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15 pages, 408 KB  
Study Protocol
HIITing Anxiety and Depression in Parkinson’s Disease and Multiple Sclerosis—A Study Protocol of a Transdiagnostic Randomized Controlled Trial (HersenFIT)
by Arianne S. Gravesteijn, Marc B. Rietberg, Vincent de Groot, Mark A. Hirsch, Tim Vanbellingen, Richard T. Jaspers, Chris Vriend, Wilma D. J. van de Berg, Odile A. van den Heuvel, Erwin E. H. van Wegen and on behalf of the HersenFIT Consortium
Brain Sci. 2025, 15(9), 945; https://doi.org/10.3390/brainsci15090945 - 29 Aug 2025
Viewed by 269
Abstract
Background/Objectives: Parkinson’s disease (PD) and multiple sclerosis (MS) are neurological conditions that result in debilitating non-motor symptoms, such as anxiety and depression, which significantly reduce quality of life and often persist despite pharmacological treatment. As a result, effective alternative treatment strategies are needed. [...] Read more.
Background/Objectives: Parkinson’s disease (PD) and multiple sclerosis (MS) are neurological conditions that result in debilitating non-motor symptoms, such as anxiety and depression, which significantly reduce quality of life and often persist despite pharmacological treatment. As a result, effective alternative treatment strategies are needed. Exercise therapy—particularly aerobic training—has shown promise in alleviating non-motor symptoms, potentially through neuroplastic adaptations. However, traditional aerobic exercise is often time-consuming and monotonous, limiting long-term adherence. High-intensity interval training (HIIT) offers a time-efficient and potentially more engaging alternative, though its effects on non-motor symptoms in PD and MS remain understudied. Methods: This transdiagnostic randomized controlled trial will enroll 48 participants (24 PD, 24 MS) with clinically significant affective symptoms (hospital anxiety and depression scale [HADS] ≥ 8). The participants will be randomly assigned to one of three 8-week interventions: (1) HIIT, 5–6 intervals of 45 s of high-intensity cycling; (2) continuous aerobic training (CAT), 50 min of low-intensity cycling; (3) movement advice (MA), step goals, and physical education. The primary (affective symptoms) and secondary outcomes (cognition, fatigue, sleep, motor function) will be assessed at four time points: 4 and 1 weeks pre intervention, and 1 and 4 weeks post intervention. Weekly blood samples and pre/post brain imaging will be collected to study biofluid and MRI measures for potential neuroplasticity. Linear mixed models will analyze the time and group effects. Discussion: This trial will assess whether HIIT can more effectively improve non-motor and motor symptoms in PD and MS than CAT or MA. A multimodal approach will explore both the clinical outcomes and underlying mechanisms, informing scalable and engaging rehabilitation strategies. Full article
(This article belongs to the Section Neuropsychiatry)
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17 pages, 687 KB  
Article
Association Between Current Suicidal Ideation and Personality Traits: Analysis of the Personality Inventory for DSM-5 in a Community Mental Health Sample
by Valeria Deiana, Pasquale Paribello, Federico Suprani, Andrea Mura, Carlo Arzedi, Mario Garzilli, Laura Arru, Mirko Manchia, Bernardo Carpiniello and Federica Pinna
Medicina 2025, 61(9), 1541; https://doi.org/10.3390/medicina61091541 - 27 Aug 2025
Viewed by 763
Abstract
Background and Objectives: Suicide is one of the leading causes of death worldwide. Identifying psychopathological factors and personality traits associated with suicidal ideation is crucial for improving prevention. This study investigates the association between current suicidal ideation—measured by item 4 of the [...] Read more.
