Primary Psychosis Research Articles

The dimensional structure of the Positive and Negative Syndrome Scale in first-episode schizophrenia spectrum disorders: an Exploratory Graph Analysis from the OPTiMiSE trial

The Positive and Negative Syndrome Scale (PANSS) is the most widely used rating scale to assess psychotic symptoms in patients with schizophrenia and other primary psychoses. However, a definitive consensus regarding its dimensional structure remains elusive. The present work aims to determine the number of dimensions of the scale through a network analysis approach in a sample of individuals experiencing first-episode schizophrenia spectrum disorder (FE-SSD) with minimal or no prior exposure to antipsychotic treatment. Baseline data of 446 participants (age 25.96 ± 5.99 years, 70% males) enrolled in the OPTiMiSE trial were analysed. Exploratory Graph Analysis (EGA) was conducted to evaluate the dimensionality of the PANSS, and a bootstrap approach (bootEGA) was employed to assess model stability. The analysis was replicated, excluding unstable items with stability values below 0.75, until a stable model was achieved. The analysis of the 30 items of the PANSS revealed inadequate structural consistency, resulting in the exclusion of 9 unstable items. The final model comprised 21 symptoms distributed across four communities (Positive, Cognitive/Disorganised, Excited/Aggressive and Negative) but lacked a depressive domain. In conclusion, we propose a concise version of the PANSS, incorporating 21 items, to better assess the core symptoms of the first episode of SSD. This revised version provides clinicians with a robust psychometric tool with reduced administration time, but the complementary administration of a dedicated instrument for evaluating affective symptoms is advisable.

Real world clinical outcomes of treatment of cannabis-induced psychosis and prevalence of cannabis-related primary psychosis: a retrospective study

BackgroundCurrent treatment of cannabis-induced psychosis (CIP) focus on the presenting symptoms of individual patient. Therefore, the objective of this study was to investigate the efficacy of pharmacological treatment for CIP in a retrospective manner.MethodsA retrospective chart review study was conducted at the Princess Mother National Institute on Drug Abuse Treatment (PMNIDAT), Thailand. Patients aged more than 12 years who met the International Classification of Disease-10 (ICD-10) criteria of CIP, had recorded of cannabis use in medical chart, and had positive urine test of cannabis on the first day of admission from October 2013 to September 2019 were enrolled. The primary outcome was the efficacy of pharmacological treatment of CIP. Brief Psychotic Rating Scale (BPRS) on the first day and weekly after receiving treatment were used to assess the primary outcome.ResultsFour hundred and three medical charts with diagnosis of CIP were enrolled into the study and only 317 charts were analyzed. Most of them were male with an average aged of 21.0 (19.0–24.0) years old. All of them used smoked cannabis from dried leaves and flowers of cannabis plant. The presented symptoms on admission were psychosis, mood symptoms, sleep problems, weight loss, and cognitive problems (100%, 64%, 61%, 11%, and 7%, respectively). Baseline BPRS score of the first day of admission was 55.2 ± 9.6. Majority of patients received antipsychotic (98.7%) followed by the combination of antipsychotics with benzodiazepines (34.5.%), antipsychotics with antidepressants (14.4%) and antipsychotics treatment with antidepressants and benzodiazepines (25.9%). Only few patients received antipsychotic monotherapy (17.9%). Risperidone was the most frequently prescribed antipsychotics (83.6%). Mean equivalence dose of risperidone was 8.0 ± 5.9 mg/day. The average hospital length of stay was 28 days (range 22-31). BPRS at 22 days significantly improved compared to the first day of admission (p < 0.001). Schizophrenia was diagnosed in 7% at 1.3 years of follow up.ConclusionAntipsychotics was still a key psychotropic drug for treatment of CIP. The symptoms were decreased rapidly and sustained among the treatment period. However, antidepressants and benzodiazepines were commonly used for treatment of other symptoms beyond psychosis.Trial registrationClinicalTrials.gov ID: NCT04945031 (Registration Date: 30 June, 2021).

Effectiveness of Acceptance and Commitment Therapy on Psychotic Severity Among Inpatients With Primary Psychoses: A Randomized Controlled Trial.

