Syntax and Schizophrenia: A meta-analysis of comprehension and production

Syntax and Schizophrenia: A meta-analysis of comprehension and production | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Syntax and Schizophrenia: A meta-analysis of comprehension and production View ORCID Profile Dalia Elleuch , View ORCID Profile Yinhan Chen , Qiang Luo , View ORCID Profile Lena Palaniyappan doi: https://doi.org/10.1101/2024.10.26.24316171 Dalia Elleuch 1 University of Sfax , Sfax, Tunisia Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Dalia Elleuch Yinhan Chen 2 Institute of Science and Technology for Brain-Inspired Intelligence, Research Institute of Intelligent Complex Systems, Fudan University , Shanghai 200433, China ; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Yinhan Chen Qiang Luo 2 Institute of Science and Technology for Brain-Inspired Intelligence, Research Institute of Intelligent Complex Systems, Fudan University , Shanghai 200433, China ; 3 State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University , Shanghai 200433, China Find this author on Google Scholar Find this author on PubMed Search for this author on this site Lena Palaniyappan 4 Douglas Mental Health University Institute, Department of Psychiatry, McGill University , Quebec, Canada 5 Robarts Research Institute & Lawson Health Research Institute , London, Ontario, Canada 6 Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University , London, Ontario, Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lena Palaniyappan For correspondence: lena.palaniyappan{at}mcgill.ca Abstract Full Text Info/History Metrics Data/Code Preview PDF Summary Background People with schizophrenia exhibit notable difficulties in the use of everyday language. This directly impacts one’s ability to complete education and secure employment. An impairment in the ability to understand and generate the correct grammatical structures (syntax) has been suggested as a key contributor; but studies have been underpowered, often with conflicting findings. It is also unclear if syntactic deficits are restricted to a subgroup of patients, or generalized across the broad spectrum of patients irrespective of symptom profiles, age, sex, and illness severity. Methods We conducted a systematic review and meta-analysis, registered on OSF, adhering to PRISMA guidelines, searching multiple databases up to May 1, 2024. We extracted effect sizes (Cohen’s d) and variance differences (log coefficient of variation ratio) across 6 domains: 2 in comprehension (understanding complex syntax, detection of syntactic errors) and 4 in production (global complexity, phrasal/clausal complexity, utterance length, and integrity) in patient-control comparisons. Study quality/bias was assessed using a modified Newcastle–Ottawa Scale. Bayesian meta-analysis was used to estimate domain-specific effects and variance differences. We tested for potential moderators with sufficient data (age, sex, study quality, language spoken) using conventional meta-regression to estimate the sources of heterogeneity between studies. Findings Overall, 45 studies (n=2960 unique participants, 64·4% English, 79 case-control contrasts, weighted mean age(sd)=32·3(5·6)) were included. Of the patient samples, only 29·2% were women. Bayesian meta-analysis revealed extreme evidence for all syntactic domains to be affected in schizophrenia with a large-sized effect (model-averaged d =0·65 to 1·01, with overall random effects d =0·86, 95% CrI [0·67-1·03]). Syntactic comprehension was the most affected domain. There was notable heterogeneity between studies in global complexity (moderated by the age), production integrity (moderated by study quality), and production length. Robust BMA revealed weak evidence for publication bias. Patients had a small-to-medium-sized excess of inter-individual variability than healthy controls in understanding complex syntax, and in producing long utterances and complex phrases (overall random effects lnCVR =0·21, 95% CrI [0·07-0·36]), hinting at the possible presence of subgroups with diverging syntactic performance. Interpretation There is robust evidence for the presence of grammatical impairment in comprehension and production in schizophrenia. This knowledge will improve the measurement of communication disturbances in schizophrenia and aid in developing distinct interventions focussed on syntax - a rule-based feature that is potentially amenable to cognitive, educational, and linguistic interventions. Evidence before this study Prior studies have documented significant language deficits among individuals with psychosis across multiple levels. However, syntactic divergence—those affecting sentence structure and grammar—have not been consistently quantified or systematically reviewed. An initial review of the literature indicated that the specific nature and severity of syntactic divergence, as well as their impact on narrative speech production, symptom burden, and daily functioning, remain poorly defined. We conducted a comprehensive search of the literature up to May 1, 2024, using databases such as PubMed, PsycINFO, Scopus, Google Scholar, and Web of Science. Our search terms combined psychosis, schizophrenia, language production, comprehension, syntax, and grammar, and we identified a scarcity of meta-analytic studies focusing specifically on syntactic comprehension and production divergence in psychosis. Added value of this study This systematic review and meta-analysis is the first to quantitatively assess syntactic comprehension and production divergence in individuals with psychosis. This study provides estimated effect sizes associated with syntactic impairments as well as a quantification of the variance within patient groups for each domain of impairment. Besides a detailed examination of this under-researched domain, we also identify critical research gaps that need to be addressed to derive benefits for patients from knowledge generated in this domain. Implications of all the available evidence This study provides robust evidence of grammatical impairments in individuals with schizophrenia, particularly in syntactic comprehension and production. These findings can enhance early detection approaches via speech/text readouts and lead to the development of targeted cognitive, educational, and linguistic interventions. By highlighting the variability in linguistic deficits, the study offers valuable insights for future therapeutic trials. It also supports the creation of personalized formats of information and educational plans aimed at improving the effectiveness of any therapeutic intervention offered to patients with schizophrenia via verbal medium. 1. Introduction The cognitive faculty of language supports interpersonal communication and thinking 1 , both of which are disrupted in psychotic disorders such as schizophrenia. Do the thought and communication disorders in people with schizophrenia result from structural issues i.e., grammatical impairment (syntactic divergence) in people with schizophrenia? This question has been studied at various times in the past, with a variety of methods and approaches 2 – 6 . Despite the substantial body of work, the existing literature presents a fragmented understanding of the nature and extent of syntactic deficits. Disorganised speech, a diagnostic feature of schizophrenia in DSM-5 7 , is assessed on the basis of incoherence that leads to a failure of effective communication. Syntax production, if impaired, can generate conversational incoherence. Similarly, impaired comprehension of syntax (i.e., who did what to whom?) may contribute to impaired meaning and misinterpretations that typify positive psychotic symptoms such as persecutory delusions. In the current study, we systematically review the literature published to date on both syntactic production and comprehension in schizophrenia. Producing and inferring meaning via language is not based on isolated lexical concepts (semantic categories), but involves the interactional basis offered by grammatical constructions. Grammar enables the signifiers and