@article{pmid40974052,

title = {Age of Onset, Brain Controllability, and Working Memory Performance in First-Episode Schizophrenia},

author = {Feiwen Wang and Zhening Liu and Jun Yang and Peng Cheng and Wenjian Tan and Danqing Huang and Xiawei Liu and Maoxing Zhong and Jie Yang and Lena Palaniyappan},

doi = {10.1093/schbul/sbaf156},

issn = {1745-1701},

year  = {2026},

date = {2026-07-01},

journal = {Schizophr Bull},

volume = {52},

number = {4},

abstract = {BACKGROUND AND HYPOTHESIS: The onset-age of schizophrenia introduces considerable heterogeneity in cognitive functions such as working memory (WM) among patients. One of the key properties of the brain that varies with age-related development is the network-level controllability of brain state transitions. We tested the effect of onset-age on brain controllability to evaluate its impact on WM deficits in schizophrenia.nnSTUDY DESIGN: We examined the average and modal controllability of the brain connectome in 85 first-episode early-onset schizophrenia (EOS), 62 younger healthy controls (yHC), 71 first-episode adult-onset schizophrenia (AOS), and 85 older healthy controls (oHC) during N-back tasks. We first detected the regions with illness and onset-age interaction in a whole-brain search, and then conducted a correlation analysis with WM performance and clinical characteristics, followed by an out-of-sample gene annotation analysis.nnSTUDY RESULTS: We detected the illness*onset-age interaction in the sensorimotor network, auditory network, and subcortical network for average controllability and the default mode network, visual network, and salience network for modal controllability (p-fdr < 0.05). The interaction effects in the visual and subcortical networks primarily resulted from the AOS vs. oHC differences; the effects in the default mode network resulted from EOS vs. yHC differences. We observed no significant correlation between controllability with cognitive performance or clinical characteristics. The affected regions had preferential expression of genes relevant to synaptic signaling and neurodegenerative processes (p-fdr < 0.05).nnCONCLUSION: Onset-age introduces considerable heterogeneity in the controllability over brain state transition during WM tasks among patients with schizophrenia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42471042,

title = {Resting magnetoencephalography alterations in severe mental illnesses: A systematic review},

author = {Fernando Gonzales-Aste and Jessica Ahrens and Dominic Boutet and Hsi Tiana Wei and Sylvain Baillet and Lena Palaniyappan},

doi = {10.1016/j.neubiorev.2026.106867},

issn = {1873-7528},

year  = {2026},

date = {2026-07-01},

journal = {Neurosci Biobehav Rev},

volume = {189},

pages = {106867},

abstract = {Schizophrenia, major depressive disorder (MDD), and bipolar disorder (Severe Mental Illnesses: SMIs), share genetic risk and brain structural changes, but their neural mechanisms remain unclear. Magnetoencephalography (MEG), with millisecond precision, enables direct examination of shared and disorder-specific disturbances in the timing of spontaneous brain activity. We reviewed resting-state MEG evidence on spectral power, connectivity, information-theoretic complexity, and brain dynamics across SMIs. A comprehensive search yielded 62 studies. Three reviewers screened, retrieved, and extracted data on MEG-related variables across regional activity (power), coordination of activity (connectivity, coherence, synchrony), regularity of activity (complexity, entropy), and overall dynamics. Three principal findings come forth. Beta oscillations emerge as a promising, albeit yet unconfirmed, candidate transdiagnostic signal, with increased power now reported across independent investigations of all three disorders and correlating with hallucinations, sleep disturbances, and cognitive deficits, consistent with disrupted predictive processing. However, direct within-study cross-diagnostic comparisons remain sparse (2 of 62 studies). Preliminary support exists for complexity-age dissociation to partition SMIs into neuroprogressive and state-dependent trajectories: neural complexity declines with age in schizophrenia and bipolar disorder (opposite to healthy aging), while depression preserves the normative trajectory. Slow-wave activity diverges sharply: schizophrenia shows a widespread increased slow-wave dominance, while mood disorders show a decrease in activity. We propose a temporal disorganisation spectrum of SMI from excessive fragmentation (schizophrenia) to pathological rigidity (depression), with bipolar disorder occupying an intermediate position. This framework offers biomarker-type utility for stratifying illness severity, tracking neuroprogression, and identifying transdiagnostic therapeutic targets, particularly beta-modulatory neuromodulation interventions applicable across SMIs. Protocol registration: Open Science Framework (http://osf.io/v2gtb/).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42476975,

