Neuropsychiatric Investigation is a peer-reviewed, open access, online-only journal published by İstanbul University-Cerrahpaşa. Neuropsychiatric Investigation is a continuously published journal in English. The journal has moved to continuous publication by volume from Volume 63.
Delusional Disorder with Incestuous Themes: A Rare and Complex Case Report Exploring Psychiatric, Psychoanalytic, and Forensic Dimensions
Cite this article as: Asan Ö, Kavla Y, Boylu ME. Delusional disorder with incestuous themes: a rare and complex case report exploring psychiatric, psychoanalytic, and forensic dimensions. Neuropsychiatr Invest. 2025, 63, 0001, doi:10.5152/NeuropsychiatrInvest.2025.25001.
Life Paralyzing Obsessive Compulsive Disorder: A Case of Flexion Contracture
Cite this article as: Parlakkaya Yıldız FB, Ereğli B, Karadere ME. Life paralyzing obsessive compulsive disorder: A case of flexion contracture. Neuropsychiatr Invest. 2025, 63, 0005, doi:10.5152/NeuropsychiatricInvest.2025.25005.
Network Meta-Analysis of Anorexia Nervosa Treatments: Toward Precision Medicine with Pharmacogenomics and Neural Nets
Objective: Anorexia nervosa (AN) affects millions of people worldwide and treatments vary widely with no set treatment guidelines. A network meta-analysis compared and contrasted treatments for adults with AN that reported body mass index (BMI) or weight changes. Methods: Embase, Medline, CINAHL, PubMed, PsycINFO, Cochrane, and clinicaltrials.gov were searched, from January 1974 to March 2024, for articles reporting weight or BMI results pre/posttreatment for anorexia treatments. Outcomes, using pooled-weighted-standard mean effect sizes and subgroup analyses per-intervention-type, were analyzed using a random effects model with bayesian and frequentist statistics. Artificial neural nets were used to predict response to future treatments. About 63 studies were included out of the 650 reviewed articles. Results: The random effects model calculated a pooled-weighted-effect size for 4366 patients of 1.43 (1.00-1.86) 95%CI for surgically invasive neuromodulation (deep brain stimulation (DBS) and Capsulotomy Surgery), 0.65, 95%CI (0.45-0.86) for pharmacological interventions, 0.10 (0.23-0.42) for non-invasive neuromodulation (repetitive transcranial magnetic stimulation, transcranial direct current stimulation, electroshock treatment), −0.02 (−0.32-0.29) for psychotherapeutic interventions, and −0.09 (−0.47-0.29) for compulsory diets. Between-study heterogeneity was tau2 =0.08. Conclusion: Subgroup analysis suggests that capsulotomy, DBS, olanzapine, and cyproheptadine may result in higher BMI/weight differences and longer posttreatment weight maintenance. Meta-regression with neural nets indicates that the mode of action of interventions, resulting in adverse drug reactions for some patients with specific pharmacogenetic profiles, has a higher chance of affecting treatment outcomes. These findings suggest that pharmacogenomic testing and precision medicine need to be explored further for AN patients. Study registration: PROSPERO:CRD42023421545 Cite this article as: Korsavva S, Valkova FB, Perez IC, Meletiadis A. Network meta-analysis of anorexia nervosa treatments: toward precision medicine with pharmacogenomics and neural nets. Neuropsychiatr Invest. 2025, 63, 0019, doi:10.5152/ NeuropsychiatricInvest.2025.25019.
A Pathological Study of Major Depressive Disorder Related to Amygdala Structure
Major depressive disorder (MDD) has severe consequences that extend beyond mental health, affecting physical health and quality of life, and raising mortality risk. The pathophysiology of MDD is still poorly understood, and current antidepressants are not completely effective. Current research identifies several key hypotheses and biochemical mechanisms involved in the pathogenesis of MDD, demonstrating that no single theory can fully explain its complexities. Recent research on MDD therapies indicates that they alter the amygdala, causing changes that can serve as markers for recovery in MDD treatment. Observations suggest that selective serotonin reuptake inhibitors, which are routinely used to treat depression, alter amygdala anatomy and function. This study used a narrative and descriptive review methodology. This review aimed to update structural and functional alterations in the amygdala that are strongly associated with MDD and its clinical symptoms. Also, some possibilities about the role of key endogenous substances were discussed, such as cortisol, epinephrine, and norepinephrine, as well as receptors for hormones and neurotransmitters in the amygdala, providing evidence and molecular mechanisms that emphasize the amygdala’s central role in MDD and its therapy. Cite this article as: Hien HTD, Bao NS, Hieu BTM, Thu NTM, Hang DTT. A pathological study of major depressive disorder related to amygdala structure. Neuropsychiatr Invest. 2025, 63, 0052, doi:10.5152/NeuropsychiatricInvest.2025.24052.
