scholarly journals Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis

2021 ◽  
pp. 1-13
Author(s):  
Edward Millgate ◽  
Olga Hide ◽  
Stephen M Lawrie ◽  
Robin M Murray ◽  
James H MacCabe ◽  
...  
Keyword(s):  
Effect Size ◽  
Verbal Memory ◽  
Meta Analysis ◽  
Treatment Resistance ◽  
Sampling Strategy ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Treatment Resistant ◽  
Memory And Learning ◽  
Visual Spatial

Abstract Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70–84% are reported to be treatment resistant from the outset. This raises the possibility that the neurobiological mechanisms of treatment resistance emerge before the onset of psychosis and have a neurodevelopmental origin. Neuropsychological investigations can offer important insights into the nature, origin and pathophysiology of treatment-resistant schizophrenia (TRS), but methodological limitations in a still emergent field of research have obscured the neuropsychological discriminability of TRS. We report on the first systematic review and meta-analysis to investigate neuropsychological differences between TRS patients and treatment-responsive controls across 17 published studies (1864 participants). Five meta-analyses were performed in relation to (1) executive function, (2) general cognitive function, (3) attention, working memory and processing speed, (4) verbal memory and learning, and (5) visual−spatial memory and learning. Small-to-moderate effect sizes emerged for all domains. Similarly to previous comparisons between unselected, drug-naïve and first-episode schizophrenia samples v. healthy controls in the literature, the largest effect size was observed in verbal memory and learning [dl = −0.53; 95% confidence interval (CI) −0.29 to −0.76; z = 4.42; p < 0.001]. A sub-analysis of language-related functions, extracted from across the primary domains, yielded a comparable effect size (dl = −0.53, 95% CI −0.82 to −0.23; z = 3.45; p < 0.001). Manipulating our sampling strategy to include or exclude samples selected for clozapine response did not affect the pattern of findings. Our findings are discussed in relation to possible aetiological contributions to TRS.

scholarly journals S62. COGNITIVE DEFICITS IN TREATMENT RESISTANT SCHIZOPHRENIA

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S56-S57
Author(s):  
Edward Millgate ◽  
Eugenia Kravariti ◽  
James MacCabe ◽  
Olga Hide
Keyword(s):  
Executive Function ◽  
Cognitive Deficits ◽  
Verbal Memory ◽  
Antipsychotic Drugs ◽  
Treatment Resistance ◽  
Antipsychotic Treatment ◽  
Verbal Intelligence ◽  
Treatment Resistant ◽  
Domain Specific ◽  
Visual Spatial

Abstract Background Schizophrenia (Sz) and other psychoses are complex mental disorders, characterised by sensory, cognitive and emotional symptoms, but mainly distinguished by positive and negative symptoms. Cognitive impairment is a core feature of schizophrenia, with research into cognitive deficits indicating that cognitive impairment precedes clinical disease onset and is still evident after positive symptoms are no longer present. The current mainstream treatment for Sz are first and second-generation antipsychotics, such as chlorpromazine and aripiprazole respectively. However, about a third of patients treated with antipsychotic drugs have no change in their symptoms despite adequate trials of several antipsychotic drugs. Treatment-resistant schizophrenia (TRS) refers to individuals with a F20-F29 diagnosis who have had at least two courses of antipsychotic treatment with little to no symptomatic relief. Emerging evidence into the factors associated with antipsychotic treatment response has investigated genetic, demographic and clinical factors and their relation to treatment response, with emerging evidence from cognitive data inferring a domain specific deficit in TRS populations for verbal, general cognition (IQ) and executive function tasks. Methods Publications were selected from a systematic search from four databases: PsycINFO, Ovid MEDLINE(R), Scopus and Web of Science. Following inclusion/exclusion criteria, cognitive test outcomes were extracted for each responder group (TRS/NTRS; treatment responders), as well as variables such as age of psychotic illness onset, average chlorpromazine equivalents and duration of illness. Neuropsychological tasks and subtests identified across publications were then grouped into one of seven exclusive cognitive domains (e.g. executive function) prior to analysis based on recommendations from existing literature. Following this, a random-effects model was adopted to test the differences between responder groups in each cognitive domain across publications. Results From the 17 publications identified, sample sizes ranged from 817 to 36, with the majority of publications using a sample size of ~65 TRS/NTRS cases, and a total sample size of N = 1,943 across studies. The random-effects model indicates that cases reaching treatment resistance criteria demonstrated marked neuropsychological performance generally across all domains (d = 0.372, 95CIs 0.29; 0.46], p&lt; .001), with this being most marked in tasks of verbal memory and learning (d = 0.49, 95CIs [0.28; 0.70], p&lt;. 001), verbal intelligence and processing (d = 0.38, 95CIs [0.17; 0.58], p&lt; .001), IQ/general cognitive functioning (d = 0.46, 95CIs [0.17; 0.75], p = 0.002), attention, Working memory and Visual-motor/processing speed (d = 0.38, 95CIs [0.24; 0.51], p&lt; 0.001) and executive function (d = 0.41, 95CIs [0.13; 0.68], p = 0.003), with these all demonstrating a close to medium effect size. There was no significant differences between responder groups in test performance for visual-spatial memory and learning (d = .16, 95CIs [-0.16; 0.48], p = 0.334) and visual-spatial intelligence and processing (d = .50, 95CIs [-0.05; 01.04], p = 0.074) tasks. Discussion In line with existing literature, treatment resistant schizophrenia appears to demonstrate domain specific marked performance on tasks relating to verbal memory, verbal intelligence, as well as tasks relating to executive function, attention and working memory in relation to responders. When considering the clinical importance of identification of treatment resistance in the early disease stages (i.e. at first episode) the use of domain specific cognitive testing could help improve prediction of future antipsychotic response/non-response.

