Prevalence of anti-N-methyl-d-aspartate (NMDA) receptor antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis

2013 ◽  
Vol 44 (12) ◽  
pp. 2475-2487 ◽  
Author(s):  
T. A. Pollak ◽  
R. McCormack ◽  
M. Peakman ◽  
T. R. Nicholson ◽  
A. S. David
Keyword(s):  
Nmda Receptor ◽  
Psychiatric Symptoms ◽  
Meta Analysis ◽  
Clinical Signs ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Significant Heterogeneity ◽  
Receptor Antibody ◽  
Receptor Antibodies

BackgroundAnti-N-methyl-d-aspartate (NMDA) receptor encephalitis is an autoimmune condition caused by immunoglobulin (Ig)G antibodies directed against the NR1 subunit of the NMDA glutamate receptor. Approximately 65% of cases present with psychiatric symptoms, particularly psychosis. It remains to be established whether anti-NMDA receptor antibodies can cause a ‘purely’ psychotic illness without overt neurological symptoms.MethodWe conducted a systematic literature search to establish what proportion of patients with schizophrenia and related psychoses have antibodies directed against the NMDA receptor. Studies were included if (a) subjects had a diagnosis of schizophrenia, schizophrenia spectrum disorder or first-episode psychosis (FEP) using standard criteria, (b) serum was analysed for the presence of anti-NMDA receptor antibodies; and (c) the purpose of the study was to look for the presence of anti-NMDA receptor antibodies in patients with a primary psychiatric diagnosis without clinical signs of encephalitis.ResultsSeven studies were included, comprising 1441 patients, of whom 115 [7.98%, 95% confidence interval (CI) 6.69–9.50] were anti-NMDA receptor antibody positive. Of these, 21 (1.46%, 95% CI 0.94–2.23) patients were positive for antibodies of the IgG subclass. Prevalence rates were greater in cases than controls only for IgG antibodies; other subclasses are of less certain aetiological relevance. There was significant heterogeneity in terms of patient characteristics and the antibody assay used.ConclusionsA minority of patients with psychosis are anti-NMDA receptor antibody positive. It remains to be established whether this subset of patients differs from antibody-negative patients in terms of underlying pathology and response to antipsychotic treatment, and whether immunomodulatory treatments are effective in alleviating psychotic symptoms in this group.

Effect of discontinuation v. maintenance of antipsychotic medication on relapse rates in patients with remitted/stable first-episode psychosis: a meta-analysis

2018 ◽  
Vol 49 (5) ◽  
pp. 772-779 ◽  
Author(s):  
Taro Kishi ◽  
Toshikazu Ikuta ◽  
Yuki Matsui ◽  
Ken Inada ◽  
Yuki Matsuda ◽  
...  
Keyword(s):  
Meta Analysis ◽  
First Episode Psychosis ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Episode Psychosis ◽  
Numbers Needed To Treat ◽  
Reported Data ◽  
Relapse Rates ◽  
Risk Of Relapse ◽  
Maintenance Group

AbstractBackgroundDiscontinuation of antipsychotics predisposes patients with remitted/stable first-episode psychosis (FEP) to a higher risk of relapse, but it remains unclear how long discontinuation increases the relapse rate in these patients compared with maintenance.MethodsThis meta-analysis of randomized controlled trials (RCTs) compared relapse rates in FEP patients between antipsychotic treatment discontinuation and maintenance groups at 1, 2, 3, 6, 9, 12 (primary), and 18–24 months. The risk ratio (RR) and numbers needed to treat/harm (NNT/NNH) were calculated using a random-effects model.ResultsTen RCTs were identified (n = 776; mean study duration, 18.6 ± 6.0 months). The antipsychotics were discontinued abruptly in four RCTs (which reported data only at 12 months) and after tapering off gradually over several months (mean length, 3 months) in six RCTs. Compared with the discontinuation group, the maintenance group experienced significantly fewer relapses at all time points except 1 month [RR (NNT): 2 months, 0.49 (13); 3 months, 0.46 (9); 6 months, 0.55 (6); 9 months, 0.48 (3); 12 months, 0.47 (3); and 18–24 months, 0.57 (4)]. The maintenance group was associated with higher discontinuation due to adverse events (RR, 2.61; NNH, not significant).ConclusionsMaintaining antipsychotic treatment prevented relapse for up to 24 months in FEP patients. Discontinuation of antipsychotics for ⩾2 months significantly increased the risk of relapse. However, 45.7% of patients who discontinued antipsychotics for 12 months (39.4% after 18–24 months) did not experience a relapse.

