed emotions among the caregivers. The numerous studies have shown that high burden and negative expressed emotions among caregivers can lead to early relapse in the patients with first episode psychosis. To evaluate the effects of the brief psychoeducation on the caregivers burden and expressed emotions. A quasi experimental - before and after with control group research design was adopted for the study. A total of 60 caregivers have participated in the study, of which 30 caregivers in experimental group and 30 caregivers in the control group. Family Burden Interview Schedule (Pai and Kapoor, 1981) and Attitude Questionnaire (Sethi et al., 1981) was used to assess caregiver's burden and expressed emotions. At end of the psychoeducation intervention, burden among caregivers and negative expressed emotions of the caregivers have significantly reduced. The positive expressed emotions have been increased. Study results demonstrates the importance of psychoeducation intervention in reducing the burden and negative expressed emotions.

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Implementation of NAVIGATE Coordinated Specialty Care for First Episode Psychosis: the Michigan Experience

CNS Spectrums ◽

10.1017/s1092852920002928 ◽

2021 ◽

Vol 26 (2) ◽

pp. 177-178

Author(s):

Eric D. Achtyes ◽

Kari Kempema ◽

Zhehui Luo ◽

Katharine N. Thakkar ◽

Catherine Adams ◽

...

Keyword(s):

Mental Health ◽

Clinical Symptoms ◽

The United States ◽

First Episode Psychosis ◽

Specialty Care ◽

First Episode ◽

Control Group ◽

Evidence Based ◽

Block Grant ◽

Episode Psychosis

AbstractStudy ObjectivesCoordinated specialty care (CSC) is widely accepted as an evidence-based treatment for first episode psychosis (FEP). The NAVIGATE intervention from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study is a CSC intervention which offers a suite of evidence-based treatments shown to improve engagement and clinical outcomes, especially in those with shorter duration of untreated psychosis (DUP). Coincident with the publication of this study, legislation was passed by the United States Congress in 2014–15 to fund CSC for FEP via a Substance Abuse and Mental Health Services Administration (SAMHSA) block grant set-aside for each state. In Michigan (MI) the management of this grant was delegated to Network180, the community mental health authority in Kent County, with the goal of making CSC more widely available to the 10 million people in MI. Limited research describes the outcomes of implementation of CSC into community practices with no published accounts evaluating the use of the NAVIGATE intervention in a naturalistic setting. We describe the outcomes of NAVIGATE implementation in the state of MI.MethodsIn 2014, 3 centers in MI were selected and trained to provide NAVIGATE CSC for FEP. In 2016 a 4th center was added, and 2 existing centers were expanded to provide additional access to NAVIGATE. Inclusion: age 18–31, served in 1 of 4 FEP centers in MI. Data collection began in 2015 for basic demographics, global illness (CGI q3 mo), hospital/ED use and work/school (SURF q3 mo) and was expanded in 2016 to include further demographics, diagnosis, DUP, vital signs; and in 2018 for clinical symptoms with the modified Colorado Symptom Inventory (mCSI q6 mo), reported via an online portal. This analysis used data until 12/31/19. Mixed effects models adjusted by age, sex and race were used to account for correlated data within patients.ResultsN=283 had useable demographic information and were included in the analysis. Age at enrollment was 21.6 ± 3.0 yrs; 74.2% male; 53.4% Caucasian, 34.6% African American; 12.9 ± 1.7 yrs of education (N=195). 18 mo retention was 67% with no difference by sex or race. CGI scores decreased 20% from baseline (BL) to 18 mo (BL=3.5, N=134; 15–18 mo=2.8, N=60). Service utilization via the SURF was measured at BL (N=172) and 18 mo (N=72): psychiatric hospitalizations occurred in 37% at BL and 6% at 18 mo (p<0.01); ER visits occurred in 40% at BL and 13% at 18 mo (p<0.01). 44% were working or in school at BL and 68% at 18 mo (p<0.01). 21% were on antipsychotics (AP) at BL (N=178) and 85% at 18 mo (N=13) with 8% and 54% on long acting injectable-AP at BL and 18 mo, respectively. Limitations include missing data and lack of a control group.ConclusionThe implementation of the NAVIGATE CSC program for FEP in MI resulted in meaningful clinical improvement for enrollees. Further support could make this evidence-based intervention available to more people with FEP.FundingSupported by funds from the SAMHSA Medicaid State Block Grant set-aside awarded to Network180 (Achtyes, Kempema). The funders had no role in the design of the study, the analysis or the decision to publish the results.

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Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study

Neuropsychopharmacology ◽

10.1038/s41386-021-00980-0 ◽

2021 ◽

Author(s):

Sidhant Chopra ◽

Alex Fornito ◽

Shona M. Francey ◽

Brian O’Donoghue ◽

Vanessa Cropley ◽

...

