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Publication Metadata only T-cell activation state differentially contributes to neuropsychiatric complications in women with HIV(Elsevier, 2022) Williams, Dionna W.; Flores, Bianca R.; Xu, Yanxun; Wang, Yuezhe; Yu, Danyang; Peters, Brandilyn A.; Adedimeji, Adebola; Wilson, Tracey E.; Merenstein, Daniel; Tien, Phyllis C.; Cohen, Mardge H.; Weber, Kathleen M.; Adimora, Adaora A.; Ofotokun, Igho; Fischl, Margaret; Turan, Janet; Laumet, Geoffroy; Landay, Alan L.; Dastgheyb, Raha M.; Gange, Stephen J.; Weiser, Sheri D.; Rubin, Leah H.; Department of Psychology; Turan, Bülent; Department of Psychology; College of Social Sciences and HumanitiesNeuropsychiatric complications are common among women with HIV (WWH). The pathophysiological mechanisms underlying these complications are not fully known but likely driven in part by immune modulation. We examined associations between T-cell activation states which are required to mount an effective immune response (activation, co-stimulation/normal function, exhaustion, senescence) and neuropsychiatric complications in WWH. 369 WWH (78% HIV RNA undetectable/<20cp/mL) enrolled in the Women's Interagency HIV Study completed neuropsychological testing and measures of depression (Center for Epidemiological Studies Depression Scale-CES-D), self-reported stress levels (Perceived Stress Scale-10), and post-traumatic stress (PTSD Checklist-Civilian Scale). Multiparametric flow cytometry evaluated T-cell activation state. Partial least squares regressions were used to examine T-cell phenotypes and neuropsychiatric outcome associations after confounder adjustment. In the total sample and among virally suppressed (VS)-WWH, CD4(+) T-cell exhaustion was associated with poorer learning and attention/working memory (P's < 0.05). In the total sample, CD4(+) T-cell activation was associated with better attention/working memory and CD8(+) T-cell co-stimulation and senescence was associated with poorer executive function (P's < 0.05). For mental health outcomes, in the total sample, CD4(+) T-cell activation was associated with more perceived stress and CD4(+) T-cell exhaustion was associated with less depressive symptoms (P's < 0.05). Among VS-WWH, CD4(+) senescence was associated with less perceive stress and CD8(+) T-cell co-stimulation and senescence was associated with higher depression (P's < 0.05). Together, results suggest the contribution of peripheral CD4(+) and CD8(+) T-cell activation status to neuropsychiatric complications in WWH.Publication Metadata only Correction: oxidatively-induced DNA base damage and base excision repair abnormalities in siblings of individuals with bipolar disorder DNA damage and repair in bipolar disorder(Springer Nature, 2024) Çelik, Hidayet Ece Arat; Yilmaz, Selda; Aksahin, Izel Cemre; Kendirlioglu, Burcu Kok; Corekli, Esma; Dal Bekar, Nazli Ecem; Celik, Omer Faruk; Yorguner, Nese; Ozturk, Bilge Targitay; Islekel, Huray; Ozerdem, Aysegul; Tuna, Gam; Akşahin, İzel Cemre; Ceylan, Deniz; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of MedicineCorrection to: Translational Psychiatryhttps://doi.org/10.1038/s41398-024-02901-3, published online 24 May 2024 In this article the funding from ‘[2021.KB.SAG.047]’ was omitted. The corrected acknowledgment should read: This research was funded by the Dokuz Eylul University Scientific Research Project Scholarship (2021.KB.SAG.047) and LithiumAssociation Scholarship. The original article has been corrected.Publication Metadata only Childhood maltreatment is linked to larger preferred interpersonal distances towards friends and strangers across the globe(SpringerNature, 2024) Haim-Nachum, Shilat; Sopp, Marie R.; Luond, Antonia M.; Afzal, Nimrah; Ahs, Fredrik; Allgaier, Antje-Kathrin; Arevalo, Adrian; Asongwe, Christian; Bachem, Rahel; Balle, Stefanie R.; Belete, Habte; Belete Mossie, Tilahun; Berzengi, Azi; Capraz, Necip; Dukes, Daniel; Essadek, Aziz; Fares-Otero, Natalia E.; Halligan, Sarah L.; Hemi, Alla; Iqbal, Naved; Jobson, Laura; Levy-Gigi, Einat; Martin-Soelch, Chantal; Michael, Tanja; Oe, Misari; Olff, Miranda; Oernkloo, Helena; Prakash, Krithika; Quaatz, Sarah M.; Raghavan, Vijaya; Ramakrishnan, Muniarajan; Reis, Dorota; Schnyder, Ulrich; Seedat, Soraya; Shihab, Ibtihal Najm; Vandhana, Susilkumar; Wadji, Dany