Changes in the cytokine profile in first episode, drug-naïve patients with psychosis after short-term antipsychotic treatment

2017 ◽  
Vol 41 (S1) ◽  
pp. S371-S371
Author(s):  
P. Petrikis ◽  
P. Voulgari ◽  
V. Boumba ◽  
D. Archimandriti ◽  
P. Skapinakis ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Transforming Growth Factor ◽  
Serum Levels ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antipsychotic Treatment ◽  
Before And After ◽  
Drug Naïve ◽  
Competing Interest

IntroductionAn increasing body of evidence suggests that antipsychotic medication can cause immunological changes that could be attributed to the amelioration of psychotic symptoms or the metabolic side effects of the drugs. So far, the results of the studies remain controversial.ObjectiveOur aim was to compare the levels of interleukin (IL) IL-2, IL-6 and transforming growth factor-β2 (TGF-β2) in drug-naïve, first-episode patients with psychosis before and after six weeks of antipsychotic medication.MethodsThirty-nine first episode patients with psychosis were enrolled in the study. Serum levels of IL-2, IL-6 and TGF-β2 were measured by enzyme linked immunosorbent assay (ELISA) before and six weeks after the initiation of antipsychotic medication. In addition, clinical psychopathology was assessed using Positive and Negative Syndrome Scale (PANSS) before and after treatment.ResultsSerum levels of IL-2 were significantly higher in the study group six weeks after the initiation of antipsychotic treatment (P < 0.001) while TGF-β2 levels were decreased (P < 0.001) and IL-6 levels were slightly reduced (P < 0.004).ConclusionThe changes in cytokine levels may be attributed to the action of antipsychotic medication and the remission of psychopathology. The reduction in TGF-β2 levels is observed in all patients and with all antipsychotic medications used. TGF-β2 may be a marker of clinical efficacy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Antipsychotic drugs increase Neuregulin1b1 serum levels in first-episode drug-naïve patients and chronic schizophrenia with suggestions for improving the treatment of psychotic symptoms

2021 ◽  
Author(s):  
Haidong Yang ◽  
Wen Pan ◽  
Wenhuan Xiao ◽  
Man Yang ◽  
Jianchun Xu ◽  
...  
Keyword(s):  
Antipsychotic Drugs ◽  
Chronic Schizophrenia ◽  
Serum Levels ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Therapeutic Effects ◽  
Pathophysiological Mechanism ◽  
Healthy Controls ◽  
Drug Naïve

Abstract Background: Neuregulin1 (NRG1) plays a role in neuronal migration, regulation of synaptic plasticity, and neural survival, and has been considered to be among the candidate genes for schizophrenia. This study focused on the variations in serum NRG1b1 levels following antipsychotic treatment and the relationship between NRG1b1 level and improvements in psychotic symptoms in first-episode drug-naïve (FEDN) patients and chronic schizophrenia.Methods: A total of 100 patients with schizophrenia were recruited and compared with 79 matched healthy controls. All patients had been drug-naïve for at least four weeks. Serum NRG1b1 levels and positive and negative syndrome scale (PANSS) scores were measured at the baseline and after four weeks. Serum NRG1b1 levels were measured using sandwich enzyme-linked immunosorbent assays (ELISA).Results: Baseline NRG1b1 levels were significantly lower in the patients with schizophrenia compared with the healthy controls. NRG1b1 levels increased significantly following antipsychotic treatment. NRG1b1 levels gradually increased with declining PANSS scores and its three subscales during antipsychotic therapy. The levels of NRG1b1 increased significantly in responders after four weeks of treatment, although non-responders showed no such effect. Correlation analyses showed that the levels of NRG1b1 were negatively correlated with the duration of illness and positively correlated with improvement in symptoms.Conclusion: The levels of serum NRG1b1 and the therapeutic effects gradually increased following treatment, indicating that NRG1b1 may be an indicator of therapy, and that it may also be associated with the pathophysiological mechanism causing schizophrenia, although this possible pathway requires further investigation. Antipsychotic drugs increase Neuregulin1b1 serum levels in first-episode drug-naïve patients and chronic schizophrenia with suggestions for improving the treatment of psychotic symptoms

scholarly journals Hospitalisation and length of hospital stay following first-episode psychosis: systematic review and meta-analysis of longitudinal studies