The Relationship Between Breastfeeding and Attention Deficit and Hyperactivity Disorder: What Do We Know? A Systematic Review
The aim of this study is to examine the relationship between breastfeeding, which is an important factor in protecting and improving child health, and attention deficit/hyperactivity disorder (ADHD), which is an increasingly common public health problem, and to determine the current situation in the literature. Studies published in English before May 2023 using the Web of Science, PubMed, and Scopus databases were searched. Ten cross-sectional, 10 case-control, 12 cohort studies, and 2 randomized controlled trials involving a total of 420 694 participants were included in this study. A total of 34 studies conducted between 2007 and 2022 were included in the systematic review. The lack of a standardized definition of ADHD diagnoses and breastfeeding categorizations in the included studies leads to different results between studies. The findings suggest that breastfeeding may be associated with a reduced risk of ADHD in children. Breastfeeding could potentially serve as a protective factor for ADHD; however, high-quality longitudinal studies are needed to confirm or refute this causality and to understand the underlying potential mechanisms. Cite this article as: Evcil FY, Batmaz K, Çoban B, Doğan E, Önal Ö, Kişioğlu AN. The relationship between breastfeeding and attention deficit and hyperactivity disorder: What we do? A systematic review. Neuropsychiatr Invest. 2025, 63, 0008, doi:10.5152/NeuropsychiatricInvest.2025.25008.
Autosomal Recessive Omodysplasia (GPC6-Related) with Treatment-Resistant Schizophrenia
Omodysplasia is an extremely rare short-limb skeletal dysplasia characterized by severe micromelic dwarfism with predominantly rhizomelic shortening of the upper and lower limbs. Type 1 omodysplasia, also known as autosomal recessive omodysplasia, is caused by a mutation in the GPC6 gene. This is the first case of a patient with schizophrenia genetically diagnosed with omodysplasia type 1. A 27-year-old, university graduate, bilingual, single white woman was brought to the emergency psychiatry clinic with psychomotor agitation, anxiety, persecutory delusions, and hallucinations. On the basis of the patient’s background, she was diagnosed with omodysplasia type 1 in early childhood. In addition, she was diagnosed with schizophrenia 8 years ago. Informed consent was obtained from the patient and her mother, who had an advance directive. Schizophrenia is a neurodevelopmental disorder caused by both genetic and environmental factors. GPC6 is also associated with formal thought disorder (FTD), which is a common symptom of schizophrenia. GPC6 gene mutation in FTD is located on chromosome 13, such as that of autosomal recessive omodysplasia. Although this case could be coincidental, it may contribute to current genetic studies that have an important place in the etiology of schizophrenia. Cite this article as: Poyraz E, Firidin S, Göverti D, Ulu B, Bülbül A, Özer T. Autosomal recessive omodysplasia (GPC6-related) with treatment-resistant schizophrenia. Neuropsychiatr Invest. 2025, 63, 0015, doi:10.5152/ NeuropsychiatricInvest.2025.25015.
Transcranial Direct Current Stimulation as an Adjuvant Therapy for Major Depressive Disorder
Objective: Major depressive disorder (MDD) is a prevalent and debilitating mental health condition, often accompanied by medical and psychiatric comorbidities. Effective treatment strategies are crucial to reducing symptoms and improving the quality of life for affected individuals. This study evaluates the effectiveness of transcranial direct current stimulation as an adjunctive treatment for MDD, analyzing its impact on depressive symptom reduction, safety, tolerability, and effectiveness when combined with conventional pharmacological treatments. Methods: A historical cohort study was conducted with 60 participants diagnosed with MDD. The Hamilton Depression Scale and 9-Item Patient Health Questionnaire were used to measure depressive symptom severity. Pre- and post-treatment scores were analyzed using ANOVA, with significance set at P < .05. Effect sizes were calculated to quantify the magnitude of treatment effects. Demographic data, comorbidities, and concurrent pharmacological treatments were also recorded. Results: The cohort had an average age of 44.22 ± 19.8 years, with 43 (71.7%) women and 17 (28.3%) men. Anxiety and insomnia were common, reported by 73.3% and 81.7% of participants, respectively, with 65% experiencing both. Medical comorbidities were present in 56.7% of participants. Antidepressant use was noted in 43.3%, with sertraline and escitalopram being the most frequently prescribed. Post-treatment Hamilton Depression Rating Scale scores decreased from 24.23 to 6.78 (P < .01), reflecting a 72.02% reduction. 9-Item Patient Health Questionnaire scores dropped from 17.83 to 4.67 (P < .01), a 73.81% reduction. No adverse effects were observed, supporting the intervention’s tolerability. Conclusion: Transcranial direct current stimulation, as an adjunct to pharmacological therapy, significantly reduces depressive symptoms in individuals with MDD. These findings support its use as an effective and tolerable treatment option, especially for patients with comorbid medical and psychiatric conditions. Cite this article as: Moya-Sánchez DN, Ochoa-Madrigal MG, Meneses-Luna Ó, et al. Transcranial direct current stimulation as an adjuvant therapy for major depressive disorder. Neuropsychiatr Invest. 2025, 63, 0020, doi:10.5152/NeuropsychiatricInvest.2025.25020.
