Dolphin CONTINUE: a multi-center randomized controlled trial to assess the effect of a nutritional intervention on brain development and long-term outcome in infants born before 30 weeks of gestation.

BACKGROUND: Preterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm. METHODS: This is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children's Abilities - Revised (PARCA-R)). DISCUSSION: The investigated nutritional intervention is hypothesized to promote brain development and subsequent neurodevelopmental outcome in preterm born infants who have an inherent risk of developmental delay. Moreover, this innovative study may give rise to new treatment possibilities and improvements in routine clinical care. TRIAL REGISTRATION: WHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021).

[Taal: een introductie]. / Taal: een introductie.

BACKGROUND: This special issue discusses the roles and functions of language in psychiatric practice from different perspectives. As an introduction, we discuss the phenomenon ‘language’ as an object of scientific investigation. AIM: To give a brief introduction to this theme issue. METHOD: After a terminological introduction and an outline of linguistics, we discuss some of the cognitive processes that enable humans to produce and interpret verbal utterances. RESULTS: The mental lexicon, the dictionary in our head, plays a central role in both language production and understanding. The starting point for language comprehension is recognizing basic form elements in the speech or sign stream (phonemes). Next, the perceiver must determine how words are related grammatically in order to deduce sentence meanings. We distinguish three successive steps in the production of language: conceptualizing, formulating and articulating. CONCLUSION: Production and understanding words and sentences rely on a complex interplay of cognitive processes. In communication, we use words and sentences to convey and recognize intentions. This requires close cooperation between interlocutors.

[Attention for language; atypical language development and psychiatric symptoms in children]. / Aandacht voor taal; afwijkende taal­ontwikkeling en psychiatrische symptomen bij kinderen.

BACKGROUND: Children with a neurodevelopmental or psychiatric disorder often have language difficulties. A large group of children has severely impaired language learning abilities in the absence of a clear cause. These children have developmental language disorder (DLD). Many children with DLD also develop psychiatric symptoms which are associated with other neurodevelopmental or psychiatric disorder. AIM: In this article, we provide information on children with DLD, on the often atypical language development of children with other neurodevelopmental or psychiatric disorder, and on the mechanisms that may explain the co-occurrence of language problems and psychiatric symptoms. METHODS: We discuss relevant literature and insights from clinical practice. RESULTS: Psychiatric symptoms can hinder language development and, vice versa, children with language problems are more vulnerable to develop behavior associated with a psychiatric diagnosis. Given the frequent co-occurrence of language problems and psychiatric symptoms in children, there is a high chance that a psychiatrist will encounter children with language difficulties in daily clinical practice. CONCLUSION: Knowledge and awareness of this co-occurrence benefits clinical care, and has important implications for diagnosis and intervention of children with neurodevelopmental or psychiatric disorders.

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.

Negative content in auditory verbal hallucinations: a natural language processing approach.

INTRODUCTION: Negative content of auditory verbal hallucinations (AVH) is a strong predictor of distress and impairment. This paper quantifies emotional voice-content in order to explore both subjective (i.e. perceived) and objectively (i.e. linguistic sentiment) measured negativity and investigates associations with distress. METHODS: Clinical and non-clinical participants with frequent AVH (n = 40) repeated and recorded their AVH verbatim directly upon hearing. The AVH were analyzed for emotional valence using Pattern, a rule-based sentiment analyzer for Dutch. The AVH of the clinical individuals were compared to those of non-clinical voice-hearers on emotional valence and associated with experienced distress. RESULTS: The mean objective valence of AVH in patients was significantly more negative than those of non-clinical voice-hearers. In the clinical individuals a larger proportion of the voice-utterances was negative (34.7% versus 18.4%) in objective valence. The linguistic valence of the AVH showed a significant, strong association with the perceived negativity, amount of distress and disruption of life, but not with the intensity of distress. CONCLUSIONS: Our results indicate that AVH of patients have a more negative linguistic content than those of non-clinical voice-hearers, which is associated with the experienced distress. Thus, patients not only perceive their voices as more negative, objective analyses confirm this.