2019 ◽  
Vol 50 (6) ◽  
pp. 991-1001 ◽  
Author(s):  
Olesya Ajnakina ◽  
Brendon Stubbs ◽  
Emma Francis ◽  
Fiona Gaughran ◽  
Anthony S. David ◽  
...  
Keyword(s):  
Systematic Review ◽  
Longitudinal Studies ◽  
Meta Analysis ◽  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Hospitalised Patients ◽  
Episode Psychosis ◽  
Over Time

AbstractBackgroundReducing hospitalisation and length of stay (LOS) in hospital following first episode psychosis (FEP) is important, yet reliable measures of these outcomes and their moderators are lacking. We conducted a systematic review and meta-analysis to investigate the proportion of FEP cases who were hospitalised after their first contact with services and the LOS in a hospital during follow-up.MethodsStudies were identified from a systematic search across major electronic databases from inception to October 2017. Random effects meta-analyses and meta-regression analyses were conducted.Results81 longitudinal studies encompassing data for 23 280 FEP patients with an average follow-up length of 7 years were included. 55% (95% CI 50.3–60.5%) of FEP cases were hospitalised at least once during follow-up with the pooled average LOS of 116.7 days (95% CI 95.1–138.3). Older age of illness onset and being in a stable relationship were associated with a lower proportion of people who were hospitalised. While the proportion of hospitalised patients has not decreased over time, LOS has, with the sharpest reduction in the latest time period. The proportion of patients hospitalised during follow-up was highest in Australia and New Zealand (78.4%) compared to Europe (58.1%) and North America (48.0%); and lowest in Asia (32.5%). Black ethnicity and longer duration of untreated psychosis were associated with longer LOS; while less severe psychotic symptoms at baseline were associated with shorter LOS.ConclusionOne in two FEP cases required hospitalisation at least once during a 7-year follow-up with an average length of hospitalisation of 4 months during this period. LOS has declined over time, particularly in those countries in which it was previously longest.

scholarly journals Brief Psychotic Disorder During the National Lockdown in Italy: An Emerging Clinical Phenomenon of the COVID-19 Pandemic

2020 ◽  
Author(s):  
Armando D′Agostino ◽  
Simone D’Angelo ◽  
Barbara Giordano ◽  
Anna Chiara Cigognini ◽  
Margherita Lorenza Chirico ◽  
...  
Keyword(s):  
Psychotic Disorder ◽  
Rating Scale ◽  
Cortical Atrophy ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Behavioral Abnormalities ◽  
Brief Psychotic Disorder ◽  
Psychiatric Rating Scale ◽  
The Impact

Abstract The impact of the COVID-19 pandemic on psychosis remains to be established. Here we report 6 cases (3 male and 3 female) of first-episode psychosis (FEP) admitted to our hospital in the second month of national lockdown. All patients underwent routine laboratory tests and a standardized assessment of psychopathology. Hospitalization was required due to the severity of behavioral abnormalities in the context of a full-blown psychosis (the Brief Psychiatric Rating Scale [BPRS] = 75.8 ± 14.6). Blood tests, toxicological urine screening, and brain imaging were unremarkable, with the exception of a mild cortical atrophy in the eldest patient (male, 73 years). All patients were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout their stay, but 3 presented the somatic delusion of being infected. Of note, all 6 cases had religious/spiritual delusions and hallucinatory contents. Despite a generally advanced age (53.3 ± 15.6), all patients had a negative psychiatric history. Rapid discharge (length of stay = 13.8 ± 6.9) with remission of symptoms (BPRS = 27.5 ± 3.1) and satisfactory insight were possible after relatively low-dose antipsychotic treatment (Olanzapine-equivalents = 10.1 ± 5.1 mg). Brief psychotic disorder/acute and transient psychotic disorder diagnoses were confirmed during follow-up visits in all 6 cases. The youngest patient (female, 23 years) also satisfied the available criteria for brief limited intermittent psychotic symptoms. Although research on larger populations is necessary, our preliminary observation suggests that intense psychosocial stress associated with a novel, potentially fatal disease and national lockdown restrictions might be a trigger for FEP.

