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Children suffering from attention deficit hyperactivity disorder (ADHD) may remit until adulthood. But, more than 60–80 % have persisting ADHD symptoms. ADHD as an early manifesting neurodevelopmental disorder is considered a major risk factor for the development of comorbid psychiatric disorders in later life. Particularly, personality disorders are oftentimes observed in adult patients suffering from ADHD. If ADHD and personality disorders share common etiological mechanisms and/or if ADHD as a severely impairing condition influences psychological functioning and learning and leads to unfavorable learning histories is unclear. The development of inflexible and dysfunctional beliefs on the basis of real and perceived impairments or otherness due to the core symptoms of ADHD is intuitively plausible. Such beliefs are a known cause for the development of personality disorders. But, why some personality disorders are more frequently found in ADHD patients as for example antisocial and borderline personality disorder remains subject of debate. Because of the high prevalence of ADHD and the high impact of personality disorders on daily functioning, it is important to take them into account when treating patients with ADHD. Research on the developmental trajectories leading to personality disorders in adult ADHD patients might open the door for targeted interventions to prevent impairing comorbid clinical pictures.

Background Overlap in symptom domains particularly in the field of impulsivity and emotional dysregulation in attention deficit hyperactivity disorder (ADHD) and borderline personality disorder (BPD) have stimulated further research activities since our last review from 2014. Main body Disentangling features of impulsivity in ADHD and BPD revealed that impulsivity is a feature of both disorders with patients suffering from both ADHD and BPD having highest impulsivity ratings. BPD individuals have more problems using context cues for inhibiting responses and their impulsivity is stress-dependent, whereas ADHD patients have more motor impulsivity and therefore difficulties interrupting ongoing responses. For emotion regulation difficulties the ranking order ranges from ADHD to BPD to the comorbid condition, again with the patients suffering from both, ADHD and BPD, having the most pronounced emotion regulation problems. Environmental influences namely adverse childhood events were shown to be linked to both ADHD and BPD. Traumatic experiences seem independently linked to impulsivity features. Thus, some authors point to the risk of misdiagnosis during childhood and the necessity to screen for traumatic experiences in both patient groups. Genetic research confirmed genetic overlap of BPD with bipolar disorder (BD) and schizophrenic disorders, as well as genetic overlap of BD and ADHD. A population-based study confirmed the high co-occurrence and familial co-aggregation of ADHD and BPD. Interesting questions in the field of gene-environment-interactions are currently dealt with by genetic and epigenetic research. Few studies have investigated treatment strategies for the comorbid condition, though the issue is highly important for the management of patients suffering from both disorders and presenting with the highest symptom scores. Conclusion Research on the different impulsivity features might point to a necessity of disorder-specific treatment strategies in the field of impulse control. Future research is needed to base treatment decisions for the comorbid condition on an evidence basis.

Background Adult attention-deficit/hyperactivity disorder (ADHD) is a serious and frequent psychiatric disorder of multifactorial pathogenesis. Several lines of evidence support the idea that ADHD is, in its core, a disorder of dysfunctional brain connectivity within and between several neurofunctional networks. The primary aim of this study was to investigate associations between the functional connectivity within resting state brain networks and the individual severity of core ADHD symptoms (inattention, hyperactivity, and impulsivity). Methods Resting state functional magnetic resonance imaging (rs-fMRI) data of 38 methylphenidate-naïve adults with childhood-onset ADHD (20 women, mean age 40.5 years) were analyzed using independent component analysis (FSL’s MELODIC) and FSL’s dual regression technique. For motion correction, standard volume-realignment followed by independent component analysis-based automatic removal of motion artifacts (FSL’s ICA-AROMA) were employed. To identify well-established brain networks, the independent components found in the ADHD group were correlated with brain networks previously found in healthy participants (Smith et al. PNAS 2009;106:13040–5). To investigate associations between functional connectivity and individual symptom severity, sex, and age, linear regressions were performed. Results Decomposition of resting state brain activity of adults with ADHD resulted in similar resting state networks as previously described for healthy adults. No significant differences in functional connectivity were seen between women and men. Advanced age was associated with decreased functional connectivity in parts of the bilateral cingulate and paracingulate cortex within the executive control network. More severe hyperactivity was associated with increased functional connectivity in the left putamen, right caudate nucleus, right central operculum and a portion of the right postcentral gyrus within the auditory/sensorimotor network. Conclusions The present study supports and extends our knowledge on the involvement of the striatum in the pathophysiology of ADHD, in particular, in the pathogenesis of hyperactivity. Our results emphasize the usefulness of dimensional analyses in the study of ADHD, a highly heterogeneous disorder. Trial registration ISRCTN12722296 ( https://doi.org/10.1186/ISRCTN12722296 ).

While the need for personalised treatment approaches grows in recognition, predicting treatment outcomes for adults with Attention-Deficit/Hyperactivity Disorder (ADHD) remains underexplored. Recent interest has turned to the brain’s surface and its association with treatment response. Although the precise interplay between cortical gyrification and ADHD treatment outcomes remains to be elucidated, preliminary investigations suggest a promising avenue for diagnostic innovation. Expanding upon the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), we investigated the prognostic value of cortical gyrification in predicting treatment response. Specifically, we explored how pre-treatment cortical gyrification might predict response to psychotherapy or clinical management in combination with either methylphenidate or placebo following a 12-week intensive treatment period. Cortical gyrification was assessed using 121 T1-weighted anatomical scans. Linear regression models investigated the predictive value of cortical gyrification, regressing baseline cortical structure against post-treatment severity. All brain structural analyses were conducted using the threshold-free cluster enhancement (TFCE) approach and the Computational Anatomy Toolbox (CAT12) within the Statistical Parametric Mapping Software (Matlab Version R2021a). Results revealed significant positive region-specific associations between cortical gyrification and treatment response across three symptom dimensions, with significant associations localised predominantly in frontal regions of the left hemisphere. Our findings emphasise that increased cortical gyrification in frontal cortical regions signifies enhanced treatment efficacy following a 12-week intervention. Further research in this area is imperative to verify the reliability of biological markers in view of treatment success to potentially reduce unnecessary drug-related side-effects, minimising delay from receiving more effective treatments, and increase treatment adherence.

Introduction: Previous neuroimaging studies have reported structural brain alterations and local network hyperexcitability in terms of increased slow-wave electroencephalography (EEG) activity in patients with borderline personality disorder (BPD). In particular, intermittent rhythmic delta and theta activity (IRDA/IRTA) has drawn attention in mental health contexts due to its links with metabolic imbalances, neuronal stress, and emotional dysregulation—processes that are highly pertinent to BPD. These functional disturbances may be reflected in corresponding structural brain changes. The current study investigated cortical thickness and subcortical volumes in BPD and examined their associations with IRDA/IRTA events per minute, symptom severity, and neuropsychological measures. Methods: Seventy female BPD patients and 36 age-matched female healthy controls (HC) were included (for clinical EEG comparisons even 72 patients were available). IRDA/IRTA rates were assessed using an automatic independent component analyses (ICA) approach. T1-weighted MRI data were obtained using a MAGNETOM Prisma 3T system and analyzed with FreeSurfer (version 7.2) for subcortical structures and CAT12 for cortical thickness and global volume measurements. Psychometric assessments included questionnaires such as Borderline Symptom List (BSL-23) and Inventory of Personality Organization (IPO). Neuropsychological performance was evaluated with the Test for Attentional Performance (TAP), Culture Fair Intelligence Test (CFT-20-R), and Verbal Learning and Memory Test (VLMT). Results: Between-group comparisons exhibited no significant increase in IRDA/IRTA rates or structural abnormalities between the BPD and HC group. However, within the BPD group, cortical thickness of the right isthmus of the cingulate gyrus negatively correlated with the IRDA/IRTA difference (after minus before hyperventilation, HV; p < 0.001). Furthermore, BPD symptom severity (BSL-23) and IPO scores positively correlated with the thickness of the right rostral anterior cingulate cortex (p < 0.001), and IPO scores were associated with the thickness of the right temporal pole (p < 0.001). Intrinsic alertness (TAP) significantly correlated with relative cerebellar volume (p = 0.01). Discussion: While no group-level structural abnormalities were observed, correlations between EEG slowing, BPD symptom severity, and alertness with cortical thickness and/or subcortical volumes suggest a potential role of the anterior cingulate cortex, temporal pole, and cerebellum in emotion regulation and cognitive functioning in BPD. Future research employing multimodal EEG-MRI approaches may provide deeper insights into the neural mechanisms underlying BPD and guide personalized therapeutic strategies.

