Natural Language Processing and Schizophrenia: A Scoping Review of Uses and Challenges

(1) Background: Approximately 1% of the global population is affected by schizophrenia, a disorder marked by cognitive deficits, delusions, hallucinations, and language issues. It is associated with genetic, neurological, and environmental factors, and linked to dopaminergic hyperactivity and neurotransmitter imbalances. Recent research reveals that patients exhibit significant language impairments, such as reduced verbal output and fluency. Advances in machine learning and natural language processing show potential for early diagnosis and personalized treatments, but additional research is required for the practical application and interpretation of such technology. The objective of this study is to explore the applications of natural language processing in patients diagnosed with schizophrenia. (2) Methods: A scoping review was conducted across multiple electronic databases, including Medline, PubMed, Embase, and PsycInfo. The search strategy utilized a combination of text words and subject headings, focusing on schizophrenia and natural language processing. Systematically extracted information included authors, population, primary uses of the natural language processing algorithms, main outcomes, and limitations. The quality of the identified studies was assessed. (3) Results: A total of 516 eligible articles were identified, from which 478 studies were excluded based on the first analysis of titles and abstracts. Of the remaining 38 studies, 18 were selected as part of this scoping review. The following six main uses of natural language processing were identified: diagnostic and predictive modeling, followed by specific linguistic phenomena, speech and communication analysis, social media and online content analysis, clinical and cognitive assessment, and linguistic feature analysis. (4) Conclusions: This review highlights the main uses of natural language processing in the field of schizophrenia and the need for more studies to validate the effectiveness of natural language processing in diagnosing and treating schizophrenia.


Introduction
Schizophrenia, a psychiatric disorder affecting approximately 1% of the global population, is marked by cognitive impairments, hallucinations, delusions, thought disorders, behavioral changes, and negative symptoms persisting most of the time for at least six months [1][2][3].Lack of drive, a lowered capacity for pleasure, and a limited ability to express emotions are examples of the negative symptoms of schizophrenia that can seriously impede day-to-day functioning and quality of life [2,3].These symptoms frequently show up as social disengagement, apathy, and a reduction in speech, which makes it difficult for the affected person to participate in daily activities or uphold relationships [2,3].Current research into hallucinations and delusions suggests that these altered perceptions of reality are linked to dopaminergic hyperactivation in the mesolimbic system [4][5][6].Schizophrenia frequently causes cognitive impairment that includes severe deficiencies in several areas, including language [7,8].Various genetic, neurological, and environmental variables are understood to induce cognitive impairment in individuals with schizophrenia [9].A person's genetic predisposition is important because different genes influence how the brain develops and functions [10].Neural pathways essential for cognitive functions are disturbed by neurotransmitter dysregulation, especially when it comes to dopamine and glutamate [11].Cognitive deficiencies are also influenced by functional brain abnormalities such as hypo-frontality and poor connection, as well as structural brain abnormalities such as lower gray matter volume in important locations such as the hippocampus and prefrontal cortex, as observed in schizophrenia [12,13].Neurodevelopmental variables are also very important; these include problems in pregnancy and early childhood that are caused by infections in the mother, starvation, and stress [14].Additionally, environmental stresses like early-life trauma, social adversity, and substance addiction increase impairments in cognition caused by inflammation and oxidative stress, which can harm brain cells and are thought to be risk factors of psychotic disorders such as schizophrenia [15,16].
Recent studies have highlighted significant language deficits in patients diagnosed with schizophrenia, providing a deeper understanding of the nuances of these impairments [17].Generally, individuals with schizophrenia demonstrate lower verbal productivity, evident in their production of fewer total words and reduced lexical diversity [18].This is often accompanied by lower verbal fluency, characterized by frequent pauses, hesitations, and difficulties in maintaining a smooth flow of speech [18,19].These disruptions in fluency can manifest as prolonged silences or repetitive non-communicative sounds, which contribute to the overall communication difficulties faced by these patients [20].For example, these individuals frequently exhibit disjointed and fragmented speech patterns, where their discourse lacks logical organization and coherence [18][19][20].This can result in abrupt topic shifts, inconsistent use of words, and difficulty in maintaining a clear narrative structure.Such semantic incoherence not only impairs effective communication but also reflects the underlying cognitive disorganization associated with schizophrenia [20].Recent cross-linguistic research has corroborated these findings, extending the validity of language biomarkers beyond English-speaking populations [21].Studies conducted in diverse linguistic and cultural contexts, including Spanish-, Italian-, Dutch-, and Portuguese-speaking communities, have consistently identified similar language impairments [22].These findings highlight the universality of language deficits in schizophrenia, suggesting that, despite linguistic and cultural variations, the core features of language impairment remain consistent.
Developments in machine learning and natural language processing have made it easier to create predictive models that can accurately distinguish between healthy individuals and patients with schizophrenia [23,24].The definition of natural language processing is imprecise, as it broadly encompasses various computational techniques for analyzing and synthesizing human language but lacks a universally agreed-upon scope or detailed boundaries for its applications and methodologies [25].As such, in the context of artificial intelligence, natural language processing is the interdisciplinary study that focuses on the communication between computers and human languages [25].It entails the creation of models and algorithms that let computers comprehend, interpret, produce, and react to human language in a meaningful and practical way [25,26].Typical examples of natural language processing cover a wide range of activities, such as text production, sentiment analysis, speech recognition, and language translation [27].These models, for example, can attempt to predict the evolution from acute psychosis to chronic schizophrenia [28].Such use of natural language processing could lead to early diagnosis and tailored treatment plans, but recent literature in this field agrees that more study is required to improve the models' clinical applicability and interpretability.Considering the vast array of applications and uses of natural language processing and the potential uses of language as a biomarker in schizophrenia, there is a need to have a comprehensive literature review on the subject.
The objective of this study is to explore the applications of natural language processing in patients diagnosed with schizophrenia.A secondary aim is to assess the efficacy and limitations of these applications.It is hypothesized that the existing literature on this topic is relatively poor.Given the increasing research focus on predictive modeling using artificial intelligence algorithms, it is anticipated that the predominant application of NLP will be in predicting the progression of the disease.Additionally, due to the novel nature of these methodologies, it is hypothesized that their effectiveness remains under-researched and limited in terms of clinical interpretation and application [29].

