Neurobiological Dysfunctional Substrates for the Self-Medication Hypothesis in Adult Individuals with Attention-Deficit Hyperactivity Disorder and Cocaine Use Disorder: A Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography Study.

Objectives: Attention-deficit hyperactivity disorder (ADHD) in adulthood shows high co-occurrence rates with cocaine use disorder (CoUD). The self-medication hypothesis (SMH) provides a theoretical explanation for this comorbidity. This study investigates the neurobiological mechanisms that could support SMH in adult patients with attention-deficit hyperactivity disorder with cocaine use disorder (ADHD-CoUD). Materials and Methods: We included 19 ADHD-CoUD patients (84.2% male; age: 32.11 years [7.18]) and 16 CoUD patients (68.7% male; age: 36.63 years [8.12]). All subjects underwent a fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) brain scan. We tested brain metabolism differences between ADHD-CoUD and CoUD patients using voxel-based and regions of interest (ROIs)-based analyses. The correlation between dependence/abstinence duration and regional brain metabolism was also assessed in the two groups. Lastly, we investigated the integrity of brain metabolic connectivity of mesocorticolimbic and nigrostriatal dopaminergic systems, and large-scale brain networks involved in ADHD and addictions. Results: The voxel-wise and ROIs-based approaches showed that ADHD-CoUD patients had a lower metabolism in the thalamus and increased metabolism in the amygdala and parahippocampus, bilaterally, than CoUD subjects and healthy controls (HCs). Metabolism in the thalamus negatively correlated with years of dependence in ADHD-CoUD patients. Moreover, connectivity analyses revealed that ADHD-CoUD patients had a more preserved metabolic connectivity than CoUD patients in the dopaminergic networks and large-scale networks involved in self-regulation mechanisms of attention and behaviors (i.e., anterior default mode network [ADMN], executive network [ECN], and anterior salience network [aSAN]). Conclusions: We demonstrated distinct neuropathological substrates underlying substance-use behaviors in ADHD-CoUD and CoUD patients. Furthermore, we provided neurobiological evidence in support of SMH, demonstrating that ADHD-CoUD patients might experience short-term advantages of cocaine assumption (i.e., compensation of dopaminergic deficiency and related cognitive-behavioral deficits).

Gambling-Related Distortions and Problem Gambling in Adolescents: A Model to Explain Mechanisms and Develop Interventions.

Although a number of gambling preventive initiatives have been realized with adolescents, many of them have been developed in absence of a clear and explicitly described theoretical model. The present work was aimed to analyze the adequacy of a model to explain gambling behavior referring to gambling-related cognitive distortions (Study 1), and to verify the effectiveness of a preventive intervention developed on the basis of this model (Study 2). Following dual-process theories on cognitive functioning, in Study 1 we tested a model in which mindware gap, i.e., susceptibility to the gambler's fallacy, and contaminated mindware, i.e., superstitious thinking, were the antecedents of gambling-related cognitive distortions that, in turn, affect gambling frequency and problem gambling. Participants were 306 male adolescents (Mage = 17.2 years). A path analysis indicated that cognitive distortions have a mediating role in the relationship that links probabilistic reasoning fallacy and superstitious thinking with problem gambling. Following these findings, in Study 2 we developed a school-based intervention aimed to reduce gambling-related cognitive distortions acting on the above cited mindware problems. A pre- and post-test design - with a 6 months follow-up - was performed with 34 male adolescents (Mage = 16.8), randomly assigned to two groups (Training and No Training), and their baseline equivalence was verified. A Mixed 2 × 2 ANOVA attested a significant Time X Group interaction, indicating a significant reduction of the cognitive distortions from pre-test to post-test only in the Training group. The follow-up attested to the stability of the training effects and the reduction of gambling frequency over time. These findings suggest that prevention strategies should address mindware problems, which can be considered as predictors of gambling-related cognitive distortions.

Genetic study of Sardinian patients with Alzheimer's disease.

We describe the genetic analysis of an Alzheimer's disease (AD) sample derived from a genetically isolated population. Genetic assessment included the analysis of genes involved in AD, such as the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). We also assessed genes for some proteins that constitute the gamma-secretase complex: nicastrin (NCSTN), presenilin enhancer-2 (PEN2), in addition to the AD risk factor apolipoprotein E (APOE). Using polymerase chain reaction and single strand conformational polymorphism method, screens for APP, PSEN1 and PSEN2 genes revealed one mutation in PSEN1. Furthermore, we found an intronic +17G>C polymorphism in PEN2 which, in homozygous form, was greater in early onset Alzheimer's disease (EOAD) compared to controls, and one haplotype in the NCSTN gene which was linked to EOAD and familial AD (FAD). Finally, the genotyping of APOE confirmed that the varepsilon4 allele could be a risk factor for the onset of AD, in particular for FAD subjects. In conclusion, these results show the existence of Sardinian genetic peculiarities, essential in studies regarding genetically inherited and multifactorial disorders, as AD.