This study investigated the effectiveness of acceptance and commitment therapy (ACT) compared to treatment as usual in managing psychotic symptoms, emotional dysregulation, recovery and psychological flexibility in inpatients with primary psychoses. The Primary outcome assessed the positive and negative syndrome scale, while the secondary outcomes were to assess difficulties in the emotion regulation scale, recovery assessment scale and acceptance and action questionnaire. An open-label, two-arm parallel randomized controlled trial was conducted. Participants diagnosed with primary psychoses were randomly assigned to either the ACT (n = 33) or treatment-as-usual (n = 32) group. The intervention included six structured sessions of ACT. ACT significantly reduced psychotic symptoms from 128 to 104 (Z = 5.01) compared to treatment as usual from 130 to 117 (Z = 4.88). Emotional regulation improved significantly in the ACT group from 73 to 55 (Z = 4.835) compared to treatment as usual from 73 to 70 (Z = 2.406). Recovery increased in the ACT group from 50 to 88 (Z = 5.01) compared to treatment as usual from 51 to 61 (Z = 4.93). Psychological flexibility improved in the ACT group from 33 to 25 (Z = 4.98) compared to treatment as usual from 33 to 31 (Z = 4.75). Between-group differences after intervention were significant for psychotic symptoms, emotional regulation, recovery and psychological flexibility (Z = 2.356, 4.652, 3.881 and 4.453, respectively). Accordingly, the current study demonstrates the effectiveness of ACT in reducing psychotic symptoms and improving emotional regulation, recovery and psychological flexibility in patients with primary psychoses. Integrating ACT into standard care protocols can enhance treatment outcomes, offering a comprehensive approach to managing complex mental health conditions. Trial Registration: ClinicalTrials.gov identifier: NCT06160869.

Comparison of cognitive functions in individuals with primary psychosis and substance-induced psychotic disorders

ABSTRACT Background Cognitive dysfunctions are common in patients with primary psychosis disorder (PPD) and substance-induced psychotic disorder (SIPD), and this problem is very important in the course of their treatment and relapse. The present research was done to study the cognitive functions in the patients suffering from PPD compared to the patients with SIPD. Methods In this analytical study, the study population included all patients admitted to Farabi Hospital, Kermanshah, Iran, diagnosed with PPD and SIPD, whose cognitive functions were compared using the Rey Auditory Verbal Learning Test (RAVLT), Symbol Digit Modalities Test (SDMT) and Verbal Fluency Test (VFT). Results Only the mean number of words in the first list that the patient was unable to identify (Miss) distinguished the two groups in terms of the mean RAVLT scores. Due to the number of accurate answers in the SDMT and the speed of visual search, there was no discernible difference between the PPD and SIPD groups. The results showed a significant difference between the two groups due to the total number of correct VFT word in two parts of letters and categories. Conclusion The results of the present study can be used in the treatment and rehabilitation of PPD and SIPD patients.

The association between visual hallucinations and secondary psychosis: a systematic review and meta-analysis

ABSTRACT Introduction: Visual hallucinations are often considered to be suggestive of a secondary cause of psychosis, however, this association has never been assessed meta-analytically. We aimed to compare the presence of visual hallucinations in patients with psychosis due to a primary or secondary cause. Method: We conducted a meta-analysis of case-control studies directly comparing primary and secondary psychosis. A random-effects model, following the DerSimonian and Laird method, was used to pool studies and generate overall odds ratios (OR), 95% confidence intervals (CI) and prediction intervals (PI). Results: Fourteen studies (904 primary and 804 secondary psychosis patients) were included. Visual hallucinations were significantly associated with secondary psychosis (OR = 3.0, 95% CI = 1.7-5.1, p < 0.001) with moderate between-study heterogeneity (I2 = 70%). Subgroup analysis by type of secondary psychosis (organic, drug-induced, mixed) was non-significant. Analysis of the content of visual hallucinations (51 primary and 142 secondary psychosis patients) found hallucinations of inanimate objects were significantly more likely to be associated with secondary psychosis (OR = 0.1, 95% CI = 0.01-0.8, p = 0.03). Conclusions: Visual hallucinations were strongly associated with a secondary cause of psychosis. The presence of visual hallucinations in a patient presenting with psychosis may serve as a potential “red flag” for a secondary cause and warrant further investigation.