Search Strategies
This review adhered to the standardized Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for scoping reviews.A comprehensive scoping search was undertaken to identify recent studies across multiple electronic databases, including Medline, PubMed, Embase, and PsycInfo, covering the period from 2008 to 2023, as they are the main databases related to psychiatric research.The last 15 years was selected as the timeframe to encompass solely recent developments in the field of natural language processing.The search strategy utilized a combination of text words and subject headings, focusing on schizophrenia (e.g., schizophrenia, schizophrenic) and natural language processing (e.g., natural language processing, semantic analysis), ensuring alignment with the study's objectives.Detailed search strategies can be found in Supplementary Material S1.The search methodology was expertly developed by an experienced librarian specialized in psychiatry (MD), and the searches were cross-validated using the Peer Review of Electronic Search Strategies (PRESS).No restrictions were applied regarding setting or geography, ensuring a comprehensive and unbiased search.

Study Eligibility
Studies were selected based on the following inclusion criteria: (1) the population of interest comprised patients diagnosed or research focused on schizophrenia or schizoaffective disorders; (2) the study utilized a natural language processing approach; (3) the natural language processing was applied to target a specific outcome.Studies were included regardless of whether they employed a single algorithm or multiple algorithms.Excluded from consideration were unpublished literature and studies employing artificial intelligence algorithms beyond the scope of natural language processing.The search was restricted to sources available in English and French.

Data Extraction
Data extraction was conducted using a standardized form in Microsoft Excel and was independently verified for consistency and integrity by two authors (A.D., A.H.).Any disagreements regarding the inclusion or exclusion of studies were resolved through mutual consensus.The systematically extracted information included authors, population (sample), primary uses (or intent) of the natural language processing algorithms, main outcomes, and limitations.