title = {Structural brain complexity is associated with linguistic complexity in psychosis},

author = {Alexandra Korda and Wolfram Hinzen and Rui He and Peter van Dyken and Michael Mackinley and Eric Toyota and Mihai Avram and Christina Andreou and Stefan Borgwardt and Lena Palaniyappan},

doi = {10.1192/j.eurpsy.2026.12242},

issn = {1778-3585},

year  = {2026},

date = {2026-07-01},

journal = {Eur Psychiatry},

pages = {1--30},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42522874,

title = {Pathways to schizophrenia: Divergent effects of childhood trauma and polygenic risk on cognition and subcortical dynamics},

author = {Danqing Huang and Yicheng Long and Zhening Liu and Wenjian Tan and Xiawei Liu and Yunzhi Pan and Feiwen Wang and Lena Palaniyappan},

doi = {10.1192/j.eurpsy.2026.12246},

issn = {1778-3585},

year  = {2026},

date = {2026-07-01},

journal = {Eur Psychiatry},

pages = {1--39},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42109592,

title = {TOPSY: A picture description dataset to examine speech, language and communication in untreated first episode psychosis},

author = {Sharan Bhullar and Chaimaa El Mouslih and Michael Mackinley and Julie Richard and Lena Palaniyappan},

doi = {10.1016/j.dib.2026.112788},

issn = {2352-3409},

year  = {2026},

date = {2026-06-01},

journal = {Data Brief},

volume = {66},

pages = {112788},

abstract = {Recordings of human behaviour provide a rich source of data to detect features of conditions such as psychosis. Advanced technologies can now detect subtle speech aberrations that often go unnoticed by clinicians and family members. This is particularly important given that behavioral data, especially from untreated samples, are scarce. Speech is a crucial verbal behavioral data point for understanding psychosis, but the lack of comprehensive datasets has been a major limitation in research. Furthermore, long-term antipsychotic treatment can significantly affect speech, impacting both its tone and content. This makes it critical to collect longitudinal data to understand these effects. Tracking Outcomes of Psychosis (TOPSY) study aims to address these gaps by providing a rich dataset that includes not only speech data collected using a semi-structured picture description protocol but also a range of other valuable measures based on a validated Thought and Language Index. The TOPSY dataset offers naturalistic speech samples from individuals in an early-stage psychosis treatment program (<2 median days of antipsychotic treatment) and demographically matched healthy controls. This data is complemented by a comprehensive neurobiological and clinical battery, including: MRS (Magnetic Resonance Spectroscopy), Structural MRI, T1 structural data with myelin mapping, DTI (Diffusion Tensor Imaging), Resting fMRI (functional Magnetic Resonance Imaging). In addition to the neuroimaging data, we have collected detailed clinical and cognitive information, including TLI scores (Thought and Language Index) verbal fluency, modified DSST, and PANSS-8 item scores. The protocol and clinical assessments were repeated after a 12-month interval to assess the longitudinal stability of speech, symptom burden, and functional status. Transcripts were extracted from conversations lasting between 3 and 5 min, allowing for in-depth analysis of acoustic, semantic, syntactic, and pragmatic measures related to psychosis. We expect this dataset to be invaluable for future investigations into the clinical utility of speech measures for assessing thought disorder and other psychosis-related symptoms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42142295,

title = {Development and in vivo proof-of-concept of delayed alternating nutation tailored excitation point resolved spectroscopy (dante-press): a frequency-selective single voxel spectroscopy sequence applied to in vivo measurements of naa and glu at 7.0 T},

author = {Kesavi Kanagasabai and Omer Oran and Lena Palaniyappan and Jean Théberge},

