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Accepted manuscripts

Contents

Original Article

  • Psychiatric sequelae after SARS-Cov-2 infection: Trajectory, predictors and associations in a longitudinal Australian cohort

  • Seetal Dodd, Mohammedreza Mohebbi, Josie O’Donohue, Gail Matthews, David R Darley, Michael Berk
  • Published online by Cambridge University Press: 08 September 2023, pp. 1-23
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  • Introduction:

    A relationship between SARS-CoV-2 infection and psychiatric symptoms has been identified but is still being fully investigated. Neuropsychiatric sequalae have been reported for several infectious agents and are not unexpected for SARS-CoV-2 infection.

    Method:

    This study follows for 12 months a general population sample (N=144) of people who have had a confirmed infection of SARS-CoV-2. Medical and neuropsychiatric data and biological specimens are collected at 6 study visits. The 34-item SPHERE questionnaire, the Depression in the Medically Ill instrument, the EQ-5D-5L quality of life instrument and the visual analogue scale of fatigue were administered at multiple timepoints and associations with measures of illness and inflammatory biomarkers were investigated using the generalised estimating equation.

    Results:

    Associations between inflammatory biomarkers and mental health measures of various effect sizes were identified. A robust inverse association was found between mental health outcomes and long covid status, but not between mental health outcomes and covid illness severity.

    Conclusion:

    This study suggests that long covid may be the strongest predictor of neuropsychiatric symptoms amongst people who have been infected with SARS-CoV-2.

  • Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviors

  • Michael Maes, Muanpetch Rachayon, Ketsupar Jirakran, Atapol Sughondhabirom, Abbas F. Almulla, Pimpayao Sodsai
  • Published online by Cambridge University Press: 08 September 2023, pp. 1-40
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  • Objectives:

    Early flow cytometry studies revealed T cell activation in major depressive disorder (MDD) (Maes et al., 1990-1993). MDD is characterised by activation of the immune-inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS), including deficits in T regulatory (Treg) cells. This study examines the number of cannabinoid type 1 (CB1) and type 2 (CB2) receptor bearing T/B lymphocytes in MDD, and the effects of in vitro cannabidiol (CBD) administration on CB1/CB2-bearing immunocytes.

    Methods:

    Using flow cytometry, we determined the percentage of CD20+CB2+, CD3+CB2+, CD4+CB2+, CD8+CB2+ and FoxP3+CB1+ cells in 19 healthy controls and 29 MDD patients in 5 conditions: baseline, stimulation with anti-CD3/CD28 with or without 0.1 µg/mL, 1.0 µg/mL or 10.0 µg/mL CBD.

    Results:

    CB2+ was significantly higher in CD20+ than CD3+ and CD4+, and CD8+ cells. Stimulation with anti-CD3/CD8 beads increases the number of CB2-bearing CD3+, CD4+, and CD8+ cells, as well as CB1-bearing FoxP3+ cells. There was an inverse association between the number of reduced CD4+CB2+ and IRS profiles, including M1 macrophage, T helper-(Th)-1 and Th-17 phenotypes. MDD is characterized by lowered basal FoxP3+CB1+% and higher CD20+CB2+%. 33.2% of the variance in the depression phenome (including severity of depression, anxiety, and current suicidal behaviors) is explained by CD20+CB2+% (positively) and CD3+CB2+% (inversely). All 5 immune cell populations were significantly increased by 10 µg/mL CBD administration.

    Conclusion:

    reductions in FoxP3+CB1+% and CD3+/CD4+CB2+% contribute to deficits in immune homeostasis in MDD, while increased CD20+CB2+% may contribute to the pathophysiology of MDD by activating T-independent humoral immunity.