Quality Assessment
The quality assessment of the identified studies was carried out using the Newcastle-Ottawa Scale (NOS) for nonrandomized controlled studies and the Cochrane Risk of Bias Tool for randomized controlled trials [30,31].The NOS is designed to evaluate cohort and case-control studies across the following three key areas: the selection of study groups, the comparability of these groups, and the ascertainment of either exposure or outcome [30].Each area comprises specific criteria, and studies receive star ratings based on how well they meet these criteria, with a maximum score of nine stars indicating the highest quality [30].
For randomized controlled trials, the Cochrane Risk of Bias Tool provides a thorough framework to determine potential biases.This tool assesses the following seven domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, handling of incomplete outcome data, selective reporting, and other potential sources of bias [31].Each domain is rated as a low, high, or unclear risk of bias according to set criteria.
In this literature review, studies were categorized by the authors based on their quality ratings.Those scoring 1-4 stars on the Newcastle-Ottawa Scale were identified as having a high risk of bias by the Cochrane tool were considered low quality.Studies with 4-6 stars were rated as moderate quality, while those achieving 7-9 stars or a low risk of bias were deemed of high quality.

Description of Identified Studies
The scoping review assessed studies at the intersection of schizophrenia and natural language processing.Initially, 516 eligible articles were identified after removing duplicates (n = 659).A total of 478 studies were excluded based on the first analysis of titles and abstracts, as they did not meet inclusion criteria.After a second round of abstract screening, 38 full-text articles were thoroughly evaluated, resulting in 20 exclusions.This left 18 studies for detailed analysis.A flowchart illustrating the inclusion process is provided in Figure 1, and specific details of the included studies are available in Table 1.The studies that met the inclusion criteria utilized natural language processing in various ways, with the most common applications being diagnostic and predictive modeling (n = 6), followed by specific linguistic phenomena (n = 3), speech and communication analysis (n = 3), social media and online content analysis (n = 3), clinical and cognitive assessment (n = 2), and linguistic feature analysis (n = 1).

Diagnostic and Predictive Modeling
Using an individually trained algorithm, prediction models showed a high correlation (up to 0.78) between predicted and actual clinical states based on providers' global assessment ratings.There was little correlation between individuals regarding which speech features correlated with their clinical state, suggesting that word choice patterns related to mental illness/wellness may be specific to individuals.Both population-based and individualized approaches can inform computational methods using behavioral markers.Statistically significant correlations were found between the model and actual scores for the summary, depression, and self-harm sub-scores of the BASIS-24, and the mental health sub-score of the SF-12.No significant correlations were found for four of the six BASIS-24 sub-scores or the physical health sub-score of the SF-12.
Variability and subjectivity in global assessment ratings due to clinician differences, a small sample size that does not account for participant characteristics, an inability to determine the strengths or weaknesses of features and algorithms for symptom-specific states or differences compared to healthy volunteers, and a predictive model that does not significantly predict the physical health subscale.

Speech and Communication Analysis
FEP patients show significant deficits in micro-level speech production, including intraphrasal discourse construction.They use fewer lexical fillers, have a lower speech rate, and shorter utterances compared to HCs.Their narratives have a lower percentage of syntactic completeness.Both affective and non-affective FEP patients exhibit significant impairments in speech rate and mean length of utterances compared to HCs, indicating that all psychotic patients have some impairment in productive aspects of phrasal construction.No significant difference was found between FEP-NA and FEP-A in language production.FEP patients performed worse than controls on neuropsychological tasks (verbal IQ, n-back, SOA).The model using only language production variables had a prediction accuracy of 76.36%.Machine learning results showed that GAF alone predicted FEP and HC groups with a 97.90% accuracy, while neuropsychological measures had a predictive power of 99% The study has several limitations: all of the participants were outpatients with only moderate impairment (GAF scores), no significant differences in language production impairments between FEP-A and FEP-NA were found, differences in sample sizes between FEP-A and FEP-NA (38