the signified to be put together. Thus, there is a strong case to be made for syntax-level deficits i.e., an aberration in the way words are put together, to have primacy in the language disorder of schizophrenia 8 – 11 . Several thoughtful reviews in recent times have hinted at the critical importance of syntactic divergence in schizophrenia 4 , 12 – 15 . Bora and colleagues highlighted a role for syntactic comprehension divergence when analyzing the linguistic correlates of the burden of formal thought disorder 16 . Nonetheless, to our knowledge, a comprehensive meta-analytic quantification of the overall magnitude of grammatical impairment in both comprehension and production in schizophrenia is still lacking. Quantifying the degree of grammatical impairment in schizophrenia is critical for two reasons. Firstly, the use of the various linguistic markers in speech to predict clinically important outcomes is an emerging pursuit in the field (e.g., onset of first episode 17 – 19 , relapses 20 ). Despite the many studies carried out to date, one major obstacle in bringing such predictive analytics to routine clinical use is the lack of empirical guidance on feature selection in these models. As a result, a large number of automatically derived linguistic variables are being tested in clinical prediction models, with minimal overlap among different studies, impeding interpretability and successful external validation (e.g., not a single linguistic feature overlapped across the 18 prediction analysis studies identified in a recent review 21 ). This can be addressed via evidence- based preselection of variables that most proximally relate to the clinical construct of interest i.e., the presence of schizophrenia in our case [see Meehan and colleagues 22 for a state-of-the-art review]. Meta-analytic estimation of the effect size of syntax production/comprehension variables will provide evidence for their utility in speech-based predictive analytics. Secondly, given the relevance of social interaction for functional recovery 23 , interventions to ameliorate communication deficits in schizophrenia are steadily growing in recent times 24 – 26 . Outcomes of these trials can be improved by identifying the most affected syntactic markers as treatment targets and identifying if distinct subgroups with varying degrees of deficits are likely to occur among patients. In the presence of a high degree of interindividual variability in syntactic deficits, stratified RCTs for communicative remediation are likely to have a better yield. Thus, meta-analytic estimation of the effect size and variability of syntactic deficits will inform forthcoming intervention trials. Our primary goal of this review is to provide a quantitative synthesis of the degree and interindividual variability of syntactic language deficit across the domains of syntactic comprehension, anomaly/error detection, and various levels of complexity and integrity of syntactic production in schizophrenia. We also aim to investigate the relationship between syntactic production, comprehension, and symptom severity and identify potential research gaps and opportunities in this area of work. 2. Methods 2.1 Search Strategy and Selection Criteria The original protocol was registered on the Open Science Framework registry (May 202), with an update after the initial search but before undertaking statistical analysis (October 2024) 27 . This update included missing information on meta-analytic methods and bias assessment framework, adding specifications (grouping of syntactic domains, metaregression variables) and planned deviations (reporting pronoun aberrations separately from the current report, dropping reaction time and parts-of-speech measures to reduce bias from reporting inconsistencies). Any further deviations that occurred after the data-analysis (the use of multivariate approach to meta- analysis) are reported as Supplemental Results. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 28 and recent recommendations to protect against researcher bias in meta-analysis 29 . We performed a literature search across multiple electronic databases, including PubMed, PsycINFO, Scopus, and Web of Science, up to May 1, 2024. Search terms included a combination of keywords and Medical Subject Headings (MeSH) terms related to schizophrenia (schizophrenia OR schizo* OR psychos* OR psychot*), language (language OR verbal OR linguistic OR speech OR communicat* OR thought), syntax (syntax OR syntactic OR gramma*). Two reviewers (DE and LP) independently screened titles and abstracts against the inclusion criteria using Rayyan software after removing duplicates. Full texts of relevant studies were assessed for eligibility. We then added further studies to the pool by screening the bibliography and hand-searching all citations received by the identified studies via Google Scholar. We included English/French language publications describing studies that (1) enrolled adults (aged 18 or above) diagnosed with schizophrenia spectrum disorders (schizophrenia, schizoaffective, or schizophreniform psychosis) and a control group of healthy adults without known psychiatric disorders (2) assessed speech production and/or comprehension, focusing on grammar and syntax. This includes evaluating either grammatical comprehension (by quantifying a person’s ability to understand complex sentences or detect errors in the syntactic formation) and/or production (by assessing the degree of global [narrative level] or local [clausal/phrasal level] complexity, length and integrity in the utterances or sentences). This grouping of domains of interest was based on Morice and Ingram’s original work 30 that separated complexity and integrity in syntax production in schizophrenia, with phrasal/clausal level complexity (coordination) later included by Thomas and colleagues 31 . This set was further extended as per Lu’s Syntactic Complexity Analyzer approach 32 to distinguish production length from other complexity measures. Only empirical studies with quantitative measures derived in the same manner from both groups were included. Studies focused on subjects <18 years of age 33 – 35 , case reports/case series 36 , and those without a healthy control group 11 , 37 – 41 were excluded. Additionally, studies focussed on high-risk subjects without a diagnosed schizophrenia spectrum disorder 42 , studies reporting verbal outputs that were either restricted (e.g., scripted conversations 43 ) or likely to have been edited after production (e.g., written reports and social media texts 44 – 48 ), non-naturalistic speech (e.g., word list generation, repetition, monitoring or recall of memorized text 49 – 51 ), analysis restricted to parts-of-speech tagging (with no sentential syntax) 52 – 55 or providing only second order derivatives (e.g., speech graph metrics 56 or factor scores 57 ) without direct indices of syntax production/comprehension were not eligible. One study with a retraction notice was also excluded. Studies with unconventional criteria for syntactic complexity 58 – 60 and those without quantitative measures or plots that allowed effect size estimation were also excluded 49 , 61 , 62 . For a list of articles excluded at the stage of data extraction with the reasons for exclusion and main results, see Supplemental Table 1. 