Relationship Between Plasma Testosterone and Suicidal Behavior in Patients with Antisocial Personality Disorder
Objective: Antisocial personality disorder (ASPD) is associated with a heightened risk of suicide, particularly among male patients, where chosen suicide methods tend to be more lethal. The link between suicidal behavior and plasma testosterone levels remains a key area of investigation. This study investigates whether plasma testosterone levels differ between ASPD patients with a history of suicide attempts, aiming to explore the hormone’s potential role as a biomarker for suicide risk. This study aimed to explore the association between plasma testosterone levels and suicidal behavior in individuals with ASPD who attempted suicide. Methods: A total of 44 patients with ASPD and 24 healthy controls were enrolled, matched by age, education, and gender. Biochemical evaluations included total and free testosterone, thyroid function tests, blood lipids, folate, ferritin, and vitamin B12 levels. Psychopathological assessments were conducted using the Hamilton Depression (HAM-D) and Anxiety (HAM-A) Scales. Results: The mean ages of the patient and control groups were 22.26 (±3.04) and 24.36 (±2.5) years, respectively. Free testosterone levels were significantly elevated in the patient group compared to controls (P=.02). Hamilton Anxiety (HAM-A) and HAM-D scores were also notably higher in the patient group. A positive correlation was identified between free testosterone levels and high-density lipoprotein in patients with ASPD (R=0.520; P < .05). Conclusion: These preliminary findings suggest that elevated free testosterone may contribute to increased suicide risk in men with ASPD, potentially through its impact on impulsivity and aggression. While the effect size was modest, identifying hormonal patterns associated with suicidal behavior may help guide future risk assessment strategies. Further research with larger and more diverse samples is warranted. Cite this article as: Garip B, İnanç Ö. Relationship between plasma testosterone and suicidal behavior in patients with antisocial personality disorder. Neuropsychiatr Invest. 2025, 63, 0017, doi:10.5152/NeuropsychiatricInvest.2025.25017.
White Matter Reductions and Basal Ganglion Asymmetries in First Manic Episode Bipolar Disorder
Objective: In this study, the volumes and asymmetries of various brain regions of drug-naive patients with first manic episode bipolar disorder type 1 (FME-BD-1) were examined via magnetic resonance imaging (MRI) and compared with the healthy control (HC) group. Methods: The current study included 54 patients diagnosed with FME-BD-1 and 67 age- and sex-matched HCs. Brain MRI segments of subjects were processed using the VolBrain software. The Young Mania Rating Scale (YMRS) was used to assess manic symptoms and their severity. Results: There were 34 males (63.00%) and 20 females (37.00%) in FME-BD-1 group, 38 males (56.7%) and 29 females (43.3%) in the HC group. The percentages of total (P=.018), right (P=.014), and left cerebrum white matter (WM) (P=.022) of the FME-BD-1 group were significantly lower than the HC group. The percentages of total (P=.020), right (P=.028), and left cerebellum WM (P=.022) of the FME-BD-1 group were significantly lower than the HC group. The volumes of the total (P=.026) and left cerebellum WM (P=.030) in the FME-BD-1 group were significantly lower than the HC group. Accumbens (P=.018) and caudatus asymmetries (P=.006) were significantly different between the FME-BD-1 and HC groups. A significant negative correlation was found between total cerebrum WM and YMRS scores (r=−0.611, P < .001). Conclusion: In conclusion, drug-naive FME-BD-1 is associated with cerebral and cerebellar volume reductions. Moreover, nucleus caudatus asymmetry and accumbens asymmetry were significantly different in FME-BD-1 compared to HCs. Cite this article as: Kapıcı OB, Kapıcı Y, Tekin A, Şirik M, Örüm D. White matter reductions and basal ganglion asymmetries in first manic episode bipolar disorder. Neuropsychiatr Invest. 2025, 63, 0059, doi:10.5152/NeuropsychiatricInvest.2025.24059.
Volumetric Magnetic Resonance Imaging Investigation of the Pituitary in Patients with Vaginismus
Objective: Many previous studies have reported decreased pituitary volume in various anxiety disorders compared to healthy controls. In this context, this study was conducted with the hypothesis that pituitary volume is reduced in this patient group as in other anxiety disorders. Methods: Ten women with vaginismus and 10 healthy controls were included in the study. Structural magnetic resonance imaging and volume measurements of the participants were performed in the radiology department. Results: The mean pituitary volume of women with vaginismus was found to be significantly decreased compared to healthy controls. Conclusion: The present findings suggest that vaginismus may be closely related to anxiety-related conditions involving at least the pituitary gland. Cite this article as: Atmaca M, Gürokk MG, Tabara MF, et al. Volumetric MRI investigation of the pituitary in patients with vaginismus. Neuropsychiatr Invest. 2025, 63, 0050, doi: 10.5152/NeuropsychiatricInvest.2025.24050.