Diagnostic and Predictive Modeling
The search approach identified a total of six studies that discussed the use of natural language processing for predictive and diagnostic modeling.In their study, Figueroa-Barra and colleagues analyzed 30 language variables from recorded interviews to perform an automated language analysis on 133 Spanish-speaking respondents, including healthy controls, patients with first-episode psychosis, and patients with persistent schizophrenia [34].Their longitudinal analysis, which was mainly based on semantic coherence information, predicted the diagnosis of schizophrenia in first-episode psychosis patients with a 77.5% accuracy [34].Their cross-sectional analysis demonstrated that language features could distinguish with an 85.9% accuracy between healthy controls and patients diagnosed with schizophrenia [34].
In another study, Voppel and colleagues used acoustic and semantic data taken from semi-structured interviews to assess speech from 94 people with schizophrenia spectrum disorders and 73 healthy controls [35].In comparison to individual classifiers for acoustic (81% accuracy) and semantic (80% accuracy) features, the combined machine learning classifier-which combined acoustic and semantic features-achieved an 85% accuracy in differentiating schizophrenia spectrum disorder from healthy controls [35].This suggests that combining these domains captures complementary aspects of speech affected by schizophrenia spectrum disorder.
Additionally, a study assessed the feasibility of gathering speech samples from 47 individuals with severe mental illness over a period of 4-14 months using a mobile intervention called MyCoachConnect, and then evaluating lexical and acoustic aspects to follow clinical states [36].Their findings demonstrated that, when compared to provider global assessment ratings, individually trained models had a strong correlation (rho = 0.78, p < 0.001), suggesting the potential value of speech features as objective markers for tracking mental health conditions like schizophrenia in a community-based clinical setting [36].Similarly, Bedi and her colleagues used baseline interviews to extract syntactic and semantic data from 34 young people who were clinically at high risk of psychosis through automated speech analysis [37].With a 100% accuracy, the analysis predicted the onset of psychosis later, outperforming conventional clinical assessments by a significant margin [37].Additionally, it showed a correlation between prodromal symptoms and speech features, indicating the potential value of automated speech analysis as a tool for early psychosis detection [37].Another study collected 22 speech samples and correlated linguistic aspects with clinical assessments of psychotic symptoms in order to investigate the use of natural language processing to detect disorganized speech in seven hospitalized schizophrenia patients [38].The findings showed that, whereas lower content density and more repetitions predicted good symptoms, reduced lexical richness and syntactic complexity were suggestive of negative symptoms [38].The authors concluded that natural language processing has the capacity to quantify psychotic symptoms objectively in acute clinical settings, as demonstrated by their machine learning models that can accurately predict symptom severity up to 82% of the time [38].
Lastly, a recent study by Rezaii and colleagues used machine learning to assess the latent content and semantic density of speech from 40 individuals who were clinically high risk for psychosis [39].They did this by comparing the speech content with a sizable corpus and measuring semantic richness using vector unpacking.It is possible for these speech characteristics to be reliable predictors of future psychosis, as evidenced by the 93% accuracy with which the combination of poor semantic density and higher discussion about voices and sounds predicted conversion to psychosis in the training set and 90% in the holdout set [39].
The quality of the identified studies for the use of natural language processing ranged from moderate to high, with the main limitation being the small sample sizes used to train the models.

Specific Linguistic Phenomena
Three studies emphasized how particular linguistic occurrences might be extracted through natural language processing to gain a better understanding of the characteristics of schizophrenia or diseases resembling schizophrenia.In one of the studies that was found, machine learning algorithms were used to compare the syntactic and semantic analysis of speech during interviews in 70 adolescents, 35 of whom had prodromal psychosis and the remaining 35 were healthy controls [44].There were notable variations between the two groups, with the prodromal group using fewer nouns, pronouns, conjunctions, adjectives, prepositions, and proper nouns, as well as less coherence overall [44].The authors support that these findings could serve as indicators for the early detection of psychosis.In another study, Parola and colleagues used a decision tree model to uncover characteristics that differentiate the two groups of 67 participants, 32 with schizophrenia and 35 healthy controls, by applying a multimodal assessment of communicative-pragmatic abilities [45].Linguistic irony and breaking Gricean maxims emerged as the most significant aspects of the 82%-accurate model, indicating that these pragmatic deficiencies are important markers of schizophrenia [45].Lastly, a different study including a bigger sample size examined how well 228 patients with first-episode psychosis, including those with affective and non-affective psychosis, and 70 healthy controls understood nonliteral language [46].The study's authors found that, particularly in open-ended tasks, patients with affective and non-affective psychosis performed worse than healthy controls when it came to comprehending metaphors and idioms [46].They also suggested that deficiencies in nonliteral language comprehension could be an early indicator of psychosis.
The quality of the phenomena identified for this use also ranged from moderate to high.The main limitations included the small sample sizes and the heterogeneity of clinical profiles of the patients diagnosed with schizophrenia.