2.2 Data Extraction We extracted the available clinical/demographic data (author(s), publication year, country, sample size, mean age, and symptom severity based on standardized scales [e.g., PANSS, SANS/SAPS, BPRS/BPRS-E, with the reported total scores in each patient sample converted to a scale of 0 to 1 via min-max transformation (See Supplement)], sex distribution, chlorpromazine equivalent of antipsychotic dose (conversions from other drug equivalents or Defined Daily Doses as per 63 ), mode [free speech, visual/verbal stimulus such as picture/proverb elaboration, sentence to picture matching] and the language of task administration). A description of the included studies is available in Table 1 . When overlapping samples were published in more than one paper, we extracted data from the largest reported sample 64 , 65 ; 66 , 67 ; 68 , 69 ; 30 , 70 ; 71 , 72 . We reached out to selected authors (12·2%) when quantitative measures were unclear for clarifications. For studies where numerical values were not provided 31 , 57 , 73 – 76 we extracted these values from published plots using a visual data extraction tool (plotdigitizer.com). When more than one mean was reported on the same measurement from the same sample (e.g., on/off medications as in 77 ), we included the average as the summary measure. Some of the studies reported median and range values instead of mean and SD required for Cohen’s d estimation 51 , 74 , 78 . In such instances, we used the five-number summary approach 79 , available at https://www.math.hkbu.edu.hk/~tongt/papers/median2mean.html . View this table: View inline View popup Table 1. Description of the included studies. 2.3 Quality Assessment The quality of the studies was assessed using a purposively modified Newcastle–Ottawa Scale 80 , widely used in psychiatry where rating scale use for exposure assignment is a common practice 81 . The following indicators were evaluated: case definition, representativeness, selection of control group, comparability of groups, ascertainment of ‘exposure’ (i.e., measurement of syntactic variables of interest), and quality of data reporting. Items in the Newcastle-Ottawa framework are known to have low reliability among raters 82 (e.g., demonstrating the timing of measurements) and lack of clarity 83 (e.g., emphasis on independent validation of the case status, response proportions, the practice of higher scores for population-based controls, statistical adjustment and blinding which are often unsatisfactory in case-control designs) were replaced these with items specific to psychiatric diagnoses and linguistic variable assessment (see Supplemental Table 2 for a description). Furthermore, we defined likely confounders a priori for bias assessment (age, sex, education, and native language being different from the language of assessment). Each study was independently rated for scores between 0-12 by two authors (DE and LP), with disagreements resolved by discussion. 2.4 Data Analysis Statistical analyses were conducted using the JASP 0.19.0.0 package 84 . Effect sizes were calculated from available means and standard deviations (Cohen’s d = (M 2 - M 1 ) ⁄ SD pooled ) from each set of analysis. As some studies reported error rates while others reported accuracy rates, all effect sizes were sign-adjusted to read as controls>patients when producing summary values. We pooled the d values using bayesian model-averaged (BMA) meta-analysis via metaBMA R package implemented in JASP 85 . BMA evaluates the likelihood of the data under a combination of models regarding the meta-analytic effect and heterogeneity, reporting model-averaged effects. Evidence in favor of a group difference was categorized as weak (for BF 10 1 to <3), moderate (BF 10 3 to <10), strong (BF 10 10 to <30), very strong (BF 10 30 to 100). Meta-regression analyses were performed when sufficient evidence for heterogeneity between studies was uncovered in any domain. We included the mean age of patients, proportion of female patients, mean chlorpromazine equivalent dose, language of the study assessment (English vs. non-English), and study quality scores as potential moderators. Robust Bayesian meta-analysis 86 was used to assess the sensitivity of the results to the potential presence of publication bias and heterogeneity. Log Coefficient of Variation Ratio 87 (lnCVR: natural log of ratio of the estimated total coefficient of variation between the patient and the control group) was used to quantify the difference in variability after scaling to the mean of each group [lnCVR= 0 indicates equal variability; >0 greater variability, while <0 indicates lower variability in patients vs. controls]. Given the between-domain heterogeneity, we used a random-effects model to pool the 6 lnCVR measures and the 6 Cohen’s d estimates across the domains to assess the overall effect. 3. Results 3.1 Study Selection A total of 463 studies were identified through the initial database search. After removing duplicates, 289 unique studies remained. Following title and abstract screening, 86 articles were retrieved as relevant, of which 45 studies met the inclusion criteria for numerical synthesis for the meta-analysis 88 – 95 , 77 , 96 , 97 , 64 , 9 , 67 , 98 , 51 , 99 – 104 , 73 , 78 , 105 , 74 , 30 , 106 – 114 , 75 , 115 – 118 , 71 , 31 (see Figure 1 ). Download figure Open in new tab Figure 1: PRISMA 2020 flow diagram for the systematic review of syntax and schizophrenia. 3.2 Study Characteristics The final list included studies published between 1982 and 2024, with summary data from a total of n= 1679 patients and n= 1281 controls available from 79 comparisons across 6 domains of interest. The weighted mean age across studies was 32·31 (SD=5·6) years, with no difference in distribution among patients and control cohorts (paired t=0·85, p=0·4). Only 29·2% of participants were women, with 5 studies recruiting only men 77 , 102 , 109 , 119 , 120 ; only 8 studies had >40% women. The studies predominantly included individuals diagnosed with established schizophrenia spectrum disorders (n=1292), with first-episode samples forming 33·59% of the total sample (n=564). A great majority of studies (64·4%) recruited English-speaking participants. Some studies reported separate contrasts based on the presence of Formal Thought Disorder (FTD/no-FTD 121 – 123 ) or stage of illness (FEP/established schizophrenia 9 , 64 , 95 ). Quality scores are presented in Supplemental Table 3. There is no single accepted index to measure grammatical impairment in mental health conditions. As a result, we found a notable variation in the method used to quantify the variables of interest, and in some cases, more than one variable for the same domain was reported. As a general principle, we chose the measures with the closest theoretical alignment to the 6 domains of interest for this meta-analysis. Within each domain, we chose tasks and variables that were most commonly used across studies. Other study-specific decisions in variable choices are discussed in the Supplement. 3.3 Data availability While mean age (93·3% of studies), language of testing (100%), and sex distribution (93·3%) were available for most studies, an estimate of antipsychotic dose exposure (48.9%) and overall symptom severity (40%) were less often reported. Most studies only provided the overall proportion of antipsychotic use and domain-specific symptom scores (generally positive symptoms). As a result, we included age, assessment language, sex, and the study quality scores in the meta-regression analyses, but only reported moderator/effect-size bivariate correlations for antipsychotic dose and total symptom severity index. 3.4 Meta-analytical results The results of Bayesian Meta-Analysis for each group of studies are shown in Table 2 along with the data on between-studies heterogeneity, log coefficient of variation ratios, and publication bias. BMA showed extreme evidence for reduced syntactic comprehension, error detection, production length, phrasal complexity, production integrity, and global complexity in patients (all BF 10 >100; Figure 2 ). Random effects analysis across the 6 domain-specific effects indicated extreme evidence (BF 10 =3173; estimated d =0·87) for an overall grammatical impairment in schizophrenia. See the supplement for multivariate meta-analysis of correlated outcomes. Download figure Open in new tab Figure 2: Forest plots for domain specific meta-analyses of syntactic production and comprehension in schizophrenia. Bayesian Model Averaged estimates of group differences in syntactic comprehension (k=16), error detection (k=6), production length (k=17), phrasal complexity (k=16), production integrity (k=11) and global complexity (k=13). Estimated (not observed) Cohen’s d values are given along with 95% credible intervals in parentheses. FTD=Formal Thought Disorder. nFTD: no-Formal Thought Disorder. FEP=First