Post-COVID depression in women – a higher symptom burden linked to lower glutamine in pgACC

2390 

Abstract Submission 

Meng Li¹, Marina Krylova¹, Lejla Colic¹, Lena Danyeli², Benjamin Giszas¹, Gerd Wagner³, Nils Opel⁴, Daniel Güllmar¹, Kathrin Finke¹, Philipp Reuken¹, Andreas Stallmach¹, Martin Walter¹, Bianca Besteher¹

¹Jena University Hospital, Jena, Germany, ²Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Thuringia, ³Jena University Hospital, Jena, Thuringia, ⁴Jena University Hospital, Germany, Jena, Germany

Meng Li  
Jena University Hospital
Jena, Germany

Marina Krylova  
Jena University Hospital
Jena, Germany

Lejla Colic  
Jena University Hospital
Jena, Germany

Lena Danyeli  
Department of Psychiatry and Psychotherapy, Jena University Hospital
Jena, Thuringia

Benjamin Giszas  
Jena University Hospital
Jena, Germany

Gerd Wagner  
Jena University Hospital
Jena, Thuringia

Nils Opel  
Jena University Hospital, Germany
Jena, Germany

Daniel Güllmar  
Jena University Hospital
Jena, Germany

Kathrin Finke  
Jena University Hospital
Jena, Germany

Philipp Reuken  
Jena University Hospital
Jena, Germany

Andreas Stallmach  
Jena University Hospital
Jena, Germany

Martin Walter  
Jena University Hospital
Jena, Germany

Bianca Besteher  
Jena University Hospital
Jena, Germany

The COVID-19 pandemic not only increases mortality and morbidity rates during the acute phase of infection but also impairs mental health in the post-infection period. The depressive symptoms post COVID infection share several demographic and clinical characteristics with major depressive disorder (MDD), particularly in its higher prevalence in women. Investigating the underlying mechanism of vulnerability to depression onset after COVID-19 infection in women would be in favor of its treatment. MDD is suggested to be associated with the imbalance of neurotransmitter metabolism, especially the excitatory neurotransmitter system including glutamate (Glu) and glutamine (Gln) (Luykx et al. 2012; Mitchell and Baker 2010; Yüksel and Öngür 2010; Moriguchi et al. 2019). Regionally specific alterations in glutamatergic neurotransmission have been reported in the anterior cingulate cortex (ACC) in MDD. A recent systematic review of neuroimaging studies revealed the ACC as one of the brain regions with sex differences in depression (Mohammadi et al. 2023). This study aims to investigate sex differences in distinct psychopathological features in COVID-19 survivors and their potential linkage with neurotransmitter metabolism in the pregenual anterior cingulate cortex (pgACC), which is crucial for the assessment of affective valence and reward-based learning (Phan et al. 2002; Rogers et al. 2004).

For the investigation of sex differences in depressive symptoms, 603 COVID-19 survivors after acute infection after acute infection were included (390 women, mean age= 48 years and 213 men, mean age= 50 years). Fifty-six individuals with post-COVID symptoms underwent thorough psychometric phenotyping and completed magnetic resonance spectroscopy at 3T, assessing Glu and Gln levels in the pgACC using the Siemens PRESS MRS sequences. All participants had verified COVID-19 via real-time reverse transcriptase-polymerase chain reaction during acute infection. To assess neuropsychiatric symptoms, participants completed the Montreal Cognitive Assessment (MoCA) for cognitive impairment, the Short-Form-36 questionnaire (SF-36) for quality-of-life measures, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Fatigue Assessment Scale (FAS) for symptoms of depression and fatigue. We conducted group comparisons and Pearson correlation tests to assess group by sex differences and their associations to Glu and Gln levels in R.

Our study revealed a significantly higher burden of mental health symptoms, especially depression, in women Post-COVID 19 survivors compared to men (Table 1). Psychometric phenotyping demonstrated a higher burden of depressive symptoms, fatigue, and subclinical stress, but not anhedonia, in women with long-COVID compared to men. Furthermore, depressive symptoms and reduced energy were linked to reduced Gln levels in the pgACC (MADRS: r= -0.49, p= 0.012; Energy, r= 0.45, p= 0.029). Notably, the Gln alteration in long-COVID participants were primarily driven by differences in women (p=0.01), not men (p = 0.52, Figure 1).

In summary, we present evidence of distinct sex-specific features of long-COVID depression with an atypical symptom profile and lower Gln in the pgACC. Both features are likely connected to sex-specific persisting immunological alterations in long-COVID, leading to sickness behavior and limbic glutamatergic metabolism dysfunction.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ²

MR Spectroscopy ¹

Physiology, Metabolism and Neurotransmission Other

Glutamate

Infections

Magnetic Resonance Spectroscopy (MRS)

MR SPECTROSCOPY

Psychiatric Disorders