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    A Systematic Review and Meta-Analysis of Arterial Spin Labeling Magnetic Resonance Imaging Studies in Psychosis Spectrum Disorders
    (Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2025) Atagun, Murat Ilhan; Korkmaz, Sukru Alperen; Bicer, Ebrar Ozden; Ozaydin, Bilgehan
    Introduction: Alterations in cerebral blood flow (CBF) in subjects with psychosis spectrum disorders (PSD) and clinical high-risk (CHR) states may provide insights into the pathophysiologyofthese disorders. Arterial spin labeling (ASL) facilitated a more comprehensive examination of CBF in these subjects. This meta-analysis synthesizes findings on CBF in PSDs and CHR states, addressing literature gaps. Methods: A systematic literature search of the PubMed database was performed using a protocol based on the PRISMA statement and the recommendations of the MOOSE group. Studies eligible for inclusion in the review involved: I) individuals with PSD, first-episode psychosis or CHR state, II) had healthy controls for comparison, III) neuroimaging should be performed with MRI using the pseudo-continuous ASL method, IV) resting cerebral blood flow (rCBF) should be recorded. Information related to participants, CBF analyses, and results were systematically extracted. Results: The PubMed search for the meta-analysis identified 69 publications, including 24 articles that met the inclusion criteria for the meta-analysis, representing 491 SSD patients, 185 CHR states, and 554 controls. Studies included rCBFs for the whole brain, gray matter, and striatum. The meta-analysis results indicated that patients with PSD had decreased gray matter rCBF compared to controls (Hedge's g=0.33, 95% CI [0.08, 0.57]), but no difference in the whole brain (Hedge's g=0.09, 95% CI [-0.70, 0.88] and striatum rCBF (Hedge's g=0.38, 95% CI [-0.23, 1.00]). Additionally, subjects with CHR state showed no differences in the striatum rCBF compared to the controls (Hedge's g=-0.15, 95% CI [-0.80, 0.51]). Conclusions: This suggests that although perfusion changes in gray matter are present in PSD, they may not extend to wider brain regions or specific structures such as the striatum. Furthermore, the results imply that rCBF may be differentially regulated in subjects with PSD and CHR. Updated findings highlight hemodynamic correlations in PSD pathophysiology.
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    A Systematic Review of the Literature Regarding the Relationship Between Oxidative Stress and Electroconvulsive Therapy
    (Aves, 2022) Atagun, Murat Ilhan; Canbek, Ozge Atay
    Objective: Brain's aerobic energy metabolism, abundance of the fatty acids and unsaturated lipids, generation of Reactive Oxygen Species (ROS) by hormones, physiological roles of transition metals (i.e., iron and copper), and free radicals in the nervous system may cause inclination to oxidative stress in psychiatric disorders. Electroconvulsive therapy (ECT) may cause oxidative stress by the electrical field or by the induced seizure. It was aimed to review the literature in terms of the influence of ECT on levels of oxidant and antioxidant compounds. Methods: The literature search was performed with the keywords that were oxidative stress or DNA damage or RNA damage or lipid peroxidase or superoxide dismutase or catalase or glutathione or nitrite or nitric oxide and electroconvulsive therapy or electroconvulsive shock or electroconvulsive seizure. Twenty of 1480 records were included. Results: Eleven studies were performed in human subjects, whereas 9 studies were performed in rats. Human studies are conducted with serum, plasma, or urine samples; rat studies include brain tissues from various sites. In rats, four independent studies showed increased levels of lipid oxidation markers, and four independent studies reported increased levels of oxidative stress markers in brain samples. In human studies, studies were performed with circulating blood samples and the results were more inconsistent. Conclusion: Although some markers like superoxide dismutase or thioredoxin imply that ECT may increase the balance for oxidative stress, this notion is not supported by other markers of ECT. The current literature does not clearly suggest that the ECT is associated with oxidative stress in psychiatric disorders. Further studies with similar methods should be performed in big samples.
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    Acute and Long Term Treatment of Manic Episodes in Bipolar Disorder
    (Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2021) Atagun, Murat Ilhan; Oral, Timucin
    Bipolar disorder is a disabling psychiatric disorder which causes premature death and loss of quality of life. Despite the developments, novel treatments are partially effective and insufficient responses to treatment may cause loss of quality of life. Contemporary approaches to treatment planning involve taking the current symptoms and the personal treatment history of the patient into account and tailoring them for the treatment of each patient, i.e. individualized treatment. In this article, effects and side effects of antipsychotics, mood stabilizers and sedative hypnotic medications are reviewed and presented briefly for clinicians. Although novel developments have been observed in the literature about mixed states and psychotic symptoms, evidence-based options are still limited. Efficacy of mood stabilizers may be prolonged and additional medications may also be needed frequently in patients treated with mood stabilizers. Antipsychotics may cause several side effects and cannot be maintained for a long time in some of those patients. These factors may limit the use of mood stabilizers or antipsychotics. Therefore, the experience of the clinician and personal history of the patient still have importance in the procedure.