Episode Psychosis. SCZ=Established schizophrenia View this table: View inline View popup Download powerpoint Table 2: Summary of Bayesian Model-Averaged Meta-Analysis of Grammatical Impairment in Schizophrenia Spectrum Disorders View this table: View inline View popup Table 3. Key variables and moderators for the case-control comparisons in the meta-analysis Between study heterogeneity (tau) was strong for global complexity, production length, and integrity. Of these domains, the meta-regression analysis revealed age as a significant moderator for global complexity while study quality was the most significant known source of heterogeneity for production integrity ( Table 2 ; Fig 3 ). The moderator/effect-size bivariate correlations were not significant for antipsychotic dose (r 31 =0·27, p=0·14) or total symptom severity index (r 33 =0·06, p=0·74) across all domains. While the number of studies on clinically detectable FTD was insufficient for a meta-regression, visual inspection of the forest plots revealed that all FTD contrasts had above-average Cohen’s d values for syntactic comprehension and phrasal complexity but not for production integrity. Download figure Open in new tab Figure 3: Observation from meta-regression analysis. Older study cohorts had more pronounced effect size differences for global syntactic complexity while better quality studies reported higher effect sizes for production integrity Meta-analysis of within-group variations indicated higher inter-individual variability in patients for syntactic comprehension, phrasal complexity, and production length (lnCVR= 0·13-0·41; medium to large variation effect 124 ) but not for other measures ( Figure 3 ). Random effects analysis across the 6 domain-specific variation estimates indicated moderate evidence (BF 10 = 5·27; estimated lnCVR = 0·21) for excess variability among patients compared to healthy controls ( Figure 4 ). Download figure Open in new tab Figure 4: Forest plots for domain specific meta-analyses of variation in syntactic production and comprehension in schizophrenia. Bayesian Model Averaged estimates of group differences in syntactic comprehension (k=16), error detection (k=6), production length (k=17), phrasal complexity (k=16), production integrity (k=11) and global complexity (k=13). Estimated (not observed) logarithm of coefficient of variation ratio (patients>controls) are given along with 95% credible intervals in parentheses. FTD=Formal Thought Disorder. nFTD: no-Formal Thought Disorder. FEP=First Episode Psychosis. SCZ=Established schizophrenia Using Robust BMA, we found no or weak evidence for publication bias in all of the individual meta-analyses, with moderate to extreme evidence retained for domain-specific impairments in syntax ( Table 2 ). 4. Discussion To our knowledge, this is the first meta-analysis on the association between schizophrenia spectrum disorders and the use of grammar/syntax. BMA reveals extreme evidence in support of a global impairment across the domains of interest in schizophrenia, with the most robust effects being noted for comprehension of complex syntax and detection of errors followed by production length and integrity. This implies that people with schizophrenia spectrum disorders understand simpler sentences better, ignore syntactical errors, and speak in less sophisticated, shorter sentences that may not have a complete syntactic structure. The evidence favoring illness-related differences was moderately strong for global and phrasal complexity, even after taking between-studies heterogeneity and publication bias into account. Within the patient group, variability in grammar production/comprehension was higher than that of the healthy control group; this may occur in the presence of subgroups with varying degrees of impairment among patients. Taken together, a broad spectrum of grammatical impairment appears to be a key feature of schizophrenia. Given the relatively modest sample sizes in individual studies (median patient n=32), our meta- analytic synthesis offers a more robust and representative effect size of grammatical impairment in SSD. Nevertheless, one limitation is our reliance on summary measures reported by authors instead of individual participant data. As 40% of case-control contrasts came from studies completed 20 years ago, we assessed (a priori) the likelihood of data availability to be low. Notable variation in study quality was noted, with representativeness across sexes and assessment languages being poor. Our synthesis is also limited by the diversity of variables used to define the domain-specific divergence; this likely accounts for the high heterogeneity observed in certain domains. Some overlap among the constructs of interest was noted (e.g., between global and phrasal complexity), while individual studies seldom reported the subject- level correlations among the various domains (especially between production and comprehension divergence), precluding our ability to test one of our pre-registered aims (but see the Supplement for the multivariate meta-analysis). We also record notable variations in clinical sampling, with some studies focussing exclusively on those with FTD 102 . We found insufficient data to estimate the effect of FTD across all domains, and excluded studies that only compared FTD and non-FTD patient groups 125 . But our results indicate that grammatical impairment occurs irrespective of the presence of FTD. It is important to note that at an individual level, the degree of grammatical impairment is likely to be much higher among patients as it is influenced by comorbid developmental disorders and poor proficiency in a non-native language, both of which led to participant exclusion in the studies we identified. Furthermore, patients with more severe linguistic deficits often lack the capacity to provide written informed consent, making the effect size reported here a highly conservative estimate of the real-world complexities of grammatical impairment in schizophrenia. We make a set of recommendations for future studies in this regard (Supplemental Table 4). One of the strengths of our review is the depth of our literature search - covering 50 years of work. In contrast to Ehlen and colleagues 4 who recently “identified no studies evaluating syntax production in individuals with schizophrenia”, our search strategy located k=29 studies on syntax production. Furthermore, our Robust BMA analytical approach accounts for the uncertainty in heterogeneity and publication bias estimates and offers a comprehensive meta-analytic quantification of the overall magnitude of grammatical impairment in schizophrenia. The robust medium-to-large deficit in syntax production makes a strong case for including speech-based predictive analytics for early detection of schizophrenia, reinforcing prior 35 , 126 and ongoing studies in this regard 127 . Deficits in syntax, being a rule-based feature of language, are potentially remediable across the lifespan, and syntactic improvement may also affect other levels of linguistic processing (see Supplement Box 1). This has been shown in aphasic disorders with structured rehabilitation/education approaches (e.g., mapping therapy, syntax stimulation 128 , 129 ) or via targeted cognitive training (e.g., working memory 130 ). By demonstrating evidence for a small-to- medium-sized increase in inter-individual variability in syntactic deficit (especially for phrasal complexity and syntactic comprehension), our synthesis encourages pre-trial selection of patients for communicative remediation. In particular, for syntactic comprehension, the combination of a large effect-size deficit, low between-studies heterogeneity, and the possibility of finding highly impaired subgroups indicate its suitability as an outcome measure for linguistic intervention trials. The neural and social interactional basis of the observed syntactic deficits warrants attention in future studies. Emerging arguments against the presence of specific neural substrates for syntax/combinatorial processing in human language 131 – 133 , indicate that the