Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [¹¹C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87±8.65) and 18 healthy male controls (age: 25.44±6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [¹¹C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [¹¹C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.     

Suicidality Over the First 5 Years of Psychosis: Does Extending Early Intervention Have Benefits?

Objective:We aimed to investigate whether individuals with first-episode psychosis (FEP) receiving extended early intervention (EI) were less likely to experience suicidal ideation and behaviors than those transferred to regular care after 2 years of EI. Another objective was to examine the 5-year course of suicidality in FEP.Methods:We conducted a secondary analysis of a randomized controlled trial where 220 patients were randomized after 2 years of EI to receive extended EI or regular care for the subsequent 3 years. Suicidality was rated using the Brief Psychiatric Rating Scale. Linear mixed model analysis was used to study time and group effects on suicidality.Results:Extended EI and regular care groups did not differ on suicidality. There was a small decrease in suicidality over time, F(7, 1038) = 1.84, P = 0.077, with an immediate sharp decline within a month of treatment, followed by stability over the remaining 5 years. Patients who endorsed suicidality at entry (46.6%) had higher baseline positive, negative, and depressive symptoms. The 5-year course fell in 3 groups: never endorsed suicidality (33.9%), endorsed suicidality at low-risk levels (43.1%), and endorsed high-risk levels (23.0%). The high-risk group had a higher proportion of affective versus nonaffective psychosis diagnosis; higher baseline positive and depressive symptoms; higher 5-year mean depression scores, and fewer weeks of positive symptom remission over the 5-year course.Conclusions:The first month of treatment is a critical period for suicide risk in FEP. Although early reductions in suicidality are often maintained, our findings make the case for sustained monitoring for suicide risk management.     

An Apical Mass of the Left Ventricle After a Myocardial Infarction: Imaging Contribution

Intramyocardial dissecting hematoma (IDH) is a rare complication of myocardial infarction (MI). It can affect the left ventricular free wall, the right ventricle, or the interventricular septum. We report a case of a 58-year-old man with an IDH following an acute anterior wall myocardial infarction detected by echocardiography and confirmed by Cardiac magnetic resonance (CMR).     

Association of methylenetetrahydrofolate reductase polymorphisms with susceptibility to Alzheimer's disease

Background

Genetic risk factors play an important role in the pathogenesis of Alzheimer's disease (AD). In this case-control study, we examined the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and their correlation with this pathology.

Objective

To verify the association between MTHFR C677T and A1298C polymorphisms and Alzheimer's disease.

Method

This work was conducted as a case–control study. Cases consisted of thirty-eight patients and 100 individuals without dementia constituted the control group. Genotyping of MTHFR polymorphisms was performed on patients and controls.

Result

Genetic analyses did not indicate a significant association between the MTHFR C677T mutation and AD (C/T: 63.15% versus 39%, p = 0.087). However, the genotype prevalence of the missense variant MTHFR A1298C was significantly different between patients and controls (A/C: 55% versus 7%, p < 10⁻³). Our data suggest an association between the MTHFR A1298C mutation and AD; however, the MTHFR C677T mutation did not contribute to susceptibility for AD.

Conclusion

The MTHFR A1298C polymorphism is a possible risk factor for Alzheimer's disease.     

High responsivity and 1/f noise of an ultraviolet photodetector based on Ni doped ZnO nanoparticles

This study involves the novel fabrication of a high responsivity, fast response, and low-cost (UV) photodetector (PD) based on ZnO/Ni nanoparticles deposited on a glass substrate. The ZnO/Ni nanoparticles were synthesized using a polyol process. The structure and the morphology of the samples were characterized by X-ray diffraction (XRD) and Transmission Electron Microscopy (TEM). Optical properties were measured using UV-visible, diffuse reflectance and photoluminescence (PL) spectroscopy. The photodetector exhibited high photoresponse characteristics under 375 nm laser excitation. Our device shows a high responsivity (121 A W⁻¹) with rise time (about 5.52 s) and fall time (about 12 s) at a bias voltage of 1 V. The device exhibits excellent reproducibility and stability characteristics with time. The noise spectra obtained from the UV photodetector were caused by the 1/f noise. The noise-equivalent power (NEP) is 1.08 × 10⁻⁹ W. Thus, the polyol process can be a useful and effective method for improving the performance of ZnO/Ni UV photodetectors.

This study involves the novel fabrication of a high responsivity, fast response, and low-cost (UV) photodetector (PD) based on ZnO/Ni nanoparticles deposited on a glass substrate.     

Molecular genetic analysis of Tunisian patients with a classic form of 21-hydroxylase deficiency: identification of four novel mutations and high prevalence of Q318X mutation

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders mainly due to defects in the steroid 21-hydroxylase (CYP21) gene. To determine the mutational spectrum in the Tunisian CAH population, the CYP21 active gene was analyzed in 51 unrelated patients using our cascade strategy (digestion by restriction enzyme, sequencing). All patients had a classical form of 21-hydroxylase deficiency. Mutations were detected in over 94% of the chromosomes examined. The most frequent mutation in the Tunisian CAH population was found to be Q318X, with large prevalence (35.3%), in contrast to 0.5-13.8% described in other series. Incidence of other mutations does not differ, as previously described: large deletions (19.6%), mutation in intron 2 (17.6%), and I172N (10.8%). Four novel mutations were found in four patients with the salt-wasting form. These four novel mutations include three point mutations that have not been reported to occur in the CYP21P pseudogene: R483W, W19X, 2669insC, and one small conversion of DNA sequence from exon 5 to exon 8. Our results have shown a good genotype/phenotype correlation in the case of most mutations. This is the first report of screening for mutations of 21-hydroxylase gene in the Tunisian population and even in the Arab population.