Immune Dysfunction in Schizophrenia Spectrum Disorders.

Evidence from epidemiological, clinical, and biological research resulted in the immune hypothesis: the hypothesis that immune system dysfunction is involved in the pathophysiology of schizophrenia spectrum disorders (SSD). The promising implication of this hypothesis is the potential to use existing immunomodulatory treatment for innovative interventions for SSD. Here, we provide a selective historical review of important discoveries that have shaped our understanding of immune dysfunction in SSD. We first explain the basic principles of immune dysfunction, after which we travel more than a century back in time. Starting our journey with neurosyphilis-associated psychosis in the nineteenth century, we continue by evaluating the role of infections and autoimmunity in SSD and findings from assessment of immune function using new techniques, such as cytokine levels, microglia density, neuroimaging, and gene expression. Drawing from these findings, we discuss anti-inflammatory interventions for SSD, and we conclude with a look into the future.

Acoustic speech markers for schizophrenia-spectrum disorders: a diagnostic and symptom-recognition tool.

BACKGROUND: Clinicians routinely use impressions of speech as an element of mental status examination. In schizophrenia-spectrum disorders, descriptions of speech are used to assess the severity of psychotic symptoms. In the current study, we assessed the diagnostic value of acoustic speech parameters in schizophrenia-spectrum disorders, as well as its value in recognizing positive and negative symptoms. METHODS: Speech was obtained from 142 patients with a schizophrenia-spectrum disorder and 142 matched controls during a semi-structured interview on neutral topics. Patients were categorized as having predominantly positive or negative symptoms using the Positive and Negative Syndrome Scale (PANSS). Acoustic parameters were extracted with OpenSMILE, employing the extended Geneva Acoustic Minimalistic Parameter Set, which includes standardized analyses of pitch (F0), speech quality and pauses. Speech parameters were fed into a random forest algorithm with leave-ten-out cross-validation to assess their value for a schizophrenia-spectrum diagnosis, and PANSS subtype recognition. RESULTS: The machine-learning speech classifier attained an accuracy of 86.2% in classifying patients with a schizophrenia-spectrum disorder and controls on speech parameters alone. Patients with predominantly positive v. negative symptoms could be classified with an accuracy of 74.2%. CONCLUSIONS: Our results show that automatically extracted speech parameters can be used to accurately classify patients with a schizophrenia-spectrum disorder and healthy controls, as well as differentiate between patients with predominantly positive v. negatives symptoms. Thus, the field of speech technology has provided a standardized, powerful tool that has high potential for clinical applications in diagnosis and differentiation, given its ease of comparison and replication across samples.

[Antipsychotic drugs for women: a narrative review and clinical guidelines]. / Antipsychotica voor vrouwen: overzicht van de literatuur en praktijkadviezen.

BACKGROUND: It has long been thought that women with a schizophrenia spectrum disorder have a more favorable course than men. However, this is not the case, even though they become ill later in life and are less likely to have comorbid drug abuse. Guidelines for prescribing antipsychotics are based on research with mostly male participants, and by following these guidelines we are doing our female patients a disservice. Gender and sex differences lead to differences in preferences, pharmacokinetics and pharmacodynamics. AIM: Providing an overview of antipsychotics for women with a schizophrenia spectrum disorder and discuss the consequences for practice. METHOD: A clinically oriented study of the literature. RESULTS: Women reach higher plasma levels than men when they receive the same dose of antipsychotic drugs (except for lurasidone and quetiapine). The effect of antipsychotics is also greater in women, because estrogens increase the brain’s dopamine sensitivity. This leads to higher risks of side effects. Clinical guidelines differ for women at different stages of life because estrogens greatly contribute to the sex differences seen in the efficacy and tolerability of antipsychotics. CONCLUSION: Clinicians should be aware that women should be treated differently with antipsychotics than men.

[Recognizing depression through computational language analysis]. / Herkennen van depressie met computationele taalanalyse.

BACKGROUND: Currently, clinical practice lacks a usable biomarker for the detection and differentiation of depression. Such a biomarker may be found in speech, from which important information can be distilled using automated speech analysis. AIM: To provide an overview of the fast-developing field of automated speech analysis for depression. METHOD: We summarize the current literature on speech features in depression. RESULTS: Current computational models can detect depression with high accuracy, rendering them applicable for diagnostic tools based on automatic speech analysis. Such tools are developing at a fast rate. CONCLUSION: Some challenges are still in the way of clinical implementation. For example, results differ largely between studies due to much variation in methodology. Furthermore, privacy and ethical issues need to be addressed before tools can be used.