Background Individuals with Borderline-Personality Disorder (BPD) experience intensive, unstable negative emotions. Hyperactivity of the amygdala is assumed to drive exaggerated emotional responses in BPD. Functional Magnetic Resonance Imaging (fMRI)-based neurofeedback is an endogenous neuromodulation method intended to address the imbalance of neural circuits and thus holds the potential as a treatment for BPD. Many original articles and meta-analyses show that fMRI-neurofeedback can improve psychiatric symptoms. In contrast, there is a lack of publications that aggregate and evaluate data of the safety of the treatment. Furthermore, evidence on the efficacy of fMRI-neurofeedback for the treatment of BPD is limited. Preliminary evidence suggests that downregulation of amygdala hyperactivation through fMRI-neurofeedback can ameliorate emotion dysregulation. To test this assumption, BrainSTEADy (Brain Signal Training to Enhance Affect Down-regulation), a multi-center clinical trial, is conducted. First, we present a systematic literature review evaluating the safety of fMRI-neurofeedback and assessing clinical performance in BPD. Second, we describe the study protocol of BrainSTEADy. Methods Literature research: From 2,609 screened paper abstracts, 758 were identified as potentially relevant. Twenty studies reported adverse events or undesirable side effects. Two papers provided relevant data for the assessment of clinical performance in BPD. BrainSTEADy study protocol: During four sessions, patients will receive graphical fMRI-neurofeedback from their right amygdala or sham-feedback while viewing images with aversive content. The primary endpoint, ‘negative affect intensity’, will be assessed after the last neurofeedback session using Ecological Momentary Assessment (EMA). Secondary endpoints will be assessed after the last neurofeedback session, at 3-month and at 6-month follow-up. This trial is a multi-center, patient- and investigator-blind, randomized, parallel-group superiority study with a planned interim-analysis once half of the recruitment target is met ( N  = 82). Discussion As suggested by literature review, fMRI-neurofeedback is a safe treatment for patients, although future studies should systematically assess and report adverse events. Although fMRI-neurofeedback showed promising effects in BPD, current evidence is limited and calls for a randomized controlled trial such as BrainSTEADy, which aims to test whether amygdala-fMRI-neurofeedback specifically reduces emotion instability in BPD beyond nonspecific benefit. Endpoint measures encompassing EMA, clinical interviews, psychological questionnaires, quality of life, and neuroimaging will enable a comprehensive analysis of effects and mechanisms of neurofeedback treatment. Trial registration The study protocol was first posted 2024/10/04 on ClinicalTrials.gov and received the ID NCT06626789.

Purpose of Review In light of the apparent symptomatic resemblance of separation anxiety disorder (SAD) symptoms on the one hand and abandonment fears, anxiousness, and separation insecurity central to borderline personality disorder (BPD) on the other hand, a comprehensive overview of separation anxiety and related traits in BPD is provided. Recent Findings Epidemiological, environmental, psychological, and neurobiological data connecting BPD to separation events, feelings of loneliness, insecure attachment styles, dimensional separation anxiety as well as SAD per se suggest a partly shared etiological pathway model underlying BPD and SAD. Differential diagnostic aspects and implications for treatment are discussed, highlighting separation anxiety as a promising transdiagnostic target for specific psychotherapeutic and pharmacological treatment approaches in BPD. Summary This innovative angle on cross-disorder symptomatology might carry potential for novel preventive and therapeutic avenues in clinical practice by guiding the development of interventions specifically targeting separation anxiety and attachment-related issues in BPD.

The original article was missing a statement regarding a shared first authorship. The authors Julia M. Geissler and Timo D. Vloet contributed equally to the manuscript.

Objective Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Relevant sex differences in symptomatology are discussed. This study compared brain neurometabolism in the anterior cingulate cortex (ACC) and left cerebellar hemisphere in age- and IQ-matched adult male (mADHD) and female (fADHD) ADHD patients. Methods We studied 48 (ACC) and 42 (cerebellum) male/female pairs of stimulant-free patients with adult ADHD. Single voxel magnetic resonance spectroscopy (MRS) was used to investigate creatine (Cre), total choline (t-Cho), glutamate + glutamine (Glx), N-acetylaspartate, and myo-inositol. The mADHD and fADHD groups were compared using robust linear regression. The level of significance was corrected for multiple tests using the Benjamini-Hochberg approach. Results For the ACC, the signals of Cre ( p  = 0.008) and t-Cho ( p  = 0.004) showed significant effects of the age covariate as well as an interaction of sex and age (Cre: p  = 0.033; t-Cho: p  = 0.040). For the Glx signal, an interaction of sex and age could also be observed ( p  = 0.033). For cerebellar neurometabolites, the signals of t-Cho ( p  = 0.049) and Glx ( p  = 0.049) showed significant effects of the factor sex. Conclusion This is the largest study yet to analyze sex differences in brain neurochemistry in adult patients with ADHD. Different age-dependent t-Cho signals in the ACC might be associated with delayed myelinization in mADHD. Further MRS studies in adult ADHD, accounting for possible sex effects, are warranted to validate the present findings.

Based on animal research several authors have warned that the application of methylphenidate, the first-line drug for the treatment of attention-deficit/hyperactivity disorder (ADHD), might have neurotoxic effects potentially harming the brain. We investigated whether methylphenidate application, over a 1-year period, results in cerebral volume decrease. We acquired structural MRIs in a double-blind study comparing methylphenidate to placebo. Global and regional brain volumes were analyzed at baseline, after 3 months and after 12 months using diffeomorphic anatomic registration through exponentiated lie algebra. We included 131 adult patients with ADHD into the baseline sample, 98 into the 3-month sample (54 in the methylphenidate cohort and 44 in the placebo cohort) and 76 into the 1-year sample (37 in the methylphenidate cohort and 29 in the placebo cohort). Methylphenidate intake compared with placebo did not lead to any detectable cerebral volume loss; there was a trend toward bilateral cerebellar grey matter increase. Detecting possible neurotoxic effects of methylphenidate might require a longer observation period. There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD.