Neuropsychobiology

Zafrilla-López, Marina; Herrera-Escartín, Daniel; Guardiola-Ripoll, Maria; García-Fernández, Arnau; Acosta-Díez, Miriam; Giménez-Palomo, Anna; Saiz, Pilar A.; García-Portilla, Maria Paz; Jiménez, Esther; Papiol, Sergi; Fañanás, Lourdes; Ruiz, Victoria; Gavín, Patricia; González-Blanco, Leticia; Vieta, Eduard; Schulze, Thomas G.; Fatjó-Vilas, Mar; Benabarre, Antoni; Mitjans, Marina; Arias, Bárbara

doi: 10.1159/000551565pmid: 41989970

AbstractIntroduction: Circadian rhythms are reflected through sleep-wake patterns and chronotype. Patients with bipolar disorder (BD) frequently exhibit disrupted sleep patterns and a tendency for evening chronotype. Also, genetic risk factors for BD partially overlap with those influencing sleep traits. Lithium (Li), the first-line therapy for BD, stabilizes circadian rhythms and promotes morningness in responders (Rp). This study aimed to evaluate whether the polygenic burden of sleep-related traits is associated with Li response in BD patients. Methods: A total of 114 European ancestry BD patients were categorized as Li Rp (N = 79) or non-responders (N = 35), based on the reduction of 50% of the episodes. Polygenic scores (PGS) for chronotype, daytime dozing, ease of getting up, insomnia, morningness, napping, sleep duration, and snoring were calculated using PRS-CS. Associations between each PGS and Li response were tested using logistic regression models. Comparisons were made between the extreme quartiles of each PGS. Results: The PGS for ease of getting up was significantly associated with Li response, explaining 9.989% of the variance based on Nagelkerke’s pseudo-R2 (FDR-adjusted p value = 0.046). Additionally, individuals with a higher genetic predisposition for ease of getting up had increased odds of a good response (FDR-adjusted p value = 0.039; OR = 5.143; 95% CI = 1.537–17.209). Conclusion: The study suggests that a higher genetic predisposition for ease of getting up in the morning may increase the likelihood of responding to Li treatment in BD patients. Our study aligns with previous evidence, highlighting the importance of sleep and chronotype patterns in response to Li in BD patients.

Todurga-Seven, Zeynep Gizem; Pekkoc-Uyanik, Kubra Cigdem; Agay, Erhan Rasit

doi: 10.1159/000551767pmid: 41961764

AbstractIntroduction: Epilepsy is a chronic neurological disorder characterized by recurrent seizures, with variants in ion channel genes such as SCN1A, SCN1B, and CACNA2D2 implicated in neuronal excitability. This research aims to explore genetic polymorphisms in the SCN1A, SCN1B, and CACNA2D2 genes among Turkish epilepsy patients and assess their impact on responsiveness to anti-seizure medications (ASMs). Methods: Targeted next-generation sequencing (tNGS) was applied to genomic DNA from 29 patients. Results: Common 15 variants were analyzed in CACNA2D2 (rs2239801, rs56287038), SCN1A (rs2298771, rs3032638, rs11394960, rs67636132, rs566839, rs1461193, rs6432861, rs2020318), and SCN1B (rs72556351, rs2278995, rs557140301, rs67701503, rs55742440). A statistically significant difference in ASM response was observed in the recessive model of SCN1A rs2298771: C>T (TT vs. CC+CT) (p = 0.044), with the TT genotype associated with improved response. CACNA2D2 rs56287038:G>T showed significance in the allelic model (p = 0.012); the T allele was found only in resistant patients. SCN1A haplotype analysis revealed reduced C allele frequency in responders (p = 0.041). The CT (rs2298771+rs2020318), CG (rs2298771+rs1461193), and CC (rs2298771+rs6432861) haplotypes also showed considerable differences among groups (p = 0.041, p = 0.023, p = 0.041, respectively). Moreover, CTG (rs2298771+rs2020318+rs1461193), CCG (rs2298771+rs6432861+rs1461193), and CTCG (rs2298771+rs2020318+rs6432861+rs1461193) haplotypes were significantly associated with treatment response (p = 0.023, p = 0.023, p = 0.022). However, none of these associations remained statistically significant after false discovery rate correction, and all findings should therefore be interpreted as exploratory. Conclusion: CACNA2D2 rs56287038:G>T and SCN1A rs2298771:C>T may effect ASM response.

Etzel, Marius Solon; Rosenblum, Yevgenia; Dresler, Martin; Steiger, Axel; Mikoteit, Thorsten; Zeising, Marcel

doi: 10.1159/000551623pmid: 41911075

AbstractIntroduction: One-third of patients with major depressive disorder (MDD) exhibit low-grade inflammation as reflected by C-reactive protein (CRP) concentrations >3 mg/L. We explored whether CRP changes from baseline to week one of antidepressant treatment (ΔCRP) can serve as a marker of treatment response. Methods: CRP serum levels were measured at baseline and after the first week of treatment in 33 MDD patients and correlated with patients’ Hamilton Depression Rating Scale (HAM-D), while adjusting for age, gender, and body mass index. We assessed antidepressant responses at weeks one and four of treatment as a >25% and >50% HAM-D score reduction (ΔHAM-D) compared to baseline, respectively. We compared baseline and week-one CRP levels with the paired t test within responders and nonresponders separately and ΔCRP between the groups with the ANCOVA. Results: Higher ΔCRP correlated with lower week-four ΔHAM-D scores (r = −0.5, p = 0.006). Nonresponders showed higher ΔCRP – but not baseline and week-one CRP – than responders (p = 0.018, Cohen’s d = 1.1). A ΔCRP increase was observed in 13/16 (81%) nonresponders and 7/17 (41%) responders (Fisher’s exact test’s p = 0.03). A ΔCRP increase combined with a week-one nonresponse was observed in 13/16 (81%) nonresponders and 1/17 (6%) responders (p < 0.0001). Conclusions: Rather ΔCRP at week one than baseline CRP might be indicative of treatment response at week four, especially if combined with week-one ΔHAM-D. In the future, ΔCRP could be introduced into psychiatric practice to guide treatment plans.

Arıcı Sağlıyan, Gökçeçiçek; Çetin, Fatih Hilmi; Akyürek, Fikret; Çiçek Zekey, Özlem; Türkoğlu, Serhat; Uçar, Halit Necmi; Öztürk, Bahadır; Altınbaş, Kürşat

doi: 10.1159/000551769pmid: 41961763