syntactic aberrations in schizophrenia may underwrite divergence at other levels of language processing, especially semantic cognition; this remains to be seen. Our observation of a generalized syntactic deficit across patient samples argues against focusing exclusively on those with clinically detectable FTD in mechanistic studies of linguistic divergence in psychosis (see 64 , 134 , 135 for a similar argument). Our estimate of overall syntactic impairment ( d =0·87) is smaller than the generalized cognitive impairment reported in schizophrenia ( d =1·2 136 ). Studies included in our meta-analysis either excluded participants with notably low IQ or matched IQ between groups; thus, we cannot attribute the observed syntactic divergence to a generalized cognitive impairment. Unlike the constrained neuropsychological tests used to assess cognitive deficits, syntactic divergence (especially in production) reported here has been observed on the basis of narratives/conversations that occur in more natural contexts. Thus, grammatical impairments, often carried by patients without much self-awareness, are likely to have intrusive effects on one’s everyday social functions. In conclusion, our meta-analysis substantiates the long-suspected role of grammatical aberrations in schizophrenia. The question of whether these deficits occur independently of lexico-semantic abnormalities or are part of a broader linguistic impairment remains unresolved. Nonetheless, the findings underscore the need for targeted interventions to address these linguistic differences. More general implications include the importance of adjusting verbal exchanges in therapeutic settings for schizophrenia. Data Availability All data produced in the present work are contained in the manuscript Funding L. Palaniyappan’s research is supported by the Canada First Research Excellence Fund, awarded to the Healthy Brains, Healthy Lives initiative at McGill University (through New Investigator Supplement) and Monique H. Bourgeois Chair in Developmental Disorders. He receives a salary award from the Fonds de recherche du Quebec-Sante. This work is supported by the FRQS Partenariat Innovation-Québec-Janssen (PIQ-J) initiative (#338282); Canadian Institutes of Health Research (CIHR) - Strategy for Patient-Oriented Research Priority Announcement (SPOR; Grant number PJK192157) and Project Grant (Grant number PJT195903); Wellcome Trust Discretionary Grant (226168/Z/22/Z) Conflicts of interest L.P. reports personal fees from Janssen Canada, Otsuka Canada, SPMM Course Limited, UK, Canadian Psychiatric Association; book royalties from Oxford University Press; investigator-initiated educational grants from Sunovion, Janssen Canada, Otsuka Canada outside the submitted work. Contributors L.P. conceptualized the study; D.E. and L.P. designed, searched, and extracted the data; L.P., Y.C., and Q.L. undertook the meta-analysis. L.P. and D.E. interpreted the findings and drafted the manuscript; All authors revised it critically for important intellectual content. Data Availability All data that support the findings are provided as supplementary materials. Any further data requests can be made to the corresponding author. REFERENCES ↵ Carruthers P . The cognitive functions of language . Behavioral and Brain Sciences 2002 ; 25 : 657 – 74 . OpenUrl CrossRef PubMed ↵ Chaika E . A unified explanation for the diverse structural deviations reported for adult schizophrenics with disrupted speech . Journal of Communication Disorders 1982 ; 15 : 167 – 89 . OpenUrl CrossRef PubMed Covington MA , He C , Brown C , et al. Schizophrenia and the structure of language: the linguist’s view . Schizophr Res 2005 ; 77 : 85 – 98 . OpenUrl CrossRef PubMed Web of Science ↵ Ehlen F , Montag C , Leopold K , Heinz A . Linguistic findings in persons with schizophrenia—a review of the current literature . Frontiers in Psychology 2023 ; 14 . https://www.frontiersin.org/articles/10.3389/fpsyg.2023.1287706 (accessed Jan 20, 2024). Hinzen W , Rosselló J . The linguistics of schizophrenia: thought disturbance as language pathology across positive symptoms . Frontiers in Psychology 2015 ; 6 : 971 . ↵ Kuperberg GR . Language in schizophrenia Part 1: an Introduction . Lang Linguist Compass 2010 ; 4 : 576 – 89 . OpenUrl CrossRef PubMed ↵ Tandon R , Gaebel W , Barch DM , et al. Definition and description of schizophrenia in the DSM-5 . Schizophrenia Research 2013 ; 150 : 3 – 10 . OpenUrl CrossRef PubMed ↵ Crow TJ . The nuclear symptoms of schizophrenia reveal the four quadrant structure of language and its deictic frame . Journal of Neurolinguistics 2010 ; 23 : 1 – 9 . OpenUrl CrossRef Web of Science ↵ DeLisi LE . Speech disorder in schizophrenia: review of the literature and exploration of its relation to the uniquely human capacity for language . Schizophr Bull 2001 ; 27 : 481 – 96 . OpenUrl CrossRef PubMed Web of Science Hinzen W , Palaniyappan L . The ‘L-factor’: Language as a transdiagnostic dimension in psychopathology . Progress in Neuro-Psychopharmacology and Biological Psychiatry 2024 ; 131 : 110952 . ↵ Pylyshyn ZW . Clinical Correlates Of Some Syntactic Features Of Patients’ Speech . The Journal of Nervous and Mental Disease 1970 ; 150 : 307 . ↵ Deneault A , Dumais A , Désilets M , Hudon A . Natural Language Processing and Schizophrenia: A Scoping Review of Uses and Challenges . Journal of Personalized Medicine 2024 ; 14 : 744 . Elvevåg B , Cohen AS , Wolters MK , et al. An examination of the language construct in NIMH’s research domain criteria: Time for reconceptualization! American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 2016 ; 171 : 904 – 19 . OpenUrl PubMed Kircher T , Bröhl H , Meier F , Engelen J . Formal thought disorders: from phenomenology to neurobiology . Lancet Psychiatry 2018 ; 5 : 515 – 26 . OpenUrl PubMed ↵ Low DM , Bentley KH , Ghosh SS . Automated assessment of psychiatric disorders using speech: A systematic review . Laryngoscope Investigative Otolaryngology 2020 ; 5 : 96 – 116 . OpenUrl PubMed ↵ Bora E , Yalincetin B , Akdede BB , Alptekin K . Neurocognitive and linguistic correlates of positive and negative formal thought disorder: A meta-analysis . Schizophrenia Research 2019 ; 209 : 2 – 11 . OpenUrl PubMed ↵ Corcoran C.M. , Cecchi G.A . Using Language Processing and Speech Analysis for the Identification of Psychosis and Other Disorders . Biol Psychiatry Cogn Neurosci Neuroimaging 2020 ; 5 : 770 – 9 . OpenUrl PubMed Corona Hernández H , Corcoran C , Achim AM , et al. Natural Language Processing Markers for Psychosis and Other Psychiatric Disorders: Emerging Themes and Research Agenda From a Cross-Linguistic Workshop . Schizophr Bull 2023 ; 49 : S86 – 92 . OpenUrl PubMed ↵ de Boer JN , Brederoo SG , Voppel AE , Sommer IEC . Anomalies in language as a biomarker for schizophrenia . Curr Opin Psychiatry 2020 ; 33 : 212 – 8 . OpenUrl CrossRef PubMed ↵ Zaher F , Diallo M , Achim AM , et al. Speech markers to predict and prevent recurrent episodes of psychosis: A narrative overview and emerging opportunities . Schizophrenia Research 2024 ; 266 : 205 – 15 . OpenUrl PubMed ↵ Deneault A , Dumais A , Désilets M , Hudon A . Natural Language Processing and Schizophrenia: A Scoping Review of Uses and Challenges . J Pers Med 2024 ; 14 : 744 . ↵ Meehan AJ , Lewis SJ , Fazel S , et al. Clinical prediction models in psychiatry: a systematic review of two decades of progress and challenges . Mol Psychiatry 2022 ; 27 : 2700 – 8 . OpenUrl PubMed ↵ Adamczyk P , Daren A , Sułecka A , et al. Do better communication skills promote sheltered employment in schizophrenia? Schizophrenia Research 2016 ; 176 : 331 – 9 . OpenUrl PubMed ↵ Bambini V , Agostoni G , Buonocore M , et al. It is time to address language disorders in schizophrenia: A RCT on the efficacy of a novel training targeting the pragmatics of communication (PragmaCom) . Journal of Communication Disorders 2022 ; 97 : 106196 . Jimeno N . Language and communication rehabilitation in patients with schizophrenia: A narrative review . Heliyon 2024 ; 10 : e24897 . OpenUrl ↵ Bosco FM , Gabbatore I , Gastaldo L , Sacco K . Communicative-Pragmatic Treatment in Schizophrenia: A Pilot Study . Front Psychol 2016 ; 7 . DOI: 10.3389/fpsyg.2016.00166 . OpenUrl CrossRef ↵ Elleuch D , Palaniyappan L. Grammar and Psychosis: A systematic review of language production and comprehension studies . 