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    Characterization and Features of Neural Oscillations in Mental Disorders
    (Springer Science+Business Media, 2025) Hirano, Yoji; Atagun, Murat Ilhan
    Viewing psychiatric disorders or symptoms as outcomes of brain dysfunction emphasizes the necessity of objectively assessing brain function for a deeper understanding of their pathophysiology. Moreover, to measure the brain’s functional abnormalities underlying the dynamically changing mental states and symptoms, EEG and MEG with high temporal resolution are optimal. Research employing EEG/MEG to investigate brain function in relation to psychiatric disorders via classical task-evoked ERP/ERF studies has produced substantial findings. Nevertheless, recent progress in equipment digitalization and analytical methodology development has facilitated the quantification of neural oscillations, inherent rhythmic periodic activities critical for sustaining complex brain functions. It is evident that these oscillations play a role in the pathophysiology of psychiatric disorders, such as schizophrenia and bipolar disorder. In this chapter, we provide an overview of previous research using EEG/MEG in major psychiatric disorders, along with the latest findings and future prospects. © 2025 Springer Nature Switzerland AG.
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    Evaluation of Antidepressant Choices for The Treatment of Depressive Symptoms in Patients with Bipolar Disorder
    (Yerkure Tanitim & Yayincilik Hizmetleri A S, 2012) Atagun, Murat Ilhan; Altinbas, Kursat; Yesilyurt, Sema; Yesilbas, Dilek; Guloksuz, Sinan; Oral, Timucin
    Objective: Antidepressants are thought to cause manic switches and accelerate cycling in the treatment of bipolar depression. On the other hand, other evidence suggests that antidepressant neither cause manic switches, nor are effective for the treatment of bipolar depression. This study aimed to assess clinicians' attitudes towards antidepressant choices for treatment of bipolar depressive episodes and subthreshold depression. Methods: Medical records of 784 patients with bipolar disorder were investigated retrospectively. Antidepressants were used in 55 of 263 depressive episodes (20.9%). Data regarding 78 episodes (23 subthreshold symptoms, 55 episodes) of 68 patients (54 female, 14 male; mean age: 39.64 +/- 10.99) were obtained. Descriptive statistics were the evaluation method. Results: In our department, antidepressants were used in 20.9% of the patients in the treatment of bipolar depression. One third of patients receiving antidepressant prescriptions had a history of manic switch, 5 (21.7%) of the patients with subthreshold symptoms receiving antidepressant prescriptions had a history of manic switch. However, manic switch occurred in only 5 (6.4%) patients. Selective serotonin reuptake inhibitors were the most common cause (58.3%) of the manic switch in patients with a history of manic switch. Discussion: Clinicians are still using antidepressants in the treatment of bipolar depression. Antidepressants targeting many neurotransmitter systems can be used in the first line treatments and antidepressants can be used even in patients with a history of manic switch. This controversial topic should be studied prospectively with larger samples and it must be clarified whether this phenomenon is a natural course of the disorder or triggered by antidepressant medications.
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    Longitudinal trajectories of major depressive disorder provide further clinical perspectives for precision psychiatry
    (Wiley, 2025) Atagun, Murat Ilhan
    Major depressive disorder (MDD) is a common and debilitating disorder. MDD was considered to be a relatively benign disorder compared to other major psychiatric disorders. However, longitudinal research revealed heterogeneous and frequently chronic course. Episodic or chronic progress reframes MDD as a disorder with a variable and enduring course. The recognition of MDD's heterogeneity has prompted a methodological evolution in psychiatric research, moving away from group-level averages toward more sophisticated, person-centered analytical techniques. In addition to inherent heterogeneity, biological, psychosocial, and environmental factors are also influential on the clinical manifestations of MDD. The course of major depressive disorder is not only heterogeneous among individuals but also varies systematically across different populations. Multiple models have consistently identified several distinct trajectory classes across diverse populations and study designs, providing a more nuanced map of how MDD unfolds over a lifetime. The concept of MDD subtyping within precision psychiatry directly addresses its inherent heterogeneity. If different subtypes of MDD possess distinct neurobiological underpinnings, then identifying these specific subtypes through biomarkers may lead to highly targeted and significantly more effective treatments. Longitudinal perspectives are indispensable for an accurate understanding of prognosis, the development of preventive strategies, and the implementation of effective long-term management plans that can alter the illness's trajectory. It was aimed to review the MDD trajectories, treatments, and symptom clusters from population and life span-based perspectives in this paper.