[Automated speech analysis can distinguish frontotemporal dementia from depression: a pilot study]. / Geautomatiseerde spraakanalyse bij onderscheiden van frontotemporale dementie en depressie.

BACKGROUND: Differentiating the behavioural variant of frontotemporal dementia from a depression is challenging. Recent development of automated speech analyses might add to diagnostic. AIM: To investigate the value of automated speech analyses in differentiating bvFTD from a depressive disorder. METHOD: A semistructured interview was recorded in 15 patients with bvFTD, 15 patients with a depressive disorder and 15 healthy controls, which was transcribed and analysed. Acoustic and semantic values were extracted and classified using machine learning. RESULTS: Acoustic values showed an 80% accuracy for differentiating bvFTD from depressive disorder and semantic values showed an 70.8% accuracy. CONCLUSION: Acoustic as well as semantic values show significant differences between bvFTD and depressive disorder. In automated speech analyses researches should consider privacy matters as well as possible confounders like age, sex and ethnicity. This study should be repeated in a larger population.

[Improving care for women with schizophrenia-spectrum disorders]. / Vrouwen met schizofreniespectrum-stoornissen verdienen betere zorg.

Background   Women with a schizophrenia-spectrum disorder (SSD) have a better clinical profile than men at the start of their illness but lose this advantage within the first few years of living with SSD. There are benefits to be gained across different areas in the care currently offered to women with psychosis. Aim   To describe point of improvement in the care for women with SSD. Method   Review or relevant literature. Results   An important point for improvement is the early detection of female-specific signs of a first episode of psychosis, to shorten the duration of untreated psychosis, with prompt access to early intervention services. Special attention should be paid to sexual health, and to any history of childhood trauma. Antipsychotics clearly require dosing and prescription tailored to the female body, considering hormonal life phases such as menopause. Switching to prolactin-sparing medications can benefit both mental and somatic health. Finally, hormone replacement therapy should be considered for postmenopausal women. Conclusion   By providing female-specific care, women with SSD can live up to their full potential.

An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis.

BACKGROUND: Accumulating evidence shows that a propensity towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might compensate this propensity. This study provides an update regarding the efficacy of agents with some anti-inflammatory actions for schizophrenia symptoms tested in randomized controlled trials (RCTs). METHODS: PubMed, Embase, the National Institutes of Health website (http://www.clinicaltrials.gov), and the Cochrane Database of Systematic Reviews were systematically searched for RCTs that investigated clinical outcomes. RESULTS: Our search yielded 56 studies that provided information on the efficacy of the following components on symptom severity: aspirin, bexarotene, celecoxib, davunetide, dextromethorphan, estrogens, fatty acids, melatonin, minocycline, N-acetylcysteine (NAC), pioglitazone, piracetam, pregnenolone, statins, varenicline, and withania somnifera extract. The results of aspirin [mean weighted effect size (ES): 0.30; n = 270; 95% CI (CI) 0.06-0.54], estrogens (ES: 0.78; n = 723; CI 0.36-1.19), minocycline (ES: 0.40; n = 946; CI 0.11-0.68), and NAC (ES: 1.00; n = 442; CI 0.60-1.41) were significant in meta-analysis of at least two studies. Subgroup analysis yielded larger positive effects for first-episode psychosis (FEP) or early-phase schizophrenia studies. Bexarotene, celecoxib, davunetide, dextromethorphan, fatty acids, pregnenolone, statins, and varenicline showed no significant effect. CONCLUSIONS: Some, but not all agents with anti-inflammatory properties showed efficacy. Effective agents were aspirin, estrogens, minocycline, and NAC. We observed greater beneficial results on symptom severity in FEP or early-phase schizophrenia.

Auditory hallucinations, top-down processing and language perception: a general population study.

