2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane and Attention-Deficit-Disorder-with-Hyperactivity

The aim was to analyze the characteristics and progression of cognitive dysfunction in non-demented idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with baseline olfactory function.. From a prospective polysomnography-confirmed iRBD cohort, 25 patients (16 patients in 2-year follow-up) and 13 normal controls were included. Initial and 2-year follow-up cognitive functions were analyzed with olfactory function and. Idiopathic RBD patients had impaired attention, memory and executive function compared to controls. Baseline cognitive tests were comparable between the iRBD subgroups with and without hyposmia.. Hyposmia may be a predictive sign of cognitive decline in iRBD patients.

Topics: Aged; Attention Deficit Disorder with Hyperactivity; Cognitive Dysfunction; Executive Function; Female; Follow-Up Studies; Humans; Male; Memory Disorders; Middle Aged; Neuropsychological Tests; Olfaction Disorders; Polysomnography; Predictive Value of Tests; Prospective Studies; Psychomotor Performance; REM Sleep Behavior Disorder; Tomography, Emission-Computed, Single-Photon; Tropanes

Methylphenidate (MPH) occupies brain striatal dopamine transporters (DATs) and is an effective treatment for attention deficit hyperactivity disorder (ADHD). However, patients with ADHD and comorbid cocaine dependence do not benefit significantly from treatment with MPH. To better understand the neurobiology of this phenomenon, we examined DAT availability and the effects of MPH treatment on DAT occupancy in ADHD patients with and without cocaine dependence. ADHD patients without a comorbid substance use disorder (N=16) and ADHD patients with comorbid cocaine dependence (N=8) were imaged at baseline and after two weeks MPH treatment using single photon emission computed tomography (SPECT) with the DAT tracer [(123)I]FP-CIT. Changes in ADHD symptoms were measured with the ADHD symptom rating scale (ASRS). At baseline, we observed lower striatal DAT availability in ADHD patients with cocaine dependence. Following fixed MPH treatment, MPH occupied significantly less striatal DATs in cocaine-dependent than in non-cocaine dependent ADHD patients. There were no significant correlations between baseline DAT availability or DAT occupancy by MPH and ADHD symptom improvement. However, we did find significant correlations between DAT occupancy by MPH and decreases in impulsivity scores and years of cocaine use. These preliminary findings suggest that low DAT occupancy is not the reason why ADHD patients with cocaine dependence do not benefit from MPH treatment. It also suggests that higher dosages of MPH in these patients are probably not the solution and that medications directed at other pharmacological targets should be considered in these comorbid ADHD patients. This trial is registered at the Dutch Trial Register, www.trialregister.nl, under Trial ID number NTR3127.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Brain; Central Nervous System Stimulants; Cocaine-Related Disorders; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Imaging, Three-Dimensional; Male; Methylphenidate; Middle Aged; Protein Binding; Psychiatric Status Rating Scales; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult

Impulsivity characterises various psychiatric disorders, particularly attention-deficit/hyperactivity disorder (ADHD). Evidence shows that ADHD symptoms are associated with dopamine dysfunction and alleviated with methylphenidate, a drug that reduces dopamine transporter availability. ADHD-like symptoms and impulsive traits are continuously distributed across the general population. Here, we aimed to investigate the dopaminergic basis of impulsivity and other ADHD-related traits in healthy individuals by studying the association of these traits with striatal dopamine transporter availability. Single-photon emission computed tomography with [(123)I] FP-CIT was performed on 38 healthy males. Impulsivity was measured using the Barratt Impulsiveness Scale (BIS) and hyperactivity-impulsivity and inattention using the Adult ADHD Self-Report Scale (ASRS). We found that greater dopamine transporter availability was associated with higher BIS impulsivity but not with ADHD-related traits. The association with BIS was significant after accounting for individual differences in age and neuroticism. These results suggest that individual differences in the dopamine system may be a neural correlate of trait impulsivity in healthy individuals.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Humans; Impulsive Behavior; Male; Psychiatric Status Rating Scales; Psychometrics; Regression Analysis; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult

The aim of this study was to provide in vivo evidence for the hypothesis that dopaminergic neurotransmission is altered in adult patients with attention-deficit/hyperactivity disorder (ADHD). We used high-resolution brain-dedicated single-photon emission computed tomography and the dopamine transporter (DAT) marker [(123)I]FP-CIT in 17 adult treatment-naïve ADHD patients and 14 age-matched controls. Magnetic resonance imaging-based region of interest analysis was performed to quantify the DAT availability (expressed as a ratio of specific to non-displaceable binding, V(3)'') in the striatum. Additionally, the specific radiotracer binding was assessed in the thalamus and the midbrain/brainstem regions (reflecting also the availability of the serotonin transporter to which [(123)I]FP-CIT binds with moderate affinity). In the striatal areas of the ADHD patients, a significantly reduced specific tracer binding was found (V(3)'': 5.18+/-0.98; controls 6.36+/-1.34). In contrast, the specific [(123)I]FP-CIT binding did not differ from controls in the thalamus and midbrain/brainstem areas. These data indicate a reduced dopaminergic but not serotonergic transmitter reuptake function in adult ADHD. Further studies will have to deal with the question of whether these findings have the potential to influence treatment decisions in this complex disorder.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Brain; Brain Stem; Caudate Nucleus; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Mesencephalon; Occipital Lobe; Putamen; Serotonin Plasma Membrane Transport Proteins; Synaptic Transmission; Thalamus; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult