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Frontiers in Psychiatry 2023The role of emotional dysregulation (ED) in attention-deficit/hyperactivity disorder (ADHD) has become an important issue. This study, in which we analyzed data from a...
INTRODUCTION
The role of emotional dysregulation (ED) in attention-deficit/hyperactivity disorder (ADHD) has become an important issue. This study, in which we analyzed data from a predictive pharmaco-EEG-trial, aimed to examine whether symptoms of ED in adult ADHD affect ADHD symptom severity, brain arousal regulation as measured by resting EEG, and the response to stimulant medication.
METHODS
ED is defined as having a sex- and age-corrected -score of >70 on the emotional lability subscale of the German version of Conners' Adult ADHD Rating Scale. A total of 115 participants were included in the study, 56 of whom had ED. Participants with ED were more impaired in terms of the severity of core ADHD symptoms, especially inattentive symptoms, comorbid depressive symptoms, interpersonal relationships, and quality of life. In addition, participants with ED were more likely to report a total score above 13 on the Beck Depression Inventory-II, which was considered to be the cutoff for mild depression.
RESULTS
No differences were found between the ED and non-ED groups in response to stimulant medication or in brain arousal regulation. In addition, there was no significant effect of ED with comorbid depressive symptoms on treatment response. There was a trend for subgroups that showed a change in brain arousal regulation associated with symptom improvement.
DISCUSSION
Our findings may support the assumption that ED may be an important feature of ADHD. The use of EEG-based brain arousal regulation as a diagnostic and predictive tool in ADHD in the presence of ED and comorbid depressive symptoms should be further investigated.
PubMed: 38250266
DOI: 10.3389/fpsyt.2023.1294314 -
Antioxidants (Basel, Switzerland) Jan 2024Although ADHD is one of the most prevalent diseases during childhood, we still do not know its precise origin; oxidative/nitrosative stress and the...
Although ADHD is one of the most prevalent diseases during childhood, we still do not know its precise origin; oxidative/nitrosative stress and the hypothalamic-pituitary-adrenal axis are suggested contributors. Methylphenidate, among others, is the main drug used in ADHD patients, but its effects on relevant markers and structures remain unclear. This study, involving 59 patients diagnosed with ADHD according to DSM-5 criteria, aimed to assess changes in cortisol levels (using cortisol awakening response, CAR) and oxidative/nitrosative status with the treatment. Blood samples before and 3 months after treatment with methylphenidate were used to measure oxidative and inflammatory markers, as well as the endogenous antioxidant activity, while saliva samples tracked cortisol awakening response (CAR). The results showed a treatment-related improvement in the redox profile, with the reduction in advanced oxidation protein products (AOPP), lipid peroxidation (LPO), and nitrite plus nitrate (NOx) levels, and the increase in the enzymatic activities of glutathione reductase (GRd) and catalase (CAT). Moreover, the area under the curve (AUC) of CAR increased significantly, indicating increased reactivity of the HPA axis. These results support, for the first time, the involvement of the endogenous antioxidant system in the pathophysiology of ADHD.
PubMed: 38247516
DOI: 10.3390/antiox13010092 -
Journal of Pharmacological Sciences Feb 2024Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood-onset psychiatric disorder. We investigated the effects of systemic administration of...
Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood-onset psychiatric disorder. We investigated the effects of systemic administration of monoamine reuptake inhibitors on long-term potentiation (LTP) formation and monoamine release in the medial prefrontal cortex (mPFC) of the stroke-prone spontaneously hypertensive rat (SHRSP)/Ezo, an animal model of ADHD, and its genetic control, Wistar Kyoto (WKY)/Ezo, to elucidate the functional changes in the mPFC monoamine neural system. Methylphenidate (dopamine (DA) and noradrenaline (NA) reuptake inhibitor) and desipramine (NA reuptake inhibitor) improved LTP formation defects in the mPFC of SHRSP/Ezo, suggesting that NA or both DA and NA are required for improvement of impaired LTP. Methylphenidate increased mPFC DA in both WKY/Ezo and SHRSP/Ezo, but the increase was greater in the former. GBR-12909 (DA reuptake inhibitor) increased mPFC DA in WKY/Ezo but had no effect in SHRSP/Ezo. This may be because DA transporter in SHRSP/Ezo is functionally impaired and contributes less to DA reuptake, so its inhibition did not increase DA level. Meanwhile, basal DA levels in the mPFC of SHRSP/Ezo were paradoxically decreased. These results suggest that functional changes in the DA and NA neural system in the frontal lobe are involved in the pathology of ADHD.
Topics: Humans; Rats; Animals; Child; Rats, Inbred WKY; Attention Deficit Disorder with Hyperactivity; Rats, Inbred SHR; Amines; Methylphenidate; Models, Animal; Dopamine
PubMed: 38246729
DOI: 10.1016/j.jphs.2023.12.002 -
Ugeskrift For Laeger Jan 2024This is a case report of two men aged 39 and 43 years with dissection of the coeliac trunk involving the splenic arteries causing splenic infarction. One case was...