Background and Objectives: Suicide is one of the leading causes of death worldwide. Identifying psychopathological factors and personality traits associated with suicidal ideation is crucial for improving prevention. This study investigates the association between current suicidal ideation—measured by item 4 of the Brief Psychiatric Rating Scale-24 items (BPRS-24)—and personality traits assessed with the Personality Inventory for DSM-5 (PID-5) in a transdiagnostic outpatient psychiatric population. The association of BPRS-24 item 4 with early traumatic experiences, attachment styles, and dissociative phenomena is also explored as a secondary objective. Materials and Methods: We propose a secondary analysis on a sample of 137 individuals receiving care at an academic community mental health center. Personality traits were assessed using the PID-5, while attachment styles were assessed with the Experiences in Close Relationships-Revised (ERC-R), childhood traumas with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q), and dissociative experiences with the Dissociative Experience Scale II (DES-II). Suicidal ideation was measured with item 4 of the BPRS-24. Associations were examined using Spearman’s correlation and ordinal logistic regression models, adjusted for age, sex assigned at birth, and global clinical severity (CGI-S). Results: We found statistically significant associations between suicidal ideation and the PID-5 trait of depressivity (OR = 1.80, 95 % CI 1.23–2.63, p = 0.002, p-value adjusted Holm’s method 0.012). However, this association lost significance after adjusting for depressive symptoms (BPRS-24 item 3), suggesting a mediating role of depression. We found no significant associations with childhood trauma, attachment styles, or dissociative experiences. Conclusions: Our findings suggest a potential link between specific personality traits and suicidal ideation, mediated by depressive symptomatology. We explore how future studies may evaluate PID-5 as a clinical tool to support the identification of individuals at long-term risk of suicidality or for targeting specific populations for tailored interventions. Full article
(This article belongs to the Section Psychiatry)
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19 pages, 1162 KB  
Article
Beyond the Scars: An Analysis of Adverse Childhood Experiences and the Interconnections Between Emotion Dysregulation, Dissociation, and Trauma in Patients with Borderline Personality Disorder
by Luciana Ciringione, Enrico Perinelli, Francesco Mancini and Elena Prunetti
Brain Sci. 2025, 15(8), 889; https://doi.org/10.3390/brainsci15080889 - 20 Aug 2025
Viewed by 835
Abstract
Background/Objectives: Borderline Personality Disorder (BPD) frequently overlaps with trauma-related conditions, particularly PTSD and Complex PTSD (cPTSD). Adverse Childhood Experiences (ACEs)—especially emotional and sexual abuse—are considered key factors in the development of emotion dysregulation and dissociation. This study investigates the impact of different [...] Read more.
Background/Objectives: Borderline Personality Disorder (BPD) frequently overlaps with trauma-related conditions, particularly PTSD and Complex PTSD (cPTSD). Adverse Childhood Experiences (ACEs)—especially emotional and sexual abuse—are considered key factors in the development of emotion dysregulation and dissociation. This study investigates the impact of different ACE dimensions on borderline symptomatology, emotion dysregulation, and dissociative symptoms. Methods: Eighty-three BPD patients were assessed using standardized self-report questionnaires: CTQ-SF (ACEs), DERS (emotion dysregulation), DES (dissociation), BSL-23 (borderline symptoms), and PDS-3 (post-traumatic symptoms). Analyses included bivariate correlations, Structural Equation Modeling (SEM), and Exploratory Graph Analysis (EGA). Results: Emotional abuse significantly predicted borderline symptoms, while sexual abuse predicted dissociation. Emotion dysregulation was strongly associated with both borderline and dissociative symptoms, emerging as a central node in the symptom network. EGA confirmed the clustering of dissociative symptoms with sexual abuse and the centrality of emotion dysregulation across domains. Conclusions: Findings support the role of specific ACEs in shaping the clinical expression of BPD. Emotion dysregulation acts as a key transdiagnostic factor linking trauma history to borderline and dissociative features. These results underscore the importance of trauma-informed assessments and interventions, such as DBT and DBT-PTSD, tailored to individual ACE profiles. Full article
(This article belongs to the Special Issue Traumatic Stress and Dissociative Disorder)
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15 pages, 894 KB  
Article
Mediating Impact of Intranasal Oxytocin on the Interaction Between Irritability and Reactive Aggression in Youth with Severe Irritability
by Jake J. Son, Ji-Woo Suk, William F. Garvey, Ryan T. Edwards, Ellen Leibenluft, R. J. R. Blair and Soonjo Hwang
Life 2025, 15(8), 1253; https://doi.org/10.3390/life15081253 - 7 Aug 2025
Viewed by 594
Abstract
Objective: Irritability and reactive aggression are transdiagnostic features that are predictive of adverse long-term outcomes. This investigation examined whether intranasal oxytocin administration impacts the interaction between irritability and reactive aggression, and whether these effects can be detected at a neural level via a [...] Read more.