BACKGROUND: Studies investigating the underlying mechanisms of hallucinations in patients with schizophrenia suggest that an imbalance in top-down expectations v. bottom-up processing underlies these errors in perception. This study evaluates this hypothesis by testing if individuals drawn from the general population who have had auditory hallucinations (AH) have more misperceptions in auditory language perception than those who have never hallucinated. METHODS: We used an online survey to determine the presence of hallucinations. Participants filled out the Questionnaire for Psychotic Experiences and participated in an auditory verbal recognition task to assess both correct perceptions (hits) and misperceptions (false alarms). A hearing test was performed to screen for hearing problems. RESULTS: A total of 5115 individuals from the general Dutch population participated in this study. Participants who reported AH in the week preceding the test had a higher false alarm rate in their auditory perception compared with those without such (recent) experiences. The more recent the AH were experienced, the more mistakes participants made. While the presence of verbal AH (AVH) was predictive for false alarm rate in auditory language perception, the presence of non-verbal or visual hallucinations were not. CONCLUSIONS: The presence of AVH predicted false alarm rate in auditory language perception, whereas the presence of non-verbal auditory or visual hallucinations was not, suggesting that enhanced top-down processing does not transfer across modalities. More false alarms were observed in participants who reported more recent AVHs. This is in line with models of enhanced influence of top-down expectations in persons who hallucinate.

Hallucinations in patients with borderline personality disorder: characteristics, severity, and relationship with schizotypy and loneliness.

OBJECTIVE: In patients with borderline personality disorder (BPD), data are lacking on characteristics and severity of hallucinations in modalities other than the auditory (verbal) type. The same applies to relationships between hallucinations and the severity of depression, anxiety, schizotypy, and loneliness. METHODS: In 60 female patients with BPD (37 also with hallucinations), this cross-sectional study explored characteristics and severity of (i) hallucinations and (ii) schizotypal features, (iii) severity of depression and anxiety, and (iv) loneliness, and the relationships between hallucinations and the other characteristics. RESULTS: In patients with hallucinations, 80% experienced hallucinations in more than one modality; in the different modalities, the characteristics of the hallucinations were similar. The criteria for loneliness were fulfilled in 81% and 48% of patients with and without hallucinations. Compared to patients with BPD without hallucinations, the presence of hallucinations was associated with higher scores for depression, anxiety, loneliness, and schizotypy. Furthermore, the severity of hallucinations showed a positive correlation with the severity of loneliness and schizotypy. CONCLUSION: Patients with BPD experienced hallucinations with characteristics similar to the more frequently studied auditory (verbal) hallucinations. Higher scores for schizotypy and loneliness indicate that patients with hallucinations had more characteristics of cluster A personality disorders.

Auditory hallucinations, not necessarily a hallmark of psychotic disorder.

Auditory hallucinations (AH) are often considered a sign of a psychotic disorder. This is promoted by the DSM-5 category of Other Specified Schizophrenia Spectrum And Other Psychotic Disorder (OSSSOPD), the diagnostic criteria for which are fulfilled with the sole presence of persistent AH, in the absence of any other psychotic symptoms. And yet, persistent AH are not synonymous with having a psychotic disorder, and should therefore not be uncritically treated as such. Many people who seek treatment for persistent AH have no other psychotic symptoms, have preserved reality-testing capacities, and will never develop a schizophrenia spectrum disorder. Instead, hallucinations may be the result of many different causes, including borderline personality disorder, post-traumatic stress disorder (PTSD), hearing loss, sleep disorders or brain lesions, and they may even occur outside the context of any demonstrable pathology. In such cases, the usage of the DSM-5 diagnosis of OSSSOPD would be incorrect, and it may prompt unwarranted treatment with antipsychotic medication. We therefore argue that a DSM-5 diagnosis of Schizophrenia Spectrum Disorder (or any other type of psychotic disorder) characterized by AH should require at least one more symptom listed under the A-criterion (i.e. delusions, disorganized speech, disorganized or catatonic behavior or negative symptoms). Adhering to these more stringent criteria may help to distinguish between individuals with persistent AH which are part of a psychotic disorder, for whom antipsychotic medication may be helpful, and individuals with AH in the absence of such a disorder who may benefit from other approaches (e.g. different pharmacological interventions, improving coping style, trauma-related therapy).

Auditory hallucinations across the lifespan: a systematic review and meta-analysis.