Factors Associated with COVID-19 Vaccination Status in Adolescents Diagnosed With Epilepsy
Objective: This study investigates coronavirus disease 2019 (COVID-19) vaccination status in adolescents diagnosed with epilepsy, focusing on its relationship with psychiatric comorbidities. Methods: Between December 2020 and June 2023, 214 adolescents aged 12-18 with epilepsy were enrolled in 2 pediatric neurology clinics. Data were collected from legal guardians and patient records. Results: Among the 214 patients, 112 (52.3%) were male, and 170 (79.4%) attended formal education. Mental illness was present in 108 patients (50.5%), with 73 (34.1%) having autism spectrum disorder or intellectual disability (ID). Eighty patients (37.4%) received the COVID-19 vaccine, predominantly mRNA vaccines (85%). Vaccinated individuals were older, had more siblings, had higher maternal education levels, and had lower rates of treatment-resistant epilepsy (P < .05 for each). There was no significant association found between the presence and number of comorbid mental health diagnoses and COVID-19 vaccination status in adolescents with epilepsy. Family preference was the main reason for vaccination (68.4%), while concerns about epilepsy worsening were the primary reason for non-vaccination. Conclusion: Factors associated with COVID-19 vaccination in adolescents with epilepsy include age, number of siblings, maternal education level, history of COVID-19 in the patient, vaccination among family members, perceived vaccine efficacy, duration of protection of the vaccine, and healthcare professionals’ opinions. Importantly, no significant association was observed between the presence and number of comorbid mental health diagnoses and COVID-19 vaccination status, underscoring that mental health conditions in this population are not barriers to vaccination. Parents have concerns about vaccine safety and the exacerbation of epilepsy, necessitating the dissemination of accurate information by healthcare professionals, especially targeting parents with lower education levels, unvaccinated parents without prior COVID-19 infection, and adolescents. Cite this article as: Mutlu C, Taspolat ER, Kırışman-Keleş H, Yapıcı Z, Topaloğlu P, Bodur M. Factors associated with COVID19 vaccination status in adolescents diagnosed with epilepsy. Neuropsychiatr Invest. 2025; 63, 0053,doi: 10.5152/NeuropsychiatricInvest.2025.24053.
Evaluation of Attention and Verbal Memory Functions of Individuals with Misophonia
Objective: The aim of this study was to evaluate the attention and verbal memory performances of individuals with symptoms of misophonia. Methods: The study included 70 participants: 30 with misophonia and 40 controls without misophonia. The Depression Anxiety Stress Scale (DASS-21), Misophonia Questionnaire, Digit Span Test (DST), Verbal Fluency Test (VFT), Stroop Test (ST), and Verbal Memory Processes Scale (VMPS) were applied to the participants. Results: The depression, anxiety, and stress scores of the misophonia group were statistically significantly higher than the control group (P < .05). The misophonia group performed poorly compared with the control group on 2 tests assessing attention (semantic fluency and ST-number of incorrect) (P < .05). No difference was found between the groups in cognitive areas such as simple attention, working memory, phonetic fluency, and verbal memory. Conclusion: Misophonia has a limited effect on attention functions. This effect was not observed in verbal memory. More comprehensive studies are needed to determine the effects of misophonia on attention, and memory. Cite this article as: Aslan D, Demirci H, Kurt-Dizdar S, Özer OA. Evaluation of attention and verbal memory functions of individuals with misophonia. Neuropsychiatr Invest. 2025; 63, 0063, doi: 10.5152/NeuropsychiatricInvest.2025.24063.
Symptom Changes in Patients with Obsessive-Compulsive Disorder During the COVID-19 Pandemic: The Impact of Cognitive Flexibility
Objective: The course of patients with obsessive-compulsive disorder (OCD) has attracted particular concern during the COVID-19 pandemic because measures to prevent the spread of COVID-19 coincide with OCD symptoms. Cognitive flexibility, which refers to the ability to adapt to changing conditions, may be a possible mechanism explaining the impact of the pandemic, considering it has been shown to be an executive function abnormality in OCD. We aimed to explore the course of OCD during the COVID-19 pandemic and the impact of cognitive flexibility on the changes in patients’ symptomatology. Methods: The course of symptoms in 81 OCD patients during the pandemic was evaluated retrospectively with a clinician-developed data form. The Cognitive Flexibility Scale was used to assess cognitive flexibility. The Yale-Brown Obsessive-Compulsive Scale, the Fear of COVID-19 Scale, the Hamilton Anxiety Scale, and the Hamilton Depression Scale were also administered. Results: We found that 68.1% of patients reported worsening. Patients with worsening symptoms had a higher fear of COVID-19. Levels of cognitive flexibility, anxiety, or depression did not differ between the patients with and without worsening. However, patients who reported more severe worsening had lower cognitive flexibility and greater levels of anxiety and depression than those with milder ones. Conclusion: Our study reveals the deterioration in OCD patients during the COVID-19 pandemic and indicates the role of cognitive inflexibility in worsening symptoms. Cite this article as: Dokuz G, Kanlı Ş, Bulçak A, Boylu ME, Dönmez Z, Kırpınar İ. Symptom changes in patients with obsessive-compulsive disorder during the COVID-19 pandemic: the impact of cognitive flexibility. Neuropsychiatr Invest. 2025, 63, 0013, doi: 10.5152/ NeuropsychiatricInvest.2024.24013.