Laure; Wamser, Rachel; Zabag, Reut; Spies, Georgina; Pfaltz, Monique C.; N/A; Şar, Vedat; Ceylan, Deniz; School of Medicine; Koç University HospitalChildhood maltreatment (CM) is thought to be associated with altered responses to social stimuli and interpersonal signals. However, limited evidence exists that CM is linked to larger comfortable interpersonal distance (CID) - the physical distance humans prefer towards others during social interactions. However, no previous study has investigated this association in a comprehensive sample, yielding sufficient statistical power. Moreover, preliminary findings are limited to the European region. Finally, it is unclear how CM affects CID towards different interaction partners, and whether CID is linked to social functioning and attachment. To address these outstanding issues, adults (N = 2986) from diverse cultures and socio-economic strata completed a reaction time task measuring CID towards an approaching stranger and friend. Higher CM was linked to a larger CID towards both friends and strangers. Moreover, insecure attachment and less social support were associated with larger CID. These findings demonstrate for the first time that CM affects CID across countries and cultures, highlighting the robustness of this association.Publication Metadata only Oxidatively-induced DNA base damage and base excision repair abnormalities in siblings of individuals with bipolar disorder DNA damage and repair in bipolar disorder(SpringerNature, 2024) Celik, Hidayet Ece Arat; Yilmaz, Selda; Kendirlioglu, Burcu Kok; Corekli, Esma; Dal Bekar, Nazli Ecem; Celik, Omer Faruk; Yorguner, Nese; Oztuerk, Bilge Targitay; Islekel, Hueray; Ozerdem, Ayseguel; Akan, Pinar; Tuna, Gamze; N/A; Akşahin, İzel Cemre; Ceylan, Deniz; Koç University Research Center for Translational Medicine (KUTTAM); School of Medicine; Graduate School of Health Sciences; Koç University HospitalPrevious evidence suggests elevated levels of oxidatively-induced DNA damage, particularly 8-hydroxy-2'-deoxyguanosine (8-OH-dG), and abnormalities in the repair of 8-OH-dG by the base excision repair (BER) in bipolar disorder (BD). However, the genetic disposition of these abnormalities remains unknown. In this study, we aimed to investigate the levels of oxidatively-induced DNA damage and BER mechanisms in individuals with BD and their siblings, as compared to healthy controls (HCs). 46 individuals with BD, 41 siblings of individuals with BD, and 51 HCs were included in the study. Liquid chromatography-tandem mass spectrometry was employed to evaluate the levels of 8-OH-dG in urine, which were then normalized based on urine creatinine levels. The real-time-polymerase chain reaction was used to measure the expression levels of 8-oxoguanine DNA glycosylase 1 (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), poly ADP-ribose polymerase 1 (PARP1), and DNA polymerase beta (POL beta). The levels of 8-OH-dG were found to be elevated in both individuals with BD and their siblings when compared to the HCs. The OGG1 and APE1 expressions were downregulated, while POL beta expressions were upregulated in both the patient and sibling groups compared to the HCs. Age, smoking status, and the number of depressive episodes had an impact on APE1 expression levels in the patient group while body mass index, smoking status, and past psychiatric history had an impact on 8-OH-dG levels in siblings. Both individuals with BD and unaffected siblings presented similar abnormalities regarding oxidatively-induced DNA damage and BER, suggesting a link between abnormalities in DNA damage/BER mechanisms and familial susceptibility to BD. Our findings suggest that targeting the oxidatively-induced DNA damage and BER pathway could offer promising therapeutic strategies for reducing the risk of age-related diseases and comorbidities in individuals with a genetic predisposition to BD.Publication Metadata only Mental health and support 1 year after the earthquakes in Türkiye(Elsevier Ltd, 2024) Kurt, Gulsah; Erşahin, Merve; Aker, A Tamer; Uygun, Ersin; Department of Psychology; Acartürk, Ceren; Department of Psychology; College of Social Sciences and HumanitiesN/APublication Metadata only Face and emotion recognition in individuals diagnosed with schizophrenia, ultra-high risk for psychosis, unaffected siblings, and healthy controls