Objective: Irritability and reactive aggression are transdiagnostic features that are predictive of adverse long-term outcomes. This investigation examined whether intranasal oxytocin administration impacts the interaction between irritability and reactive aggression, and whether these effects can be detected at a neural level via a facial expression processing task during functional MRI (fMRI). Methods: In this study, 40 children and adolescents with severe irritability and psychiatric diagnoses of disruptive mood and behavioral disorders were assigned to either intranasal oxytocin or placebo administration over a 3-week period in a randomized, double-blind trial (ClinicalTrials, NCT02824627). Clinical measures and fMRI during a facial expression processing task were collected pre- and post-intervention. Brain regions sensitive to oxytocin administration were determined using whole-brain statistical analyses, with post hoc analyses to determine whether changes in the neural activity mediated the relationship between changes in irritability and reactive aggression across the intervention period. Results: Youth who received intranasal oxytocin administration exhibited significant decreases in irritability and reactive aggression compared to their counterparts in the placebo group. Further, oxytocin administration was associated with significant increases in neural activity in the right superior prefrontal cortex, which fully mediated the relationship between improvements in irritability and improvements in reactive aggression. Conclusions: Intranasal oxytocin significantly reduced irritability and reactive aggression in youth, as well as neural activity in the prefrontal cortex, such that increases in the cortical activity fully mediated the relationship between changes in irritability and reactive aggression. Taken together, these findings may reflect oxytocin-related enhancements in emotional regulation in youth with severe irritability, a potential therapeutic mechanism for mitigating reactive aggression. Full article
(This article belongs to the Section Physiology and Pathology)
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13 pages, 657 KB  
Article
Physical Fitness, Experiential Avoidance, and Psychological Inflexibility Among Adolescents: Results from the EHDLA Study
by Maria Mendoza-Muñoz, José Francisco López-Gil, Damián Pereira-Payo and Raquel Pastor-Cisneros
Children 2025, 12(8), 1032; https://doi.org/10.3390/children12081032 - 6 Aug 2025
Viewed by 301
Abstract
Background/Introduction: Psychological inflexibility, which includes experiential avoidance, is a transdiagnostic process associated with multiple mental health issues in adolescence. Physical fitness (PF) has shown benefits for mental well-being, yet its specific relationship with psychological inflexibility remains understudied, particularly among youth. Objectives: To examine [...] Read more.
Background/Introduction: Psychological inflexibility, which includes experiential avoidance, is a transdiagnostic process associated with multiple mental health issues in adolescence. Physical fitness (PF) has shown benefits for mental well-being, yet its specific relationship with psychological inflexibility remains understudied, particularly among youth. Objectives: To examine the association between components of PF and psychological inflexibility, measured by the Acceptance and Action Questionnaire-II (AAQ-II), in a representative sample of Spanish adolescents. Methods: A cross-sectional analysis was conducted using data from 631 adolescents (aged 12–17) participating in the Eating Healthy and Daily Life Activities (EHDLA) study. PF was assessed by the Assessing the Levels of PHysical Activity and Fitness (ALPHA-Fit) Test Battery (cardiorespiratory fitness, muscular strength, agility, and flexibility). Psychological inflexibility was measured using the AAQ-II. Generalized linear models (GLMs) were used to evaluate associations, adjusting for age, sex, body mass index, socioeconomic status, physical activity, sedentary behavior, sleep duration, and energy intake. Results: Unadjusted analyses showed weak but significant associations between psychological inflexibility and performance in the 20 m shuttle run test (p = 0.002), the 4 × 10 shuttle run test (p = 0.005), and the sit-and-reach test (p < 0.001). However, after adjusting for covariates, none of the PF components maintained a statistically significant association with the AAQ-II scores. Conclusions: In this adolescent sample, PF components were not independently associated with psychological inflexibility after adjustment for key confounders. These findings suggest that, while PF may contribute to general well-being, it is not a primary determinant of psychological inflexibility. Further longitudinal and intervention studies are needed to clarify the mechanisms linking physical and psychological health in youth. Full article
(This article belongs to the Special Issue Physical Fitness and Health in Adolescents)
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23 pages, 869 KB  
Article
Cognitive Behavioral Therapy for Muscle Dysmorphia and Anabolic Steroid-Related Psychopathology: A Randomized Controlled Trial
by Metin Çınaroğlu, Eda Yılmazer, Selami Varol Ülker and Gökben Hızlı Sayar
Pharmaceuticals 2025, 18(8), 1081; https://doi.org/10.3390/ph18081081 - 22 Jul 2025
Viewed by 770
Abstract
Background/Objectives: Muscle dysmorphia (MD), a subtype of body dysmorphic disorder, is prevalent among males who engage in the non-medical use of anabolic–androgenic steroids (AASs) and performance-enhancing drugs (PEDs). These individuals often experience severe psychopathology, including mood instability, compulsivity, and a distorted body [...] Read more.