scholarly journals Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors

2017 ◽  
Vol 47 (11) ◽  
pp. 1981-1989 ◽  
Author(s):  
A. Demjaha ◽  
J. M. Lappin ◽  
D. Stahl ◽  
M. X. Patel ◽  
J. H. MacCabe ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Age At Onset ◽  
Treatment Resistance ◽  
First Episode Psychosis ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Treatment Resistant ◽  
Illness Onset ◽  
Episode Psychosis

BackgroundWe examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.MethodThe study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.ResultsFrom the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.ConclusionsThe striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

ECT in schizophrenia: a review of the evidence

2018 ◽  
Vol 31 (03) ◽  
pp. 115-127 ◽  
Author(s):  
Sandeep Grover ◽  
Swapnajeet Sahoo ◽  
Anjumoni Rabha ◽  
Raman Koirala
Keyword(s):  
Effective Treatment ◽  
Electroconvulsive Therapy ◽  
Suicidal Behaviour ◽  
Treatment Guidelines ◽  
Meta Analysis ◽  
Treatment Resistance ◽  
First Episode ◽  
Treatment Resistant ◽  
Predictors Of Response ◽  
First Episode Schizophrenia

AbstractElectroconvulsive therapy (ECT) was initially used for the treatment of schizophrenia, but over the years with the advent of antipsychotics, its use in schizophrenia has been limited. Treatment guidelines vary in their recommendations for the use of ECT in schizophrenia. The usual indications of its use among patients with schizophrenia include treatment resistance, to augment pharmacotherapy, to manage catatonia, suicidal behaviour, severe agitation and clozapine-resistant schizophrenia. Available literature, including meta-analysis and systematic reviews, suggest that ECT is a safe and effective treatment in patients with schizophrenia. However, despite the available evidence, it is highly underutilised and is often used as one of the last resort among patients with schizophrenia. This review focuses on the indications of use of ECT in schizophrenia, studies evaluating its effectiveness, efficacy in certain special situations like first episode schizophrenia, adolescents, catatonia etc., predictors of response to ECT in schizophrenia and influence of various ECT-related parameters on efficacy/effectiveness among patients with schizophrenia. From the review, it can be concluded that ECT is not only is beneficial as an augmenting strategy in treatment-resistant schizophrenia but also can be used effectively in patients with schizophrenia in various other situations.

scholarly journals Cross-sectional study comparing cognitive function in treatment responsive versus treatment non-responsive schizophrenia: evidence from the STRATA study

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e054160
Author(s):  
Edward Millgate ◽  
Eugenia Kravariti ◽  
Alice Egerton ◽  
Oliver D Howes ◽  
Robin M Murray ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Verbal Memory ◽  
Treatment Resistance ◽  
Cross Sectional Study ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Sectional Study ◽  
Cross Sectional ◽  
Language Functions ◽  
Brief Assessment

