Biomedical subjects

Paola Dazzan

Publications and source records attributed to Paola Dazzan.

4 recordsLinked to original sources

PubMed2026

Neurometabolites and Antipsychotic Response in Psychosis: A Mega-Analysis.

IMPORTANCE: Revealing neurobiological markers of antipsychotic nonresponse in psychosis may aid outcome prediction and inform novel treatment targets. OBJECTIVE: To examine differences in neurometabolites in antipsychotic nonresponsive compared to antipsychotic-responsive psychosis using individual participant data and meta-analysis. DATA SOURCES: Web of Science was searched for studies published between January 1, 1980, and November 1, 2025. Authors of 21 eligible studies identified before August 2024 were invited to contribute individual participant data. STUDY SELECTION: Eighteen studies examining neurometabolites by treatment response in psychosis contributed individual participant data for the mega-analysis. These studies plus a further 5 studies were included in the meta-analyses of standardized mean differences and variability. DATA EXTRACTION AND SYNTHESIS: Individual participant data were analyzed using linear mixed models with study as a random effect. Subgroup analyses examined prospective designs and treatment-resistant samples. Published group means and standard deviations were extracted for meta-analyses. MAIN OUTCOMES AND MEASURES: Group differences in glutamate, glutamate plus glutamine, choline, myo-inositol, N-acetylaspartate, γ-aminobutyric acid, and glutathione in the medial frontal cortex, dorsolateral prefrontal cortex, thalamus, and basal ganglia. RESULTS: The mega-analysis included 1189 participants from 18 studies; of these, 476 were treatment nonresponders (mean [SD] age, 33.0 [12.5] years; 340 male), 427 were treatment responders (mean [SD] age, 30.3 [11.5] years; 299 male), and 286 were healthy control individuals (mean [SD] age, 31.0 [12.5] years; 170 male). Compared with the antipsychotic response group, nonresponders showed elevations in medial frontal glutamate (Glass Δ = 0.21; P = .02), glutamate plus glutamine (Glass Δ = 0.29; P = .002), choline (Glass Δ = 0.22; P = .03), and myo-inositol (Glass Δ = 0.35; P = .001); similar elevations were observed relative to control individuals. Elevated medial frontal glutamate plus glutamine in antipsychotic nonresponders compared with responders was also observed prospectively in first-episode psychosis (Glass Δ = 0.41; P = .002), whereas myo-inositol elevations were greatest in individuals meeting criteria for treatment-resistance (Glass Δ = 0.64; P = .001). The meta-analysis of 23 studies (1844 participants) also showed elevated medial frontal choline and myo-inositol in antipsychotic nonresponse compared with response. CONCLUSIONS AND RELEVANCE: These findings provide evidence of an association between antipsychotic nonresponse in psychosis with elevations in medial frontal glutamate, choline, and myo-inositol. The presence of elevations in these markers supports the continued investigation of glutamate-acting and inflammatory pathway-associated interventions for psychosis and schizophrenia.

Humans↗

PubMed2025

Premorbid functioning trajectories and the one-year course of cognitive performance in first-episode psychosis: a cluster analysis in PSYSCAN.

BACKGROUND: We examined the course of cognitive performance in first-episode psychosis (FEP) compared to healthy controls (HC), and whether this varied across subgroups of patients defined by premorbid functioning (PMF) trajectories, using a clustering approach. METHODS: Data were collected in 302 FEP and 136 HC subjects participating in PSYSCAN (HEALTH.2013.2.2.1-2-FEP). K-means clustering (Euclidean distance) was used to cluster longitudinal trajectories of different PMF domains simultaneously. Since PMF was assessed retrospectively using the Premorbid Adjustment Scale (PAS), findings should be interpreted with caution, although PAS ratings have shown reasonable validity against prospective data. RESULTS: As expected, FEP showed impaired performance across all cognitive domains compared to HC. We identified four trajectories of PMF: a normal premorbid developmental trajectory (globally-normal, 21 %), stable intermediate PMF across domains (stable-intermediate, 29 %), stable poor or deteriorating PMF in the academic domain (normal-social/poor-academic, 29 %), and a globally impaired group with poor/deteriorating PMF across domains (globally-poor, 21 %). These clusters showed distinct levels of post-onset impairments in sustained visual attention, visual working memory and emotion recognition. CONCLUSIONS: This study confirms a positive association between PMF and cognitive performance in the early years following psychosis onset. It aligns with findings that individuals later diagnosed with schizophrenia already show developmental deficits/lags from childhood to early adolescence compared to normally developing children. As PMF can be considered a proxy for cognitive reserve, our results suggest that higher reserve acts as a buffer against cognitive decline and supports better performance on sustained visual attention, complex visual working memory, and aspects of emotion recognition.

Clustering↗

PubMed2025

Human development, inequality, and their associations with brain structure across 29 countries.

BACKGROUND: The macro-social and environmental conditions in which people live, such as the level of a country's development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults. METHODS: We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country's level of development and inequality. RESULTS: Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain. CONCLUSIONS: Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants' brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.

Humans↗

PubMed2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Brain↗