doi = {10.1007/s10334-026-01365-4},

issn = {1352-8661},

year  = {2026},

date = {2026-05-01},

journal = {MAGMA},

abstract = {OBJECTIVE: Single-voxel proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive in vivo imaging technique used to quantify the concentration of human brain metabolites. Frequency-selective 1H-MRS techniques reduce spectral complexity and simplify spectral modeling. We introduce a single-shot frequency-selective sequence known as Delays-Alternating-Nutation-Tailored-Excitation-Point-RESolved-Spectroscopy (DANTE-PRESS) and test its precision when measuring glutamate and NAA at 7 Tesla in phantoms and human brain in vivo.nnMATERIAL AND METHODS: DANTE-PRESS was programmed within the software environment of the Siemens Magnetom 7 Tesla MR scanner at the Centre for Functional Metabolic Mapping in London, Ontario. Two scans were obtained on phantoms and in 4 healthy volunteers (20 × 20x20mm voxel at the dorsal anterior cingulate cortex) as an in vivo proof-of-concept to refocus glutamate or NAA.nnRESULTS: DANTE-PRESS preserves the signal of the metabolite of interest while suppressing unwanted signals via a narrow-band frequency-selective refocusing pulse. DANTE-PRESS produces metabolite spectral signatures with J-evolution equivalent to that seen in a PRESS sequence with less than half the echo time. The inter-individual coefficients of variance were low and Cramer-Rao Lower Bounds were less than 5.1% for glutamate and NAA.nnDISCUSSION: Future work involving test-retest in vivo study in healthy volunteers to get measurements of glutamate along with other metabolites such as glutathione and GABA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42142164,

title = {Age of onset: static and dynamic brain regional activity in first-episode drug-naïve schizophrenia},

author = {Maoxing Zhong and Jie Yang and Miao Zhang and Feiwen Wang and Yiju Wang and Lifu Tan and Zhening Liu and Lena Palaniyappan},

doi = {10.1007/s00787-026-03056-w},

issn = {1435-165X},

year  = {2026},

date = {2026-05-01},

journal = {Eur Child Adolesc Psychiatry},

abstract = {The age at which schizophrenia manifests is a critical factor influencing long-term outcomes. It is essential to distinguish the effects of the illness phase from those of the age of onset. We assessed static/dynamic brain regional activity from 428 participants, split into four groups based on onset-age (early-onset schizophrenia [EOS] and adult-onset schizophrenia [AOS]) and treatment status: (1) drug-naïve first-episode patients (48 EOS and 62 AOS); (2) patients treated for ≤ 12 months (60 EOS and 53 AOS); (3) patients treated for > 12 months (56 EOS and 56 AOS); and (4) 93 healthy controls (32 age-matched with EOS, 61 age-matched with AOS). We conducted a principal component analysis and subsequent 2 × 2 factorial analysis on the extracted first component representing static/dynamic regional activity, followed by an out-of-sample imaging transcriptomics analysis. The stability of results from the drug-naïve groups were tested on the treated groups to account for antipsychotic effects. Onset-age had a notable interaction with diagnosis on the static activity of the thalamus, mid-cingulate cortex (MCC), cerebellum posterior lobe (CPL), precuneus, and putamen, and on the dynamic stability of the CPL, thalamus, and superior parietal lobule (SPL). Phase of illness and medication exposure did not affect the onset-age effect seen at the MCC, thalamus, and SPL. Transcriptomics analysis pointed to the possibility of a shared disruption in neuronal differentiation across the MCC, thalamus and SPL. Onset-age affects thalamo-fronto-parietal regional hemodynamic activity, possibly through disrupted neuronal differentiation, in schizophrenia. Exposure to antipsychotics do not reverse this functional imprint of the earlier illness onset, raising the question of alternate therapeutic approaches to close the observed "neurophysiological gap".},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42187272,

title = {The functional relevance of a short assessment of formal thought disorder in psychosis},

author = {Fatme Abboud and Jessica Ahrens and Estèe Ballès and Valentina Bambini and Bill Deakin and Neil A Harrison and Tilo Kircher and Gina Kuperberg and Peter F Liddle and Rohit Lodhi and Michael Mackinley and Susan L Rossell and Krish D Singh and Iris E Sommer and Alban Voppel and Farida Zaher and Nadia Zeramdini and Lena Palaniyappan},