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Suicidal Ideation and Attempts in Trichotillomania and Skin-Picking Disorder: A Comparative Study with Healthy Controls
Objective: The relationship between trichotillomania (TTM) and skin picking disorder (SPD), classified under the category of obsessive-compulsive and related disorders (OCRDs) in the DSM-5, and suicidal behavior remains unclear. The aim of this study is to investigate sociodemographic characteristics, clinical variables, psychiatric comorbidities, suicidal ideation, and behavior in treatment-seeking individuals diagnosed with TTM and SPD, as well as to identify the determinants of the severity of suicidal behavior. Methods: The study included patients who were diagnosed with TTM (n=26) or SPD (n=40) according to DSM-5, and healthy controls (n=54). Comorbidities were determined by the Clinician Version of the Structured Clinical Interview for DSM-IV Disorders (SCID-I). Beck Depression Inventory (BDI), The Scale for Suicidal Ideation (SSI), and Suicidal Behavior Scale (SBQ) were administered to all participants. Results: The lifetime prevalence of suicide attempts, BDI scores, SSI and SBQ subscale and total scores, as well as the rates of suicidal ideation, were statistically significantly higher in TTM and SPD patients compared to the control group (P < .05). Psychiatric comorbidity, BDI scores, and the course of the disorder were identified as predictors of SBQ scores (P < .05). Conclusion: Suicidal ideation and behaviors are significantly higher in individuals with TTM and SPD compared to healthy controls. Psychiatric comorbidities, depression severity, and the chronic course of the disorders were found to be significantly associated with suicidal behavior. These findings highlight the need for comprehensive suicide risk assessments in TTM and SPD patients to guide effective interventions. Cite this article as: Pirdoğan Aydın E, Yıldırım F, Kenar JG. Suicidal ideation and attempts in trichotillomania and skin- picking disorder: a comparative study with healthy controls. Neuropsychiatr Invest. 2025, 63, 0002, doi:10.5152/NeuropsychiatricInvest.2025.25002.
Psychological Resilience, Body Appreciation, and Associations with Anxiety and Depression in Pubertal Gynecomastia: A Case-Controlled Study
Objective: Pubertal gynecomastia may have adverse psychosocial consequences, yet the influence of psychological resilience has been insufficiently explored. Methods: In this case-control study, 36 adolescents with clinically and ultrasonographically confirmed pubertal gynecomastia and 40 healthy controls (ages 11-18) were assessed. Body mass index (BMI) and gynecomastia severity (Rohrich classification) were recorded. Participants completed the Revised Child Anxiety and Depression Scale–Child Version (RCADS-CV), the Adolescent Psychological Resilience Scale (APRS), and the Body Appreciation Scale (BAS). Between-group comparisons and correlations were examined, and MANCOVA was conducted to control for potential confounders. Results: Adolescents in the pubertal gynecomastia group reported significantly lower levels of psychological resilience (F(1, 70)= 62.198, P < .001, η²P= 0.471) and body appreciation (F(1, 70)= 5.21, P= .026, η²P = 0.069) compared to the control group, even after controlling for BMI. Although overall anxiety and depression scores did not differ significantly, social phobia approached the significance threshold (t(74) = 1.893, P = .062). Gynecomastia severity was linked to reduced body appreciation (F(2, 28) = 6.621, P = .004, η²P = 0.321). BMI independently predicted lower resilience (F(1, 70) = 4.77, P= .032, η²P= 0.064) and body appreciation (r= −0.308, P = .007) but did not directly contribute to anxiety or depression. Conclusion: While pubertal gynecomastia may not invariably manifest as clinical anxiety or depression, it appears to elevate social phobia risk and undermine both body image and resilience. Psychosocial interventions can mitigate these adverse effects, especially in adolescents who are not candidates for surgical intervention. Cite this article as: Meral Y, Sezgin M, Özer Y. Psychological resilience, body appreciation, and associations with anxietyand depression in pubertal gynecomastia: A case-controlled study. Neuropsychiatr Invest. 2025; 63, 0018, doi:10.5152/NeuropsychiatricInvest.2025.25018.
Comparative Analysis of Irritable Bowel Syndrome Symptom Severity in Adults With Attention-Deficit/Hyperactivity Disorder and Healthy Controls: A Case-Control Study
Objective: The aim is to assess the severity of irritable bowel syndrome (IBS) symptoms in adults with attention deficit/hyperactivity disorder (ADHD) in comparison to a control group and to examine the relationship between the symptom severities of adults with ADHD and IBS. Methods: This cross-sectional study included 40 adults with ADHD and 40 matched healthy controls. Adults with ADHD was diagnosed using the Structured Clinical Interview for DSM-5 Disorders, and symptom severity was assessed with the Adult ADHD Self-Report Scale. Irritable bowel syndrome severity was determined using Irritable Bowel Syndrome Severity Scoring System. Major psychiatric disorders, chronic gastrointestinal (GI) diseases, and recent use of GI medications were among the exclusion criteria. Statistical analyses used t-tests, chi-square tests, and Pearson’s correlation (P < .05). Results: The group with ADHD showed significantly higher IBS symptom severity scores (114.73 ± 125.16) than the control group (55.82 ± 85.51) (t=2.167, P=.016). A strong positive correlation was observed between ADHD symptom severity and IBS symptom severity (r=0.689, P < .001). Conclusion: Individuals with ADHD experience more severe IBS symptoms than healthy controls. The positive correlation between the severity of ADHD symptoms and IBS suggests a potential link requiring further investigation. Cite this article as: Sağlam T, Takım U. Comparative analysis of irritable bowel syndrome symptom severity in adults with attention-deficit/hyperactivity disorder and healthy controls: A case-control study. Neuropsychiatr Invest. 2025, 63, 0031, doi:10.5152/NeuropsychiatricInvest.2025.25031.
