Background: Psychedelics are increasingly recognized as a promising and innovative treatment strategy for several mental disorders. However, there is still a lively controversy in the medical community as regards the rationale of their employment, specifically their indications and potential dangers. Methods: A comprehensive literature search on “MEDLINE/PubMed” and “Web of Science” was performed from inception to 26 June 2024, cross-checking the obtained references. We included all studies, i.e., both clinical and preclinical, that supplied original data. Results: We initially obtained a total of 1083 entries, 813 from MEDLINE/PubMed and 270 from Web of Science. After duplicate elimination, 903 underwent systematic literature selection. Primary abstract screening yielded a total of 572 candidates for eligibility assessment and excluded 331 entries on formal grounds. Eligibility assessment led to the exclusion of 501 titles. Finally, a total of 70 articles were included in this review. Discussion: Preclinical evidence from genetic expression, histology and behavioral studies is soundly consistent with psychedelics possessing neuroplasticity-inducing properties. Despite methodological difficulties, clinical evidence seems to be inferentially in agreement with preclinical findings. However, it is still unclear whether the “neuroplastic boost” induced by classic psychedelics might be dissociable from the psychodysleptic effects, thereby reducing the psychopathological hazards implied by these compounds. Moreover, the fact that the so-called “relaxation of priors” should be unconditionally beneficial appears debatable, and further research should clarify the possible indications and contraindications of psychedelic psychoplastogens within a precision medicine perspective.

Objectives: The treatment of emotional dysregulation (ED) poses a major challenge for clinicians managing adult attention-deficit/hyperactivity disorder (ADHD). This naturalistic longitudinal study aimed to evaluate the effects of combining mood stabilizers (MS) with standard pharmacotherapy in this population. Methods: Fifty-six adult patients with ADHD, with or without bipolar spectrum disorders, who were followed-up for at least 4 months at Pisa University Hospital were included and grouped based on the prescription of ADHD treatment with prior MS, with conomitant MS and without MS. Changes in self-reported ED, self-reported and informant-reported ADHD severity were assessed using RIPoSt-40, ASRS-v1.1, and CAARS-O:SV. Longitudinal analyses were conducted separately for each group using a pairwise one-sample paired Student’s t-test. Results: A significant reduction in ED severity was observed in those treated with methylphenidate (MPH) and concomitant MS and in those with atomoxetine (ATX) without MS. Negative emotionality and emotional impulsivity significantly decreased in both these groups, while affective instability only improved in those with MPH and concomitant MS. Self-reported ADHD improvements were significant in all groups receiving MPH, whether with concomitant, prior, or without MS. Significant changes in informant-reported ADHD severity were found in those receiving MPH with concomitant or prior MS. Conclusions: The findings highlight the benefits of concomitant MS and MPH treatment on ED, suggest a preferential effect of ATX on negative emotionality, and confirm the effectiveness of MPH for adult ADHD symptoms, regardless of additional treatment with MS. Further studies are needed to explore whether and how MS and MPH may complement each other in reducing ED.

Background: The association between emotional dysregulation (ED) and attention-deficit/hyperactivity disorder (ADHD) has been widely documented. However, a consensus has yet to be reached on how to conceptualize this domain within ADHD. Particularly, ADHD + ED may represent a distinct condition, a more severe ADHD, or a comorbidity. We explored these three main hypotheses, investigating clinical differences between patients with ADHD, ADHD + ED, and ED. Methods: In total, 101 participants (ages 18–50) were recruited and divided into four groups: ADHD (N = 23), ED (N = 28), ADHD + ED (N = 27), and HC (N = 23). ADHD and ED were assessed using the Diagnostic Interview for ADHD in adults (DIVA-5) and the Wender–Reimherr Adult Attention Deficit Disorder Scale (WRAADDS). Sociodemographic and clinical variables were compared among the groups. Results: Participants with ADHD and ADHD + ED exhibited comparably high ADHD severity and executive dysfunction ratings. While participants with ADHD + ED shared elevated negative emotionality and higher rates of mood disorders and anxiety disorders with participants with ED compared with those with ADHD, they showed specifically increased developmental and disruptive comorbidities, as well as earlier onset and greater cyclicity of comorbid mood disorders. Psychosocial functional impairments were similarly elevated on average in ADHD + ED and ADHD, but ADHD + ED showed more pronounced and widespread deficits across multiple domains. Conclusions: ADHD + ED is unlikely to represent a more severe form of ADHD but may be more appropriately conceptualized as either a distinct entity or a “comorbid” phenotype. Comparisons with ED without ADHD highlighted clinical features specific to ADHD + ED, including a higher neurodevelopmental load, impulse-control disorders, and a poorer course of mood disorders.