Background/Objectives: Muscle dysmorphia (MD), a subtype of body dysmorphic disorder, is prevalent among males who engage in the non-medical use of anabolic–androgenic steroids (AASs) and performance-enhancing drugs (PEDs). These individuals often experience severe psychopathology, including mood instability, compulsivity, and a distorted body image. Despite its clinical severity, no randomized controlled trials (RCTs) have evaluated structured psychological treatments in this subgroup. This study aimed to assess the efficacy of a manualized cognitive behavioral therapy (CBT) protocol in reducing MD symptoms and associated psychological distress among male steroid users. Results: Participants in the CBT group showed significant reductions in MD symptoms from the baseline to post-treatment (MDDI: p < 0.001, d = 1.12), with gains sustained at follow-up. Large effect sizes were also observed in secondary outcomes including depressive symptoms (PHQ-9: d = 0.98), psychological distress (K10: d = 0.93), disordered eating (EDE-Q: d = 0.74), and exercise addiction (EAI: d = 1.07). No significant changes were observed in the control group. Significant group × time interactions were found for all outcomes (all p < 0.01), indicating CBT’s specific efficacy. Discussion: This study provides the first RCT evidence that CBT significantly reduces both core MD symptoms and steroid-related psychopathology in men engaged in AAS/PED misuse. Improvements extended to mood, body image perception, and compulsive exercise behaviors. These findings support CBT’s transdiagnostic applicability in addressing both the cognitive–behavioral and affective dimensions of MD. Materials and Methods: In this parallel-group, open-label RCT, 59 male gym-goers with DSM-5-TR diagnoses of MD and a history of AAS/PED use were randomized to either a 12-week CBT intervention (n = 30) or a waitlist control group (n = 29). CBT sessions were delivered weekly online and targeted distorted muscularity beliefs, compulsive behaviors, and emotional dysregulation. Primary and secondary outcomes—Muscle Dysmorphic Disorder Inventory (MDDI), PHQ-9, K10, EDE-Q, EAI, and BIG—were assessed at the baseline, post-treatment, and 3-month follow-up. A repeated-measures ANOVA and paired t-tests were used to analyze time × group interactions. Conclusions: CBT offers an effective, scalable intervention for individuals with muscle dysmorphia complicated by anabolic steroid use. It promotes broad psychological improvement and may serve as a first-line treatment option in high-risk male fitness populations. Future studies should examine long-term outcomes and investigate implementation in diverse clinical and cultural contexts. Full article
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28 pages, 1358 KB  
Review
Understanding the Borderline Brain: A Review of Neurobiological Findings in Borderline Personality Disorder (BPD)
by Eleni Giannoulis, Christos Nousis, Ioanna-Jonida Sula, Maria-Evangelia Georgitsi and Ioannis Malogiannis
Biomedicines 2025, 13(7), 1783; https://doi.org/10.3390/biomedicines13071783 - 21 Jul 2025
Viewed by 2511
Abstract
Borderline personality disorder (BPD) is a complex and heterogeneous condition characterized by emotional instability, impulsivity, and impaired regulation of interpersonal relationships. This narrative review integrates findings from recent neuroimaging, neurochemical, and treatment studies to identify core neurobiological mechanisms and highlight translational potential. Evidence [...] Read more.
Borderline personality disorder (BPD) is a complex and heterogeneous condition characterized by emotional instability, impulsivity, and impaired regulation of interpersonal relationships. This narrative review integrates findings from recent neuroimaging, neurochemical, and treatment studies to identify core neurobiological mechanisms and highlight translational potential. Evidence from 112 studies published up to 2025 is synthesized, encompassing structural MRI, resting-state and task-based functional MRI, EEG, PET, and emerging machine learning applications. Consistent disruptions are observed across the prefrontal–amygdala circuitry, the default mode network (DMN), and mentalization-related regions. BPD shows a dominant and stable pattern of hyperconnectivity in the precuneus. Transdiagnostic comparisons with PTSD and cocaine use disorder (CUD) suggest partial overlap in DMN dysregulation, though BPD-specific traits emerge in network topology. Machine learning models achieve a classification accuracy of 70–88% and may support the tracking of early treatment responses. Longitudinal fMRI studies indicate that psychodynamic therapy facilitates the progressive normalization of dorsal anterior cingulate cortex (dACC) activity and reductions in alexithymia. We discuss the role of phenotypic heterogeneity (internalizing versus externalizing profiles), the potential of neuromodulation guided by biomarkers, and the need for standardized imaging protocols. Limitations include small sample sizes, a lack of effective connectivity analyses, and minimal multicenter cohort representation. Future research should focus on constructing multimodal biomarker panels that integrate functional connectivity, epigenetics, and computational phenotyping. This review supports the use of a precision psychiatry approach for BPD by aligning neuroscience with scalable clinical tools. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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19 pages, 631 KB  
Article
Feeling the World Differently: Sensory and Emotional Profiles in Preschool Neurodevelopmental Disorders
by Federica Gigliotti, Maria Eugenia Martelli, Federica Giovannone and Carla Sogos
Children 2025, 12(7), 958; https://doi.org/10.3390/children12070958 - 21 Jul 2025
Viewed by 927
Abstract
Background/Objectives: Atypical sensory processing is increasingly recognized as a transdiagnostic dimension of neurodevelopmental disorders (NDDs), with critical implications for emotional and behavioral regulation. This study aimed to identify distinct sensory profiles in preschool children with NDDs and to examine their associations with emotional–behavioral [...] Read more.