Speech and Communication Analysis
Another primary usage that the literature search revealed was the analysis of speech content.Such use was reported in three investigations.The first study that was found assessed the test-retest reliability and generalizability of automated speech organization and content measures in 47 people over a one-year period and 101 participants with schizophrenia over a six-month period [47].The results demonstrated that speech organization measures had fair-to-good reliability, while speech content measures had fair reliability.Moreover, there were notable differences in speech indices according to education, income, and race, underscoring the necessity of taking demographic factors into account when using these automated measures [47].The second study used video "selfies" to evaluate the validity and reliability of natural language processing metrics to diagnose paranoia in 35 patients with bipolar disorder or schizophrenia over the course of a week [48].The integrated measure of paranoia showed strong convergent validity and test-retest reliability, but it also indicated demographic biases, with female and white subjects showing higher criterion validity [48].Finally, a study by Gargano and colleagues employed a systematic procedure to assess the micro-(lexicon, morphology, syntax) and macro-linguistic (discourse coherence, pragmatics) levels of the narrative discourse in 133 patients with first-episode psychosis (95 non-affective, 38 affective) and 133 healthy controls [49].With a machine learning model achieving a 76.36% accuracy in classifying first-episode psychosis patients versus healthy controls based on micro-and macro-linguistic levels, the results highlighted the utility of language features as potential diagnostic markers [49].The patients' significant language production deficits were found in both micro-and macro-linguistic domains.The studies identified for this use were of high quality, also reporting small sample sizes and that natural language processing approaches are time-consuming.

Social Media and Online Content Analysis
Three of the identified studies concerned content analysis of social media posts.A systematic review that focused on 7 out of 93 studies that were found to meet the inclusion criteria examined the use of social media data in conjunction with artificial intelligence natural language processing algorithms to diagnose and track psychotic illnesses [41].Their research revealed that, although social media data show promise for diagnosing and tracking schizophrenia, the studies' quality varied and they encountered issues like small sample sizes and restricted access to clinical diagnostic data, which made more research with better methodologies necessary to fully realize these tools' potential [41].
The second study found in the literature review collected 60,009 posts from the Reddit subreddit dedicated to schizophrenia and 425,341 posts from six other subreddits related to non-mental health issues [42].The study employed machine learning to identify schizophrenia from the social media material.The potential of social media analysis for the detection of schizophrenia is highlighted by the random forest algorithm's 96% accuracy in identifying posts linked to the disorder [42].Significant linguistic markers, such as an increase in the use of third-person plural pronouns and words that convey negative emotions, were also identified.Similarly, the last study for this use analyzed Twitter (now X) data from 671 users who self-disclosed their illness to uncover social media signs of schizophrenia using a human-machine partnered strategy [43].A classifier that identified users with schizophrenia with an 88% accuracy using linguistic features was created by combining clinician assessments with machine learning to separate genuine disclosures from noisy data [43].This highlights the significance of combining clinical expertise with computational methods to improve the accuracy of mental health diagnoses on social media.
The quality of the studies ranged from moderate to high, with the main limitation being that assumptions are made regarding potential users having schizophrenia when assessing the online content of social media, as there is no way to counter-verify self-claims of being diagnosed with schizophrenia.

Clinical and Cognitive Assessment
Two of the identified studies were relevant to clinical and cognitive assessment.Using CoVec, an automated language tool, Ku and colleagues tested semantic coherence in a semantic fluency task completed by 197 first-episode psychosis patients and compared those with and without derailment and tangentiality [32].Coherence-5 and Coherence-10 levels were significantly lower in derailed patients, according to the results, indicating the possibility of automated methods like CoVec to objectively detect formal thought problems in schizophrenia [32].Another type of clinical assessment, concentrating on the Theory of the Mind, utilized machine learning, specifically Bayesian network analysis, to characterize the relationships between cognitive functions, Theory of Mind, and pragmatic abilities in 32 individuals with schizophrenia and 35 healthy controls [33].The Bayesian network classifier achieved a 95.5% accuracy in distinguishing patients from controls, identifying linguistic pragmatic ability as the most significant factor in classification, suggesting that pragmatic impairment is a core dysfunction in schizophrenia [33].Quality assessment of both studies was deemed high.Small sample sizes were reported as limitations in both studies when assessing the models.