Keyword(s):

Antipsychotic Medication ◽

Brain Volume ◽

First Episode Psychosis ◽

Common Finding ◽

First Episode ◽

Control Group ◽

Grey Matter Volume ◽

Long Term Effects ◽

Significant Group ◽

Episode Psychosis

AbstractChanges in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. In this study, 62 antipsychotic-naïve patients with first-episode psychosis (FEP) received either a second-generation antipsychotic (risperidone or paliperidone) or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n = 27) was also recruited. Structural MRI scans were obtained at baseline, 3 months and 12 months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p < 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. Across the entire patient sample, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia.

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Brain structural correlates of functional capacity in first-episode psychosis

Scientific Reports ◽

10.1038/s41598-020-73553-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Erkan Alkan ◽

Geoff Davies ◽

Kathy Greenwood ◽

Simon L. Evans

Keyword(s):

Functional Capacity ◽

Gray Matter Volume ◽

Brain Regions ◽

First Episode Psychosis ◽

First Episode ◽

Control Group ◽

Neural Basis ◽

Antipsychotic Therapy ◽

Brain Volumes ◽

Episode Psychosis

Abstract Impaired functional capacity is a core feature of schizophrenia and presents even in first-episode psychosis (FEP) patients. Impairments in daily functioning tend to persist despite antipsychotic therapy but their neural basis is less clear. Previous studies suggest that volume loss in frontal cortex might be an important contributor, but findings are inconsistent. We aimed to comprehensively investigate the brain structural correlates of functional capacity in FEP using MRI and a reliable objective measure of functioning [University of California, San Diego Performance-Based Skills Assessment (UPSA)]. In a sample of FEP (n = 39) and a well-matched control group (n = 21), we measured cortical thickness, gray matter volume, and white matter tract integrity (fractional anisotropy, FA) within brain regions implicated by previous work. The FEP group had thinner cortex in various frontal regions and fusiform, and reduced FA in inferior longitudinal fasciculus (ILF). In FEP, poorer functional capacity correlated with reduced superior frontal volume and lower FA in left ILF. Importantly, frontal brain volumes and integrity of the ILF were identified as the structural correlates of functional capacity in FEP, controlling for other relevant factors. These findings enhance mechanistic understanding of functional capacity deficits in schizophrenia by specifying the underlying neural correlates. In future, this could help inform intervention strategies.

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Volumetric and morphological characteristics of the hippocampus are associated with progression to schizophrenia in patients with first-episode psychosis

European Psychiatry ◽

10.1016/j.eurpsy.2017.06.006 ◽

2017 ◽

Vol 45 ◽

pp. 1-5 ◽

Cited By ~ 16

Author(s):

R. Sauras ◽

A. Keymer ◽

A. Alonso-Solis ◽

A. Díaz ◽

C. Molins ◽

...

Keyword(s):

Morphological Changes ◽

Morphological Characteristics ◽

First Episode Psychosis ◽

First Episode ◽

Control Group ◽

Subcortical Structures ◽

Episode Psychosis ◽

Left Hippocampus ◽

One Year

AbstractBackground:Abnormalities in the hippocampus have been implicated in the pathophysiology of psychosis. However, it is still unclear whether certain abnormalities are a pre-existing vulnerability factor, a sign of disease progression or a consequence of environmental factors. We hypothesized that first-episode psychosis patients who progress to schizophrenia after one year of follow up will display greater volumetric and morphological changes from the very beginning of the disorder.Methods:We studied the hippocampus of 41 patients with a first-episode psychosis and 41 matched healthy controls. MRI was performed at the time of the inclusion in the study. After one year, the whole sample was reevaluated and divided in two groups depending on the diagnoses (schizophrenia vs. non-schizophrenia).Results:Patients who progressed to schizophrenia showed a significantly smaller left hippocampus volume than control group and no-schizophrenia group (F = 3.54; df = 2, 77; P = 0.03). We also found significant differences in the morphology of the anterior hippocampus (CA1) of patients with first-episode psychosis who developed schizophrenia compared with patients who did not.Conclusions:These results are consistent with the assumption of hyperfunctioning dopaminergic cortico-subcortical circuits in schizophrenia, which might be related with an alteration of subcortical structures, such as the hippocampus, along the course of the disease. According with these results, hippocampus abnormalities may serve as a prognostic marker of clinical outcome in patients with a first-episode psychosis.

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Neurological abnormalities and cognitive ability in first-episode psychosis

The British Journal of Psychiatry ◽

10.1192/bjp.bp.107.045450 ◽

2008 ◽

Vol 193 (3) ◽

pp. 197-202 ◽

Cited By ~ 41

Author(s):

Paola Dazzan ◽

Tuhina Lloyd ◽

Kevin D. Morgan ◽

Jolanta Zanelli ◽

Craig Morgan ◽

...

Keyword(s):

General Population ◽

Cognitive Ability ◽

Motor Coordination ◽

First Episode Psychosis ◽

First Episode ◽

Control Group ◽

General Cognitive Ability ◽

Affective Psychosis ◽

Neurological Soft Signs ◽

Episode Psychosis

BackgroundIt remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis.AimsTo investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ).MethodEvaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239).ResultsPrimary (P<0.001), motor coordination (P<0.001), and motor sequencing (P<0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ.ConclusionsHigher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.