This is a case report of two men aged 39 and 43 years with dissection of the coeliac trunk involving the splenic arteries causing splenic infarction. One case was associated with an increase in abdominal pressure during defaecation and the other occurred during treatment with methylphenidate. Based on the published 43 cases, risk factors include male sex, increased intraabdominal pressure or increased vascular pressure. Methylphenidate most likely increased the blood pressure, and dissections of other arteries have been described during treatment with this and the similar drug amphetamine.
Topics: Humans; Male; Amphetamine; Blood Pressure; Celiac Artery; Methylphenidate; Splenic Artery; Adult
PubMed: 38235724
DOI: 10.61409/V07230468 -
Neural Regeneration Research Sep 2024Preclinical and clinical studies indicate that psychostimulants, in addition to having abuse potential, may elicit brain dysfunctions and/or neurotoxic effects. Central...
Preclinical and clinical studies indicate that psychostimulants, in addition to having abuse potential, may elicit brain dysfunctions and/or neurotoxic effects. Central toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and adults. The present review provides an overview of recent research, conducted between 2018 and 2023, focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine, cocaine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylphenidate, caffeine, and nicotine. Detailed elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.
PubMed: 38227515
DOI: 10.4103/1673-5374.390971 -
Addiction Neuroscience Dec 2023The medical psychostimulant methylphenidate (MP) is used to treat attention-deficit hyperactivity disorder and recreationally as a "cognitive enhancer". MP is a dopamine...
The medical psychostimulant methylphenidate (MP) is used to treat attention-deficit hyperactivity disorder and recreationally as a "cognitive enhancer". MP is a dopamine reuptake inhibitor, but does not affect serotonin. Serotonin contributes to addiction-related gene regulation and behavior. Previously, we showed that enhancing serotonin action by adding a selective serotonin reuptake inhibitor, fluoxetine (FLX), to MP potentiates MP-induced gene regulation in striatum and nucleus accumbens, mimicking cocaine effects. Here, we investigated the behavioral consequences of MP+FLX treatment. Young adult male rats received MP (5 mg/kg, i.p.) or MP+FLX (5 mg/kg each) daily for 6-8 days. Behavioral effects were assessed in an open-field test during the repeated treatment. Two weeks later the motor response to a cocaine challenge (25 mg/kg) and the rate of acquisition of cocaine self-administration behavior were determined. Our results demonstrate that FLX potentiates effects of MP on open-field behavior. However, we found differential behavioral responses to MP+FLX treatment, as approximately half of the rats developed high rates of focal stereotypies (termed "MP+FLX/high reactivity" group), whereas the other half did not, and only showed increased locomotion ("MP+FLX/low reactivity" group). Two weeks later, cocaine-induced locomotion and stereotypies were positively correlated with MP+FLX-induced behavior seen at the end of the repeated MP+FLX treatment. Moreover, the MP+FLX/high reactivity group, but not the low reactivity group, showed facilitated acquisition of cocaine self-administration. These results demonstrate that repeated MP+FLX treatment can facilitate subsequent cocaine taking behavior in a subpopulation of rats. These findings suggest that MP+FLX exposure in some individuals may increase the risk for psychostimulant use later in life.
PubMed: 38222942
DOI: 10.1016/j.addicn.2023.100131 -
Soa--ch'ongsonyon Chongsin Uihak =... Jan 2024This study aimed to investigate the effectiveness and safety of combining psychostimulants and nonstimulants for patients under treatment for attention deficit...
OBJECTIVES
This study aimed to investigate the effectiveness and safety of combining psychostimulants and nonstimulants for patients under treatment for attention deficit hyperactivity disorder (ADHD).
METHODS
The study included 96 patients aged 6-12 years who were diagnosed with ADHD, among whom 34 received combination pharmacotherapy, 32 received methylphenidate monotherapy, and 30 received atomoxetine monotherapy. Statistical analysis was conducted to compare treatment and adverse effects among groups and to analyze changes before and after combination pharmacotherapy. The difference between combination pharmacotherapy and monotherapy was investigated. Logistic regression analysis was used to identify the predictors of combination pharmacotherapy.
RESULTS
No significant differences were observed between the groups in terms of age or pretreatment scores. The most common adverse effect experienced by 32% of patients in the combination pharmacotherapy group was decreased appetite. Clinical global impression- severity score decreased significantly after combination pharmacotherapy. All three groups showed significant clinical global impression- severity score improvements over time, with no significant differences among them. The predictive factors for combination pharmacotherapy included the Child Behavior Checklist total score internalizing subscale.
CONCLUSION
Combination pharmacotherapy with methylphenidate and atomoxetine is a relatively effective and safe option for patients with ADHD who do not respond to monotherapy.
PubMed: 38204741
DOI: 10.5765/jkacap.230048 -
Journal of Family Medicine and Primary... Nov 2023Traumatic brain injuries (TBIs) can have numerous neurologic and cognitive sequelae. The road to recovery can be long and arduous for many patients. Improving cognition...