Linguistic Feature Analysis
To better understand the language associated with self-experience, a study by Chan and colleagues examined the use of natural language processing to analyze autobiographical narratives from 167 patients with schizophrenia or schizoaffective disorder and 90 healthy controls [40].A machine learning classifier trained on these features achieved an area under the curve of 0.80, indicating its potential for differentiating between schizophrenia and healthy controls and highlighting significant relationships between self-experience language features and clinical symptoms [40].The analysis showed that topics related to self-experience were significantly more expressed in patients with schizophrenia.The quality of the study was evaluated as high and the authors reported major limitations of their approach such as a validated measure of self-disturbance not being used; comprehensive speech signals (including speech sounds and facial expressions) not being sufficiently evaluated; disruptions in self-experience being more common in trauma, with a disproportionate number of veterans in the schizophrenia group; text embedding only revealing the frequency of phrases, not their relationships; no information on the rates of trauma or comorbid disorders.

Discussion
The main objective of this scoping review was to identify the main uses of natural language processing in the field of schizophrenia.Six major uses were identified by the literature review, and using natural language processing for diagnostic and predictive modeling was the most prevalent.The authors of the identified studies reported many limitations, most of them highlighting the small sample sizes used to train the models, which may hinder their performances.
With the rise of machine learning in the field of healthcare to help clinicians in predicting outcomes of mental health disorders, as well as predicting the course of mental illnesses, it is unsurprising that the most prevalent use of natural language processing in the field of schizophrenia is about diagnostic and predictive modeling [50].
Considering the impairments of language observed in patients suffering from schizophrenia, many of the uses identified focused on linguistic, speech analysis, and social media contents, as they encompass various heterogeneous components of language.A recent study by de Boer and colleagues investigated the relationship between language characteristics, schizophrenia diagnosis, symptom severity, and white matter integrity using spontaneous speech recordings and diffusion tensor imaging in 26 schizophrenia patients and 22 healthy controls [8].The analysis classified schizophrenia with 89% sensitivity and 82% specificity, found language disturbances linked to negative symptom severity, and showed that computational language measures predicted white matter integrity, indicating the potential clinical and biological validity of quantitative language analysis in schizophrenia research [8].The performance of their classification is like the natural language processing models identified in this literature review.Furthermore, another recent study examined language dysfunction in schizophrenia by assessing neural tracking using electroencephalography in response to naturalistic speech stimuli [7].Their results indicated that schizophrenia patients exhibited impaired neural tracking of speech, particularly in theta-band oscillations, suggesting deficits in both auditory-sensory and abstract linguistic processing, which may contribute to the language-related symptoms observed in schizophrenia, and this should be further studied [7].Using these findings and natural language processing modeling could help clinicians in their assessment and monitoring of patients diagnosed with schizophrenia.The study identified also aligns with recent literature reporting that patients with schizophrenia (or schizoaffective disorder) had intact lexical processing but exhibited significant deficits in sentence comprehension, particularly in syntactic processing, which correlated with the severity of formal thought disorder symptoms, highlighting a potential link between language comprehension and thought disorder in schizophrenia [51].As an example, the authors reported that, in schizophrenia, word form recognition remained intact, suggesting normal lexical processing [51].With increasing severity of formal thought disorder, there was a propensity to impute word meanings based on phonetic similarities, although single-word synonym recognition was not significantly affected [51].
While there is a vast array of literature on the cognitive impairments observed in patients suffering with schizophrenia, this literature review highlighted a small number of studies that used natural language processing for assessing such impairments.As an example, in the field of dementia, notably Alzheimer's Disease, natural language processing is being studied extensively, as it may be a good avenue to screen cognitive decline.For instance, a recent study investigated the Pre-screening Tool for Language and Cognition Assessment Model (PST-LCAM), using a combination of psycholinguistic and cognitive adequacy (PCA) of Role and Reference Grammar (RRG) mapped to speech production parameters from the DementiaBank dataset [52].The main results show that the PST-LCAM effectively correlates with clinical assessments, demonstrating consistent indicators of cognitive decline as validated against the Global Deterioration Scale (GDS), suggesting its potential utility for the early detection of dementia [52].Conducting further research on the applications of natural language processing to assess cognitive impairments in patients with schizophrenia could yield potential therapeutic or preventive approaches.