Evaluation of Panic Agoraphobic Spectrum and Sociodemographic Characteristics in Terms of Depression Types
Objective: One of the most important predictors of the severity of major depressive disorder is the presence of a comorbid anxiety disorder. Independent of treatment, depressed patients with a lifetime anxiety disorder are found to have a slower response to treatment and lower symptomatic recovery rates compared to depressed patients without a lifetime anxiety disorder. In this study, the aim was to compare the Lifetime Panic-Agoraphobic Spectrum and sociodemographic characteristics of patients with major depressive disorder and healthy controls and to investigate its relationship with depressive disorder severity and anxiety levels. Methods: A total of 135 participants were included in the study, 80 of whom were major depressive disorder patients. Beck Anxiety Scale, Beck Depression Scale, Lifetime Panic Agoraphobic Spectrum Scale, and a sociodemographic and clinical data form were applied to all participants. Results: All Lifetime Panic Agoraphobic Spectrum subscale scores, Lifetime Panic Agoraphobic Spectrum total score, Beck Depression Inventory, and Beck Anxiety Inventory scores are found to be significantly higher in the major depressive group compared to healthy controls. Also, Lifetime Panic Agoraphobic Spectrum scores and Beck Depression Inventory scores are found to be significantly higher in patients with melancholic depression compared to patients with atypical depression. Conclusion: The findings demonstrate that panic-agoraphobic spectrum characteristics are significantly associated with depression severity, especially in melancholic depression. Even in the absence of a comorbid anxiety disorder, the assessment of Panic-Agoraphobic Spectrum features and identification of the depression subtype can provide valuable insights for personalized treatment approaches and may lead to improved clinical outcomes. Cite this article as: Gürbüz MS, Erzincan E, İzci F, Beştepe EE. Evaluation of panic agoraphobic spectrum and sociodemographic characteristics in terms of depression types. Neuropsychiatr Invest. 2025, 63, 0051, doi:10.5152/ NeuropsychiatricInvest.2025.24051.
Inflammatory and Neurodegenerative Biomarkers in Bipolar I Disorder: A Cross-Sectional Study
Objective: Bipolar disorder (BD) is increasingly recognized as a systemic illness involving chronic inflammation, glial dysfunction, and neuronal dysregulation in addition to mood instability. Recent studies have suggested that biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 receptor antagonist (IL-1RA), S100B, and neuron-specific enolase (NSE) may reflect underlying pathophysiological processes in BD. However, findings remain inconsistent, particularly across mood states. This study aimed to investigate serum levels of IL-6, TNF-α, IL-1RA, S100B, and NSE in patients with bipolar I disorder (BD-I) across euthymic, manic, and depressive phases, and to compare them with healthy controls. Additionally, correlations between biomarker levels and clinical symptom severity were examined. Methods: Serum levels were measured in 77 patients with BD-I (50 euthymic, 20 manic, and 7 depressed) and 50 healthy controls. Correlations were assessed between these levels and the Young Mania Rating Scale (YMRS), the Montgomery–Åsberg Depression Rating Scale, the Clinical Global Impressions-Severity Scale (CGI-S), and the Positive and Negative Syndrome Scale (PANSS)–positive symptoms subscale, as well as other clinical variables. Results: Indicating a trait-like inflammatory profile, IL-6 levels were considerably higher in the BD group and had a positive correlation with YMRS, PANSS, and CGI scores. Conversely, levels of IL-1RA, TNF-α, S100B, and NSE were markedly decreased in patients. NSE levels exhibited an inverse connection with clinical severity, potentially signifying neuroprogressive alterations. Conclusion: The findings support the role of IL-6 as a state-independent inflammatory marker in BD, while reductions in NSE may reflect chronic neurobiological dysregulation. These findings may have implications for biomarker-guided monitoring or treatment stratification in BD. Further research is warranted to determine whether these biomarkers can serve as reliable indicators of disease progression, treatment response, and mood state in clinical settings. Cite this article as: Taşdemir İ, Çakır S. Inflammatory and neurodegenerative biomarkers in bipolar I disorder: a crosssectional study. Neuropsychiatr Invest. 63, 0044, doi:10.5152/NeuropsychiatricInvest.2025.25044.