BACKGROUND: Auditory Hallucinations (AH) are nowadays regarded as symptoms following a continuum; from a (transient) phenomenon in healthy individuals on one end to a symptom of (psychiatric) illnesses at the other. An accumulating number of epidemiological studies focused on the prevalence of AH in the general population, but results vary widely. The current meta-analysis aims to synthesize existing evidence on lifetime prevalence of AH across the lifespan. METHODS: We conducted a quantitative review and meta-analysis according to PRISMA guidelines. Studies were combined to calculate a mean lifetime general population AH prevalence rate. Moreover, prevalences were calculated for four age groups: children (5-12 years), adolescents (13-17 years), adults (18-60 years) and elderly (⩾60 years). RESULTS: We retrieved 25 study samples including 84 711 participants. Mean lifetime prevalence rate of AH was 9.6% (95% CI 6.7-13.6%). The mean lifetime prevalence was similar in children (12.7%) and adolescents (12.4%), but these two groups differed significantly from the adults (5.8%) and the elderly (4.5%). Significant heterogeneity indicated that there is still dispersion in true prevalence rates between studies, even within the different age categories. CONCLUSIONS: Current meta-analysis shows that AH are quite common (up to one in ten individuals) in the general population during lifetime, with children and adolescents reporting these experiences significantly more often compared with adults and elderly. Large follow-up studies on the longitudinal course of AH are needed to reveal associated risk and resilience factors.

Clozapine as a first- or second-line treatment in schizophrenia: a systematic review and meta-analysis.

OBJECTIVE: No consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta-analysis therefore focus on the use of clozapine as first-line or second-line treatment in non-treatment-resistant patients. METHODS: Articles were eligible if they investigated clozapine compared to another antipsychotic as a first- or second-line treatment in non-treatment-resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random-effects meta-analyses. RESULTS: Fifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta-analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges' g = 0.220, P = 0.026, 95% CI = 0.026-0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges' g = 0.274, P = 0.030, 95% CI = 0.027-0.521). CONCLUSION: The few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first- or second-line treatment. Only large clinical trials may comprehensively probe disease stage-dependent superiority of clozapine and investigate overall tolerability.

[Personalised medicine for psychosis]. / Personalised medicine bij psychotische stoornissen.

BACKGROUND: Personalised medicine (pm) means treatment that specifically targets the needs of individual patients on the basis of genetic, biomarker, phenotypic or psychosocial characteristics.
AIM: To update our knowledge about the current use of pm in the treatment of psychotic disorders.
METHOD: Review of the literature on pm for psychoses.
RESULTS: At the moment, genetic and other biological characteristics cannot be used for the diagnosis and treatment of psychotic disorders because they are not sensitive enough and their specificity is too low. We investigated immunulogical, oxidative, metabolic, hormonal and dopaminergic aspects that could lead to the use of pm. pm is already being used on the basis of phenotypical, cognitive and psychosocial characteristics; those characteristics include substance abuse, cognitive dysfunction, ethnicity and childhood trauma.
CONCLUSION: In the next years there may be more opportunities for using for pm in psychosis. The increase may results from large genetic network studies and treatment studies involving stratification based on hypothetical specific mechanisms instead of on the categorical diagnosis of illnesses such as schizophrenia.

Auditory verbal hallucinations: neuroimaging and treatment.

Auditory verbal hallucinations (AVH) are a frequently occurring phenomenon in the general population and are considered a psychotic symptom when presented in the context of a psychiatric disorder. Neuroimaging literature has shown that AVH are subserved by a variety of alterations in brain structure and function, which primarily concentrate around brain regions associated with the processing of auditory verbal stimuli and with executive control functions. However, the direction of association between AVH and brain function remains equivocal in certain research areas and needs to be carefully reviewed and interpreted. When AVH have significant impact on daily functioning, several efficacious treatments can be attempted such as antipsychotic medication, brain stimulation and cognitive-behavioural therapy. Interestingly, the neural correlates of these treatments largely overlap with brain regions involved in AVH. This suggests that the efficacy of treatment corresponds to a normalization of AVH-related brain activity. In this selected review, we give a compact yet comprehensive overview of the structural and functional neuroimaging literature on AVH, with a special focus on the neural correlates of efficacious treatment.

Five year follow-up of non-psychotic adults with frequent auditory verbal hallucinations: are they still healthy?