Prevalence of tobacco smoking among U.S. individuals with primary psychosis: a systematic review of national and regional samples

Prevalence of tobacco smoking among U.S. individuals with primary psychosis: a systematic review of national and regional samples

The impact of COVID-19 on acute psychiatric admissions for first and repeated episode psychosis.

There is limited evidence of the longer-term impact of the COVID-19 pandemic on acute admissions for psychosis in the UK. We examined the impact of COVID-19 on rates of admissions for first and repeated episode psychosis, and changes in patient profile and seasonal patterns, over a period of 12 months. We conducted a retrospective case note review of all patients admitted with a primary psychosis (F20-29 ICD 10 diagnosis) to an NHS psychiatric inpatient unit. We compared the 12 months pre-COVID-19 period between 1 March 2019 and 28 February 2020, and the 12 months post-COVID-19 period between 1 March 2020 and 28 February 2021. The results showed increase rates of admissions post-COVID-19 in both first and repeated episode psychosis, the patient profile had more females and older age in the repeated episode group, with increased employment rates. Combined group data for both pre- and post-COVID-19 periods showed an increased trend in spring and summer admissions, and even though not statistically significant, more pronounced post-COVID-19. Our findings highlight the effect of the COVID-19 pandemic on acute psychosis admissions over a 12-month period. The results provide evidence for the 'stress-pathogenesis' in the context of genetic vulnerability in psychosis. Preventative strategies in the context of the 'stress-pathogenesis model', improved access to and responsiveness within NHS transformation efforts needs to be adjusted to fit local need and environmental changes.

Psychosis Secondary to Traumatic Brain Injury: Critical Literature Review and Illustrative Case Study

Psychosis secondary to traumatic brain injury (PSTBI) is rare yet a serious sequela of traumatic brain injury (TBI).We provide a critical literature review on PSTBI, outlining clinical features and approach to the diagnosis and treatment. Finally, we illustrate a case description, to discuss its conceptual framework. Conceptualizing PSTBI as a neurobiological syndrome has clinical relevance, insofar as, it facilitates a rational scheme, by which specific diagnostic dilemmas should be tackled in the workup, to provide a tailored treatment. Additionally, it may shed light on the understanding of psychotic disorders by integrating data on primary and secondary psychosis. TBI can contribute to the emergence of psychotic symptoms in various manners. It may precipitate psychosis in susceptible individuals, occur in a direct relationship to post‐traumatic epilepsy, or develop directly due to brain injury. It is this last clinical entity that we focus on in this article. Its neurobiological underpinnings comprise the following mechanisms: damage to frontal and temporal lobes (primary injury); structural and/or functional dysconnectivity in sensory‐ and other information‐ ‐processing networks, such as the Default‐Mode network, which stem from diffuse axonal injury (DAI) (primary injury); neuroinflammation and neurodegeneration (secondary injury). The clinical presentation may take two forms: delusional disorder or schizophrenia‐like psychosis. Both subtypesare often preceded by a prodromal phase superimposed on other sequelae, namely affective instability, social and occupational functional decline. In comparison to primary schizophrenia, PSTBI has a lower genetic load, fewer negative symptoms, more neurocognitive symptoms, which may be intertwined with frontal‐subcortical system dysfunction/ frontal syndromes and are more likely to present findings on neuroimaging and electroencephalographic studies. PSTBI has a bimodal distribution of onset. Latencies of under a year (early‐onset) have been associated with DAI and delusional disorder subtype. Schizophrenia‐like psychosis subtype usually develops after a latency of 1‐5 years (late‐onset), and has been more associated with epilepsy, focal brain lesions and a chronic course. Antipsychotics should be used cautiously considering the increased sensitivity to the sedating, anticholinergic, and seizure threshold‐lowering side effects. Late‐onset PSTBI might benefit from anticonvulsants, by virtue of its anti‐ ‐kindling properties. Additionally, further pharmacological approaches may be used to address cognitive, emotional, and behavioural issues.

Early Non-Response to Antipsychotic Treatment in Schizophrenia: A Systematic Review and Meta-Analysis of Evidence-Based Management Options.