Verbal Mental Capacity and Medication Adherence in Psychiatric Outpatients: The Impact of Verbal Cognitive Reserve and Side Effects
Objective: Medication adherence is a critical determinant of treatment outcomes in psychiatric disorders, yet the underlying factors remain unclear. This study aimed to examine the role of verbal mental capacity and clinical variables in predicting medication adherence among psychiatric outpatients. Methods: A total of 67 patients (aged 18-60 years) were assessed using the Medication Adherence Rating Scale (MARS), Beck Anxiety Inventory, Beck Depression Inventory, Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), and the Turkish version of the National Adult Reading Test (NART-TR). Participants were categorized into good adherence (n=33) and poor adherence (n=34) groups based on MARS scores. Comparative analyses between these groups, as well as correlation and multiple regression analyses, were conducted. Results: Patients with poor adherence had significantly higher anxiety, depression, side effect scores, and NART-TR errors than patients with good adherence (P < .05). Correlation analysis revealed negative associations between MARS scores and anxiety, depression, side effects, and NART-TR errors. Regression analysis identified NART-TR errors (β=−.342, P=.009) and LUNSERS scores (β=−.512, P=.022) as independent predictors of medication adherence. Conclusion: Verbal mental capacity and medication side effects emerged as critical determinants of adherence in psychiatric patients. Incorporating cognitive screening tools like NART-TR into routine practice may help identify individuals at risk of nonadherence and guide tailored interventions. Cite this article as: Bakay H, Karaagac M, Yaman NÖ, Gica S. Verbal mental capacity and medication adherence in psychiatric outpatients: the impact of verbal cognitive reserve and side effects. Neuropsychiatr Invest. 2025, 63, 0045, doi:10.5152/NeuropsychiatricInvest.2025.25045.
Mental Health Challenges Among Psychiatric Healthcare Workers During the COVID-19 Pandemic: Insights from Türkiye and Future Directions
Objective: This study aimed to examine the psychological challenges faced by mental health professionals working in COVID-19-specific psychiatric inpatient units compared to those working in regular (nonCOVID) psychiatric inpatient settings. Additionally, it explored differences across hospital types (mental health hospitals vs. general hospitals) and professional roles. Methods: A total of 153 mental health professionals, including psychiatrists, nurses, and support staff, were recruited from psychiatric units in general and mental health hospitals in Türkiye. Among them, 82 were assigned to COVID-19-specific psychiatric services, while 71 worked in regular psychiatric units. Participants completed an online survey including the Perceived Stress Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale, and Fear of COVID-19 Scale. Results: Nurses reported significantly higher levels of anxiety, depression, somatic symptoms, fear of COVID-19, and perceived stress compared to other staff (P < .01). Perceived stress was significantly higher among professionals working in mental health hospitals compared to general hospitals (P=.024). However, no significant differences were found between those working in COVID-19-specific and regular psychiatric units in terms of anxiety, depression, somatic symptoms, or fear of COVID-19. Conclusion: Mental health professionals in psychiatric settings experienced substantial psychological burden during the pandemic, with nurses and staff in mental health hospitals being particularly vulnerable. These findings highlight the need for targeted psychological support and institutional interventions in psychiatric inpatient care. Cite this article as: Ergelen M, Sayıner ACT, Kaya H, et al. Mental health challenges among psychiatric healthcare workers during the COVID-19 pandemic: insights from Türkiye and future directions. Neuropsychiatr Invest. 2025, 63, 0034, doi:10.5152/NeuropsychiatricInvest.2025.25034.
Factors Predicting the Outcome of Treatment for Individuals with Alcohol Use Disorder: A Study of the YEDAM Cohort
Objective: Alcohol use disorder (AUD) is a psychiatric disorder that progresses with relapse and remission. The objective of this study was to examine the progress of treatment and the factors influencing it in individuals who sought assistance from Green Crescent Counselling Center (YEDAM) for AUD. Methods: For the purposes of the retrospective cohort follow-up study, participants who applied to the YEDAM for AUD were demographic information form, Addiction Profile Index (API), API Clinical Form, Kocaeli Psychological Trauma Brief Screening Scale, and Addiction Outcome Assessment Index. Of the 5090 participants in the study, 307 were followed up for 1.5 years. Results: Those who consistently engaged in the program demonstrated more pronounced improvement and a reduction in alcohol consumption frequency. Furthermore, factors predicting treatment outcome were found to be a dysfunctional relationship with a partner, alcohol use characteristics, craving and anxiety. Conclusion: This study yielded 2 significant findings. First, the efficacy of the YEDAM treatment program on AUD prognosis was demonstrated. Second, individuals with AUD who are likely to have a poorer prognosis could be identified. In this regard, it will be feasible to implement modifications to the YEDAM treatment program for individuals who are likely to have a less favorable prognosis, thereby enhancing the efficacy of these treatment programs.
The Relationship of Eating Patterns with Emotion Regulation Difficulties and Psychopathology in Obesity Patients
Objective: This study aims to examine the relationship between eating styles (emotional eating, external eating, and restrained eating), emotion regulation difficulties, and psychopathological conditions in indi viduals with obesity. Given the strong association between pathological eating behaviors—such as emo tional eating and binge eating disorder—and psychological factors like depression, anxiety, and stress, this study explores how these interactions contribute to obesity. Understanding these relationships may provide valuable insights for developing more effective intervention strategies in obesity treatment. Methods: This study included obese patients, demographically matched controls recruited from a univer sity hospital outpatient clinic, and social media announcements. Participants aged 18-55 with sufficient cognitive ability to complete assessments were included, while those with severe psychopathology or substance misuse were excluded. Data were collected using the Dutch eating behavior questionnaire, the difficulties in emotion regulation scale, and the symptom checklist-90-revised. Ethical approval was obtained, and all participants gave informed consent. Results: Obese individuals showed significantly higher emotional eating, emotion regulation difficulties, and psychological distress than controls. Emotional eating was positively correlated with impulse regu lation difficulties, depression, anxiety, and phobic anxiety. Regression analysis identified depression and phobic anxiety as key predictors of emotional eating, emphasizing the impact of psychological distress on eating behaviors. Conclusion: The study reveals the exacerbation of symptoms in obese individuals during emotional dis tress and highlights the role of emotion regulation difficulties in the worsening of eating behaviors. Cite this article as: Polat I, Kızılateş-Evin G, Hun Gökçe S, et al. The relationship of eating patterns with emotion regulation difficulties and psychopathology in obesity patients. Neuropsychiatr Invest. 2025, 63, 0012, doi:10.5152/NeuropsychiatricInvest.2025.25012.