in a sample from Turkey(Elsevier, 2024) Sağdıç, Meylin; Erciş, Mete; Üçok, Alp; İzgi, Büşra; Eser, Hale Yapıcı; Kuşçu, Kemal; Graduate School of Health Sciences; School of MedicineFace and emotion recognition are crucial components of social cognition. We aimed to compare them in patients diagnosed with schizophrenia (SCZ), ultra-high risk for psychosis (UHR), unaffected siblings of schizophrenia patients (SIB), and healthy controls (HC). Methods: One hundred sixty-six participants (45 SCZ, 14 UHR, 45 SIB, and 62 HC) were interviewed with the Structured Clinical Interview for DSM-5 (SCID-5). Positive and Negative syndrome scale (PANSS), PennCNB Facial Memory (CPF), and Emotion Recognition Task (ER40) were applied. Results: In CPF, SCZ performed significantly lower than SIB and HC. SIB was also significantly lower than HC for total correct responses. The sample size of the UHR group was small, and the statistical comparisons did not reach a significance, however, a trend towards decreased performance between the SCZ and SIB was found. In ER40, SCZ performed significantly lower than HC and SIB in all domains, except for the insignificant findings for angry ER between SIB and SCZ. SIB also performed significantly lower than HC for angry, negative, and total ER. UHR was similar to SCZ for happy and sad ER and performed significantly lower than HC for happy ER. The effect of SCZ diagnosis on the efficiency of CPF and ER40 was significant when corrected for age and education. For SCZ, PANSS also significantly affected the CPF and ER40. Conclusion: Our findings suggest varying levels of face and emotion recognition deficits in individuals with SCZ, UHR, and SIB. Face and emotion recognition deficits are promising schizophrenia endophenotypes related to social cognition.Publication Metadata only Effect of clozapine on suicidality in patients with schizophrenia at a university hospital in Turkey(Elsevier B.V., 2023) Gürcan, Gamze; Yağcıoğlu, A. Elif Anıl; Ertuğrul, Aygün; Koç University Hospital[No abstract available]Publication Metadata only Baseline prepulse inhibition dependency of orexin A and REM sleep deprivation(Springer, 2024) Öz, Pınar; Kamali, Osman; Gör, Ceren; Uzbay, İsmail Tayfun; Saka, Hacer Begüm; Graduate School of Health SciencesRationalePrepulse inhibition (PPI) impairment reflects sensorimotor gating problems, i.e. in schizophrenia. This study aims to enlighten the role of orexinergic regulation on PPI in a psychosis-like model.ObjectivesIn order to understand the impact of orexinergic innervation on PPI and how it is modulated by age and baseline PPI (bPPI), chronic orexin A (OXA) injections was carried on non-sleep-deprived and sleep-deprived rats that are grouped by their bPPI.MethodsbPPI measurements were carried on male Wistar rats on P45 or P90 followed by grouping into low-PPI and high-PPI rats. The rats were injected with OXA twice per day for four consecutive days starting on P49 or P94, while the control groups received saline injections. 72 h REMSD was carried on via modified multiple platform technique on P94 and either OXA or saline was injected during REMSD. PPI tests were carried out 30 min. after the last injection.ResultsOur previous study with acute OXA injection after REMSD without bPPI grouping revealed that low OXA doses might improve REMSD-induced PPI impairment. Our current results present three important conclusions: (1) The effect of OXA on PPI is bPPI-dependent and age-dependent. (2) The effect of REMSD is bPPI-dependent. (3) The effect of OXA on PPI after REMSD also depends on bPPI.ConclusionOrexinergic regulation of PPI response with and without REMSD can be predicted by bPPI levels. Our findings provide potential insights into the regulation of sensorimotor gating by sleep/wakefulness systems and present potential therapeutic targets for the disorders, where PPI is disturbed.Publication Metadata only Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study(BMJ Publishing Group, 2024) Dekeyser, Catherine; Hautekeete, Matthias; Cambron, Melissa; Van Pesch, Vincent; Patti, Francesco; Kuhle, Jens; Khoury, Samia; Scott, Jeanette Lechner; Gerlach, Oliver; Lugaresi, Alessandra; Maimone, Davide; Surcinelli, Andrea; Grammond, Pierre; Kalincik, Tomas; Habek, Mario; Willekens, Barbara; Macdonell, Richard; Lalive, Patrice; Csepany, Tunde; Butzkueven, Helmut; Boz, Cavit; Tomassini, Valentina; Foschi, Matteo; Sanchez-Menoyo, Jose