doi = {10.1192/bjp.2026.10650},

issn = {1472-1465},

year  = {2026},

date = {2026-05-01},

journal = {Br J Psychiatry},

pages = {1--9},

abstract = {BACKGROUND: Formal thought disorder (FTD) is a highly disabling transdiagnostic feature that impedes communication and social ties. Progress in understanding and treating FTD has been hampered by the uncertainties in its assessment.nnAIMS: We examined if a short 3-5min assessment of transcribed speech can capture the latent dimensions and network structure of FTD and predict functional outcomes.nnMETHOD: In a transdiagnostic sample ( = 666) with a single longitudinal follow-up over 3-12 months ( = 244), we administered the short form of the Thought and Language Index to measure eight individual features of FTD. We determined the baseline factor structure of FTD, its temporal invariance at follow-up, and the predictive validity of FTD dimensions on the global single-item Social and Occupational Functioning Assessment Scale scores at baseline and follow-up. We identified the most influential and putative primary phenomena within the FTD syndrome, using network analysis.nnRESULTS: Factor analyses revealed a stable three-factor model of FTD: impoverishment (poverty of speech, weakening of goal), loosening (looseness, illogicality) and peculiarities (peculiar words, peculiar sentences), with excellent fit (Comparative Fit Index: 0.997, root mean square error of approximation: 0.040) and metric invariance over time. Impoverishment and peculiarities predicted functioning at baseline and 3-12 months later (cross-sectional:  = -0.196,  < 0.001 and  = -0.298,  = 0.001, respectively; longitudinal:  = -0.201,  = 0.037 and  = -0.336,  = 0.042, respectively). Looseness and poverty of speech were putative primary features influencing other FTD phenomena. Weakening of goal and peculiar sentences were the most connected phenomena.nnCONCLUSIONS: By integrating latent variable and network approaches, we provide a unified, empirically grounded framework to interpret FTD assessed using a brief speech task. We report a replicable three-dimensional structure, identify central symptoms that may maintain the FTD syndrome, and the specific dimensions that influence functional disability. These findings clarify the prognostically valuable features of FTD for future mechanistic and interventional research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42204548,

title = {Putative glymphatic dysfunction links extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis},

author = {Xin Jin and Yan Fu and Ting Qiu and Jianyu Li and Huixiong Zhang and Yifan Chen and Kewei Chen and Yuanchao Zhang and Junling Wang and Xiaoping Yi and Lena Palaniyappan and B Blair Braden},

doi = {10.1186/s12916-026-04948-z},

issn = {1741-7015},

year  = {2026},

date = {2026-05-01},

journal = {BMC Med},

volume = {24},

number = {1},

abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration and prominent extra-motor involvement. Impaired clearance of neurotoxic proteins has led to increasing interest in the brain glymphatic system; however, its in vivo associations with brain microstructure and clinical heterogeneity remain incompletely understood.nnMETHODS: One hundred forty-six patients with ALS and 149 demographically matched healthy controls (HCs) underwent multimodal MRI and comprehensive clinical assessments. Putative glymphatic function was quantified using diffusion tensor imaging along perivascular space (DTI-ALPS). Extracellular free water fraction (FWF) and free-water-corrected fractional anisotropy (fwcFA) were derived to characterize extracellular fluid and white matter microstructure. Group differences were assessed using vertex-wise and voxel-wise analyses with correction for multiple comparisons. Associations among imaging metrics and clinical measures were evaluated using correlation and serial mediation analyses.nnRESULTS: Compared with HCs, patients with ALS exhibited significantly reduced DTI-ALPS index, widespread increases in cortical FWF, bidirectional alterations in white matter FWF, and extensive reductions in fwcFA across major white matter tracts. Reduced DTI-ALPS was associated with changes in extracellular free water and white matter microstructural integrity, whereas FWF and fwcFA measures were associated with functional, cognitive, and emotional outcomes. Mediation analyses identified significant indirect associations between DTI-ALPS and both functional and cognitive measures through a pathway involving cortical FWF, white matter FWF, and fwcFA, although direct associations were not observed.nnCONCLUSIONS: These findings provide in vivo evidence that putative glymphatic dysfunction co-occurs with extracellular fluid alterations, white matter microstructural changes, and clinical impairment in ALS. Multi-compartment diffusion imaging may offer complementary markers for characterizing brain microstructure and its clinical relevance in ALS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41704505,

title = {The DISCOURSE in psychosis (London Ontario): A speech dataset to examine communication disturbances in early-stage psychosis},

author = {Brian Cho and Estée Balles and Michael Mackinley and Paulina Dzialoszynski and Sabrina Ford and Rohit Lodhi and Lena Palaniyappan},