Traumatic brain injuries (TBIs) can have numerous neurologic and cognitive sequelae. The road to recovery can be long and arduous for many patients. Improving cognition can assist in a shorter recovery time as patients may be more in tune with their plan of care. Family physicians may be helpful in assisting with the recovery process post-hospital discharge. This case report seeks to educate family physicians on the use of methylphenidate in the ambulatory setting after TBI. Here, a case of a 51-year-old man on methylphenidate after a traumatic brain injury is presented.
PubMed: 38186797
DOI: 10.4103/jfmpc.jfmpc_326_23 -
The International Journal of... Jan 2024The catecholaminergic system influences response inhibition, but the magnitude of the impact of catecholaminergic manipulation is heterogeneous. Theoretical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The catecholaminergic system influences response inhibition, but the magnitude of the impact of catecholaminergic manipulation is heterogeneous. Theoretical considerations suggest that the voluntary modulability of theta band activity can explain this variance. The study aimed to investigate to what extent interindividual differences in catecholaminergic effects on response inhibition depend on voluntary theta band activity modulation.
METHODS
A total of 67 healthy adults were tested in a randomized, double-blind, cross-over study design. At each appointment, they received a single dose of methylphenidate or placebo and performed a Go/Nogo task with stimuli of varying complexity. Before the first appointment, the individual's ability to modulate theta band activity was measured. Recorded EEG data were analyzed using temporal decomposition and multivariate pattern analysis.
RESULTS
Methylphenidate effects and voluntary modulability of theta band activity showed an interactive effect on the false alarm rates of the different Nogo conditions. The multivariate pattern analysis revealed that methylphenidate effects interacted with voluntary modulability of theta band activity at a stimulus processing level, whereas during response selection methylphenidate effects interacted with the complexity of the Nogo condition.
CONCLUSIONS
The findings reveal that the individual's theta band modulability affects the responsiveness of an individual's catecholaminergic system to pharmacological modulation. Thus, the impact of pharmacological manipulation of the catecholaminergic system on cognitive control most likely depends on the existing ability to self-modulate relevant brain oscillatory patterns underlying the cognitive processes being targeted by pharmacological modulations.
Topics: Adult; Humans; Cross-Over Studies; Methylphenidate; Brain; Multivariate Analysis; Cognition; Electroencephalography
PubMed: 38181228
DOI: 10.1093/ijnp/pyae003 -
Trials Jan 2024Attention-deficit hyperactivity disorder (ADHD) is characterized by difficulty paying attention, poor impulse control, and hyperactive behavior. It is associated with...
Protocol of a monocentric, double-blind, randomized, superiority, controlled trial evaluating the effect of in-prison OROS-methylphenidate vs. placebo treatment in detained people with attention-deficit hyperactivity disorder (BATIR).
BACKGROUND
Attention-deficit hyperactivity disorder (ADHD) is characterized by difficulty paying attention, poor impulse control, and hyperactive behavior. It is associated with several adverse health and social outcomes and leads to an increased risk of criminality and recidivism. Worldwide, ADHD is thus highly prevalent in prisons. However, ADHD treatment has been neglected in such environments. Stimulant medications such as osmotic-release oral system methylphenidate (OROS-MPH) are first-line treatments in the general population, but they are under-prescribed in prisons due to concerns about abuse, even though such claims are not empirically supported. This project aims to compare the efficacy of a 3-month in-prison OROS-MPH vs. placebo treatment on the severity of core ADHD symptoms and relevant in- and post-prison outcomes.
METHODS
This study is a phase III, double-blinded, randomized, superiority, controlled trial of OROS-MPH vs. placebo. After randomization, the participants will receive 3 months of treatment with OROS-MPH or placebo (1:1 ratio) while incarcerated. Upon release, all participants will be offered the treatment (OROS-MPH) for 1 year but will remain blinded to their initial study group. The study will be conducted at the Division of Prison Health, Geneva, Switzerland, among incarcerated men (n = 150). Measures will include (1) investigator-rated ADHD symptoms, (2) acute events collected by the medical and prison teams, (3) assessment of the risk of recidivism, (4) medication side effects, (5) medication adherence, (6) study retention, (7) health care/prison costs, and (8) 1-year recidivism. Analyses will include bivariable and multivariable modeling (e.g., regression models, mixed-effects models, survival analyses) and an economic evaluation (cost-benefit analysis).
DISCUSSION
We expect that early identification and treatment of ADHD in prison will be an important public health opportunity and a cost-effective approach that is likely to reduce the vulnerability of incarcerated individuals and promote pathways out of criminal involvement. The study will also promote standards of care for people with ADHD in prison and provide recommendations for continuity of care after release.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05842330 . Registered on June 5, 2023. Kofam.ch SNCTP000005388. Registered on July 17, 2023.
Topics: Male; Humans; Methylphenidate; Attention Deficit Disorder with Hyperactivity; Prisons; Central Nervous System Stimulants; Delayed-Action Preparations; Treatment Outcome; Double-Blind Method; Randomized Controlled Trials as Topic; Clinical Trials, Phase III as Topic
PubMed: 38178233
DOI: 10.1186/s13063-023-07827-7