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Longitudinal Changes in Functional Connectivity in Antipsychotic-treated and Antipsychotic-naive Patients with First Episode Psychosis

10.1101/2021.04.13.21255375 ◽

2021 ◽

Author(s):

Sidhant Chopra ◽

Shona M. Francey ◽

Brian O’Donoghue ◽

Kristina Sabaroedin ◽

Aurina Arnatkeviciute ◽

...

Keyword(s):

Functional Connectivity ◽

First Episode Psychosis ◽

Common Finding ◽

First Episode ◽

Control Group ◽

Antipsychotic Treatment ◽

Long Term Effects ◽

Limbic Systems ◽

Episode Psychosis ◽

The Brain

AbstractBackgroundAltered functional connectivity (FC) is a common finding in resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotics may influence the temporal evolution of these disturbances, remains unclear. Here, we scanned first episode psychosis (FEP) patients who were and were not exposed to antipsychotic medication during the first six months of illness at baseline, three months, and 12 months, to characterize how FC changes over time and in relation to medication use.MethodsSixty-two antipsychotic-naïve patients with FEP received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n=27) was also recruited. A total of 202 rs-fMRI scans were obtained across three timepoints: baseline, 3-months and 12-months. Our primary aim was to differentiate patterns of FC in antipsychotic-treated and antipsychotic-naive patients within the first 3 months of treatment, and to examine associations with clinical and functional outcomes. A secondary aim was to investigate long-term effects at the 12-month timepoint.ResultsAt baseline, FEP patients showed widespread functional dysconnectivity in comparison to controls, with reductions predominantly affecting interactions between the default mode network (DMN), limbic systems, and the rest of the brain. From baseline to 3 months, patients receiving placebo showed increased FC principally within the same systems, and some of these changes correlated with improved clinical outcomes. Antipsychotic exposure was associated with increased FC primarily between the thalamus and the rest of the brain. At the 12-month follow-up, antipsychotic treatment was associated with a prolonged increase of FC primarily in the DMN and limbic systems.Conclusions and RelevanceAntipsychotic-naïve FEP patients show widespread functional dysconnectivity at baseline, followed by an early normalization of DMN and paralimbic dysfunction in patients receiving a psychosocial intervention only. Antipsychotic exposure is associated with distinct FC changes, principally concentrated on thalamo-cortical and limbic networks.

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Videogame Play and Wellbeing Among a First Episode Psychosis Population

Proceedings of the ACM on Human-Computer Interaction ◽

10.1145/3474708 ◽

2021 ◽

Vol 5 (CHI PLAY) ◽

pp. 1-23

Author(s):

Daniel Johnson ◽

Victoria Gore-Jones ◽

Frances Dark ◽

Stephen D. Parker ◽

Sharon Foley ◽

...

Keyword(s):

Stressful Life Events ◽

Control Sample ◽

First Episode Psychosis ◽

Need Satisfaction ◽

First Episode ◽

Control Group ◽

Harmonious Passion ◽

Episode Psychosis ◽

Group A ◽

The Relationship

With ongoing interest in the relationship between videogame and mental health alongside recent focus on gaming's role in coping with stressful life events, we sought to explore the relationship between videogame play and wellbeing among people experiencing their first episode of psychosis. Specifically, we aimed to explore the associations between videogame play and wellbeing among consumers of a first episode psychosis (FEP) service and further to compare their motivations for play, need satisfaction, passion for play and wellbeing to a control group. A sample of 88 people experiencing FEP (57 who played videogames and 31 who did not) and a control sample of 46 (all of whom played videogames) completed a survey containing a range of questionnaires related to the variables of interest. Key findings include that among those experiencing FEP, people who played videogames reported better wellbeing outcomes than those who did not. Among participants who played videogames, the FEP sample reported lower levels of need satisfaction through gaming, lower levels of harmonious passion, higher levels of external types of motivation and lower levels of internal types of motivation for play than the control group. Finally, the relationships between passion orientation (both harmonious and obsessive) and psychological distress were stronger in the control group than the FEP sample, suggesting that passion for gaming may be less influential on wellbeing for those experiencing FEP.

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Failure to find association between childhood abuse and cognition in first-episode psychosis patients

European Psychiatry ◽

10.1016/j.eurpsy.2013.02.006 ◽

2014 ◽

Vol 29 (1) ◽

pp. 32-35 ◽

Cited By ~ 14

Author(s):

L. Sideli ◽

H.L. Fisher ◽

M. Russo ◽

R.M. Murray ◽

S.A. Stilo ◽

...

Keyword(s):

Executive Function ◽

Childhood Abuse ◽

Cognitive Functions ◽

First Episode Psychosis ◽

First Episode ◽

Control Group ◽

Episode Psychosis ◽

Function Domain ◽

The Relationship

AbstractThis study investigated the relationship between severe childhood abuse and cognitive functions in first-episode psychosis patients and geographically-matched controls. Reports of any abuse were associated with lower scores in the executive function domain in the control group. However, in contrast with our hypothesis, no relationships were found amongst cases.

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