doi = {10.1016/j.dib.2026.112517},

issn = {2352-3409},

year  = {2026},

date = {2026-04-01},

journal = {Data Brief},

volume = {65},

pages = {112517},

abstract = {Advances in speech technology and Natural Language Processing (NLP) have demonstrated promise in using speech as a valid source of data to detect features of psychosis. These technologies can potentially detect subtle speech aberrations that often go unnoticed by clinicians and family members. However, research in this area is hindered by a significant limitation: a lack of sufficient and appropriate speech corpora from psychosis patients, especially datasets containing naturalistic speech that reflects typical clinical interactions. This scarcity limits the development, testing, and generalization of new computational methods for psychosis prediction. To address this gap, our new dataset offers naturalistic speech samples collected using the semi-structured DISCOURSE protocol. This resource includes both raw audio recordings and transcribed speech from individuals participating in an early-stage psychosis treatment program (<5 years of illness), alongside demographically matched healthy controls, in English. In addition to speech data, the dataset provides comprehensive clinical, cognitive, and demographic information for each participant. Importantly, the DISCOURSE protocol and clinical assessments were repeated after a 12-month follow-up to assess stability and change in speech, symptom burden and functional status. As the inaugural dataset released by the DISCOURSE consortium, this resource marks the beginning of a series of harmonized data collection efforts across multiple countries and languages. This multi-site, multi-language approach enables validation of findings in diverse psychosis populations, allowing researchers to address questions that cannot be resolved at individual research sites. Transcripts were extracted from conversations lasting between 15 and 35 minutes in total. This data herein can be used to perform analyses on acoustic, semantic, syntactic and pragmatic measures related to psychosis, as well as in understanding the nature of communication difficulties faced by patients. We expect this dataset to be useful for future investigations into speech data's clinical utility in assessing thought disorder and psychosis-related symptoms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41943939,

title = {Dynamic frontoparietal flexibility and cognitive dysfunction in schizophrenia: disentangling the roles of symptom burden and childhood trauma},

author = {Danqing Huang and Zhening Liu and Wenjian Tan and Michel Sopodenkiewicz and Xiawei Liu and Jun Yang and Feiwen Wang and Weiqing Huang and Jie Yang and Yicheng Long and Lena Palaniyappan},

doi = {10.1017/S0033291726103869},

issn = {1469-8978},

year  = {2026},

date = {2026-04-01},

journal = {Psychol Med},

volume = {56},

pages = {e93},

abstract = {BACKGROUND: Working memory (WM) impairment is a core cognitive deficit in schizophrenia, associated with dysfunction of large-scale brain networks, particularly the triple-network system comprising the default mode, frontoparietal, and salience networks. Given the role of environmental risks like childhood trauma (CT) in cognitive deficits, we investigated whether trauma relates to altered triple-network flexibility and WM in schizophrenia.nnMETHODS: We enrolled 190 patients with schizophrenia (SZ) and 117 healthy controls (HCs). Among them, 162 SZ and 99 HCs underwent -back task-based functional magnetic resonance imaging. We computed temporal variability (TV) in the triple-network connectivity, defining ΔTV as the change between 0-back and 2-back conditions. Subgroup comparisons of ΔTV were conducted within each group based on trauma status. Associations of ΔTV with WM performance and clinical symptoms were examined in SZ, followed by mediation analyses testing whether ΔTV mediates the relationship between trauma and WM.nnRESULTS: Among HCs, individuals with childhood trauma showed reduced ΔTV across triple-network connections, whereas no such differences appeared in SZ. In SZ, greater ΔTV within the frontoparietal network (FPN) was correlated with lower positive symptom severity ( = -0.211, -fdr = 0.046) and better -back target accuracy ( = 0.303, -fdr = 0.002). Furthermore, ΔTV within the FPN partially mediated the association between trauma and -back accuracy.nnCONCLUSIONS: Our findings highlight the central role of FPN flexibility in mediating childhood trauma's effect on working memory in schizophrenia. This outlines a key pathway through which an early environmental risk (trauma) translates into cognitive and clinical manifestations in schizophrenia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41969055,

title = {What is being measured by formal thought disorder scales? An item-level content analysis},

author = {Vanteemar S Sreeraj and Alban Voppel and Ganesan Venkatasubramanian and Lena Palaniyappan},