Early non-response is a well-established prognostic marker but evidence-based and consistent recommendations to manage it are limited. The aim of this systematic review and meta-analysis was to generate evidence-based strategies for the management of schizophrenia patients with early non-response to 2 weeks of antipsychotic treatment. We conducted a systematic review and meta-analysis of randomized trials comparing antipsychotic dose escalation, switch, augmentation and continuation in individuals with study-defined early antipsychotic treatment non-response. Eligibility criteria were (1) clinical trials of primary psychosis treating for at least 2 weeks with antipsychotic monotherapy with study-defined operationalized criteria for early non-response; and (2) randomization to at least two of the following treatment strategies: dose escalation, switch, augmentation, or treatment continuation. Information sources were Pubmed, PsycINFO, and EMBASE, and risk of bias was assessed using Jadad scores. Results were synthesized using random-effects meta-analysis, comparing each intervention with treatment continuation for total symptom change as the primary outcome, generating standardized mean differences (SMDs) and 95% confidence intervals (CIs). Studies meeting the selection criteria but providing insufficient data for a meta-analysis were presented separately. We screened 454 records by 1 August 2022, of which 12 individual datasets met the inclusion criteria, representing 947 research participants. Of those studies, five provided data to include in the meta-analysis (four with early non-response at 2 weeks, one at 3 weeks). Early non-response was defined within a timeline of 2 weeks in eight datasets, with the remaining datasets ranging between 3 and 4 weeks. The rates of early non-response ranged between 72.0 and 24.1%, and the endpoint ranged within 4-24 weeks post randomization. Quality was good (i.e., Jadad score of ≥3) in 8 of the 12 datasets. Overall, three studies compared antipsychotic switch versus continuation and two compared antipsychotic switch versus augmentation, in both cases without significant pooled between-group differences for total symptom severity (n=149, SMD 0.18, 95% CI -0.14 to 0.5). Individually, two relatively large studies for antipsychotic switch versus continuation found small advantages for switching antipsychotics for total symptom severity (n=149, SMD -0.49, 95% CI -1.05 to -0.06). One relatively large study found an advantage for dose escalation, although this finding has not been replicated and was not included in the meta-analysis. None of the alternatives included antipsychotic switch to clozapine. Despite robust accuracy of early antipsychotic non-response predicting ultimate response, the evidence for treatment strategies that should be used for early non-response after 2-3 weeks is limited. While meta-analytic findings were non-significant, some individual studies suggest advantages of antipsychotic switch or dose escalation. Therefore, any conclusions should be interpreted carefully, given the insufficient high-quality evidence.

LATE ONSET PSYCHOSIS AND VERY LATE ONSET PSYCHOSIS: WHAT ARE THE POSSIBLE ETHIOLOGIES?

IntroductionPsychotic symptoms have long been known to show up earlier in life, typically during adolescence and early adulthood. Late Onset Psychosis (LOP), in which symptoms start between 40 and 60 years of age, and Very Late Onset Psychosis (VLOP), in which onset of symptoms happens after 60 years of age, although classically rare, have had a growing prevalence in the last decades.ObjectivesTo access the definition and main etiologies of LOP and VLOP, based on the current literature.MethodsNon-systematic review of literature using the terms “late onset psychosis” and “very late onset psychosis”. Case report of a patient who was admitted and treated in our inward patient field.Results51-year-old female patient. She is divorced (two previous marriages) and has two daughters (26 and 16, respectively). She was brought by police officers because of behavior problems at the shelter where she was living. She was evicted from the house she was living in because of delay in paying the rent. On observation, she verbalizes persecutory and prejudicial delusions and auditory hallucinations on the 2nd and 3rd person (commenting voices) with at least 5 years of duration. She was hospitalized for almost 3 months, with slow but progressive clinical improvement on haloperidol 7,5mg/day. At the date of discharge, she did not spontaneously verbalize her symptoms, although she did not recognize them as delusional. Recent studies have shown that the prevalence of Schizophrenia in the typical age range is 75-80%, which means that an important proportion of diagnosis is made after that age span. Primary causes of LOP and VLOP are schizophrenia (of late onset), schizophrenia-like very late onset psychosis, delusion disorder, unipolar depression with psychotic symptoms and bipolar disorder. Secondary causes should also be considered, such as delirium, dementia (Alzheimer’s, Lewi bodies and vascular), and substances abuse; even more rare, other conditions should be considered, as cerebrovascular accident, encephalitis, epilepsy, and multiple sclerosis.ConclusionsLOP and VLOP have been a growing diagnosis in the past decades. In the assessment of these patients, we must consider the importance of secondary etiologies besides the primary psychiatric ones. Primary psychosis is a diagnosis of exclusion, and the clinician must rule out secondary causes. Recent data point out these symptoms as markers for an increased risk of dementia in these patients. Further research involving individuals with LOP and VLOPs is required to increase the evidence base for treatment and improve outcomes of care.Disclosure of InterestNone Declared