Background/Objectives: Atypical sensory processing is increasingly recognized as a transdiagnostic dimension of neurodevelopmental disorders (NDDs), with critical implications for emotional and behavioral regulation. This study aimed to identify distinct sensory profiles in preschool children with NDDs and to examine their associations with emotional–behavioral and cognitive/developmental functioning. Methods: A total of 263 children (aged 21–71 months) diagnosed with autism spectrum disorder (ASD), language disorder (LD), or other NDDs (ONDD) were recruited. Sensory processing was assessed using the SPM-P, emotional–behavioral functioning was assessed via the CBCL 1½–5, and cognitive/developmental levels were assessed through standardized instruments. Latent profile analysis (LPA) was conducted to identify sensory subtypes. Group comparisons and multinomial logistic regression were used to examine profile characteristics and predictors of profile membership. Results: Three sensory profiles emerged: (1) Multisystemic Sensory Dysfunction (20.1%), characterized by pervasive sensory and emotional difficulties, primarily observed in ASD; (2) Typical Sensory Processing (44.9%), showing normative sensory and emotional functioning, predominantly LD; and (3) Mixed Subclinical Sensory Processing (35%), with subclinical-range scores across multiple sensory and emotional domains, spanning all diagnoses. Higher cognitive functioning and fewer internalizing symptoms significantly predicted membership in the typical profile. A gradient of symptom severity was observed across profiles, with the Multisystemic group showing the most pronounced emotional–behavioral impairments. Conclusions: Distinct sensory–emotional phenotypes were identified across diagnostic categories, supporting a dimensional model of neurodevelopment. Sensory profiles were strongly associated with emotional functioning, independently of diagnostic status. Early sensory assessment may therefore offer clinically meaningful insights into emotional vulnerability and inform targeted interventions in preschool populations with NDDs. Full article
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15 pages, 360 KB  
Article
The Association Between Identity Functioning and Personality Pathology in Female Patients with Eating Disorders
by Laurence Claes, Annabel Bogaerts, Tim Bastiaens, Glenn Kiekens, Eva Dierckx, Katrien Schoevaerts and Koen Luyckx
Nutrients 2025, 17(14), 2329; https://doi.org/10.3390/nu17142329 - 16 Jul 2025
Viewed by 493
Abstract
Aims. In the present study, we investigated the associations between the three identity dimensions of Kaufman (Consolidated Identity, Disturbed Identity, Lack of Identity) and symptoms of personality disorders (PDs) in 176 female inpatients with an eating disorder (ED). We examined five aspects: the [...] Read more.
Aims. In the present study, we investigated the associations between the three identity dimensions of Kaufman (Consolidated Identity, Disturbed Identity, Lack of Identity) and symptoms of personality disorders (PDs) in 176 female inpatients with an eating disorder (ED). We examined five aspects: the prevalence of categorical PD diagnoses in patients with EDs; the relationship between dimensional PD scores and identity dimensions as well as their relationships with age and ED subtype; and the unique variance in dimensional PD scores explained by identity dimensions, while controlling for age and ED subtype. Methods. To assess identity functioning, we made use of the Self-Concept and Identity Measure, and to assess PDs, we used the categorical and dimensional scores of the Assessment of DSM-IV Personality Disorders. Results. The findings showed that the avoidant, obsessive–compulsive, and borderline categorical PDs were the most frequently reported PDs. Age was negatively related to all Cluster B PDs and Disturbed Identity, and binge-eating/purging ED patients reported significantly more Cluster B PD features compared to restrictive ED patients. ED subtype and identity dimensions were unrelated. Correlational analysis showed that all dimensional PD scores were positively related to Disturbed Identity and Lack of Identity and negatively related to Consolidated Identity. The results of the hierarchical regression analyses showed that Cluster A PDs were significantly predicted by Lack of Identity, controlled for age and ED subtype. Additionally, Cluster B PDs were significantly predicted by Disturbed Identity. Finally, two of the three cluster C PDs were predicted by Lack of Identity (avoidant and obsessive–compulsive PD), whereas the dependent PD was explained by Disturbed Identity. Conclusions. The co-occurrence of identity issues in both PDs and EDs underscores the role of identity as a transdiagnostic feature. Accordingly, using identity-based interventions in treatment may have broad therapeutic benefits across these disorders. Full article
(This article belongs to the Special Issue Eating and Mental Health Disorders)
16 pages, 656 KB  
Article
The Mediating Role of Misinterpretations and Neutralizing Responses to Unwanted Intrusive Thoughts in Obsessive-Compulsive Spectrum Disorders
by Belén Pascual-Vera, Guy Doron, Mujgan Inozu, Fernando García and Amparo Belloch
Eur. J. Investig. Health Psychol. Educ. 2025, 15(7), 135; https://doi.org/10.3390/ejihpe15070135 - 15 Jul 2025
Viewed by 544
Abstract
Background. Cognitive-behavioral theories suggest that obsessions in obsessive-compulsive disorder (OCD) develop from maladaptive misinterpretations and coping strategies of unwanted intrusive thoughts (UITs). Models of Body Dysmorphic Disorder (BDD) and Illness Anxiety Disorder (IAD) propose that these symptoms stem from similar misinterpretations of common [...] Read more.