Background70%–84% of individuals with antipsychotic treatment resistance show non-response from the first episode. Emerging cross-sectional evidence comparing cognitive profiles in treatment resistant schizophrenia to treatment-responsive schizophrenia has indicated that verbal memory and language functions may be more impaired in treatment resistance. We sought to confirm this finding by comparing cognitive performance between antipsychotic non-responders (NR) and responders (R) using a brief cognitive battery for schizophrenia, with a primary focus on verbal tasks compared against other measures of cognition.DesignCross-sectional.SettingThis cross-sectional study recruited antipsychotic treatment R and antipsychotic NR across four UK sites. Cognitive performance was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS).ParticipantsOne hundred and six participants aged 18–65 years with a diagnosis of schizophrenia or schizophreniform disorder were recruited according to their treatment response, with 52 NR and 54 R cases.OutcomesComposite and subscale scores of cognitive performance on the BACS. Group (R vs NR) differences in cognitive scores were investigated using univariable and multivariable linear regressions adjusted for age, gender and illness duration.ResultsUnivariable regression models observed no significant differences between R and NR groups on any measure of the BACS, including verbal memory (ß=−1.99, 95% CI −6.63 to 2.66, p=0.398) and verbal fluency (ß=1.23, 95% CI −2.46 to 4.91, p=0.510). This pattern of findings was consistent in multivariable models.ConclusionsThe lack of group difference in cognition in our sample is likely due to a lack of clinical distinction between our groups. Future investigations should aim to use machine learning methods using longitudinal first episode samples to identify responder subtypes within schizophrenia, and how cognitive factors may interact within this.Trail registration numberREC: 15/LO/0038.

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.

scholarly journals Meta-analysis of cognitive function in Chinese first-episode schizophrenia: MATRICS Consensus Cognitive Battery (MCCB) profile of impairment

2019 ◽  
Vol 32 (3) ◽  
pp. e100043 ◽  
Author(s):  
Huijuan Zhang ◽  
Yao Wang ◽  
Yuliang Hu ◽  
Yikang Zhu ◽  
Tianhong Zhang ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Effect Size ◽  
Meta Analysis ◽  
Verbal Learning ◽  
Chinese Patients ◽  
First Episode ◽  
Neurocognitive Deficits ◽  
Cognitive Domains ◽  
Significant Difference ◽  
First Episode Schizophrenia

BackgroundCompromised neurocognition is a core feature of schizophrenia. With increasing studies researching cognitive function of Chinese patients with first-episode schizophrenia (FES) using MATRICS Consensus Cognitive Battery (MCCB), it is not clear about the level and pattern of cognitive impairment among this population.AimTo provide a meta-analysis systematically analysing studies of neurocognitive function using MCCB in Chinese patients with FES.MethodsAn independent literature search of both Chinese and English databases up to 13 March 2019 was conducted by two reviewers. Standardised mean difference (SMD) was calculated using the random effects model to evaluate the effect size.Results56 studies (FES=3167, healthy controls (HC)=3017) were included and analysed. No study was rated as ‘high quality’ according to Strengthening the Reporting of Observational Studies in Epidemiology. Compared with HCs, Chinese patients with FES showed impairment with large effect size in overall cognition (SMD=−1.60, 95% CI −1.82 to −1.38, I2=67%) and all seven cognitive domains, with the SMD ranging from −0.87 to −1.41. In nine MCCB subtests, patients with FES showed significant difference in Symbol Coding (SMD=−1.90), Trail Making Test (TMT) (SMD=−1.36), Continuous Performance Test-Identical Pairs (SMD=−1.33), Hopkins Verbal Learning Test (SMD=−1.24), Brief Visuospatial Memory Test (SMD=−1.18), Mazes (SMD=−1.16), Category Fluency (SMD=−1.01), Spatial Span (SMD=−0.69) and Mayer-Salovey-Caruso Emotional Intelligence Test (SMD=−0.38).ConclusionsOur meta-analysis demonstrates that Chinese patients with FES show neurocognitive deficits across all seven MCCB cognitive domains and all nine subtests, particularly in two neurocognitive domains: speed of processing and attention/vigilance, with the least impairment shown in social cognition. Symbol Coding and TMT may be the most sensitive tests to detect cognitive deficit in Chinese patients with FES.

scholarly journals Neuropsychological functioning in first-episode schizophrenia

2009 ◽  
Vol 195 (4) ◽  
pp. 336-345 ◽  
Author(s):  
Eugenia Kravariti ◽  
Kevin Morgan ◽  
Paul Fearon ◽  
Jolanta W. Zanelli ◽  
Julia M. Lappin ◽  
...  
Keyword(s):  
Executive Function ◽  
Schizoaffective Disorder ◽  
Processing Speed ◽  
Verbal Memory ◽  
Spatial Perception ◽  
Neuropsychological Functioning ◽  
A Priori ◽  
First Episode ◽  
Visual Spatial ◽  
First Onset