BACKGROUND: Previously, we described 103 adults (mean age 41 years) who experienced frequent, auditory verbal hallucinations (AVH), in the absence of a need for mental healthcare. Importantly, these adults were largely past the peak incidence age for psychosis (15-35 years). It is unclear if these older individuals with AVH are still at increased risk for psychosis or other psychopathology. To address this question, we conducted a 5-year follow-up of previously included individuals (103 with AVH, 60 controls). METHOD: Eighty-one adults with AVH (78.6%) and forty-nine controls (81.7%) could be contacted and were willing to participate. Participants were screened for psychosis and a need for mental healthcare at follow-up using the Comprehensive Assessment of Symptoms and History interview (CASH). Need for mental healthcare was defined as a clinical diagnosis as identified using the CASH and/or treatment by a mental healthcare specialist. Phenomenology of AVH was assessed with the PSYRATS Auditory Hallucinations Rating Scale. RESULTS: Five individuals with AVH (6.2%) had developed psychosis and 32 (39.5%) had developed a need for mental healthcare. Voice-related distress at baseline significantly predicted need for mental healthcare. AVH persisted in most individuals (86.4%), without significant changes in phenomenology. None of the controls had developed psychotic symptoms, and need for mental healthcare (n = 6, 12.2%) was significantly lower in this group. CONCLUSIONS: These findings suggest that frequent AVH in non-psychotic adults past the peak incidence age for psychosis constitute a rather static symptom and that individuals with AVH may be best viewed as situated on a need for care continuum.

[Auto-immune encephalitis in psychiatric practice]. / Auto-immune encefalitis in de psychiatrische praktijk.

BACKGROUND: Our knowledge about auto-immune limbic encephalitis is increasing rapidly and it is now evident that patients with this disease can present with psychiatric symptoms. AIM: To propose practical guidelines for the recognition and diagnosis of an underlying auto-immune limbic encephalitis in patients with acute psychiatric symptoms. METHOD: We studied recent reviews on the topic and had discussions with psychiatrists, a neurologist and a neuroimmunologist in order to reach consensus. RESULTS: Auto-immune limbic encephalitis is a rather rare but important diagnostic consideration in patients with acute psychiatric symptoms. We describe the different steps in the diagnostic work-up and mention features that can point to an underlying auto-immune encephalitis. These include atypical psychiatric symptoms, seizures, movement disorders and autonomic instability. CONCLUSION: Since patients with autoimmune limbic encephalitis often present with psychiatric symptoms, curative treatment is often available and the prognosis depends on the delay from presentation to treatment, psychiatrists should be aware of the signs of an underlying autoimmune encephalitis which have been described in this article.

[Treatment strategies for auditory verbal hallucinations]. / Behandelmogelijkheden voor auditieve verbale hallucinaties.

BACKGROUND: Auditory verbal hallucinations (AVH) are experienced not only by patients diagnosed with schizophrenia, but also by patients with other disorders (some of which may be psychiatric) and in the general population. The ensuing affliction may be severe and can sometimes result in dangerous behaviour. Although various treatment options are available for AVH, only a few have been investigated in randomised placebo-controlled trials. AIM: To provide an overview of the literature relating to the effectiveness of antipsychotics, cognitive-behavioural therapy (CBT), electroconvulsive therapy (ect), and transcranial magnetic stimulation (TMS) in the treatment of avh. METHOD: This review paper is based on the Ph.D. study of the first author; in addition, a literature search was carried out using PubMed. RESULTS: Antipsychotics have never been studied specifically with regard to their effect on AVH, but they are known to lead to a significant decrease in the severity and frequency of hallucinations in general. cbt can reduce the torment caused by AVH, but not the severity or frequency. ect can be helpful in the treatment of drug-resistant psychosis, but it has never been studied specifically with regard to its effect on avh or on other types of hallucinations. tms is effective for the treatment of drug-resistant AVH, but in the cases where it has been used so far, the beneficial effects seem to have been of limited duration. CONCLUSION: Very few of the available treatment strategies have been used specifically to relieve the distress caused by avh. tms and cbt have proved reasonably effective, but there is a need for further research into additional treatment strategies, particularly into those involving TMS.

Cognitive biases and auditory verbal hallucinations in healthy and clinical individuals.