Limitations
The heterogeneity of diagnostic criteria for schizophrenia is a key concern that is not addressed in most of the examined research, as Table 1 shows.Concerns regarding the results' generalizability are further raised by the absence of external validation in populations that differ from the training sample, such as those belonging to various nations.Performance comparisons were not carried out because of the variability of the listed research and the different measures utilized to evaluate precision and validate the natural processing algorithms.The studies identified also reported various ways of diagnosing schizophrenia or related psychotic disorders which may affect the external validity of these results.

Conclusions
Considering the importance of language and its impairment in patients diagnosed with schizophrenia, this literature review offered a first overview of natural language processing applications in this field.The review identified six primary natural language processing uses in schizophrenia.The main uses encompassed diagnostic and predictive modeling, which is the use of natural language processing to predict schizophrenia or related psychotic disorders.It also reported specific linguistic phenomena as attempting to model how linguistic characteristics can help in better understanding schizophrenia.A more specific speech and communication analysis made by a natural language processing model reported how speech organization can be used to understand schizophrenia as compared to healthy controls.Social media and online content analysis combined with natural language processing enabled the early identification of schizophrenia using verbatims on social media platforms.The last main two uses were the use of clinical and cognitive assessment as well as linguistic feature analysis to further comprehend the clinical presentations of schizophrenia.However, the field's novelty is underscored by the small sample sizes and lack of clinical validation in many studies.Future research should focus on larger, diverse samples and practical clinical applications to confirm the utility of natural language processing in schizophrenia diagnosis and treatment.

Figure 1 .
Figure 1.PRISMA flow diagram of identified studies.

Table 1 .
Systematic review study selection detailed results.

Table 1 .
Systematic review study selection detailed results.

Type of Participants, N) Main Use of NLP Outcomes Limitations Quality
There was a less clear association for paralinguistic abilities and cognitive flexibility, where patients showed a wider range of performance values.Relatively small sample size.High Figueroa-Barra, A., et al. (2022) [34] N = 133 (HC = 49; FEP = 40; Chronic SCZ = 44).All exclusively Spanish-speaking subjects from Chile.Diagnostic and Predictive Modeling Using the top ten ranked variables, the model's accuracy in differentiating between groups was 80.97% (HC vs. SCZ), 85.93% (HC vs. FEP + SCZ), and 91.11% (HC vs FEP) with a random forest classifier.To evaluate FEP conversion to SCZ, accuracy was measured.Results were poor with only demographic information (43.33%) but improved with PANSS information (65.83%).PANSS allowed for a 67.5% prediction accuracy.Language-only provided a 75.83% accuracy.Combining all information and using the top ten features resulted in a 77.5% accuracy for predicting if an FEP patient would have a confirmed SCZ diagnosis.Use of exclusively Chilean HCs, self-reported comorbidities like drug abuse, and differing demographic variables between healthy and psychotic subjects, which may introduce potential bias.There was no record of refusals at recruitment.The random forest model used for analysis has a simple and broad interpretation, and the study's limited sample size may lead to overfitting.Additionally, the longitudinal analysis classes were unbalanced.Significant differences in years of education between groups, possible audio contamination from background noise, low test-retest validity for acoustic features, and the use of cross-validation to estimate the generalizability of the models.High
[38], G., et al. (2015)[37]N = 34.Participants were help-seeking youths aged 14-27; referred by school, clinicians or self-referred through the Center of Prevention and Evaluation website.Diagnostic and Predictive ModelingBaseline speech recordings and transcriptions accurately predicted the transition to psychosis in a high-risk clinical group.Automated analysis outperformed clinical ratings, showing that automated speech analysis can enhance predictive accuracy beyond expert clinical opinion.Small sample size.HighJeong, L., et al. (2023)[38]