BackgroundIdentifying neurocognitive subtypes in schizophrenia may help establish neurobiologically meaningful subtypes of the disorder, but is frequently confounded by differences in intellectual function between individuals with schizophrenia and controls.AimsTo examine neuropsychological performance in individuals with epidemiologically based, first-onset schizophrenia and intellectually matched controls.MethodUsing standard IQ and reading tests, we examined the proportions of 101 people with epidemiologically derived, first-onset schizophrenia/schizoaffective disorder and 317 community controls, falling into three a priori defined intellectual categories: ‘stable good’, ‘deteriorated poor’ and ‘stable poor’. Neuropsychological function was compared between intellectually matched participants with schizophrenia and control subgroups.ResultsMultiple deficits in executive function, processing speed and verbal memory, but not visual/spatial perception/memory, were detected in all participant groups with schizophrenia compared with controls. The average effect size across the affected domains ranged from small to medium to large in the stable good, deteriorated poor and stable poor subgroups of participants with schizophrenia, respectively.ConclusionsCompared with intellectually matched controls, people with epidemiologically derived, first-onset schizophrenia/schizoaffective disorder show multiple deficits in executive function, processing speed and verbal memory.

scholarly journals A Meta-Analysis of the Influence of Antipsychotics on Cytokines Levels in First Episode Psychosis

2021 ◽  
Vol 10 (11) ◽  
pp. 2488
Author(s):  
Piotr Marcinowicz ◽  
Magdalena Więdłocha ◽  
Natalia Zborowska ◽  
Weronika Dębowska ◽  
Piotr Podwalski ◽  
...  
Keyword(s):  
Meta Analysis ◽  
First Episode Psychosis ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Episode Psychosis ◽  
Tnf Α ◽  
Before And After ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Meta Analyses

Background: Cytokines have a major impact on the neurotransmitter networks that are involved in schizophrenia pathophysiology. First Episode Psychosis (FEP) patients exhibit abnormalities in cytokines levels prior to the start of treatment. Previous studies showed that antipsychotic treatment modulates cytokines levels. The aim of this meta-analysis is to further investigate this relationship. Methods: Several online databases were searched. For meta-analysis of selected studies, we analysed variables containing the number of cases, mean and standard deviation of IL-1β, IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFN-γ levels before, and after, antipsychotic treatment. Results: 12 studies were included in the meta-analysis. Our main results demonstrate that, in FEP patients, antipsychotic treatment is related to decreased concentrations of pro-inflammatory IL-1β, IL-6, IFN-γ, TNF-α and anti-inflammatory IL-4, IL-10 cytokines. On the other hand, levels of pro-inflammatory IL-2 and IL-17 remain unaffected. Conclusions: When compared with other meta-analyses of studies involving FEP individuals, results we obtained are consistent regarding decrease in IL-1β, IL-6. Comparing outcomes of our study with meta-analyses of schizophrenic subjects, in general, our results are consistent in IL-1β, IL-6, TNF-α, IFN-γ, IL-2. Our meta-analysis is the only one which indicates a decrease in anti-inflammatory IL-10 in FEP patients after antipsychotic treatment.

Common pattern of gray-matter abnormalities in drug-naive and medicated first-episode schizophrenia: a multimodal meta-analysis

2016 ◽  
Vol 47 (3) ◽  
pp. 401-413 ◽  
Author(s):  
C. Shah ◽  
W. Zhang ◽  
Y. Xiao ◽  
L. Yao ◽  
Y. Zhao ◽  
...  
Keyword(s):  
Gray Matter ◽  
Meta Analysis ◽  
Insular Cortex ◽  
Middle Temporal Gyrus ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Cross Sectional ◽  
Drug Naïve ◽  
Meta Analyses ◽  
First Episode Schizophrenia

Studies of schizophrenia at drug-naive state and on antipsychotic medication have reported a number of regions of gray-matter (GM) abnormalities but the reports have been inconsistent. The aim of this study was to conduct multimodal meta-analysis to compare the cross-sectional voxel-based morphometry studies of brain GM in antipsychotic-naive first-episode schizophrenia (AN-FES) and those with antipsychotic treatment within 1 year (AT-FES) to determine the similarities and differences in these groups. We conducted two separate meta-analyses containing 24 studies with a sample size of 801 patients and 957 healthy controls. A multimodal meta-analysis method was used to compare the findings between AN-FES and AT-FES. Meta-regression analyses were done to determine the influence of different variables including age, duration of illness, and positive and negative symptom scores. Finally, jack-knife analyses were done to test the robustness of the results. AN-FES and AT-FES showed common patterns of GM abnormalities in frontal (gyrus rectus), superior temporal, left hippocampal and insular cortex. GM in the left supramarginal gyrus and left middle temporal gyrus were found to be increased in AN-FES but decreased in AT-FES, whereas left median cingulate/paracingulate gyri and right hippocampus GM was decreased in AN-FES but increased in AT-FES. Findings suggest that both AN-FES and AT-FES share frontal, temporal and insular regions as common anatomical regions to be affected indicating these to be the primary regions of GM abnormalities in both groups.

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