Personalisation of the management of schizophrenia and other primary psychoses

AbstractIn the treatment of persons with schizophrenia the goal has gradually shifted from the reduction of symptoms and prevention of relapse to recovery. However, this goal is achieved for a minority of persons with schizophrenia, while for most of them the disorder still is a major cause of disability, poor quality of life and premature death, and presents considerable social and economic costs.Studies aimed at identifying variables with a significant impact on schizophrenia outcome indicate that early intervention, shared decision making, treatment continuity, physical comorbidities, negative symptoms, deficits in cognitive functions and functional capacity account for most of the functional impairment of patients but are often neglected in current clinical practice.In this presentation, I will illustrate the role of these variables and the need for an in-depth clinical characterization of persons with primary psychoses to implement personalized treatment plans and improve the care of people with schizophrenia.Disclosure of InterestNone Declared

Strength, resilience, and diversity in psychotic spectrum disorders of late-life

Approximately one in four people will develop psychosis in their lifetime. Late-life psychosis carries significant risks of isolation, caregiver distress, polypharmacy, and mortality. Unfortunately, there is a gap between the prevalence of psychotic disorders in older adults and the strategies available for assessment and intervention. There are scarce reliable pathognomonic signs to diagnose primary or secondary psychosis. Therefore, a comprehensive evaluation to establish the correct diagnosis is crucial for developing appropriate treatment. There is a consensus to categorize late-life psychosis as either primary or secondary psychosis. Primary psychoses include schizophrenia (early, late, or very late onset), affective psychosis, and delusional disorders. Secondary psychoses can be due to delirium, disease, drugs or dementia. Each condition would benefit from further diagnostic testing, psychosocial and environmental interventions, and judicious use of pharmacotherapy.This session will present an updated review of the assessment of psychotic spectrum disorders of late-life, as well as evidence-based psychosocial and pharmacological interventions. Dr. Michael will emphasize strength-based assessment and goals of care. Dr. Hashem will provide an overview of longitudinal trajectories and outcomes of late-life psychosis, as well as judicious use of pharmacotherapy when indicated. Dr. Kumar will review evidence-based psychosocial interventions in primary and secondary late-life psychotic disorders. Dr. Reinhardt will serve as a discussant and introduce the panel to the participants.

The evolutionary origin of psychosis.

Imagination, the driving force of creativity, and primary psychosis are human-specific, since we do not observe behaviors in other species that would convincingly suggest they possess the same traits. Both these traits have been linked to the function of the prefrontal cortex, which is the most evolutionarily novel region of the human brain. A number of evolutionarily novel genetic and epigenetic changes that determine the human brain-specific structure and function have been discovered in recent years. Among them are genomic loci subjected to increased rates of single nucleotide substitutions in humans, called human accelerated regions. These mostly regulatory regions are involved in brain development and sometimes contain genetic variants that confer a risk for schizophrenia. On the other hand, neuroimaging data suggest that mind wandering and related phenomena (as a proxy of imagination) are in many ways similar to rapid eye movement dreaming, a function also present in non-human species. Furthermore, both functions are similar to psychosis in several ways: for example, the same brain areas are activated both in dreams and visual hallucinations. In the present Perspective we hypothesize that imagination is an evolutionary adaptation of dreaming, while primary psychosis results from deficient control by higher-order brain areas over imagination. In the light of this, human accelerated regions might be one of the key drivers in evolution of human imagination and the pathogenesis of psychotic disorders.

