2026 ECNP Congress

PS02-2182

Maternal TNF gene expression and clinical functioning during pregnancy: a longitudinal multi-domain analysis

Isidora Tesic — S. Peri, P. Enrico, C. Cabasino, M.C. Carloni, G. Delvecchio, L. Squarcina, A. Ferro, Y. Barone, S. Pozzoli, V. Favalli, A. Marano, V. Tombola, A. Finardi, C. Pini, S. Busilacchi, E. Rossi, S. Boito, C. Scacchetti, I. Cetin, N. Persico, M. Fumagalli, R. Furlan, P. Brambilla · Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico, Department of Neurosciences and Mental Health, Milano, Italy

2026 ECNP Congress

Background

The perinatal period represents a window of heightened vulnerability to psychiatric disorders, characterized by complex bidirectional interactions between the maternal immune system and psychological state [1, 2]. Evidence increasingly links dysregulated pro-inflammatory signaling to the pathophysiology of depression and anxiety, yet clinical research in the perinatal period is often restricted by a reliance on cross-sectional, symptom-based snapshots [3, 4]. There is a critical clinical need for longitudinal, multidomain frameworks that synchronize biological trajectories with clinical progression. Mapping these parallel changes is essential for identifying objective biomarkers of psychiatric risk in this vulnerable population.

Aims

To develop and apply a longitudinal multidomain statistical framework to identify associations between maternal gene-expression trajectories and psychiatric symptom changes during pregnancy.

Methods

A longitudinal cohort of 394 pregnant women (Department of Psychiatry, Policlinico Hospital, Milan), was stratified into 3 groups: healthy controls (N=193), individuals with a history of anxiety/depression (N=139), and with current anxious/depressive symptoms (N=62), diagnosed using the Structured Clinical Interview for DSM V (SCID-V).

Maternal evaluations occurred at four gestational visits – V1: 14th gestational week (GW); V2: 15th–19th GW; V3: 20th GW; and V4: 30th GW.

At each time point, clinical assessments were performed using validated clinician administered scales for maternal psychopathology, i.e. Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Global Assessment of Functioning (GAF), and the Brief Psychiatric Rating Scale (BPRS).

Maternal peripheral blood was collected concurrently at three gestational timepoints (V2, V3, and V4). Immune gene expression was longitudinally profiled utilizing whole blood RNA extraction and cDNA synthesis, followed by custom OpenArray PCR profiling.

Longitudinal gene-expression trajectories across pregnancy were summarized using empirical Bayes slope estimates derived from repeated measurements between visits 2 and 4. Clinical symptom trajectories were summarized as subject-level slopes across the same window. Spearman correlations were computed between gene-expression trajectories and psychiatric scale changes, both in the overall sample and stratified by diagnostic group. Multiple testing was controlled using the Benjamini–Hochberg false discovery rate correction.

Results

In the overall sample, a significant negative correlation was found between Tumor Necrosis Factor (TNF) trajectory and the GAF trajectory (ρ = −0.188, p < 0.001, FDR = 0.046), indicating that increasing TNF levels were associated with worsening global functioning. Other associations showed small effect sizes (|ρ| ≈ 0.10–0.15) and did not survive correction. Stratified analyses revealed no significant correlations after FDR correction, though exploratory moderate associations were noted in smaller subgroups, particularly among participants with current symptoms.

Conclusions

These preliminary findings identify a longitudinal association between increasing maternal TNF expression and declining global functioning during pregnancy. This is consistent with previous evidence linking pro-inflammatory markers, including TNF-α, to perinatal depressive symptoms, and extends this framework to clinician-rated functioning [5].

Further analyses will adjust for relevant covariates and examine a broader range of psychopathological dimensions, including non-diagnostic stress-related measures and medical comorbidities, to better define the clinical context of this association.

Overall, these results support the value of longitudinal multidomain approaches integrating immune gene-expression trajectories with clinician-rated clinical measures.

References

  1. Brown, A. S., & Meyer, U. (2018). Maternal Immune Activation and Neuropsychiatric Illness: A Translational Research Perspective. The American journal of psychiatry, 175(11), 1073–1083. https://doi.org/10.1176/appi.ajp.2018.17121311
  2. Leff-Gelman, P., Mancilla-Herrera, I., Flores-Ramos, M. et al. The Immune System and the Role of Inflammation in Perinatal Depression. Neurosci. Bull. 32, 398–420 (2016). https://doi.org/10.1007/s12264-016-0048-3
  3. Buglione-Corbett, R., Deligiannidis, K. M., Leung, K., Zhang, N., Lee, M., Rosal, M. C., & Moore Simas, T. A. (2018). Expression of inflammatory markers in women with perinatal depressive symptoms. Archives of women’s mental health, 21(6), 671–679. https://doi.org/10.1007/s00737-018-0834-1
  4. Bränn, E., Papadopoulos, F., Fransson, E., White, R., Edvinsson, Å., Hellgren, C., Kamali-Moghaddam, M., Boström, A., Schiöth, H. B., Sundström-Poromaa, I., & Skalkidou, A. (2017). Inflammatory markers in late pregnancy in association with postpartum depression-A nested case-control study. Psychoneuroendocrinology, 79, 146–159. https://doi.org/10.1016/j.psyneuen.2017.02.029
  5. Silva-Fernandes, A., Conde, A., Marques, M., Caparros-Gonzalez, R. A., Fransson, E., Mesquita, A. R., Figueiredo, B., & Skalkidou, A. (2024). Inflammatory biomarkers and perinatal depression: A systematic review. PloS one, 19(5), e0280612. https://doi.org/10.1371/journal.pone.0280612