doi = {10.1017/S0033291726104152},

issn = {1469-8978},

year  = {2026},

date = {2026-04-01},

journal = {Psychol Med},

volume = {56},

pages = {e106},

abstract = {BACKGROUND: Formal thought disorder (FTD), characterized by disruptions in the flow and form of thought, is a core feature of psychosis. But its measurement is fragmented across numerous rating scales, leading to its continued neglect in both research and clinical practice. To determine if different FTD scales measure the same underlying construct, we need to assess the degree to which the content of commonly used FTD scales overlaps with each other.nnMETHODS: We conducted a systematic review to identify all standardized, clinician-rated scales used to measure FTD in psychotic disorders. From this set, we extracted individual items and derived a consensus list of 56 discrete FTD phenomena. Two independent clinical experts conducted item-to-item mapping for every scale item onto these FTD phenomena. Content overlap between scales was quantified using Jaccard Similarity Index (JSI). We determined the overall coverage achieved via several combinations of FTD scales.nnRESULTS: The 15 scales, comprising 207 items, showed weak content overlap. The mean JSI across all scale pairs was low, and no single phenomenon featured across all scales. While some core FTD phenomena (e.g. 'incoherence', 'poor speech content', 'drifting-off') were represented in many scales, 20% of all identified features were idiosyncratic, appearing in only one scale.nnCONCLUSIONS: Existing FTD rating scales capture a wide but heterogeneous array of symptoms with poor content overlap. This lack of harmonization challenges the comparability of mechanistic and interventional studies. We highlight the need for a consensus-based, standardized measurement of FTD and provide a comprehensive checklist to advance the research and clinical practice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42033337,

title = {High-Risk Human-AI Engagement: Clinical Assessment and Management Considerations},

author = {Lena Palaniyappan and Vincent Paquin and Etienne Barou-Laforie},

doi = {10.1177/07067437261445770},

issn = {1497-0015},

year  = {2026},

date = {2026-04-01},

journal = {Can J Psychiatry},

pages = {7067437261445770},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42037310,

title = {Increasing Participation of People with Thought Disorder in Clinical Research},

author = {Lena Palaniyappan and Sylvain Baillet and Valentina Bambini and Etienne Barou-Laforie and Marta Bosia and Oli Delgaram-Nejad and Hashwin Ganesh and Ranjini Garani and Neil Harrison and Vegas Hodgins and Ridha Joober and Gina Kuperberg and Tilo Kircher and Chantal Murthy and Susan Rossell and Krish D Singh and Iris E Sommer and Sunny X Tang and Debra Titone and Alban Voppel and Tosh Watson and Irnes Zeljkovic},

doi = {10.1192/j.eurpsy.2026.12211},

issn = {1778-3585},

year  = {2026},

date = {2026-04-01},

journal = {Eur Psychiatry},

pages = {1--36},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42061696,

title = {Reading between the lines: Combining pause dynamics and semantic coherence for automated assessment of thought disorder},

author = {Feng Chen and Weizhe Xu and Changye Li and Serguei Pakhomov and Alex Cohen and Simran Bhola and Sandy Yin and Sunny X Tang and Michael Mackinley and Lena Palaniyappan and Dror Ben-Zeev and Trevor Cohen},

doi = {10.1016/j.neuropsychologia.2026.109473},

issn = {1873-3514},

year  = {2026},

date = {2026-04-01},

journal = {Neuropsychologia},

volume = {228},

pages = {109473},

abstract = {Formal thought disorder (FTD), a hallmark of schizophrenia spectrum disorders, manifests as incoherent speech and poses challenges for clinical assessment. Traditional clinical rating scales, though validated, are resource-intensive and lack scalability. Automated speech recognition (ASR) allows for objective quantification of linguistic and temporal features of speech, offering scalable alternatives. Furthermore, ASR-derived utterance timestamps provide access to pause dynamics, which are thought to reflect the cognitive processes underlying speech production. Yet, their added value beyond semantic measures remains insufficiently explored. In this study, we evaluated a scalable multimodal framework that integrates pause features with semantic coherence metrics across three datasets: naturalistic self-recorded diaries (AVH, n = 140 participants), structured picture descriptions (TOPSY, n = 72 participants), and dream narratives (PsyCL, n = 43 participants). Pause-related features were evaluated alongside established coherence measures using support vector regression (SVR) to predict clinical FTD scores. Models using pause features alone robustly predict manually rated FTD severity consistently across datasets. Integrating pause features with semantic coherence metrics enhanced predictive performance compared to coherence-only models, with late fusion yielding the most robust and consistent gains in all three datasets. On average across datasets, Spearman correlation increased from ρ = 0.413 for semantic-only models to ρ = 0.455 with late fusion. The performance gains from semantic and pause features integration held consistently across all contexts, though the nature of the most informative pause patterns was dataset-dependent. These findings suggest that both pause dynamics and semantic coherence reflect complementary aspects of thought disorganization. Our integration framework provides a scalable approach for refining the assessment of disorganized speech to advance automated speech analysis in psychosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41327800,