scholarly journals Cannabis use and nonuse in patients with first-episode psychosis: A systematic review and meta-analysis of studies comparing neurocognitive functioning

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Teresa Sánchez-Gutiérrez ◽  
Belén Fernandez-Castilla ◽  
Sara Barbeito ◽  
Ana González-Pinto ◽  
Juan Antonio Becerra-García ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
First Episode Psychosis ◽  
Cannabis Use ◽  
Effect Sizes ◽  
Neurocognitive Functioning ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Moderator Variables ◽  
Episode Psychosis

Abstract Background. The implications of cannabis use in the onset of early psychosis and the severity of psychotic symptoms have resulted in a proliferation of studies on this issue. However, few have examined the effects of cannabis use on the cognitive symptoms of psychosis (i.e., neurocognitive functioning) in patients with first-episode psychosis (FEP). This systematic review and meta-analysis aim to assess the neurocognitive functioning of cannabis users (CU) and nonusers (NU) with FEP. Methods. Of the 110 studies identified through the systematic review of 6 databases, 7 met the inclusion criteria, resulting in 14 independent samples and 78 effect sizes. The total sample included 304 CU with FEP and 369 NU with FEP. The moderator variables were age at first use, duration of use, percentage of males, and age. Results. Effect sizes were not significantly different from zero in any neurocognitive domain when users and NU were compared. Part of the variability in effect sizes was explained by the inclusion of the following moderator variables: (1) frequency of cannabis use (β = 0.013, F = 7.56, p = 0.017); (2) first-generation antipsychotics (β = 0.019, F = 34.46, p ≤ 0.001); and (3) country where the study was carried out (β = 0.266, t = 2.06, p = 0.043). Conclusions. This meta-analysis indicates that cannabis use is not generally associated with neurocognitive functioning in patients with FEP. However, it highlights the deleterious effect of low doses of cannabis in some patients. It also stresses the importance of the type of antipsychotic prescription and cannabis dose as moderator variables in the neurocognitive functioning of CU with FEP.

scholarly journals M192. SENSITIVITY FOR MOTION IS WEAKENED IN FIRST EPISODE PSYCHOSIS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S209-S209
Author(s):  
Francina Badia ◽  
Daniel Linares ◽  
Albert Compte ◽  
Mireia Rosa ◽  
Josep Dalmau ◽  
...  
Keyword(s):  
Motion Perception ◽  
Response To Treatment ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Psychotic Episode ◽  
Antipsychotic Treatment ◽  
Healthy Controls ◽  
Exclusion Criteria ◽  
Motion Sensitivity ◽  
First Psychotic Episode

