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Research Articles, Neurobiology of Disease

Neural and Behavioral Markers of Negative Symptoms and Cognitive Impairment in Patients with Psychosis

Raquel van Gool, Mariesa Cay, Hanne van der Heijden, Emma Golden, Amanda Cao, Boyu Ren, Joseph Gonzalez-Heydrich, Ann K. Shinn and Jaymin Upadhyay
Journal of Neuroscience 23 July 2025, 45 (30) e0039252025; https://doi.org/10.1523/JNEUROSCI.0039-25.2025
Raquel van Gool
1Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
2Department of Neurology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht 6229 ER, The Netherlands
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Mariesa Cay
1Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
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Hanne van der Heijden
1Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
3Faculty of Science, University of Amsterdam, Amsterdam 1090 GE, The Netherlands
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Emma Golden
1Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
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Amanda Cao
1Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
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Boyu Ren
4Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478
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Joseph Gonzalez-Heydrich
5Department of Psychiatry and Behavioral Sciences, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
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Ann K. Shinn
4Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478
6Schizophrenia and Bipolar Disorder Program, Psychotic Disorders Division, McLean Hospital, Belmont, Massachusetts 02478
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Jaymin Upadhyay
1Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
3Faculty of Science, University of Amsterdam, Amsterdam 1090 GE, The Netherlands
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Abstract

Negative and cognitive symptoms impair functioning in patients with psychotic illnesses [i.e., schizophrenia spectrum disorders (SZ) and bipolar I disorder with psychotic features (BD)]. Disruptions in mesocorticolimbic circuitry are hypothesized to underpin negative symptoms and cognitive impairment in patients with psychosis and may also facilitate reward-motivational deficits. In male and female patients with psychosis (N = 44) and healthy controls (HC = 27), we used neuroimaging to define gray matter morphology and white matter microstructure. We examined negative symptom severity with the Clinical Assessment Interview for Negative Symptoms (CAINS), effort allocation during reward processing with the Effort Expenditure for Rewards Task (EEfRT), and cognitive performance with the MATRICS cognitive consensus battery (MCCB). Reduced nucleus accumbens volumes in patients with psychosis were associated with higher CAINS total and motivation and pleasure subscale scores as well as lower effort expenditure for medium (50%) and high (88%) reward probability conditions during EEfRT. The fornix showed reduced fractional anisotropy in patients with psychosis. Negative associations were present between CAINS motivation and pleasure subscores and MCCB composite and subscale scores. Lower gray matter volume in cerebellar Lobule IV corresponded with impaired effort allocation during medium and high reward probability conditions and lower cognitive performance. However, Lobule IV was not correlated with CAINS scores. While nucleus accumbens volume may serve as a marker of negative symptoms in psychotic illnesses, cerebellar Lobule IV morphology may inform on cognitive impairment in patients with SZ and BD. The nucleus accumbens and Lobule IV may each contribute to reduced effort allocation during reward processing.

  • bipolar disorder
  • CAINS
  • cerebellum
  • cognition
  • nucleus accumbens
  • reward
  • schizophrenia

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The Journal of Neuroscience: 45 (30)
Journal of Neuroscience
Vol. 45, Issue 30
23 Jul 2025
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Neural and Behavioral Markers of Negative Symptoms and Cognitive Impairment in Patients with Psychosis
Raquel van Gool, Mariesa Cay, Hanne van der Heijden, Emma Golden, Amanda Cao, Boyu Ren, Joseph Gonzalez-Heydrich, Ann K. Shinn, Jaymin Upadhyay
Journal of Neuroscience 23 July 2025, 45 (30) e0039252025; DOI: 10.1523/JNEUROSCI.0039-25.2025

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Neural and Behavioral Markers of Negative Symptoms and Cognitive Impairment in Patients with Psychosis
Raquel van Gool, Mariesa Cay, Hanne van der Heijden, Emma Golden, Amanda Cao, Boyu Ren, Joseph Gonzalez-Heydrich, Ann K. Shinn, Jaymin Upadhyay
Journal of Neuroscience 23 July 2025, 45 (30) e0039252025; DOI: 10.1523/JNEUROSCI.0039-25.2025
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Keywords

  • bipolar disorder
  • CAINS
  • cerebellum
  • cognition
  • nucleus accumbens
  • reward
  • schizophrenia

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