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).

Response acceleration with mirtazapine augmentation of citalopram in obsessive-compulsive disorder patients without comorbid depression: a pilot study.

BACKGROUND: Therapeutic action of selective serotonin reuptake inhibitors (SSRIs) is delayed from 8 to 12 weeks in patients with obsessive-compulsive disorder (OCD). Several different agents have been tested to reduce the SSRI therapeutic latency time. Mirtazapine, an antagonist at alpha2-adrenoceptors, does not enhance serotonin (5-HT) neurotransmission directly but disinhibits the norepinephrine activation of 5-HT neurons and thereby increases 5-HT neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. The present study was undertaken to determine whether the mirtazapine-citalopram combination could induce an earlier and/or greater effect on the 5-HT system in OCD subjects than citalopram alone. METHOD: Forty-nine patients with OCD (DSM-IV) without comorbid depression were randomly assigned to a 2-tailed, single-blind, 12-week clinical trial with citalopram (20-80 mg/day) plus placebo or citalopram plus mirtazapine (15-30 mg/day). Assessments were performed weekly with the Yale-Brown Obsessive Compulsive Scale (YBOCS), the Hamilton Rating Scale for Depression, and the Clinical Global Impressions scale. Data were collected from November 2001 to July 2003. RESULTS: The citalopram plus mirtazapine group achieved a reduction of at least 35% in YBOCS score and a "much improved" or "very much improved" rating on the Clinical Global Impressions-Improvement scale from the fourth week, while the citalopram plus placebo group obtained these results only from the eighth week. The number of responders was higher in the citalopram plus mirtazapine group at the fourth week of treatment, while no difference between groups in the response rate was noted at the eighth and twelfth weeks of treatment. CONCLUSIONS: We found an earlier onset of response action in OCD symptoms and reduced undesired side effects when mirtazapine was added to citalopram. This augmentation strategy deserves clinical and research consideration through further double-blind, placebo-controlled studies.