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    Machine learning algorithms revealed distorted retinal vascular branching in individuals with bipolar disorder
    (Elsevier, 2022) Atagun, Murat Ilhan; Sonugur, Guray; Yusifova, Aygun; Celik, Ibrahim; Ugurlu, Nagihan
    Background: Converging evidence designate vascular vulnerability in bipolar disorder. The predisposition pro-gresses into distortion in time, thus detection of the vascular susceptibility may help reducing morbidity and mortality. It was aimed to assess retinal fundus vasculature in cardiovascular risk-free patients with bipolar disorder. Methods: Total of 68 individuals (38 patients with bipolar disorder, 30 healthy controls) were enrolled. In order to avoid from degenerative processes, participants were between 18 and 45 years of age, vascular risk factors were eliminated. Microscopic retinal fundus images were processed with machine learning algorithms (multi -layer perceptron and support vector machine) and artificial neural network approaches. Results: In comparison to the healthy control group, the bipolar disorder group had lower number of breaking points (P < 0.001), lower number of curved vessel segments (P < 0.001). Total length of smooth vessels was longer (P = 0.040), and total length of curved vessel segments was significantly shorter (P < 0.001) than the control group. Vascular endothelial growth factor levels and gender were the confounders. There were significant correlations between vascular measures and serum lipid levels.Limitations: Sample size was small and patients were on various medications. Conclusions: These results indicate distortion in retinal vascular branching in bipolar disorder. Disrupted branching may reflect disturbed prosperity of retinal vascular plexus in patients with bipolar disorder. Alter-ations in the retinal vessels might be indicators of disruption in cerebral vascular system efficiency and thus neurovascular unit dysfunction in bipolar disorder.
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    Methods for Measuring Neural Oscillations in Mental Disorders
    (Springer Science+Business Media, 2025) Atagun, Murat Ilhan; Tamura, Shunsuke; Hirano, Yoji
    Electroencephalography (EEG) and magnetoencephalography (MEG) are neurophysiological methods for recording brain electrical signals. The signals consisting of excitatory post-synaptic potentials and fields summate and propagate through brain surface and cranium and thereby captured by the EEG and MEG. The signal gets contribution from several sources and become convoluted by detached inputs. The signal could be altered by inputs according to the network and task demands. Cognitive, sensory, or motor tasks invoke associated neural networks. Stimulation characteristics determine analysis strategies. Decomposition of the EEG data has three phases including (i) preprocessing, (ii) processing, and (iii) post-processing. Within the recent years, deep learning and classification systems are added into EEG data analysis. In this chapter, we aimed to introduce methods for experimental and analytical procedures of EEG research. © 2025 Springer Nature Switzerland AG.
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    Rethinking Treatment-Resistant Depression: A Systematic Review of Novel Therapeutic Strategies and Precision Medicine Approaches
    (STM Editores S.A, 2025) Tatli, Safiye Zeynep; Atagun, Murat Ilhan
    Background: Treatment-resistant depression (TRD) is a complex and heterogeneous condition affecting a considerable subset of patients who do not respond to conventional antidepressants. Given the limitations of traditional treatment strategies, there is a growing need for alternative and personalized approaches. Objective: This review explores the neurobiological underpinnings of TRD and examines the efficacy of emerging pharmacological and neuromodulatory interventions. We also highlight the potential role of the bipolar spectrum in TRD and the need for tailored treatment strategies. Methods: A systematic review of literature from 2015 to 2025 was conducted using PubMed and Scopus. Studies on TRD treatment modalities, including augmentation strategies, mood stabilizers, atypical antipsychotics, and neuromodulation techniques, were analyzed. Results: Our findings indicate that novel interventions, such as ketamine, esketamine, psychedelics, and neuromodulation therapies (e.g., repetitive transcranial magnetic stimulation, magnetic seizure therapy) show promise in addressing TRD. Additionally, biomarker-driven and pharmacogenetic approaches may enhance treatment selection and improve outcomes. Evidence suggests that a subset of patients with TRD could fall within the bipolar spec-trum, requiring mood stabilizers and antipsychotics rather than standard antidepressant regimens. Conclusion: A multidisciplinary and precision-based approach is essential for optimizing TRD management. Future research should focus on biomarker-driven treatment selection, artificial intelligence-assisted decision making, and large-scale trials to refine personalized therapeutic strategies. © 2025 The Author(s).