Background. Cognitive-behavioral theories suggest that obsessions in obsessive-compulsive disorder (OCD) develop from maladaptive misinterpretations and coping strategies of unwanted intrusive thoughts (UITs). Models of Body Dysmorphic Disorder (BDD) and Illness Anxiety Disorder (IAD) propose that these symptoms stem from similar misinterpretations of common UITs relating to perceived defects in appearance and illness. This study examines whether maladaptive misinterpretations and control strategies leading to the escalation of obsessional UITs to OCD symptoms also have a similar effect on the development of BDD and IAD. More specifically, we examined whether misinterpretations and neutralizing responses mediate the associations between the frequency of disorder-specific UITs and symptoms of these disorders. Method. A total of 625 non-clinical participants from four countries completed the Questionnaire of Unpleasant Intrusive Thoughts (QUIT) that assesses OCD, BDD and IAD-related UITs and their associated misinterpretations and neutralizing strategies, as well as self-report measures of OCD, BDD, and IAD symptoms. Parallel multiple mediation models were conducted. Results. The frequency of OCD, BDD and IAD-related UITs predicted symptoms of each disorder. Dysfunctional appraisals and neutralizing behaviors mediated the associations between disorder-specific UITs and symptoms in OCD and IAD. The IAD model accounted for a smaller proportion of variance than the OCD model. No mediating effects were found for BDD symptoms. Conclusions. Experiencing disturbing UITs is a transdiagnostic risk factor of OCD, BDD and IAD, and is associated with symptoms of these disorders. Maladaptive interpretation of UITs and neutralizing strategies should be specific targets in the assessment and treatment of OCD and IAD. The absence of mediation effects for BDD could be due to the limitations observed on the self-report used to assess BDD symptoms and/or the low relevance of the misinterpretations and control strategies assessed by the QUIT, which are more typically endorsed by individuals with OCD. Full article
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21 pages, 523 KB  
Review
Wired for Intensity: The Neuropsychological Dynamics of Borderline Personality Disorders—An Integrative Review
by Eleni Giannoulis, Christos Nousis, Maria Krokou, Ifigeneia Zikou and Ioannis Malogiannis
J. Clin. Med. 2025, 14(14), 4973; https://doi.org/10.3390/jcm14144973 - 14 Jul 2025
Viewed by 1442
Abstract
Background: Borderline personality disorder (BPD) is a severe psychiatric condition characterised by emotional instability, impulsivity, interpersonal dysfunction, and self-injurious behaviours. Despite growing clinical interest, the neuropsychological mechanisms underlying these symptoms are still not fully understood. This review aims to summarise findings from neuroimaging, [...] Read more.
Background: Borderline personality disorder (BPD) is a severe psychiatric condition characterised by emotional instability, impulsivity, interpersonal dysfunction, and self-injurious behaviours. Despite growing clinical interest, the neuropsychological mechanisms underlying these symptoms are still not fully understood. This review aims to summarise findings from neuroimaging, psychophysiological, and neurodevelopmental studies in order to clarify the neurobiological and physiological basis of BPD, with a particular focus on emotional dysregulation and implications for the treatment of adolescents. Methods: A narrative review was conducted, integrating results from longitudinal neurodevelopmental studies, functional and structural neuroimaging research (e.g. FMRI and PET), and psychophysiological assessments (e.g., heart rate variability and cortisol reactivity). Studies were selected based on their contribution to understanding the neural correlates of BPD symptom dimensions, particularly emotion dysregulation, impulsivity, interpersonal dysfunction, and self-harm. Results: Findings suggest that early reductions in amygdala volume, as early as age 13 predict later BPD symptoms. Hyperactivity of the amygdala, combined with hypoactivity in the prefrontal cortex, underlies deficits in emotion regulation. Orbitofrontal abnormalities correlate with impulsivity, while disruptions in the default mode network and oxytocin signaling are related to interpersonal dysfunction. Self-injurious behaviour appears to serve a neuropsychological function in regulating emotional pain and trauma-related arousal. This is linked to disruption of the hypothalamic-pituitary-adrenal (HPA) axis and structural brain alterations. The Unified Protocol for Adolescents (UP-A) was more effective to Mentalization-Based Therapy for Adolescents (MBT-A) at reducing emotional dysregulation compared, though challenges in treating identity disturbance and relational difficulties remain. Discussion: The reviewed evidence suggests that BPD has its in early neurodevelopmental vulnerability and is sustained by maladaptive neurophysiological processes. Emotional dysregulation emerges as a central transdiagnostic mechanism. Self-harm may serve as a strategy for regulating emotions in response to trauma-related neural dysregulation. These findings advocate for the integration of neuroscience into psychotherapeutic practice, including the application of neuromodulation techniques and psychophysiological monitoring. Conclusions: A comprehensive understanding of BPD requires a neuropsychologically informed framework. Personalised treatment approaches combining pharmacotherapy, brain-based interventions, and developmentally adapted psychotherapies—particularly DBT, psychodynamic therapy, and trauma-informed care—are essential. Future research should prioritise interdisciplinary, longitudinal studies to further bridge the gap between neurobiological findings and clinical innovation. Full article
(This article belongs to the Special Issue Neuro-Psychiatric Disorders: Updates on Diagnosis and Treatment)
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13 pages, 237 KB  
Article
Can Adjunctive Lithium Therapy Influence Emotional Dysregulation in Adolescents? Findings from a Retrospective Study
by Federica Gigliotti, Luca Cammisa, Sara Riezzo and Arianna Terrinoni
J. Clin. Med. 2025, 14(13), 4807; https://doi.org/10.3390/jcm14134807 - 7 Jul 2025
Viewed by 474
Abstract
Background: Emotional dysregulation (ED) is a transdiagnostic feature of multiple adolescent psychiatric disorders and a predictor of functional impairment and self-harming behaviors. Despite its clinical relevance, pharmacological treatments targeting ED in youth remain underexplored. This retrospective study investigated the clinical effectiveness and [...] Read more.
