la Fougère C, Krause J, Krause K-H, Josef Gildehaus F, Hacker M, Koch W et al. Value of 99mTc-TRODAT-1 SPECT to predict clinical response to methylphenidate treatment in adults with attention deficit hyperactivity disorder. Nucl Med Commun 27: 733-737
In a previous study, binding of Tc-TRODAT-1 to the dopamine transporter (DAT) was found to be higher in patients with attention deficit hyperactivity disorder (ADHD) as compared to healthy controls.
To determine whether the degree of Tc-TRODAT-1 binding to the striatal DAT may have a predictive role on the response to methylphenidate (MPH) in patients with ADHD.
Twenty-two adult patients suffering from ADHD underwent a brain SPECT scan with Tc-TRODAT-1. After the scan patients received MPH, individually medicated up to 60 mg.day. Severity of illness was estimated using the Clinical Global Impression (CGI-S) Scale before treatment. Ten weeks after the beginning of MPH treatment the improvement in global symptoms was rated by the Clinical Global Improvement Scale (CGI-I).
Before treatment 17/22 patients with ADHD presented with higher striatal DAT binding as compared to age-matched healthy controls (+23.8%; P<0.01). After treatment with MPH a significant improvement of ADHD symptoms was demonstrated by the CGI-I in 16 of these 17 patients (CGI-S before: 4.8; CGI-I after MPH: 1.9; P<0.01). Five patients showed reduced DAT binding prior to therapy (-14.4%; P=0.04); these patients did not respond to MPH therapy (CGI-S before: 4.5; CGI-I after MPH: 4.2; P=0.40).
Our findings suggest that ADHD patients with primarily elevated binding of Tc-TRODAT-1 to the striatal DAT responded better to therapy with MPH as compared to those with normal or low DAT binding. Consequently, our results - even if obtained on a small collective indicate that measurement of DAT may be an important prognostic predictor for therapy response to MPH.
"We observed no correlation between MPH efficacy and baseline characteristics such as ADHD-RS-IV, CBCL internalizing score, age, IQ, or sex, which is consistent with the outcomes reported for a previous event-related potential study (Hermens et al, 2005). Although other neuroimaging modalities have predicted the effects of MPH (An et al, 2013; Cho et al, 2007; Ilgin et al, 2001; la Fougere et al, 2006; Sangal et al, 2004; Schweitzer et al, 2003), we used NIRS because of its simplicity and safety, which are beneficial in a clinical setting. Because only NAÏVE were used to predict the effect of MPH, supplementary NIRS measurements may be applied in clinical situations in which a physician must decide whether a child should begin taking the medication. "
[Show abstract][Hide abstract] ABSTRACT: Although methylphenidate hydrochloride (MPH) is a first-line treatment for children with ADHD, the non-response rate is 30%. Our aim was to develop a supplementary neuroimaging biomarker for predicting the clinical effect of continuous MPH administration by using near-infrared spectroscopy (NIRS). After baseline assessment, we performed a double-blind, placebo-controlled, crossover trial with a single dose of MPH, followed by a prospective 4-to-8-week open-trial with continuous MPH administration, and an ancillary 1-year follow-up. Twenty-two drug-naïve and eight previously treated children with ADHD (NAÏVE and NON-NAÏVE) were compared with 20 healthy controls (HCs) who underwent multiple NIRS measurements without intervention. We tested whether NIRS signals at the baseline assessment or ΔNIRS (single dose of MPH minus baseline assessment) predict the CGI-S score after 4-to-8-week or 1-year MPH administration. The secondary outcomes were the effect of MPH on NIRS signals after single-dose, 4-8-week, and 1-year administration. ΔNIRS significantly predicted CGI-S after 4-to-8-week MPH administration. The leave-one-out classification algorithm had 81% accuracy using the NIRS signal. ΔNIRS also significantly predicted CGI-S scores after 1 year of MPH administration. For secondary analyses, NAÏVE exhibited significantly lower prefrontal activation than HCs at the baseline assessment, whereas NON-NAÏVE and HCs showed similar activation. A single dose of MPH significantly increased activation compared to the placebo in NAÏVE. After 4-to-8-week administration, and even after MPH washout following 1-year administration, NAÏVE demonstrated normalized prefrontal activation. Supplementary NIRS measurements may serve as an objective biomarker for clinical decisions and monitoring concerning continuous MPH treatment in children with ADHD.Neuropsychopharmacology accepted article preview online, 04 May 2015. doi:10.1038/npp.2015.128.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 05/2015; 40(12). DOI:10.1038/npp.2015.128 · 7.05 Impact Factor
"Krause et al. (2002) replicated increased DAT availability in non-smokers but not in smokers with ADHD. La Fougère et al. (2006) found higher striatal DAT availability in 17 out of 22 adult ADHD patients, but reduced striatal DAT availability in further five study participants who did not respond well to subsequent methylphenidate treatment. This led to the hypothesis that the subgroup of ADHD patients with low DAT activity may have a poor response to drug therapy (Krause et al., 2005). "
[Show abstract][Hide abstract] ABSTRACT: 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.
Psychiatry Research 02/2009; 171(2):120-8. DOI:10.1016/j.pscychresns.2008.01.002 · 2.47 Impact Factor
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