Neuroimaging in Psychiatric Pharmacogenetics Research: The Promise and Pitfalls.

Neuroimaging in Psychiatric Pharmacogenetics Research: The Promise and Pitfalls.

Neuropsychopharmacology. 2013 Jun 24;
Falcone M, Smith RM, Chenoweth MJ, Kumar Bhattacharjee A, Kelsoe JR, Tyndale RF, Lerman C

The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype x drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment.Neuropsychopharmacology accepted article preview online, 24 June 2013; doi:10.1038/npp.2013.152. HubMed – addiction


Rimonabant precipitates anxiety in rats withdrawn from palatable food: role of the central amygdale.

Neuropsychopharmacology. 2013 Jun 24;
Blasio A, Iemolo A, Sabino V, Petrosino S, Steardo L, Rice KC, Orlando P, Arturo Iannotti F, Di Marzo V, Zorrilla EP, Cottone P

The anti-obesity medication rimonabant, an antagonist of cannabinoid type-1 (CB1) receptor, was withdrawn from the market because of adverse psychiatric side effects, including a negative affective state. We investigated whether rimonabant precipitates a negative emotional state in rats withdrawn from palatable food cycling. The effects of systemic administration of rimonabant on anxiety-like behavior, food intake, body weight, and adrenocortical activation were assessed in female rats during withdrawal from chronic palatable diet cycling. The levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and the CB1 receptor mRNA and the protein in the central nucleus of the amygdala (CeA) were also investigated. Finally, the effects of microinfusion of rimonabant in the CeA on anxiety-like behavior, and food intake were assessed. Systemic administration of rimonabant precipitated anxiety-like behavior and anorexia of the regular chow diet in rats withdrawn from palatable diet cycling, independently from the degree of adrenocortical activation. These behavioral observations were accompanied by increased 2-AG, CB1 receptor mRNA, and protein levels selectively in the CeA. Finally, rimonabant, microinfused directly into the CeA, precipitated anxiety-like behavior and anorexia. Our data shows that (i) the 2-AG-CB1 receptor system within the CeA is recruited during abstinence from palatable diet cycling as a compensatory mechanism to dampen anxiety, and (ii) rimonabant precipitates a negative emotional state by blocking the beneficial heightened 2-AG-CB1 receptor signaling in this brain area. These findings help elucidate the link between compulsive eating and anxiety, and it will be valuable to develop better pharmacological treatments for eating disorders and obesity.Neuropsychopharmacology accepted article preview online, 24 June 2013; doi:10.1038/npp.2013.153. HubMed – addiction


FACS analysis of neuronal-glial interactions in the nucleus accumbens following morphine administration.

Psychopharmacology (Berl). 2013 Jun 22;
Schwarz JM, Smith SH, Bilbo SD

Glia, including astrocytes and microglia, can profoundly modulate neuronal function and behavior; however, very little is known about the signaling molecules that govern neuronal-glial communication and in turn affect behavior. Morphine treatment activates microglia and astrocytes in the nucleus accumbens (NAcc) to induce the synthesis of cytokines and chemokines, and this has important implications for addictive behavior. Blocking morphine-induced glial activation using the nonspecific glial inhibitor, ibudilast, has no effect on the initial rewarding properties of morphine, but completely prevents the relapse of drug-seeking behavior months later.We sought to determine the cellular source of these cytokines and chemokines in the NAcc in response to morphine, and the cell-type-specific expression pattern of their receptors to determine whether neurons have the capacity to respond to these immune signals directly.We used fluorescence-activated cell sorting of neurons (Thy1+), astrocytes (GLT1+), and microglia (CD11b+) from the NAcc for the analysis of cell type specific gene expression following morphine or saline treatment.The results indicate that microglia and neurons each produce a subset of chemokines in response to morphine and that neurons have the capacity to respond directly to a select group of these chemokines via their receptors. In addition, we provide evidence that microglia are capable of responding directly to dopamine release in the NAcc.Future studies will examine the mechanism(s) by which neurons respond to these immune signals produced by microglia in an effort to understand their effect on addictive behaviors. HubMed – addiction


Can antipsychotic treatment contribute to drug addiction in schizophrenia?

Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jun 20;
Samaha AN

Individuals with schizophrenia are at very high risk for drug abuse and addiction. Patients with a coexisting drug problem fare worse than patients who do not use drugs, and are also more difficult to treat. Current hypotheses cannot adequately account for why patients with schizophrenia so often have a co-morbid drug problem. I present here a complementary hypothesis based on evidence showing that chronic exposure to antipsychotic medications can induce supersensitivity within the brain’s dopamine systems, and that this in turn can enhance the rewarding and incentive motivational effects of drugs and reward cues. At the neurobiological level, these effects of antipsychotics are potentially linked to antipsychotic-induced increases in the striatal levels of dopamine D2 receptors and D2 receptors in a high-affinity state for dopamine, particularly at postsynaptic sites. Antipsychotic-induced dopamine supersensitivity and enhanced reward function are not inevitable consequences of prolonged antipsychotic treatment. At least two parameters appear to promote these effects; the use of antipsychotics of the typical class, and continuous rather than intermittent antipsychotic exposure, such that silencing of dopaminergic neurotransmission via D2/3 receptors is unremitting. Thus, by inducing forms of neural plasticity that facilitate the ability of drugs and reward cues to gain control over behaviour, some currently used treatment strategies with typical antipsychotics might contribute to compulsive drug seeking and drug taking behaviours in vulnerable schizophrenia patients. HubMed – addiction


The Impact of Internet and PC Addiction In School Performance of Cypriot Adolescents.

Stud Health Technol Inform. 2013; 191: 90-94
Siomos K, Paradeisioti A, Hadjimarcou M, Mappouras DG, Kalakouta O, Avagianou P, Floros G

In this paper we present the results of a cross-sectional survey designed to ascertain Internet and personal computer (PC) addiction in the Republic of Cyprus. This is a follow-up to a pilot study conducted one year earlier. Data were collected from a representative sample of the adolescent student population of the first and fourth grades of high school. Total sample was 2684 students, 48.5% of them male and 51.5% female. Research material included extended demographics and an Internet security questionnaire, the Young’s Diagnostic questionnaire (YDQ), the Adolescent Computer Addiction Test (ACAT). Results indicated that the Cypriot population had comparable addiction statistics with other Greek-speaking populations in Greece; 15.3% of the students were classified as Internet addicted by their YDQ scores and 16.3% as PC addicted by their ACAT scores. Those results are among the highest in Europe. Our results were alarming and have led to the creation of an Internet and PC addiction prevention program which will focus on high-school professor training and the creation of appropriate prevention material for all high-schools, starting immediately after the conclusion of the pan-Cypriot survey, focusing especially on those areas where the frequency of addictive behaviors will be highest. HubMed – addiction



Eminem on drugs, addiction and rehab