Approach to acute psychosis in older adults.

Approach to acute psychosis in older adults.

"Primary Hyperparathyroidism and Psychosis: A Case Report and Review of the Literature"

"Primary Hyperparathyroidism and Psychosis: A Case Report and Review of the Literature"

The validity of atypical psychosis diagnostic criteria to detect anti-NMDA receptor encephalitis with psychiatric symptoms

Anti-NMDAR encephalitis has a psychotic presentation that is difficult to distinguish from primary psychosis. An atypical psychosis that is similar to schizophrenia, mood disorder, and epilepsy is unique, and the original diagnostic criteria exist only in Japan. The clinical symptoms and courses of anti-NMDAR encephalitis and atypical psychosis are very similar. We investigated whether the diagnostic criteria of atypical psychosis are useful to increase the detection rate of anti-NMDAR encephalitis with psychiatric symptoms.The presence of anti-NR1/NR2B IgG antibodies in the cerebrospinal fluid of 218 newly admitted inpatients initially diagnosed with schizophrenia (n = 151), mood disorder (n = 47), or epilepsy with psychiatric symptoms (n = 20) was assessed by cell-based assay.Of 218 patients, 123 (36.3 years ± SD 17.2, 69.9 % females) fulfilled the diagnostic criteria of category B for atypical psychosis. All 12 patients (9.8 %, 12/123) with anti-NR1/NR2B IgG antibodies fulfilled category B of atypical psychosis statistically better than the patients without anti-NR1/NR2B IgG antibodies (P = 0.0009). Of the 12 patients with anti-NMDAR antibodies, two did not fulfill either criteria of catatonia (DSM-5) or Graus' diagnostic criteria of anti-NMDAR encephalitis during the time course, and 11 patients showed good prognosis with early immunotherapies. In ROC analysis, abnormal electroencephalogram findings showed the highest sensitivity (0.833) for detection of anti-NR1/NR2B IgG antibodies, and 31.3 % of patients with category B atypical psychosis and abnormal electroencephalogram findings had anti-NMDAR antibodies.Lumbar puncture and detection of anti-NMDAR antibodies should be considered for patients who fulfill atypical psychosis diagnosis criteria with an abnormal electroencephalogram.

Reader Response: Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis.

In their otherwise excellent article, Guasp et al.1 studied the role of neurofilament light chain (NfL) in NMDA receptors (NMDAR) encephalitis and primary psychiatric psychosis. However, their results may be limited to the laboratory setting. The NMDAR autoantibodies are not essential for diagnosing autoimmune encephalitis (AE). Other autoantibodies can cause the same psychotic phenotype, and a normal CSF is not rare.2 The presence of the neurofilament light indicates neuroaxonal damage, central and peripheral. Its positivity in AE may reflect some comorbidities.3 The authors advise that “patients with FEP of unclear etiology and NfL ≥15 pg/mL should undergo CSF NMDAR antibody testing.”1 I argue that obtaining the NMDAR antibodies is limited to making a more specific diagnosis.

Author Response: Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis.

We appreciate the comments of Dr. Vale on our study,1 reminding us that psychosis is a severe ailment and that patients may benefit from CSF studies. As shown by most of our work, we agree that CSF studies should be reincorporated in the evaluation of patients with new onset psychosis.1,2 Dr. Vale also indicates that there are other types of autoimmune encephalitis (AE), and the detection of NMDA receptors (NMDAR) antibodies is not essential for AE diagnosis. We are aware of this concept.3 As indicated in our manuscript, most cases of AE can associate with symptoms of psychosis, but the presence of concurrent neurologic alterations readily excludes a primary psychiatric etiology on clinical grounds. By contrast, the initial symptoms of anti-NMDAR encephalitis can mimic to perfection a first episode of psychosis due to a primary psychiatric disorder.2,4 For this reason, we narrowed our study to this specific AE. Regardless of whether neurofilament light chain (NfL) levels can be found to be elevated in many disorders with neuronal/axonal damage, determination of NfL showed clinical utility in the context of our study.

Editors' Note: Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis

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.

Computer-based virtual reality assessment of functional capacity in primary psychosis.

Computer-based virtual reality assessment of functional capacity in primary psychosis.