Genomic and Personalized Medicine Approaches for Substance Use Disorders (SUDs) Looking at Genome-Wide Association Studies.

Drug addiction, or substance use disorder (SUD), is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behaviour persist despite serious negative consequences. Drug abuse represents a problem that deserves great attention from a social point of view, and focuses on the importance of genetic studies to help in understanding the genetic basis of addiction and its medical treatment. Despite the complexity of drug addiction disorders, and the high number of environmental variables playing a role in the onset, recurrence, and duration of the symptoms, several studies have highlighted the non-negligible role of genetics, as demonstrated by heritability and genome-wide association studies. A correlation between the relative risk of addiction to specific substances and heritability has been recently observed, suggesting that neurobiological mechanisms may be, at least in part, inherited. All these observations point towards a scenario where the core neurobiological factors of addiction, involving the reward system, impulsivity, compulsivity, stress, and anxiety response, are transmitted, and therefore, genes and mutations underlying their variation might be detected. In the last few years, the development of new and more efficient sequencing technologies has paved the way for large-scale studies in searching for genetic and epigenetic factors affecting drug addiction disorders and their treatments. These studies have been crucial to pinpoint single nucleotide polymorphisms (SNPs) in genes that affect the reaction to medical treatments. This is critically important to identify pharmacogenomic approaches for substance use disorder, such as OPRM1 SNPs and methadone required doses for maintenance treatment (MMT). Nevertheless, despite the promising results obtained by genome-wide association and pharmacogenomic studies, specific studies related to population genetics diversity are lacking, undermining the overall applicability of the preliminary findings, and thus potentially affecting the portability and the accuracy of the genetic studies. In this review, focusing on cannabis, cocaine and heroin use, we report the state-of-the-art genomics and pharmacogenomics of SUDs, and the possible future perspectives related to medical treatment response in people that ask for assistance in solving drug-related problems.

Are IGF-I and IGF-BP3 useful for diagnosing growth hormone deficiency in children of short stature?

BACKGROUND: The diagnosis of growth hormone deficiency (GHD) is based on clinical and auxological characteristics combined with the results of growth hormone provocation tests. AIM: To evaluate the utility of IGF-I and IGF-BP3 serum levels in the diagnosis of GHD among children of short stature. SUBJECTS/METHODS: We recruited 207 short pre-pubertal children and divided them into two groups. One group consisted of 70 children (mean age 7.93 +/- 2.35 SD) with a growth hormone (GH) response on two provocative tests of < or = 8 ng/ml, while the other group contained 137 children (mean age 7.92 +/- 2.11 SD) with a peak GH value of > 8 ng/ml. Serum IGF-1 and IGF-BP3 levels were determined in the two groups. RESULTS: The difference in serum IGF-I between the two groups was not significant (p= 0.26), while the difference in IGF-BP3 between the two groups was statistically significant (p= 0.004). The performance of serum IGF-1 and IGF-BP3 as a diagnostic tool, expressed as AUC by ROC analyses, was quite low. CONCLUSION: Neither IGF-I nor IGF-BP3 are an adequate substitute for the stimulus test in the diagnosis of growth hormone deficiency among children of short stature.

Diagnosis of growth hormone deficiency by using the arginine provocative test: is it possible to shorten testing time without altering validity?

BACKGROUND: The arginine test is used for the diagnosis of growth hormone deficiency (GHD), but its duration is not uniform and varies from 180 to 90 min. SUBJECTS AND METHODS: To standardize this test, evaluating the possibility to shorten it to 90 min, we investigated the response of GH to the arginine test in 208 children evaluated for short stature (height less than -2 SD); 67 were diagnosed with idiopathic short stature (ISS) and 141 with GHD. We calculated the frequency distribution of the GH peaks to arginine in GHD and in ISS at various times and the percentage of GH peaks to arginine before and after 90 min in all and in ISS children. RESULTS: The GH peak distribution varied between 30 and 120 min, even though the vast majority of peaks occurred between 30 and 90 min. There was no significant difference (p > 0.05) in the peak distribution between ISS and GHD children. The percentages of GH peaks within 90 min were 95.2% in all children and 100% in ISS. CONCLUSION: The arginine test can be administered for only 90 min without significantly changing its validity, in order to reduce the discomfort of patients and the cost of the test.