title = {"I felt like that was a safe place to go": a qualitative study of help-seeking experiences for early psychosis in primary care},

author = {Rebecca Rodrigues and Candice Madakadze and Jordan Edwards and Richard Booth and Suzanne Archie and Lena Palaniyappan and Sarah Chan and Kerri Nagy and Kelly K Anderson and },

doi = {10.1080/09638237.2025.2595617},

issn = {1360-0567},

year  = {2026},

date = {2026-04-01},

journal = {J Ment Health},

volume = {35},

number = {2},

pages = {199--207},

abstract = {BACKGROUND: Contacts with primary care for early psychosis are common, and there is a need for further insight into help-seeking patterns.nnAIMS: We sought to describe the help-seeking experiences in primary care for people with early psychosis and their caregivers.nnMETHODS: Using a qualitative descriptive approach, we recruited 22 clients with first-episode psychosis and 13 caregivers from seven specialized clinics to participate in a semi-structured interview. Interviews were audio recorded, transcribed, and coded thematically using conventional content analysis.nnRESULTS: Help-seeking experiences in primary care were varied. We identified themes describing client- and caregiver-level challenges and supports: impaired mental state, help-seeking decisions and support, and conflicting cultural beliefs and values (between clients and physicians). We also identified physician-level challenges and supports: physician knowledge (perceived as adequate or inadequate), follow-up (close or lack thereof), and supportive relationship with the client and/or caregiver. Finally, we identified health system-level themes: appointment availability and virtual care (described as insufficient).nnCONCLUSIONS: Interventions to increase help-seeking for early psychosis more broadly may facilitate earlier primary care help-seeking. Primary care physician education, closer follow-up of young people with mental health issues, timely access, and in-person care could improve pathways to care in early psychosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41579632,

title = {Formal thought disorder and familial risk in first-episode psychosis: A study of cortical thickness and neuroimaging-transcriptomic association analysis},

author = {Tuğçe Çabuk and Yuanchao Zhang and Lena Palaniyappan and Didenur Şahin-Çevik and Hanife Avcı and Işık Batuhan Çakmak and Helin Yılmaz Kafalı and Bedirhan Şenol and Kader Karlı Oğuz and Timothea Toulopoulou},

doi = {10.1016/j.pscychresns.2026.112148},

issn = {1872-7506},

year  = {2026},

date = {2026-04-01},

journal = {Psychiatry Res Neuroimaging},

volume = {357},

pages = {112148},

abstract = {Formal thought disorder (FTD), a prominent feature of schizophrenia, encompasses disruptions in thought, language, and communication. This study examines cortical thickness (CT) alterations in first-episode psychosis (FEP) patients (N = 24), their siblings (SIB) (N = 21), and healthy controls (CON) (N = 21) to explore potential neural correlates of FTD. Using structural MRI, we analyzed whole-brain CT and its relationship with positive and negative FTD measured by Thought and Language Index. Out-of-sample spatial correlations of gene expression with regional CT were also performed using a transcriptomic dataset. FEP had significant CT reductions in right middle frontal gyrus (MFG) compared with SIB and CON and in superior frontal gyrus (SFG) compared to CON; but SIB did not differ from CON. GLM analyses demonstrated that negative FTD exerted a significant main effect on CT in the MFG and SFG. By contrast, positive FTD showed no significant associations with CT. Neuroimaging-transcriptomic association analysis identified key biological pathways linked to cortical morphology. These findings emphasize the specific association between negative FTD and CT alterations in frontal brain regions, confirming prior reports. Future research should examine larger cohorts and investigate additional FTD subtypes to further elucidate neural correlates and potential familial risks of schizophrenia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41146942,

title = {Exploring the interplay between language use and cognitive function in schizophrenia spectrum disorders: Insights from patients, first degree relatives, and healthy controls},