Background: Emotional dysregulation (ED) is a transdiagnostic feature of multiple adolescent psychiatric disorders and a predictor of functional impairment and self-harming behaviors. Despite its clinical relevance, pharmacological treatments targeting ED in youth remain underexplored. This retrospective study investigated the clinical effectiveness and tolerability of adjunctive lithium therapy in adolescents with severe ED, independent of specific diagnostic categories. Methods: A total of 35 inpatients (13–17 years) with significant ED were divided into two groups based on pharmacological treatment: lithium add-on therapy (Li group, n = 17) and standard therapy without lithium (Control group, n = 18). Clinical severity (CGI-S) and global functioning (C-GAS) were assessed at baseline (T0), 6 months (T1), and 12 months (T2). A mixed-design ANOVA was performed to assess group × time interactions. Adverse events and treatment adherence were also examined. Results: At T1, the Li group showed a significantly greater reduction in symptom severity (CGI-S) compared to the Control group (p = 0.029). Global functioning (C-GAS) improved over time in both groups (p < 0.001), with no significant interaction effects. Adverse effects, primarily metabolic and endocrine, were more frequent in the Li group but did not reduce adherence. Conclusions: Adjunctive lithium therapy may reduce symptom severity in adolescents with severe ED without negatively affecting treatment tolerability or adherence. These findings support the potential utility of lithium in complex adolescent cases and warrant further prospective research. Full article
(This article belongs to the Section Mental Health)
27 pages, 1110 KB  
Systematic Review
Transdiagnostic Efficacy of Cariprazine: A Systematic Review and Meta-Analysis of Efficacy Across Ten Symptom Domains
by Agota Barabassy, Réka Csehi, Zsófia Borbála Dombi, Balázs Szatmári, Thomas Brevig and György Németh
Pharmaceuticals 2025, 18(7), 995; https://doi.org/10.3390/ph18070995 - 2 Jul 2025
Viewed by 1689
Abstract
Introduction: The introduction of the transdiagnostic approach in psychiatry shifts the focus from discrete diagnoses to shared symptoms across various disorders. The Transdiagnostic Global Impression—Psychopathology (TGI-P) scale is a newly developed tool designed to assess psychiatric symptoms across diagnostic boundaries. It evaluates [...] Read more.
Introduction: The introduction of the transdiagnostic approach in psychiatry shifts the focus from discrete diagnoses to shared symptoms across various disorders. The Transdiagnostic Global Impression—Psychopathology (TGI-P) scale is a newly developed tool designed to assess psychiatric symptoms across diagnostic boundaries. It evaluates ten core symptom domains—positive, negative, cognitive, manic, depressive, addiction, anxiety, sleep, hostility, and self-harm—regardless of specific diagnoses. Objective: This study aims to evaluate the efficacy of cariprazine across these ten transdiagnostic symptom domains. Methods: A systematic literature review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were performed on EMBASE and clinicaltrials.gov. Efficacy measures such as the Positive and Negative Syndrome Scale (PANSS), Montgomery–Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Hamilton Anxiety Rating Scale (HAM-A), and Columbia-Suicide Severity Rating Scale (C-SSRS) were used to assess cariprazine’s effect on the ten transdiagnostic symptoms. Multilevel random-effects meta-analyses were conducted to evaluate the efficacy of cariprazine versus placebo in alleviating depressive and anxiety symptoms across clinical trials. Results: A total of 30 studies were included in the review. Cariprazine showed therapeutic benefits on positive, negative, manic, and depressive symptoms in specifically designed trials. Preliminary positive effects were seen on anxiety, hostility, and cognitive symptoms across disorders. However, specific trials have not been conducted for anxiety disorders or cognitive impairment. Meta-analyses demonstrated that cariprazine significantly reduces both depressive and anxiety symptoms compared to placebo. Cariprazine significantly improved sleep-related symptoms in both mania and depression trials. Suicidality was evaluated in non-suicidal populations, and no increase was observed. Addiction symptoms were part of the exclusion criteria in the RCTs, so they could not be assessed. Previous reports of cariprazine’s anti-craving and anti-abuse effects come from real-world evidence rather than RCT data. Conclusions: Cariprazine appears to be promising in addressing a broad range of symptom domains across psychiatric conditions. Full article
(This article belongs to the Special Issue Recent Advances in Psychopharmacology)
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19 pages, 1718 KB  
Review
Harnessing Extended Reality for Neurocognitive Training in Chronic Pain: State of the Art, Opportunities, and Future Directions
by Javier Guerra-Armas, Alberto Roldán-Ruiz, Mar Flores-Cortes and Daniel S. Harvie
Healthcare 2025, 13(11), 1338; https://doi.org/10.3390/healthcare13111338 - 4 Jun 2025
Viewed by 1484
Abstract
Chronic pain is a significant burden affecting more than 30% of people worldwide. Within the multiple biopsychosocial factors affected in people suffering from chronic pain, neurocognitive impairments represent a significant but often under-recognized aspect of the chronic pain experience that impacts daily life [...] Read more.