Abstract Background Perceptual spatial suppression is a phenomenon in which the perceived strength of a stimulus in space is reduced when the stimulus is surrounded by other stimuli. For motion perception, two studies so far have suggested that spatial suppression and sensitivity to motion perception is also reduced in patients with schizophrenia. Studies to date have been conducted in patients with chronic schizophrenia, however, whether these abnormalities are present at the onset of the disorder or whether they emerge during the course of the illness has not been examined, and no study has assessed whether these abnormalities are specific to schizophrenia or whether they are present in other psychotic disorders. Furthermore, if reduced spatial suppression and sensitivity for motion in schizophrenia are related to a glutamatergic hypofunction, as suggested by a recent study (Schallmo et al., 2019), these reductions may be more accentuated in patients who fail to respond to first-line antipsychotic treatment. Methods Sample: 33 patients with a first psychotic episode (16 females, age=16.4±0.6) and 17 healthy controls (9 females, age=17.2±0.61). Exclusion criteria for both groups were: intellectual disability according to DSM-V criteria. For healthy controls, exclusion criteria also included having a first degree relative with a history of psychotic disorder, current or past diagnosis of psychiatrics disorders. Instruments: The perceptual test was performed on a tablet, and consisted of a briefly presented grating (small or large) drifted sideways (the direction was chosen at random with equal probability), in which the participant was instructed to report the perceived direction. Clinical assessment at illness onset and 12 week follow-up: Positive and Negative Symptom Scales (PANSS), Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version and Structured Clinical Interview for DSM-IV. Non-response to treatment was defined as lack of 50% reduction in PANSS positive or negative scores at 12 weeks, any change in antipsychotics or need for combinations due to lack of clinical response. Psychophysical analysis: Motion sensitivity was estimated independently of lapses of attention, which were assessed by including trials in which the motion stimulus was easily discriminated. Results Patients and healthy controls were homogeneous in age (t=-.720, p=,537) and sex (X2=0.38, p=0.542). In patients, mean treatment response rates was 56.5%. Patients had similar scores of positive and negative symptomatology (positive symptoms= 21±7,13; negative symptoms= 18,4±8,18; general symptoms= 40,7±13,07). At 12 weeks 43,8% had a diagnosis of affective psychosis (bipolar disorder, depressive disorder with psychotic symptoms). Patients with a first psychotic episode, regardless of diagnosis or response to treatment, had less motion sensitivity than healthy controls (f=6.397, p=0.0148). No significant differences were found between groups in surround suppression and no significant correlations were observed between spatial suppression and clinical symptoms. Discussion To our knowledge, this is the first study to find abnormal motion sensitivity in patients with a first episode of psychosis. Our measure of sensitivity, given that it was not contaminated by lapses, indicates that patients had a genuine motion perception deficit rather than an inability to focus on the task. Our results also suggest that motion sensitivity may not be specific to patients with schizophrenia but may also characterize affective psychoses. Larger studies may be needed to clarify whether there is a relationship between motion sensitivity and severity of symptoms and response to treatment.

scholarly journals Effectiveness of Family Intervention for Preventing Relapse in First-Episode Psychosis Until 24 Months of Follow-up: A Systematic Review With Meta-analysis of Randomized Controlled Trials

2019 ◽  
Vol 46 (1) ◽  
pp. 98-109 ◽  
Author(s):  
Miguel Camacho-Gomez ◽  
Pere Castellvi
Keyword(s):  
Meta Analysis ◽  
Psychosocial Interventions ◽  
Family Intervention ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Randomized Controlled ◽  
Episode Psychosis ◽  
Duration Of Hospitalization ◽  
Relapse Rates

Abstract Background Relapse risk during the early years of first-episode psychosis (FEP) considerably increases the risk of chronicity. The effectiveness of family intervention for psychosis (FIp) for preventing relapse after FEP remains unknown. We assessed the effectiveness of FIp until 24 months of follow-up for preventing relapse and other relapse-related outcomes in patients following FEP. Methods We searched the Cochrane, PubMed, PsycINFO, and ProQuest databases in June 2018. A systematic review with meta-analysis of randomized controlled trials (RCTs), sensitivity analyses, and publication bias were performed, comparing to treatment as usual (TAU) or TAU plus other psychosocial interventions. Outcomes assessed were relapse rates, duration of hospitalization, psychotic symptoms, and functionality. Risk ratios (RRs) and (standardized) mean differences (SMD; MD) were calculated. Results Of the 2109 records retrieved, 14 (11 RCTs) were included. Pooled results showed that FIp was effective for preventing relapse (RR = 0.42; 95% CI = 0.29 to 0.61) compared to TAU and/or other psychosocial interventions. It also proved effective when compared to TAU alone (RR = 0.36) and TAU plus other psychosocial interventions (RR = 0.48). FIp showed benefits in reducing duration of hospitalization (TAU, MD = −3.31; other interventions, MD = −4.57) and psychotic symptoms (TAU, SMD = −0.68), and increased functionality (TAU, SMD = 1.36; other interventions, SMD = 1.41). Conclusions These findings suggest that FIp is effective for reducing relapse rates, duration of hospitalization, and psychotic symptoms, and for increasing functionality in FEP patients up to 24 months. The study’s main limitations were the inclusion of published research only; authors were not contacted for missing/additional data; and high heterogeneity regarding relapse definition was observed.

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