Background: Attention-deficit/hyperactivity disorder (ADHD) is characterized by emotional dysregulation, such as emotional instability, and by non-emotional symptoms, including inattention. These symptom domains are dimensionally distributed in the general population and are hypothesized to reflect both overlapping and distinct structural and functional features of cortical and subcortical brain networks. Methods: We applied a dimensional symptom approach in a sample of adults with ADHD (n = 71) and healthy controls (n = 59) to investigate structural brain correlates of inattention and emotional instability, as measured by the Brown Attention-Deficit Disorder Scales. Structural magnetic resonance imaging (MRI) data were analysed to examine cortical and subcortical associations with these symptom dimensions. Performance in an emotional Stroop task was assessed in conjunction with MRI acquisition in a subsample to explore neural correlates of emotion-related cognitive control. Data were collected between 2012 and 2017. Results: Emotional instability was negatively associated with nucleus accumbens volume, independent of inattention symptoms and ADHD diagnosis (β = -0.29, p = 0.016). Additionally, while controlling for inattention symptoms, a negative correlation between emotional instability and cortical surface area was found in a cluster comprising the left dorsolateral prefrontal cortex and right medial/superior frontal cortex. Moreover, cortical thickness in the lateral orbitofrontal cortex was positively associated with performance in the Stroop task in ADHD (r = 0.44, p = 0.027) while being negatively associated in healthy controls (r = -0.40 p = 0.028). Limitations: Medication use within the ADHD group might influence brain-symptom-associations. The cross-sectional design of the study precludes conclusions about causality. Conclusions: These findings suggest that structural alterations in the nucleus accumbens are more strongly related to emotional, rather than attentional symptoms after accounting for their shared variance. Furthermore, altered prefrontal and orbitofrontal morphology may underlie impairments in emotional regulation, supporting the role of frontostriatal circuits in the dimensional expression of emotional instability across clinical and non-clinical populations.

Thoughts are traditionally classified by their cognitive contents, such as task-related versus task-unrelated or internally versus externally oriented. However, content-based distinctions often lack diagnostic specificity in psychiatric disorders, where similar thought contents may manifest across conditions such as schizophrenia and major depressive disorder. Here, we propose a complementary framework that characterizes thoughts by their dynamics, the pattern of changes in the thought contents over time-that is, their duration, speed, and temporal precision. Converging evidence in healthy individuals shows that distinct thought dimensions map onto specific neural timescales, ranging from fine-grained oscillatory phase dynamics to coarse-grained temporal windows. Extending this framework to psychopathology, schizophrenia is characterized by temporal imprecision of thought contents across shorter and longer timescales, yielding fragmented and poorly differentiated thoughts. In contrast, major depressive disorder is marked by abnormally prolonged timescales with abnormal slowness leading to rarely changing thought contents, e.g., ruminations. We propose that the timescales of thought contents and, more generally, thought dynamics may serve as a promising marker for the differential diagnosis of thought disturbances in mental disorders.

Erythropoietin-producing hepatocellular (Eph) receptors are tyrosine kinase receptors that are canonically activated by their membrane tethered ligands, the ephrins. The Eph-ephrin system is critical in neurodevelopment, involved in processes such as neuronal growth and proliferation, axonal growth cone guidance, and cell survival. However, there is a significant knowledge gap in our understanding of the functional role of the Eph-ephrin system in later development, in both the adolescent and the adult brain. As various Eph receptor subtypes, and their associated ephrin ligands, are involved in the regulation of processes implicated in brain disorder pathogenesis, the Eph-ephrin system may represent an unexplored avenue for therapeutic target identification. Here, we will consolidate what is known about the Eph-ephrin system in synaptic plasticity, inflammation, and vascular permeability, linking the effects of specific ephrins and Eph receptors to depression and anxiety, autism, and schizophrenia. Novel insights into those Eph receptors with the most therapeutic promise will be provided and potential challenges of targeting these widely expressed receptor kinases discussed.