Maria Lee

All Publications

• Cognition before and after psychosis onset: A naturalistic study of change, heterogeneity, and prognosis. Schizophrenia research. Cognition Lee, M., Cullen, A. E., Matheson, G. J., Lu, Z. A., Bergen, S. E., Sellgren, C. M., Erhardt, S., Fatouros-Bergman, H., Cervenka, S. 2025; 42: 100387

  Abstract

  Cognitive dysfunction is a core feature of psychotic disorders. The degree of impairment varies greatly between individuals, which may reflect different levels of decline from pre-morbid functioning. Diverse trajectories of cognitive change prior to or during development of psychosis have been hypothesized to reflect distinct underlying pathological processes. Our primary aim was to model cognitive change over time in a sample of individuals with first-episode psychosis (FEP) and controls. The secondary aim was to explore associations between cognitive change, clinical outcomes and select biological markers.Our sample consisted of 72 individuals with FEP and 53 controls. School grades from nationwide population registers were used as a proxy for pre-morbid cognitive ability. All participants underwent formal cognitive testing at psychosis onset, with a subset returning for testing at 1,5 year follow up. Cognitive change was modelled using linear mixed-effects models, and resulting change scores were correlated to polygenic risk scores, cerebrospinal fluid levels of complement protein C4A and clinical outcomes.Groups did not differ in school performance prior to psychosis. Psychosis onset was associated with marked cognitive decline in FEP individuals, who subsequently performed significantly worse than controls. However, cognitive change over time varied widely between FEP individuals. Degree of cognitive change was not associated with the selected biological variables but did predict worse clinical outcomes.Individual cognitive trajectories may be a clinically relevant topic for further study, and larger studies are needed to further explore their potential role in stratified models of care.

  View details for DOI 10.1016/j.scog.2025.100387

  View details for PubMedID 40933840

  View details for PubMedCentralID PMC12419124

• Pain threshold and pain tolerance in young people with self-injurious behavior: A systematic review and meta-analysis. Psychiatry research Pontén, M., Lee, M., Khoo, S., Nilsson, G., Nevin, E., Walldén, Y., Ougrin, D., Cummins, T. M., Flygare, O., Bjureberg, J. 2025; 351: 116638

  Abstract

  Pain sensitivity has been proposed as a contributing factor to self-injurious behavior (SIB). Meta-analytic results show that individuals with SIB have lower pain sensitivity than healthy controls (HC). However, these findings are primarily based on adult populations. SIB typically begins in the early teen years and is most prevalent among youth. The aim of the present meta-analysis was to quantify the association of SIB and pain thresholds and pain tolerance in young people aged 10 to 24 years.We performed a systematic search of the literature (MEDLINE, Web of Science Core Collection and PsycINFO) up until 10 December 2024. Titles, abstracts, and full texts were independently screened by multiple reviewers. Random-effects meta-analysis was performed on two pain-related outcomes: pain threshold and pain tolerance. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Quality assessment was performed using the Newcastle-Ottawa scale.Of 5200 screened studies, 221 full-text articles were retrieved whereof 8 studies fulfilled the criteria (n=592). Participants ranged from 10 to 22 years. Meta-analysis demonstrated statistically significantly higher pain threshold (Hedges' g = 0.79, 95 % CI [0.13, 1.46]) in individuals with SIB compared to HC and no statistically significant difference in pain tolerance (Hedges' g = 0.39, 95 % CI [-0.02; 0.79], p = 0.056).Young people with SIB demonstrate higher pain thresholds compared to healthy controls, suggesting that lower sensitivity to painful stimulation may be a risk factor for SIB across developmental stages. Future studies should examine whether this association is independent of psychiatric comorbidity and other confounding factors.

  View details for DOI 10.1016/j.psychres.2025.116638

  View details for PubMedID 40714719

• Cognitive Function and Variability in Antipsychotic Drug-Naive Patients With First-Episode Psychosis: A Systematic Review and Meta-Analysis. JAMA psychiatry Lee, M., Cernvall, M., Borg, J., Plavén-Sigray, P., Larsson, C., Erhardt, S., Sellgren, C. M., Fatouros-Bergman, H., Cervenka, S. 2024; 81 (5): 468-476

  Abstract

  Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset at a group level; however, the question of heterogeneity in cognitive function among patients has not been systematically investigated.To provide an updated quantification of cognitive impairment at psychosis onset before patients receive potentially confounding antipsychotic treatment, and to investigate variability in cognitive function compared with healthy controls.In this systematic review and meta-analysis, PubMed articles were searched up to September 15, 2022.Original studies reporting data on cognitive function in antipsychotic drug-naive patients with first-episode psychosis (FEP) were included.Data were independently extracted by 2 researchers. Cognitive tasks were clustered according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias.The main outcome measure was Hedges g for mean differences in cognition and CVR for within-group variability.Fifty studies were included in the analysis with a total of 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). In all cognitive domains, the FEP group displayed significant impairment compared with controls (speed of processing: Hedges g = -1.16; 95% CI, -1.35 to -0.98; verbal learning: Hedges g = -1.08; 95% CI, -1.28 to -0.88; visual learning: Hedges g = -1.05; 95% CI, -1.27 to -0.82; working memory: Hedges g = -1.04; 95% CI, -1.35 to -0.73; attention: Hedges g = -1.03; 95% CI, -1.24 to -0.82; reasoning/problem solving: Hedges g = -0.90; 95% CI, -1.12 to -0.68; executive function: Hedges g = -0.88; 95% CI, -1.07 to -0.69). Individuals with FEP also exhibited a larger variability across all domains (CVR range, 1.34-1.92).Results of this systematic review and meta-analysis identified cognitive impairment in FEP before the initiation of antipsychotic treatment, with large effect sizes. The high variability within the FEP group suggests the need to identify those individuals with more severe cognitive problems who risk worse outcomes and could benefit the most from cognitive remediation.

  View details for DOI 10.1001/jamapsychiatry.2024.0016

  View details for PubMedID 38416480

  View details for PubMedCentralID PMC10902783

• Facial affect recognition in first-episode psychosis is impaired but not associated with psychotic symptoms. Heliyon Larsson, C., Lee, M., Lundgren, T., Erhardt, S., Sellgren, C. M., Cervenka, S., Borg, J., Bölte, S., Fatouros-Bergman, H. 2022; 8 (9): e10424

  Abstract

  Social dysfunction is a key feature of psychotic disorders such as schizophrenia linked to disability. Less is known about social functioning in the early stages of the disorder and if there is an association to psychotic symptoms.Investigate if antipsychotic drug-naïve or briefly medicated individuals with first-episode psychosis (FEP), have impaired facial affect recognition (FAR) compared to control participants and if psychotic symptoms are associated with the FAR ability.Individuals with FEP (n = 67) and control participants (n = 51) performed a computer-aided FAR task on basic emotions. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Group performances were compared using age and gender as covariates. The associations between FAR and performance on the subscales of PANSS were analyzed.Compared to control participants, individuals with FEP were impaired in general FAR (Beta = -2.04 [95 % conf: -3.75/-1.62], p < 0.001) and FAR of negative emotions (Beta = -1.74 [95 % conf: -3.08/-1.22], p < 0.001), driven by difficulties in recognition of anger and disgust. In both groups, there was a pattern of mistaking negative emotions for other negative emotions. There were no significant group differences in FAR of happiness. No significant associations between FAR and psychotic symptoms were observed.The results indicate that FAR, an underlying mechanism of social functioning is impaired early in the course of psychotic disorders. Current findings do not support the hypothesis that misinterpretation of facial expressions in individuals with FEP underlies or contributes to symptoms of psychosis.

  View details for DOI 10.1016/j.heliyon.2022.e10424

  View details for PubMedID 36097491

  View details for PubMedCentralID PMC9463369

• Thalamic dopamine D2-receptor availability in schizophrenia: a study on antipsychotic-naive patients with first-episode psychosis and a meta-analysis. Molecular psychiatry Plavén-Sigray, P., Ikonen Victorsson, P., Santillo, A., Matheson, G. J., Lee, M., Collste, K., Fatouros-Bergman, H., Sellgren, C. M., Erhardt, S., Agartz, I., Halldin, C., Farde, L., Cervenka, S. 2022; 27 (2): 1233-1240

  Abstract

  Pharmacological and genetic evidence support a role for an involvement of the dopamine D2-receptor (D2-R) in the pathophysiology of schizophrenia. Previous molecular imaging studies have suggested lower levels of D2-R in thalamus, but results are inconclusive. The objective of the present study was to use improved methodology to compare D2-R density in whole thalamus and thalamic subregions between first-episode psychosis patients and healthy controls. Differences in thalamocortical connectivity was explored based on the D2-R results. 19 antipsychotic-naive first-episode psychosis patients and 19 age- and sex-matched healthy controls were examined using high-resolution Positron Emission Tomography (PET) and the high-affinity D2-R radioligand [11C]FLB457. The main outcome was D2-R binding potential (BPND) in thalamus, and it was predicted that patients would have lower binding. Diffusion tensor imaging (DTI) was performed in a subgroup of 11 patients and 15 controls. D2-R binding in whole thalamus was lower in patients compared with controls (Cohen's dz = -0.479, p = 0.026, Bayes Factor (BF) > 4). Among subregions, lower BPND was observed in the ROI representing thalamic connectivity to the frontal cortex (Cohen's dz = -0.527, p = 0.017, BF > 6). A meta-analysis, including the sample of this study, confirmed significantly lower thalamic D2-R availability in patients. Exploratory analyses suggested that patients had lower fractional anisotropy values compared with controls (Cohen's d = -0.692, p = 0.036) in the inferior thalamic radiation. The findings support the hypothesis of a dysregulation of thalamic dopaminergic neurotransmission in schizophrenia, and it is hypothesized that this could underlie a disturbance of thalamocortical connectivity.

  View details for DOI 10.1038/s41380-021-01349-x

  View details for PubMedID 34759359

  View details for PubMedCentralID PMC9054658

• No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis. NPJ schizophrenia Lee, M., Fatouros-Bergman, H., Plavén-Sigray, P., Ikonen Victorsson, P., Sellgren, C. M., Erhardt, S., Flyckt, L., Farde, L., Cervenka, S. 2021; 7 (1): 46

  Abstract

  Cognitive impairment is an important predictor of disability in schizophrenia. Dopamine neurotransmission in cortical brain regions has been suggested to be of importance for higher-order cognitive processes. The aim of this study was to examine the relationship between extrastriatal dopamine D2-R availability and cognitive function, using positron emission tomography and the high-affinity D2-R radioligand [11C]FLB 457, in an antipsychotic-naive sample of 18 first-episode psychosis patients and 16 control subjects. We observed no significant associations between D2-R binding in the dorsolateral prefrontal cortex or hippocampus (β = 0.013-0.074, partial r = -0.037-0.273, p = 0.131-0.841). Instead, using Bayesian statistics, we found moderate support for the null hypothesis of no relationship (BFH0:H1 = 3.3-8.2). Theoretically, our findings may suggest a lack of detrimental effects of D2-R antagonist drugs on cognition in schizophrenia patients, in line with clinical observations.

  View details for DOI 10.1038/s41537-021-00176-x

  View details for PubMedID 34548499

  View details for PubMedCentralID PMC8455597