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Nano-Assisted Drug Delivery Systems for the Improved Treatment of Neuropsychiatric Disorders
Abstract: Psychiatric disorders are among the top causes of disability and morbidity worldwide. Despite the rapid progression of psychiatric pharmaceuticals, there are still significant challenges for the effective management of psychiatric disorders. The blood–brain barrier significantly restricts the access of psychiatric drugs to target cells in the brain tissues. The use of drug-loaded nanoparticles (NPs) is now well considered a viable option for improving the treatment efficacy of currently available drugs and reducing adverse effects. This review summarizes the recent advances and provides the unique characteristics of NP-based formulations as a promising avenue for targeted drug delivery for psychiatric disorders. Cite this article as: Shafiee-Kandjani AR, Hamidi S, Azarfarin M, Valipour F, Salatin S. Nano-assisted drug delivery systems for the improved treatment of neuropsychiatric disorders. Neuropsychiatr Invest. 2025, 63, 0058, doi: 10.5152/ NeuropsychiatricInvest.2025.24058.
Cognitive Impairment in Bipolar Disorder
Cognitive impairment is recognized as a common aspect of bipolar disorder (BD), persisting beyond acute episodes and extending into euthymic periods. Verbal learning, memory, and executive functions exhibit the most pronounced impairments among the affected cognitive domains. Patients with BD also demonstrate social cognitive deficits. However, all patients with BD do not exhibit similar cognitive features. Recent data-driven studies emphasize the heterogeneity of cognitive impairment in BD, identifying 3 distinct subgroups: preserved cognition, selective impairment in specific domains, and global cognitive deficits. This classification highlights the variability in cognitive functioning among individuals with the disorder. The presence of cognitive deficits in healthy relatives of bipolar disorder patients, in individuals at high risk for BD, and in the firstepisode of BD patients suggest a potential neurodevelopmental component. Conversely, studies associating cognitive decline with factors such as illness duration, the number of manic episodes, and age of onset underscore a possible neuroprogressive aspect. There is no consensus on whether BD is a neurodevelopmental or a neuroprogressive disease. Longitudinal studies are needed to clarify the trajectory of cognitive impairment. Although cognitive deficits in BD resemble those observed in schizophrenia, they tend to be less severe, pointing to a transdiagnostic dimension of impairment. Cognitive deficits negatively impact the clinical course, functional outcomes, and quality of life. Future research should focus on the cognitive subgroups, the trajectory of cognitive impairment, personalized treatment strategies, and cognitive rehabilitation. Cite this article as: Uzman Özbek S, Bora E. Cognitive impairment in bipolar disorder. Neuropsychiatr Invest. 2025, 63, 0007, doi:10.5152/NeuropsychiatricInvest.2025.25007.
A Systematic Review and Meta-Analysis of Attention, Memory, Learning, and Fluency Deficits Associated with Gambling Behavior
Objective: The study aimed to systematically review and analyze the association of gambling behavior with deficits in attention, memory, learning, verbal fluency, and figural fluency. Methods: A comprehensive search was conducted across 4 databases (PubMed, Scopus, Embase, and Web of Science) using a set of keywords related to cognitive impairment and gambling behavior. The selection process began with de-duplication, followed by a preliminary screening of titles and abstracts, and a subsequent full-text review of relevant articles. The risk of bias in the included studies was assessed using the Joanna Briggs Critical Appraisal Checklists. Studies were categorized based on the cognitive domains evaluated. Qualitative data were used for the systematic review, comparing gambling groups with controls or independently. For the meta-analysis, quantitative data from neuropsychological tests were analyzed using fixed or random-effects models, depending on heterogeneity. All analyses were conducted using<Open Meta-Analyst software. Results: Of the 12488 records initially screened, 303 articles were selected for a full-text review. Of these, 14 studies with an average quality score of 80.38% met the eligibility criteria, and 7 of them provided sufficient quantitative data for the meta-analysis. The findings indicated no substantial cognitive deficits in individuals with gambling behavior across the domains of attention, memory, learning, verbal fluency, and figural fluency. Conclusion: The cognitive domains of attention, memory, learning, verbal fluency, and figural fluency remain intact in gamblers. While these domains may not require direct intervention, their stability can provide a foundational framework for implementing treatments that target other, potentially weaker cognitive and behavioral domains. Cite this article as: Ahluwalia Y, Negi PS, Singh S, Sarkar S, Balhara YPS. A systematic review and meta-analysis of attention, memory, learning, and fluency deficits associated with gambling behavior. Neuropsychiatr Invest. 2025, 63, 0011, doi: 10.5152/NeuropsychiatricInvest.2025.25011.