author = {Rosa Ayesa-Arriola and Carlos Martinez-Asensi and Alexandre Díaz-Pons and Víctor Ortiz-García de la Foz and Claudia Parás and Chaimaa El Mouslih and Roozbeh Sattari and Sara Incera and Lena Palaniyappan},

doi = {10.1016/j.scog.2025.100398},

issn = {2215-0013},

year  = {2026},

date = {2026-03-01},

journal = {Schizophr Res Cogn},

volume = {43},

pages = {100398},

abstract = {BACKGROUND: For people with schizophrenia spectrum disorders (SSD), communication characterized by disrupted language use is common. However, the role of cognitive function in everyday language disruptions in SSD remains unclear. Family studies help control for confounding factors such as symptom burden, medication use and environment, offering insight into the interplay between language and cognition in SSD.nnSTUDY DESIGN: We examined linguistic features in naturalistic speech from 176 individuals (51 with SSD, 77 first-degree relatives [50 parents, 27 siblings], and 48 healthy controls). Tasks included conversations, picture descriptions, story narration, reading and recall. We assessed cognitive domains: attention, verbal/visual memory, working memory, executive function, processing speed, motor dexterity, and theory of mind. We then studied associations between cognition and language.nnRESULTS: Different patterns emerged across groups. In controls, longer speech and fewer pronouns were linked to better cognition. In SSD, greater adposition use and fewer pronouns related to better memory, executive function, and IQ. Among parents, more coordinating conjunctions during narration correlated with better visual memory and motor dexterity. Siblings showed the strongest, broadest associations: better cognition predicted richer language and fewer pronouns, especially tied to global and motor function. Story narration revealed the richest cognitive-linguistic links.nnCONCLUSIONS: In people with SSD and their relatives, specific cognitive deficits are reflected in everyday speech, regardless of content. These findings highlight the role of discourse context in shaping language-cognition relationships and support future research using language markers in psychosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41820654,

title = {Setting digital psychiatry in motion: towards dynamic digital markers for digital phenotyping},

author = {Axel Constant and C Emre Koksal and Lena Palaniyappan},

doi = {10.1038/s44277-026-00059-y},

issn = {2948-1570},

year  = {2026},

date = {2026-03-01},

journal = {NPP Digit Psychiatry Neurosci},

volume = {4},

number = {1},

abstract = {Digital phenotyping uses data from smartphones and wearables to extract behavioural and biosocial markers of psychopathology in situ. Traditional entropy-based measures capture static system properties that neglect temporal dependencies critical to psychiatric phenomena. We propose a "dynamic" approach to the modelling of digital data capturing the time-varying aspects of processes of mental disorders. We defend that the resulting dynamic digital markers better capture variability in regulatory mechanisms of psychopathology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41050346,

title = {Clinical psychopathology-based early relapse prediction model using speech and language in psychosis},

author = {Tyler C Dalal and Min Tae M Park and Angelica M Silva and Svetlana Iskhakova and Alban Voppel and Noah J Brierley and Michael MacKinley and Emmanuel Olarewaju and Lena Palaniyappan},

doi = {10.1016/j.scog.2025.100392},

issn = {2215-0013},

year  = {2026},

date = {2026-03-01},

journal = {Schizophr Res Cogn},

volume = {43},

pages = {100392},

abstract = {INTRODUCTION: Prediction of psychotic relapse using speech-derived markers promises targeted early intervention. However, the sheer number of speech markers and the 'black box' nature of predictive models challenges clinical translation.nnMETHODS: We propose a psychopathology-based systematic approach to identify likely relapse. We draw on the notion that the predictors of relapse should mark (1) the presence of schizophrenia in its untreated early stages and (2) track disorganization in psychosis. By leveraging Natural Language Processing, we derive 3 lexical, syntactic and narrative markers -semantic similarity, clause complexity, and analytic thinking index from speech samples of people with acute psychosis ( = 68) followed up for subsequent relapses over a year (12 out of 68).nnRESULTS: Speech-based model predicted relapse status with strong evidence (Bayes Factor BF = 79.5) against the clinical intuition model.nnCONCLUSION: Using a Bayesian approach, this preliminary study demonstrates the utility of psychopathology-guided variable selection for speech-based relapse prediction complementing clinical intuition in practice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}