Tag: Reality testing and perceptual stability

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Clinical correlates and cognitive associations of the neutrophil-to-lymphocyte ratio in first-episode psychosis and at-risk mental states

ObjectiveClinical high-risk for psychosis (CHR-P) and first-episode psychosis (FEP) individuals present immune alterations that precede treatment initiation. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a simple, accessible marker of systemic inflammation. This study investigates differences across CHR-P, FEP, and healthy control (HC) populations and explores peripheral associations between NLR and demographic, clinical, and cognitive variables.MethodsData were collected from 63 FEP, 56 CHR-P, and 27 HC individuals from two early intervention services in Spain. Socio-demographic, clinical, and neurocognitive data were collected from all participants, along with peripheral blood samples for NLR calculation. Correlations between NLR and clinical and neurocognitive variables were analyzed using multivariate models to control for potential confounders.ResultsNo significant differences in NLR were observed between the FEP, CHR-P, and HC groups (F = 1.04; p=0.36). In the FEP population, NLR was positively correlated with higher levels of positive symptoms (β=0.035; p=0.01) and longer duration of untreated psychosis (β=0.003; p=0.04) after adjusting for sex and age. In CHR-P individuals, NLR was negatively correlated with antidepressant use (β=-0.664; p=0.02). No significant associations were found between NLR and neurocognitive performance or antipsychotic treatment in any clinical group.ConclusionsOur findings do not support the utility of NLR as a diagnostic biomarker in early psychosis. However, the observed association between elevated NLR and positive psychotic symptoms in FEP suggests that NLR could serve as a state biomarker, reflecting inflammatory status related to symptom severity. Further research is needed to explore NLR dynamics in larger samples and its potential role in monitoring clinical progression in psychosis.
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Reduced left dorsolateral prefrontal activation and right inferior frontal de-oxygenation differ between psychotic and non−psychotic adolescent depression during verbal fluency

BackgroundAdolescents with major depressive disorder (MDD) who exhibit psychotic symptoms (MDD-Psy) often show greater clinical severity and higher suicide risk than those without psychosis (MDD-NonPsy). It remains unclear whether prefrontal hemodynamic responses during cognitive challenge can differ between these subgroups.MethodsWe recruited 273 adolescents aged 14–16 years (110 MDD-NonPsy, 163 MDD-Psy). All completed a 60-s verbal fluency task (VFT) while 53-channel functional near-infrared spectroscopy recorded oxy- and deoxyhemoglobin (HbO, HbR) from six frontal ROIs. Whole-brain FDR correction identified baseline-deviated channels, and ROC analyses tested the discriminative value of significant channels/ROIs. Clinical severity was indexed by the Kutcher Adolescent Depression Scale (KDAS) and the Brief Psychiatric Rating Scale (BPRS).ResultsCompared with MDD-NonPsy, adolescents with MDD-Psy exhibited higher KDAS (median 16 vs 13; z = -7.07, p < 0.001) and BPRS total scores (median 35 vs 28; z = -11.02, p < 0.001). After FDR correction, MDD-NonPsy showed positive deviations at channels 8 and 23 (t = 2.10-2.70, pFDR=0.038), whereas MDD-Psy exhibited negative deviation at channel 2 (MNI –60, 19, 18; left middle frontal gyrus; t =-2.89, pFDR = 0.004). Across ROIs, only right inferior frontal gyrus HbR differed between groups (median –0.03 vs 0.00 mM·mm; z = -2.18, pFDR = 0.030). No ROI-level HbO differences survived correction. At the single-channel level, HbO at channel 2 and HbR in IFG_R correlated modestly with lower KDAS and restlessness scores (ρ = –0.14 to –0.16, p <0.050). ROC analyses indicated modest but significant classification accuracy for psychosis (AUC = 0.577-0.581, p = 0.030).ConclusionsLeft dorsolateral and right inferior prefrontal hemodynamic signatures differ between adolescents with MDD who present with versus without psychotic features. However, given the absence of healthy control or other psychiatric comparison groups, these findings cannot establish diagnostic specificity. Pending replication in independent samples, these fNIRS−derived hemodynamic signatures may inform future hypothesis−driven research.
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<![CDATA[New analysis finds postpartum depression and postpartum psychosis have distinct underlying biological mechanisms.]]>
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Plasma microRNA signatures in drug-naïve Romanian adolescents with first-episode psychosis