Luis; Mrabet, Saloua; Iuliano, Gerardo; Sa, Maria Jose; Alroughani, Raed; Karabudak, Rana; Aguera-Morales, Eduardo; Gray, Orla; de Gans, Koen; van der Walt, Anneke; McCombe, Pamela A.; Deri, Norma; Garber, Justin; Al-Asmi, Abdullah; Skibina, Olga; Duquette, Pierre; Cartechini, Elisabetta; Spitaleri, Daniele; Gouider, Riadh; Soysal, Aysun; Van Hijfte, Liesbeth; Slee, Mark; Amato, Maria Pia; Buzzard, Katherine; Laureys, Guy; Altıntaş, Ayşe; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of MedicineBackground It remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course.Methods This large-scale cohort study included persons with MS with CSF data documented in the MSBase registry. CSF parameters to predict time to reach confirmed Expanded Disability Status Scale (EDSS) scores 4, 6 and 7 and annualised relapse rate in the first 2 years after diagnosis (ARR2) were assessed using (cox) regression analysis.Results In total, 11 245 participants were included of which 93.7% (n=10 533) were persons with relapsing-remitting MS (RRMS). In RRMS, the presence of CSF oligoclonal bands (OCBs) was associated with shorter time to disability milestones EDSS 4 (adjusted HR=1.272 (95% CI, 1.089 to 1.485), p=0.002), EDSS 6 (HR=1.314 (95% CI, 1.062 to 1.626), p=0.012) and EDSS 7 (HR=1.686 (95% CI, 1.111 to 2.558), p=0.014). On the other hand, the presence of CSF pleocytosis (>= 5 cells/mu L) increased time to moderate disability (EDSS 4) in RRMS (HR=0.774 (95% CI, 0.632 to 0.948), p=0.013). None of the CSF variables were associated with time to disability milestones in persons with primary progressive MS (PPMS). The presence of CSF pleocytosis increased ARR2 in RRMS (adjusted R2=0.036, p=0.015).Conclusions In RRMS, the presence of CSF OCBs predicts shorter time to disability milestones, whereas CSF pleocytosis could be protective. This could however not be found in PPMS. CSF pleocytosis is associated with short-term inflammatory disease activity in RRMS. CSF analysis provides prognostic information which could aid in clinical and therapeutic decision-making.Publication Metadata only An examination of the mediating role of maladaptive emotion regulation strategies in the complex relationship between interpersonal needs and suicidal behavior(Frontiers Media Sa, 2024) Bakhshesh-Boroujeni, Michael; Farajpour-Niri, Sepideh; Hekmati, Issa; Asgarabad, Mojtaba Habibi; Department of Psychology; Eskin, Mehmet; Department of Psychology; Graduate School of Social Sciences and Humanities; College of Social Sciences and HumanitiesBackground: Studies have shown that psychological factors, notably interpersonal needs and emotion regulation, play a significant role in suicidal behavior. Interpersonal needs are significant contextual components that affect emotion regulation and contribute to a wide range of dysfunctional behaviors, such as suicidal behavior. It has been postulated that emotion regulation mediates the associations between proximal and distal risk factors of suicidal behavior. Method: The sample consisted of 340 community-dwelling individuals (62.5% women;SD = 0.48) with an age range of 18 through 55 (M = 30.23;SD = 8.54) who completed the interpersonal needs questionnaire, the suicide behaviors questionnaire-revised, and the cognitive emotion regulation questionnaire. The Structural Equation Modeling (SEM) approach was utilized to evaluate a mediation model. Results: The findings indicate that interpersonal needs (i.e., perceived burdensomeness r = .55, p <.01 and thwarted belongingness r = .25, p <.01) and putatively maladaptive cognitive emotion regulation strategies (i.e., self-blame;r = .38, p <.01, catastrophizing;r = .55, p <.01, rumination;r = .40, p <.01, and other blame;r = .44, p <.01) have strong associations with suicidal behavior, and these strategies have a mediating effect on the association between interpersonal needs and suicidal behavior. Conclusions: Our findings show that contextual-interpersonal needs, which underpin suicidal behavior, are significantly influenced by maladaptive emotional processes. Thus, therapeutic outcomes might be enhanced by focusing on the content of the associated cognitions and trying to reduce maladaptive regulatory processes like rumination and catastrophization.