Language disturbances in schizophrenia: the relation with antipsychotic medication.

Language disturbances are key aberrations in schizophrenia. Little is known about the influence of antipsychotic medication on these symptoms. Using computational language methods, this study evaluated the impact of high versus low dopamine D2 receptor (D2R) occupancy antipsychotics on language disturbances in 41 patients with schizophrenia, relative to 40 healthy controls. Patients with high versus low D2R occupancy antipsychotics differed by total number of words and type-token ratio, suggesting medication effects. Both patient groups differed from the healthy controls on percentage of time speaking and clauses per utterance, suggesting illness effects. Overall, more severe negative language disturbances (i.e. slower articulation rate, increased pausing, and shorter utterances) were seen in the patients that used high D2R occupancy antipsychotics, while less prominent disturbances were seen in low D2R occupancy patients. Language analyses successfully predicted drug type (sensitivity = 80.0%, specificity = 76.5%). Several language disturbances were more related to drug type and dose, than to other psychotic symptoms, suggesting that language disturbances may be aggravated by high D2R antipsychotics. This negative impact of high D2R occupancy drugs may have clinical implications, as impaired language production predicts functional outcome and degrades the quality of life.

Language in schizophrenia: relation with diagnosis, symptomatology and white matter tracts.

Language deviations are a core symptom of schizophrenia. With the advances in computational linguistics, language can be easily assessed in exact and reproducible measures. This study investigated how language characteristics relate to schizophrenia diagnosis, symptom, severity and integrity of the white matter language tracts in patients with schizophrenia and healthy controls. Spontaneous speech was recorded and diffusion tensor imaging was performed in 26 schizophrenia patients and 22 controls. We were able to classify both groups with a sensitivity of 89% and a specificity of 82%, based on mean length of utterance and clauses per utterance. Language disturbances were associated with negative symptom severity. Computational language measures predicted language tract integrity in patients (adjusted R2 = 0.467) and controls (adjusted R2 = 0.483). Quantitative language analyses have both clinical and biological validity, offer a simple, helpful marker of both severity and underlying pathology, and provide a promising tool for schizophrenia research and clinical practice.

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.

A linguistic comparison between auditory verbal hallucinations in patients with a psychotic disorder and in nonpsychotic individuals: Not just what the voices say, but how they say it.

BACKGROUND: Auditory verbal hallucinations (AVH) in psychotic patients are associated with activation of right hemisphere language areas, although this hemisphere is non-dominant in most people. Language generated in the right hemisphere can be observed in aphasia patients with left hemisphere damage. It is called "automatic speech", characterized by low syntactic complexity and negative emotional valence. AVH in nonpsychotic individuals, by contrast, predominantly have a neutral or positive emotional content and may be less dependent on right hemisphere activity. We hypothesize that right hemisphere language characteristics can be observed in the language of AVH, differentiating psychotic from nonpsychotic individuals. METHOD: 17 patients with a psychotic disorder and 19 nonpsychotic individuals were instructed to repeat their AVH verbatim directly upon hearing them. Responses were recorded, transcribed and analyzed for total words, mean length of utterance, proportion of grammatical utterances, proportion of negations, literal and thematic perseverations, abuses, type-token ratio, embeddings, verb complexity, noun-verb ratio, and open-closed class ratio. RESULTS: Linguistic features of AVH overall differed between groups F(13,24)=3.920, p=0.002; Pillai's Trace 0.680. AVH of psychotic patients compared with AVH of nonpsychotic individuals had a shorter mean length of utterance, lower verb complexity, and more verbal abuses and perseverations (all p<0.05). Other features were similar between groups. CONCLUSION: AVH of psychotic patients showed lower syntactic complexity and higher levels of repetition and abuses than AVH of nonpsychotic individuals. These differences are in line with a stronger involvement of the right hemisphere in the origination of AVH in patients than in nonpsychotic voice hearers.