Psychotic disorders are a group of severe psychiatric conditions with onset typically occurring in adolescence or early adulthood. Despite significant efforts to identify clinically useful candidates, no validated biomarkers for psychiatric disorders currently exist. The diagnosis of psychotic disorders is exclusively based on clinical assessment, significantly affected by individual differences and symptom overlap. Although circulating microRNAs (miRNAs) have emerged as potential peripheral biomarkers for early diagnosis and disease evolution, most studies concentrate on adult, medicated cohorts. Studies on miRNA profiles in drug-naïve adolescents with first-episode psychosis (FEP) are scarce. This study aims to identify the plasma miRNA profile in treatment-naïve Romanian adolescents with first-episode psychosis and to compare it with that of age- and sex-matched healthy controls. The plasma from 14 adolescents, seven drug-naïve FEP and seven and age-matched controls (CTRL) aged 15–18 years was collected. Psychiatric symptoms were assessed using PANSS, HAM-D, and YMRS scales. The levels of 179 miRNAs were assessed using qRT-PCR. A case-control analysis on miRNAs levels between FEP and CTRL was performed, as well as correlations with clinical measures. Twenty-one miRNAs showed significantly lower levels and two higher levels in FEP patients compared to controls. After adjustment for multiple comparisons, miR-125a-5p, miR-205-5p, miR-145-5p, miR-363-3p, and miR-23b-3p remained statistically significant (FDR<0.05). Notably, miR-125a-5p, miR-23b-3p, and miR-146a-5p levels negatively correlated with psychotic, depressive, and manic symptom severity, while miR-16-5p and miR-363-3p positively correlated with symptom scores. Comparison with previous studies indicated limited overlap, reflecting potential influences of age, treatment status, and genetic or environmental factors. This work demonstrates that Romanian treatment-naïve adolescents with first-episode psychosis had a unique circulating miRNA profile correlated with symptom severity, indicating their potential as early-stage biomarkers. The results underscore the necessity of accounting for age, treatment status, and environmental variables in the interpretation of miRNA modifications in psychotic illnesses.
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<![CDATA[ASCP 2026 leaders share practical ways to engage patients in acute psychosis—active listening, noncollusive language, and rapport before assessment.]]>
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ESMR: a process framework for calibration dynamics across psychosomatic and psychiatric phenomena

The brain can be modeled as a generative system that predicts bodily and environmental input and reduces mismatch through updating and action. From this perspective, stress is treated not as prediction error per se, but as a condition in which mismatch persists without sufficient recalibration. Health is therefore defined not as the absence of symptoms, but as the preservation of recalibrability, whereas psychopathology is conceptualized as the progressive fixation of recalibration failure. This paper proposes ESMR as a four-layer, two-timescale process framework for comparing psychosomatic conditions, psychiatric disorders, and psychosis-level phenomena in terms of partially shared failures of recalibration rather than as a single disease continuum. ESMR distinguishes E (Embodied Constraints), S (Salience Calibration), M (Metacognitive Model Revision), and R (Reality-Grounding Interface) across learning (L) and development (D). Development is treated not merely as slower accumulation of prior learning, but as change in the biological, representational, and self-regulatory architecture that alters both what forms of recalibration are possible and the background conditions under which learning can be taken up. A central distinction is that M concerns whether corrective information can be converted into updating, whereas R concerns whether already understood correction can be adopted as self-relevant reality under embodied, practical, and interpersonal constraints, with downstream transfer treated as a consequence rather than part of the R core. The framework predicts layer-specific cross-signatures rather than a single undifferentiated burden effect and outlines a staged empirical program using framing, disconfirmation, reality-grounding, and embodied/interoceptive tasks. ESMR is offered as a revisable, clinically oriented intermediate framework rather than a completed computational model.
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<![CDATA[Analysis of speech, acoustics, and facial cues reveals early psychosis and suicide risk.]]>
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<![CDATA[Computational phenotyping reveals prodromal psychosis clues, connects biomarkers to symptoms, and shows why stress and cannabis reduction matters.]]>