BACKGROUND: Several cognitive biases are related to psychotic symptoms, including auditory verbal hallucinations (AVH). It remains unclear whether these biases differ in voice-hearers with and without a 'need-for-care'. METHOD: A total of 72 healthy controls, 72 healthy voice-hearers and 72 clinical voice-hearers were compared on the Cognitive Biases Questionnaire for psychosis (CBQp), which assesses 'intentionalizing', 'jumping to conclusions', 'catastrophizing', 'dichotomous thinking' and 'emotional reasoning' in vignettes characterized by two themes, 'threatening events' and 'anomalous perceptions'. RESULTS: Healthy voice-hearers scored intermediately on total CBQp between the control and clinical groups, differing significantly from both. However, on four out of five biases the scores of the healthy voice-hearers were comparable with those of the healthy controls. The only exception was 'emotional reasoning', on which their scores were comparable with the clinical group. Healthy voice-hearers demonstrated fewer biases than the psychotic patients on the 'threatening events', but not the 'anomalous perceptions', vignettes. CBQp scores were related to both cognitive and emotional, but not physical, characteristics of voices. CONCLUSIONS: Most cognitive biases prevalent in clinical voice-hearers, particularly with threatening events themes, are absent in healthy voice-hearers, apart from emotional reasoning which may be specifically related to the vulnerability to develop AVH. The association between biases and both beliefs about voices and distress/emotional valence is consistent with the close links between emotions and psychotic phenomena identified by cognitive models of psychosis. The absence of reasoning biases might prevent the formation of threatening appraisals about anomalous experiences, thereby reducing the likelihood of distress and 'need for care'.

Aberrant resting-state connectivity in non-psychotic individuals with auditory hallucinations.

BACKGROUND: Although auditory verbal hallucinations (AVH) are a core symptom of schizophrenia, they also occur in non-psychotic individuals, in the absence of other psychotic, affective, cognitive and negative symptoms. AVH have been hypothesized to result from deviant integration of inferior frontal, parahippocampal and superior temporal brain areas. However, a direct link between dysfunctional connectivity and AVH has not yet been established. To determine whether hallucinations are indeed related to aberrant connectivity, AVH should be studied in isolation, for example in non-psychotic individuals with AVH. METHOD: Resting-state connectivity was investigated in 25 non-psychotic subjects with AVH and 25 matched control subjects using seed regression analysis with the (1) left and (2) right inferior frontal, (3) left and (4) right superior temporal and (5) left parahippocampal areas as the seed regions. To correct for cardiorespiratory (CR) pulsatility rhythms in the functional magnetic resonance imaging (fMRI) data, heartbeat and respiration were monitored during scanning and the fMRI data were corrected for these rhythms using the image-based method for retrospective correction of physiological motion effects RETROICOR. RESULTS: In comparison with the control group, non-psychotic individuals with AVH showed increased connectivity between the left and the right superior temporal regions and also between the left parahippocampal region and the left inferior frontal gyrus. Moreover, this group did not show a negative correlation between the left superior temporal region and the right inferior frontal region, as was observed in the healthy control group. CONCLUSIONS: Aberrant connectivity of frontal, parahippocampal and superior temporal brain areas can be specifically related to the predisposition to hallucinate in the auditory domain.

Combining automatic speech recognition with semantic natural language processing in schizophrenia.

Natural language processing (NLP) tools are increasingly used to quantify semantic anomalies in schizophrenia. Automatic speech recognition (ASR) technology, if robust enough, could significantly speed up the NLP research process. In this study, we assessed the performance of a state-of-the-art ASR tool and its impact on diagnostic classification accuracy based on a NLP model. We compared ASR to human transcripts quantitatively (Word Error Rate (WER)) and qualitatively by analyzing error type and position. Subsequently, we evaluated the impact of ASR on classification accuracy using semantic similarity measures. Two random forest classifiers were trained with similarity measures derived from automatic and manual transcriptions, and their performance was compared. The ASR tool had a mean WER of 30.4%. Pronouns and words in sentence-final position had the highest WERs. The classification accuracy was 76.7% (sensitivity 70%; specificity 86%) using automated transcriptions and 79.8% (sensitivity 75%; specificity 86%) for manual transcriptions. The difference in performance between the models was not significant. These findings demonstrate that using ASR for semantic analysis is associated with only a small decrease in accuracy in classifying schizophrenia, compared to manual transcripts. Thus, combining ASR technology with semantic NLP models qualifies as a robust and efficient method for diagnosing schizophrenia.