Chronic pain is a significant burden affecting more than 30% of people worldwide. Within the multiple biopsychosocial factors affected in people suffering from chronic pain, neurocognitive impairments represent a significant but often under-recognized aspect of the chronic pain experience that impacts daily life and healthcare. Multiple neurocognitive domains, including attention, executive function, learning, and memory, have been commonly associated with chronic pain. Within novel approaches, extended reality (XR) has been highlighted for its potential in chronic pain management. XR offers unique features to enhance traditional neurocognitive interventions, including dual tasks, gamification, ecological validity, and enriched experience, to increase engagement and motivation in rehabilitation. This systematic–narrative hybrid literature review aims to shed light on the potential benefits, challenges, and future directions of XR technology to address neurocognitive impairments associated with chronic pain. While preliminary evidence suggests that XR-based neurocognitive training may be beneficial in overcoming neurocognitive impairments found in chronic pain, some challenges still need to be addressed for effective translation into clinical practice. Within a transdiagnostic approach, XR-based neurocognitive training appears to be valuable across different diagnoses in chronic pain, wherein XR may emerge as a promising first-line intervention toward personalized multimodal management for chronic pain. Despite the rapid development of substantial growing evidence for XR, enhanced methodological rigor and reporting quality are recommended in future studies. More research is needed to fully understand the mechanisms and optimal application of XR-based neurocognitive training in different chronic pain conditions. Full article
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17 pages, 696 KB  
Review
Emotional Dysregulation and Cognitive Disengagement Syndrome: Exploring Their Relationship Through the Lens of Twin Studies
by Gaia De Giuli, Cecilia Amico, Stefano De Francesco, Ludovica Giani, Gülşah Tüzün, Federico Galli, Marcella Caputi, Barbara Forresi and Simona Scaini
Appl. Sci. 2025, 15(11), 6067; https://doi.org/10.3390/app15116067 - 28 May 2025
Cited by 1 | Viewed by 737
Abstract
Cognitive Disengagement Syndrome (CDS) is a clinical construct characterized by symptoms such as excessive daydreaming, mental confusion, slowed behavior, and reduced cognitive and motor activity. Increasing evidence suggests a potential overlap between CDS and Emotional Dysregulation (ED), a transdiagnostic construct associated with difficulties [...] Read more.
Cognitive Disengagement Syndrome (CDS) is a clinical construct characterized by symptoms such as excessive daydreaming, mental confusion, slowed behavior, and reduced cognitive and motor activity. Increasing evidence suggests a potential overlap between CDS and Emotional Dysregulation (ED), a transdiagnostic construct associated with difficulties in regulating emotional responses. This narrative review synthesizes current empirical findings and theoretical perspectives on the co-occurrence of CDS and ED, with a particular focus on insights provided by behavioral genetics—especially twin studies. We describe the core principles and models used in twin research and evaluate how they have been applied to disentangle genetic and environmental contributions to these phenotypes and their overlap. While some studies support a shared etiology between CDS and ED, particularly through non-shared environmental influences, research in this area remains limited and conceptually fragmented. The review identifies critical knowledge gaps, including the lack of longitudinal studies, inconsistent definitions of ED, and limited exploration of developmental trajectories. We argue that future twin studies are essential for clarifying these unresolved issues. Nonetheless, limitations include the scarcity of twin-based studies directly examining the CDS–ED association and methodological inconsistencies across the existing literature. Full article
(This article belongs to the Special Issue Feature Review Papers in Theoretical and Applied Neuroscience)
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