Attention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) frequently co-occur. However, evidence on the clinical effects of stimulant treatment in ADHD-BPD comorbidity remains limited. This prospective study aimed to investigate the longitudinal effects of methylphenidate (MPH) on borderline personality features in adults with ADHD-BPD. Thirty-six adults diagnosed with ADHD who also met the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria for BPD were treated with MPH and followed for at least 16 weeks. Clinical ratings of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition BPD criteria and psychometric measures assessing symptom severity and personality functioning were obtained at baseline and follow-up. Twenty-four participants (66.7%) completed the follow-up. Follow-up duration ranged from 3.9 to 12.3 months, with a mean duration of 7.8 ± 2.48 months. The number of BPD criteria significantly decreased after treatment ( r = 0.82, P < 0.001). Nineteen participants no longer met the diagnostic threshold for BPD, and 10 achieved remission (≤2 BPD criteria). Baseline anger dysregulation ( P = 0.009) and mood stabilizer use ( P = 0.029) were associated with continued MPH treatment. Our findings preliminarily suggest that MPH, especially combined with mood stabilizers, may be associated with clinical benefits and acceptable tolerability in patients with comorbid ADHD-BPD. While causal conclusions cannot be drawn, replication in randomized controlled trials is warranted.

Background/Objectives: Sex differences in adult attention-deficit/hyperactivity disorder (ADHD) remain insufficiently characterized, particularly in clinically referred samples assessed through multidimensional and multi-informant approaches. This study investigated sex differences in clinical presentation, psychiatric comorbidity, psychometric features, and ADHD severity in adults with ADHD, with a specific focus on emotional dysregulation and rating-source effects. Methods: A total of 212 consecutively recruited adults with ADHD, including 93 females and 119 males, underwent a comprehensive assessment at a tertiary referral service. Sex differences were examined across sociodemographic, clinical, comorbidity, functional, and psychometric domains. ADHD severity was assessed using both self-rated and observer-rated measures. Regression, mediation, and repeated-measures mixed-effects models were fitted to examine the role of emotional dysregulation in the association between sex and ADHD severity. Results: Females showed a higher frequency of predominantly inattentive presentation; higher rates of mood, anxiety, and eating disorders; and more pronounced emotional dysregulation, affective temperamental traits, personality-related impairment, and biological rhythm disturbances. Observer-rated ADHD severity did not differ by sex, while females reported higher self-rated ADHD severity. Emotional dysregulation was associated with both observer-rated and self-rated ADHD severity, with a stronger association for self-rated symptoms. Mediation analysis showed a significant indirect effect of female sex on self-reported ADHD severity through emotional dysregulation, accounting for 79.4% of the total association. Mixed-effects models further indicated that sex differences in ADHD severity varied according to rating source and persisted, although attenuated, after accounting for emotional dysregulation. Conclusions: Adult females with ADHD showed a different clinical profile, characterized by greater internalizing comorbidity, emotional dysregulation, personality-related impairment, and biological rhythm disturbances. Emotional dysregulation accounted for a substantial part of the higher self-reported ADHD severity observed among females, while rating-source effects suggested that sex differences in adult ADHD may partly depend on how symptom severity is assessed.