2024 ; published online May 16. DOI:10.17605/OSF.IO/7FZUC. ↵ Page MJ , McKenzie JE , Bossuyt PM , et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews . BMJ 2021 ; 372 : n71 . ↵ Baldwin JR , Pingault J-B , Schoeler T , Sallis HM , Munafò MR . Protecting against researcher bias in secondary data analysis: challenges and potential solutions . European Journal of Epidemiology 2022 ; 37 : 1 . ↵ Morice RD , Ingram JCL . Language Analysis in Schizophrenia: Diagnostic Implications . Aust N Z J Psychiatry 1982 ; 16 : 11 – 21 . OpenUrl CrossRef PubMed Web of Science ↵ Thomas P , King K , Fraser WI . Positive and negative symptoms of schizophrenia and linguistic performance . Acta Psychiatr Scand 1987 ; 76 : 144 – 51 . OpenUrl CrossRef PubMed Web of Science ↵ Lu X . Automatic analysis of syntactic complexity in second language writing . International Journal of Corpus Linguistics 2010 ; 15 : 474 – 96 . OpenUrl CrossRef ↵ Silberg JL . The development of pronoun usage in the psychotic child . J Autism Dev Disord 1978 ; 8 : 413 – 25 . OpenUrl Solomon M , Olsen E , Niendam T , et al. From lumping to splitting and back again: atypical social and language development in individuals with clinical-high-risk for psychosis, first episode schizophrenia, and autism spectrum disorders . Schizophr Res 2011 ; 131 : 146 – 51 . OpenUrl CrossRef PubMed ↵ Corcoran CM , Carrillo F , Fernández-Slezak D , et al. Prediction of psychosis across protocols and risk cohorts using automated language analysis . World Psychiatry 2018 ; 17 : 67 – 75 . OpenUrl CrossRef PubMed ↵ Noël-Jorand MC , Reinert M , Giudicelli S , Dassa D . A new approach to discourse analysis in psychiatry, applied to a schizophrenic patient’s speech . Schizophr Res 1997 ; 25 : 183 – 98 . OpenUrl CrossRef PubMed Web of Science ↵ Barch DM , Berenbaum H . The effect of language production manipulations on negative thought disorder and discourse coherence disturbances in schizophrenia . Psychiatry Research 1997 ; 71 : 115 – 27 . OpenUrl CrossRef PubMed Web of Science Barch DM , Berenbaum H . Language generation in schizophrenia and mania: the relationships among verbosity, syntactic complexity, and pausing . J Psycholinguist Res 1997 ; 26 : 401 – 12 . OpenUrl PubMed Lelekov T , Franck N , Dominey PF , Georgieff N . Cognitive sequence processing and syntactic comprehension in schizophrenia . Neuroreport 2000 ; 11 : 2145 – 9 . OpenUrl CrossRef PubMed Lott PR , Guggenbühl S , Schneeberger A , Pulver AE , Stassen HH . Linguistic Analysis of the Speech Output of Schizophrenic , Bipolar, and Depressive Patients. PSP 2002 ; 35 : 220 – 7 . OpenUrl ↵ Jeong L , Lee M , Eyre B , Balagopalan A , Rudzicz F , Gabilondo C. Exploring the Use of Natural Language Processing for Objective Assessment of Disorganized Speech in Schizophrenia . Psychiatric Research and Clinical Practice 2023 ; 5: 84–92. ↵ Haas SS , Doucet GE , Garg S , et al. Linking language features to clinical symptoms and multimodal imaging in individuals at clinical high risk for psychosis . Eur Psychiatry 2020 ; 63 : e72 . OpenUrl PubMed ↵ Dwyer K , David AS , McCarthy R , McKenna P , Peters E . Linguistic alignment and theory of mind impairments in schizophrenia patients’ dialogic interactions . Psychological Medicine 2020 ; 50 : 2194 – 202 . OpenUrl PubMed ↵ Thomas P , Leudar I , Newby D , Johnston M . Syntactic processing and written language output in first onset psychosis . Journal of Communication Disorders 1993 ; 26 : 209 – 30 . OpenUrl PubMed Jo YT , Lee J , Park J , Lee J , Joo Y . Linguistic anomalies observed in the Sentence Completion Test in patients with schizophrenia . Cognitive neuropsychiatry 2023 ; 28 . DOI: 10.1080/13546805.2023.2209313 . OpenUrl CrossRef Hoffman RE , Hogben GL , Smith H , Calhoun WF . Message disruptions during syntactic processing in schizophrenia . Journal of Communication Disorders 1985 ; 18 : 183 – 202 . OpenUrl PubMed Ellsworth RB . The regression of schizophrenic language . J Consult Psychol 1951 ; 15 : 387 – 91 . OpenUrl CrossRef PubMed ↵ Gupta T , Hespos SJ , Horton WS , Mittal VA . Automated analysis of written narratives reveals abnormalities in referential cohesion in youth at ultra high risk for psychosis . Schizophr Res 2018 ; 192 : 82 – 8 . OpenUrl PubMed ↵ Ruchsow M , Trippel N , Groen G , Spitzer M , Kiefer M . Semantic and syntactic processes during sentence comprehension in patients with schizophrenia: evidence from event-related potentials . Schizophr Res 2003 ; 64 : 147 – 56 . OpenUrl CrossRef PubMed Web of Science Kuperberg GR , McGuire PK , David AS . Sensitivity to linguistic anomalies in spoken sentences: a case study approach to understanding thought disorder in schizophrenia . Psychol Med 2000 ; 30 : 345 – 57 . OpenUrl CrossRef PubMed Web of Science ↵ Dwyer K , David A , McCarthy R , McKenna P , Peters E . Higher-order semantic processing in formal thought disorder in schizophrenia . Psychiatry Research 2014 ; 216 : 168 – 76 . OpenUrl PubMed ↵ Tan EJ , Meyer D , Neill E , Rossell SL . Investigating the diagnostic utility of speech patterns in schizophrenia and their symptom associations . Schizophr Res 2021 ; 238 : 91 – 8 . OpenUrl CrossRef PubMed He R , Palominos C , Zhang H , Alonso-Sánchez MF , Palaniyappan L , Hinzen W . Navigating the semantic space: Unraveling the structure of meaning in psychosis using different computational language models . Psychiatry Res 2024 ; 333 : 115752 . Takashima A , Ohta K , Matsushima E , Toru M . The event-related potentials elicited by content and function words during the reading of sentences by patients with schizophrenia . Psychiatry Clin Neurosci 2001 ; 55 : 611 – 8 . OpenUrl PubMed ↵ Rossell SL , Batty RA . Elucidating semantic disorganisation from a word comprehension task: do patients with schizophrenia and bipolar disorder show differential processing of nouns, verbs and adjectives? Schizophr Res 2008 ; 102 : 63 – 8 . OpenUrl PubMed ↵ Ciampelli S , de Boer JN , Voppel AE , et al. Syntactic Network Analysis in Schizophrenia-Spectrum Disorders . Schizophrenia Bulletin 2023 ; 49 : S172 – 82 . OpenUrl CrossRef PubMed ↵ Voleti R , Woolridge SM , Liss JM , et al. Language Analytics for Assessment of Mental Health Status and Functional Competency . Schizophrenia Bulletin 2023 ; 49 : S183 – 95 . OpenUrl PubMed ↵ Alqahtani A , Kayi ES , Hamidian S , Compton M , Diab M. A Quantitative and Qualitative Analysis of Schizophrenia Language . In: Lavelli A , Holderness E , Jimeno Yepes A , Minard A-L , Pustejovsky J , Rinaldi F , eds. Proceedings of the 13th International Workshop on Health Text Mining and Information Analysis (LOUHI). Abu Dhabi, United Arab Emirates (Hybrid): Association for Computational Linguistics , 2022 : 173 – 83 . Zhang H , Parola A , Zhou Y , et al. Linguistic markers of psychosis in Mandarin Chinese: Relations to theory of mind . Psychiatry Research 2023 ; 325 : 115253 . ↵ Wiltschko M . Is grammar affected in Schizophrenia? Psychiatry Research 2024 ; 339 : 116061 . ↵ DeLisi LE , Sakuma M , Kushner M , Finer DL , Hoff AL , Crow TJ . Anomalous cerebral asymmetry and language processing in schizophrenia . Schizophr Bull 1997 ; 23 : 255 – 71 . OpenUrl CrossRef PubMed ↵ Thomas P , King K , Fraser WI , Kendell RE . Linguistic performance in schizophrenia: a comparison of acute and chronic patients . Br J Psychiatry 1990 ; 156 : 204 – 10 , 214–5. OpenUrl Abstract / FREE Full Text ↵ Leucht S , Samara M , Heres S , Davis JM . Dose Equivalents for Antipsychotic Drugs: The DDD Method . Schizophr Bull 2016 ; 42 : S90 – 4 . OpenUrl CrossRef PubMed ↵ Dalal TC , Liang L , Silva AM , Mackinley M , Voppel A , Palaniyappan L . Speech based natural language profile before, during and after the onset of psychosis: A cluster analysis . Acta Psychiatrica Scandinavica 2024 ; n/a . DOI:10.1111/acps.13685. ↵ Silva AM , Limongi R , MacKinley M , Ford SD , Alonso-Sánchez MF , Palaniyappan L . Syntactic complexity of spoken language in the diagnosis of schizophrenia: A probabilistic Bayes network model . Schizophr Res 2023 ; 259 : 88 – 96 . OpenUrl PubMed ↵ de Boer JN , Voppel AE , Brederoo SG , Wijnen FNK , Sommer IEC. Language disturbances in schizophrenia: the relation with antipsychotic medication . npj Schizophrenia 2020 ; 6 : 1 – 9 . OpenUrl PubMed ↵ de Boer JN , van Hoogdalem M , Mandl RCW , et al. Language in schizophrenia: relation with diagnosis, symptomatology and white matter tracts . npj Schizophrenia 2020 ; 6 : 1 – 10 . OpenUrl PubMed ↵ Obrębska M . Frequency analysis of singular first-person pronouns and verbs in the utterances of schizophrenia patients and healthy controls: A research report . Lingua Posnaniensis 2013 ; 55 : 87 – 98 . OpenUrl ↵ Obrębska M , Kleka P . Lexical indicators of anxiety in schizophrenia . Anxiety, Stress, & Coping 2023 ; 36 : 382 – 97 . OpenUrl PubMed ↵ Morice RD , Ingram JCL . Language complexity and age of onset of schizophrenia . Psychiatry Research 1983 ; 9 : 233 – 42 . OpenUrl CrossRef PubMed Web of Science ↵ Thomas P. , Kearney G. , Napier E. , Ellis E. , Leudar I. , Johnston M . Speech and language in first onset psychosis differences between people with schizophrenia, mania, and controls . BR J PSYCHIATRY 1996 ; 168 : 337 – 43 . OpenUrl Abstract / FREE Full Text ↵ Thomas P , Leudar I , Napier E , et al. Syntactic Complexity and Negative Symptoms in First Onset Schizophrenia . Cognitive Neuropsychiatry 1996 ; 1 : 191 – 200 . OpenUrl PubMed ↵ Lee CW , Kim SH , Shim M , et al. P600 alteration of syntactic language processing in patients with bipolar mania: Comparison to schizophrenic patients and healthy subjects . Journal of Affective Disorders 2016 ; 201 : 101 – 11 . OpenUrl PubMed ↵ Morgan SE , Diederen K , Vértes PE , et al. Natural Language Processing markers in first episode psychosis and people at clinical high-risk . Transl Psychiatry 2021 ; 11 : 630 . ↵ Stephane M , Pellizzer G , Fletcher CR , McClannahan K . Empirical evaluation of language disorder in schizophrenia . J Psychiatry Neurosci 2007 ; 32 : 250 – 8 . OpenUrl PubMed ↵ Ziv I. , Baram H. , Bar K. , et al. Morphological characteristics of spoken language in schizophrenia patients - an exploratory study . Scand J Psychol 2022 ; 63 : 91 – 9 . OpenUrl PubMed ↵ Condray R , van Kammen DP , Steinhauer SR , Kasparek A , Yao JK . Language comprehension in schizophrenia: Trait or state indicator? Biological Psychiatry 1995 ; 38 : 287 – 96 . OpenUrl CrossRef PubMed Web of Science ↵ Li R , Cao M , Fu D , et al. Deciphering language disturbances in schizophrenia: A study using fine-tuned language models . Schizophrenia Research 2024 ; 271 : 120 – 8 . OpenUrl PubMed ↵ Shi J , Luo D , Weng H , et al. Optimally estimating the sample standard deviation from the five-number summary . Res Synth Methods 2020 ; 11 : 641 – 54 . OpenUrl PubMed ↵ Wells G , Shea B , O’Connell D , et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses . https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp . ↵ Luchini C , Stubbs B , Solmi M , Veronese N . Assessing the quality of studies in meta- analyses: Advantages and limitations of the Newcastle Ottawa Scale . World Journal of Meta-Analysis 2017 ; 5 : 80 – 4 . OpenUrl CrossRef ↵ Hartling L , Milne A , Hamm MP , et al. Testing the Newcastle Ottawa Scale showed low reliability between individual reviewers . Journal of Clinical Epidemiology 2013 ; 66 : 982 – 93 . OpenUrl CrossRef PubMed ↵ Stang A . Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses . Eur J Epidemiol 2010 ; 25 : 603 – 5 . OpenUrl CrossRef PubMed Web of Science ↵ JASP Team . JASP (Version 0.19.0). 2024 . https://jasp-stats.org/ . ↵ Berkhout SW , Haaf JM , Gronau QF , Heck DW , Wagenmakers E-J . A tutorial on Bayesian model-averaged meta-analysis in JASP . Behav Res 2024 ; 56 : 1260 – 82 . OpenUrl ↵ Bartoš F , Maier M , Quintana DS , Wagenmakers E-J . Adjusting for Publication Bias in JASP and R: Selection Models , PET-PEESE, and Robust Bayesian Meta-Analysis. Advances in Methods and Practices in Psychological Science 2022 ; 5 : 25152459221109259 . ↵ Senior AM , Viechtbauer W , Nakagawa S . Revisiting and expanding the meta-analysis of variation: The log coefficient of variation ratio . Res Synth Methods 2020 ; 11 : 553 – 67 . OpenUrl CrossRef PubMed ↵ Anand A , Wales RJ , Jackson HJ , Copolov DL . Linguistic impairment in early psychosis . J Nerv Ment Dis 1994 ; 182 : 488 – 93 . OpenUrl CrossRef PubMed Web of Science Arslan B , Kizilay E , Verim B , et al. Computational analysis of linguistic features in speech samples of first-episode bipolar disorder and psychosis . J Affect Disord 2024 ; 363 : 340 – 7 . OpenUrl PubMed Bagner DM , Melinder MRD , Barch DM . Language comprehension and working memory language comprehension and working memory deficits in patients with schizophrenia . Schizophr Res 2003 ; 60 : 299 – 309 . OpenUrl PubMed Web of Science Barattieri di San Pietro C , Barbieri E , Marelli M , de Girolamo G , Luzzatti C. Processing Argument Structure and Syntactic Complexity in People with Schizophrenia Spectrum Disorders . J Commun Disord 2022 ; 96 : 106182. Barrera A , McKENNA PJ , Berrios GE . Formal thought disorder in schizophrenia: an executive or a semantic deficit? Psychological Medicine 2005 ; 35 : 121 – 32 . OpenUrl CrossRef PubMed Buck B , Penn DL . Lexical characteristics of emotional narratives in schizophrenia: Relationships with symptoms, functioning, and social cognition . J Nerv Ment Dis 2015 ; 203 : 702 – 8 . OpenUrl PubMed Çabuk T , Sevim N , Mutlu E , Yağcıoğlu AEA , Koç A , Toulopoulou T . Natural language processing for defining linguistic features in schizophrenia: A sample from Turkish speakers . Schizophr Res 2024 ; 266 : 183 – 9 . OpenUrl PubMed ↵ Chaves MF , Rodrigues C , Ribeiro S , Mota NB , Copelli M . Grammatical impairment in schizophrenia: An exploratory study of the pronominal and sentential domains . PLOS ONE 2023 ; 18 : e0291446 . OpenUrl PubMed ↵ Çokal D , Sevilla G , Jones WS , et al. The language profile of formal thought disorder . npj Schizophrenia 2018 ; 4 : 1 – 8 . OpenUrl PubMed ↵ Çokal D , Zimmerer V , Varley R , Watson S , Hinzen W . Comprehension of Embedded Clauses in Schizophrenia With and Without Formal Thought Disorder . J Nerv Ment Dis 2019 ; 207 : 384 – 92 . OpenUrl PubMed ↵ Delvecchio G , Caletti E , Perlini C , et al. Altered syntactic abilities in first episode patients: An inner phenomenon characterizing psychosis . European Psychiatry 2019 ; 61 : 119 – 26 . OpenUrl PubMed ↵ Fraser WI , King KM , Thomas P , Kendell RE . The diagnosis of schizophrenia by language analysis . Br J Psychiatry 1986 ; 148 : 275 – 8 . OpenUrl Abstract / FREE Full Text Gargano G , Caletti E , Perlini C , et al. Language production impairments in patients with a first episode of psychosis . PLOS ONE 2022 ; 17 : e0272873 . OpenUrl PubMed King K , Fraser WI , Thomas P , Kendell RE . Re-examination of the language of psychotic subjects . Br J Psychiatry 1990 ; 156 : 211 – 5 . OpenUrl Abstract / FREE Full Text ↵ Kircher TTJ , Oh TM , Brammer MJ , McGuire PK . Neural correlates of syntax production in schizophrenia . The British Journal of Psychiatry 2005 ; 186 : 209 – 14 . OpenUrl Abstract / FREE Full Text Kuperberg GR , Kreher DA , Goff D , McGuire PK , David AS . Building up linguistic context in schizophrenia: evidence from self-paced reading . Neuropsychology 2006 ; 20 : 442 – 52 . OpenUrl PubMed ↵ Kuperberg GR , Sitnikova T , Goff D , Holcomb PJ . Making sense of sentences in schizophrenia: electrophysiological evidence for abnormal interactions between semantic and syntactic processing . J Abnorm Psychol 2006 ; 115 : 251 – 65 . OpenUrl CrossRef PubMed ↵ Liang L , Silva AM , Jeon P , et al. Widespread cortical thinning, excessive glutamate and impaired linguistic functioning in schizophrenia: A cluster analytic approach . Frontiers in Human Neuroscience 2022 ; 16 . ↵ Morice R , McNicol D . The comprehension and production of complex syntax in schizophrenia . Cortex 1985 ; 21 : 567 – 80 . OpenUrl CrossRef PubMed Web of Science Moro A , Bambini V , Bosia M , et al. Detecting syntactic and semantic anomalies in schizophrenia . Neuropsychologia 2015 ; 79 : 147 – 57 . OpenUrl PubMed Özcan A , Kuruoglu G , Alptekin K , et al. The Production of Simple Sentence Structures in Schizophrenia . International Journal of Arts & Sciences 2016 ; 9 : 159 – 64 . OpenUrl ↵ Panikratova YaR , Vlasova RM , Akhutina TV , Tikhonov DV , Pluzhnikov IV , Kaleda VG . Executive Regulation of Speech Production in Schizophrenia: A Pilot Neuropsychological Study . Neurosci Behav Physi 2021 ; 51 : 415 – 22 . OpenUrl Perlini C. , Marini A. , Fabbro F. , et al. Linguistic production and comprehension deficits in schizophrenia and bipolar disorder . Eur Psychiatry 2010 ; 25 . DOI: 10.1016/S0924-9338%2810%2971073-7 . OpenUrl CrossRef Sanders LM , Adams J , Tager-Flusberg H , Shenton ME , Coleman M . A comparison of clinical and linguistic indices of deviance in the verbal discourse of schizophrenics . Applied Psycholinguistics 1995 ; 16 : 325 – 38 . OpenUrl Schneider K , Leinweber K , Jamalabadi H , et al. Syntactic complexity and diversity of spontaneous speech production in schizophrenia spectrum and major depressive disorders . Schizophr 2023 ; 9 : 1 – 10 . OpenUrl CrossRef Sevilla G , Rosselló J , Salvador R , et al. Deficits in nominal reference identify thought disordered speech in a narrative production task . PLOS ONE 2018 ; 13 : e0201545 . OpenUrl PubMed ↵ Shedlack K , Lee G , Sakuma M , et al. Language processing and memory in ill and well siblings from multiplex families affected with schizophrenia . Schizophr Res 1997 ; 25 : 43 – 52 . OpenUrl CrossRef PubMed ↵ Stirling J , Hellewell J , Blakey A , Deakin W . Thought disorder in schizophrenia is associated with both executive dysfunction and circumscribed impairments in semantic function . Psychol Med 2006 ; 36 : 475 – 84 . OpenUrl CrossRef PubMed Web of Science Tan EJ , Yelland GW , Rossell SL . Characterising receptive language processing in schizophrenia using word and sentence tasks . Cogn Neuropsychiatry 2016 ; 21 : 14 – 31 . OpenUrl PubMed Tang SX , Kriz R , Cho S , et al. Natural language processing methods are sensitive to sub- clinical linguistic differences in schizophrenia spectrum disorders . npj Schizophr 2021 ; 7 : 1 – 8 . OpenUrl CrossRef PubMed ↵ Tavano A , Sponda S , Fabbro F , et al. Specific linguistic and pragmatic deficits in Italian patients with schizophrenia . Schizophrenia Research 2008 ; 102 : 53 – 62 . OpenUrl CrossRef PubMed ↵ Condray R , Steinhauer SR , van Kammen DP , Kasparek A . The Language System in Schizophrenia: Effects of Capacity and Linguistic Structure . Schizophrenia Bulletin 2002 ; 28 : 475 – 90 . OpenUrl PubMed Web of Science ↵ Vogel AP , Chenery HJ , Dart CM , Doan B , Tan M , Copland DA . Verbal fluency, semantics, context and symptom complexes in schizophrenia . J Psycholinguist Res 2009 ; 38 : 459 – 73 . OpenUrl CrossRef PubMed ↵ Cokal D. , Sevilla G. , Jones W.S. , et al. The language profile of formal thought disorder . NPJ Schizophr 2018 ; 4 : 18 . Çokal D , Palominos-Flores C , Yalınçetin B , Türe-Abacı Ö , Bora E , Hinzen W . Referential noun phrases distribute differently in Turkish speakers with schizophrenia . Schizophr Res 2023 ; 259 : 104 – 10 . OpenUrl PubMed ↵ Cokal D. , Zimmerer V. , Varley R. , Watson S. , Hinzen W . Comprehension of embedded clauses in schizophrenia with and without formal thought disorder . J Nerv Ment Dis 2019 ; 207 : 384 – 92 . OpenUrl PubMed ↵ Howes OD , Chapman GE . Understanding variability: the role of meta-analysis of variance . Psychological Medicine 2024 ; : 1 – 4 . ↵ Rodriguez-Ferrera S , McCARTHY RA , McKENNA PJ . Language in schizophrenia and its relationship to formal thought disorder . Psychological Medicine 2001 ; 31 : 197 – 205 . OpenUrl CrossRef PubMed ↵ Bedi G , Carrillo F , Cecchi GA , et al. Automated analysis of free speech predicts psychosis onset in high-risk youths . npj Schizophrenia 2015 ; 1 : 1 – 7 . OpenUrl ↵ Bayer JMM , Spark J , Krcmar M , et al. The SPEAK study rationale and design: A linguistic corpus-based approach to understanding thought disorder . Schizophr Res 2023 ; 259 : 80 – 7 . OpenUrl PubMed ↵ Poirier S-È , Fossard M , Monetta L . The efficacy of treatments for sentence production deficits in aphasia: a systematic review . Aphasiology 2023 ; 37 : 122 – 42 . OpenUrl ↵ Rochon E , Laird L , Bose A , Scofield J . Mapping therapy for sentence production impairments in nonfluent aphasia . Neuropsychol Rehabil 2005 ; 15 : 1 – 36 . OpenUrl PubMed ↵ Roque-Gutierrez E , Ibbotson P . Working memory training improves children’s syntactic ability but not vice versa: A randomized control trial . J Exp Child Psychol 2023 ; 227 : 105593 . ↵ Fedorenko E , Blank IA , Siegelman M , Mineroff Z . Lack of selectivity for syntax relative to word meanings throughout the language network . Cognition 2020 ; 203 : 104348 . Mollica F , Siegelman M , Diachek E , et al. Composition is the Core Driver of the Language- selective Network . Neurobiology of Language 2020 ; 1 : 104 – 34 . OpenUrl PubMed ↵ Fedorenko E , Blank IA , Siegelman M , Mineroff Z . Lack of selectivity for syntax relative to word meanings throughout the language network . Cognition 2020 ; 203 : 104348 . ↵ Bambini V , Frau F , Bischetti L , et al. Deconstructing heterogeneity in schizophrenia through language: a semi-automated linguistic analysis and data-driven clustering approach . Schizophr 2022; 8: 1 – 12 . ↵ Oomen PP , de Boer JN , Brederoo SG , et al. Characterizing speech heterogeneity in schizophrenia-spectrum disorders . J Psychopathol Clin Sci 2022 ; 131 : 172 – 81 . OpenUrl CrossRef PubMed ↵ Schaefer J , Giangrande E , Weinberger DR , Dickinson D . The global cognitive impairment in schizophrenia: Consistent over decades and around the world . Schizophrenia research 2013 ; 150 : 42 . View the discussion thread. Back to top Previous Next Posted October 27, 2024. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Syntax and Schizophrenia: A meta-analysis of comprehension and production Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Syntax and Schizophrenia: A meta-analysis of comprehension and production Dalia Elleuch , Yinhan Chen , Qiang Luo , Lena Palaniyappan medRxiv 2024.10.26.24316171; doi: https://doi.org/10.1101/2024.10.26.24316171 Share This Article: Copy Citation Tools Syntax and Schizophrenia: A meta-analysis of comprehension and production Dalia Elleuch , Yinhan Chen , Qiang Luo , Lena Palaniyappan medRxiv 2024.10.26.24316171; doi: https://doi.org/10.1101/2024.10.26.24316171 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Psychiatry and Clinical Psychology Subject Areas All Articles Addiction Medicine (573) Allergy and Immunology (865) Anesthesia (303) Cardiovascular Medicine (4457) Dentistry and Oral Medicine (445) Dermatology (383) Emergency Medicine (610) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1517) Epidemiology (15244) Forensic Medicine (30) Gastroenterology (1132) Genetic and Genomic Medicine (6619) Geriatric Medicine (669) Health Economics (1002) Health Informatics (4556) Health Policy (1372) Health Systems and Quality Improvement (1614) Hematology (543) HIV/AIDS (1271) Infectious Diseases (except HIV/AIDS) (15934) Intensive Care and Critical Care Medicine (1106) Medical Education (624) Medical Ethics (147) Nephrology (670) Neurology (6634) Nursing (346) Nutrition (999) Obstetrics and Gynecology (1148) Occupational and Environmental Health (957) Oncology (3348) Ophthalmology (980) Orthopedics (369) Otolaryngology (421) Pain Medicine (436) Palliative Medicine (130) Pathology (665) Pediatrics (1696) Pharmacology and Therapeutics (693) Primary Care Research (714) Psychiatry and Clinical Psychology (5463) Public and Global Health (9255) Radiology and Imaging (2210) Rehabilitation Medicine and Physical Therapy (1371) Respiratory Medicine (1197) Rheumatology (598) Sexual and Reproductive Health (716) Sports Medicine (532) Surgery (714) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a030cc7ae8545f95',t:'MTc4MDAwODQyMQ=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();