Addiction, Author Interviews / 11.06.2018
Major Brain Networks With Altered Brain Function In Individuals with Addiction Identified
MedicalResearch.com Interview with:
Professor, Rita Z. Goldstein, PhD
Department of Psychiatry (primary)
and Department of Neuroscience, Friedman Brain Institute (secondary)
Chief, Neuropsychoimaging of Addiction and Related Conditions (NARC) Research Program
Anna Zilverstand PhD
Assistant Professor, Psychiatry
Icahn School of Medicine at Mount Sinai
The Leon and Norma Hess Center for Science and Medicine
New York, NY 10029
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In comparison to previous reviews that often focused on investigating select brain circuits, such as the reward network, our review is the first to systematically discuss all brain networks implicated in human drug addiction. Based on more than 100 neuroimaging studies published since 2010, we found that six major brain networks showed altered brain function in individuals with addiction. These brain circuits are involved in a person’s ability to select their actions (executive network), in directing someone’s attention (salience network), in adaptive learning of new behaviors (memory network), in the automatization of behaviors (habit network), in self-reflection (self-directed network) and the valuation of different options (reward network).
When individuals with addiction are confronted with pictures of drug taking, all of these networks become very highly engaged; however, when the same individuals are confronted with scenes depicting other people, their brains show a reduced reaction as compared to healthy individuals, indicating less involvement. Similarly, the brain of an addicted individual is less engaged when making decisions (that are not relevant to their drug taking) or when trying to inhibit impulsive actions. We further found that some impairments of brain functions, such as alterations underlying the difficulty to inhibit impulsive actions, seem to precede drug addiction, as we observe similar impairments in adolescents that later go on to abuse drugs. However, particularly the impairments in the executive network (involved in the ability to inhibit impulsive actions), the valuation network (which computes the value of an option) and the salience network (that directs attention towards events) seem to be getting worse with more severe drug use and also predict if someone is likely to relapse or not.
The good news is that we also found that it is possible to (partially) recover and normalize brain function in these networks through treatment. Importantly, the widespread alterations of brain function were independent of what drug an individual was addicted to (marijuana, alcohol, cigarettes, cocaine, methamphetamine, heroin, amongst others).
Naoto Tada Ueno, M.D., Ph.D., F.A.C.P.
Executive Director, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic
Section Chief, Section of Translational Breast Cancer Research, Department of Breast Medical Oncology
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The best outcome of inflammatory breast cancer (IBC) is dependent on achieving a pathological completed response after neoadjuvant chemotherapy for primary inflammatory breast cancer, which is the most aggressive type of breast cancer.
We have conducted extensive preclinical work, which showed that EGFR is a potential therapeutic targets of IBC.
Based on this preclinical data, we have conducted a phase II study to determine the pathological complete response rate of panitumumab plus neoadjuvant chemotherapy for HER2 negative primary inflammatory breast cancer. 
Ali Khashan, PhD
Senior Lecturer in Epidemiology
School of Public Health & INFANT Centre
University College Cork
Cork, Ireland
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: There is some evidence to suggest an increased likelihood of neurodevelopmental disorders in relation to hypertensive disorders in pregnancy, however consensus is lacking. Considering hypertensive disorders in pregnancy are among the most common prenatal complication, we decided to synthesise the published literature on this topic by conducting a comprehensive systematic review and meta-analysis.
Our main findings suggest that hypertensive disorders in pregnancy are associated with about 30% increase in the likelihood of autism spectrum disorders (ASD) and ADHD in the offspring, compared to offspring not exposed to hypertensive disorders in pregnancy.
Rebecca Ivy Hartman, M.D
Instructor in Dermatology
Brigham and Women's Hospital
Boston MA 02115
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Organ transplant recipients (OTR) are at 100-fold higher risk to develop certain skin cancers compared to the general population due to immunosuppression, and thus preventing skin cancer in this population is critical.
Our study found that in a high-risk Australian OTR population, only half of patients practiced multiple measures of sun protection regularly.
However, after participating in a research study that required dermatology visits, patients were over 4-times more likely to report using multiple measures of sun protection regularly. Patients were more likely to have a positive behavioral change if they did not already undergo annual skin cancer screening prior to study participation.
Dr. Ishida[/caption]
Dr. Julie H. Ishida MD
Department of Medicine, Division of Nephrology
University of California, San Francisco and
San Francisco Veterans Affairs Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Gabapentin and pregabalin are used for the management of symptoms such as neuropathic pain, itching, and restless leg syndrome in patients receiving hemodialysis. However, hemodialysis patients may be particularly vulnerable to adverse events related to these agents, which are cleared by the kidney, but there is limited data evaluating their risk in this population.
Gabapentin and pregabalin use were associated with risk for altered mental status, fall, and fracture, and in some cases, even at doses that would be considered safe for use in this population. 
Dr. Maggiolini[/caption]
Alfio Maggiolini, MD
Minotauro, Milan
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Antisocial behaviour is common during adolescence and it incurs significant costs both for society and for the young people themselves. Persistent antisocial behaviour places a heavy burden on the community, the justice system and the public health system. Responses to juvenile crime have always seen a tension between a focus on the understanding and the rehabilitation of the youth and the need to enforce discipline and public safety through punishment and threat.
The treatment of young offenders was traditionally deemed particularly difficult, and often ineffective. In recent years, therapeutic nihilism has given way to cautious optimism. While punitive-based approaches, at all levels, are hardly ever effective in the long term, the most popular and effective programs tend to focus on behaviour control. Common core elements of such programs include positive reinforcement, problem solving skills training and role playing, as behavioral problems are often assumed somewhat inherently wrong, or a “lack of something”, the programs aims at improving or changing.
The study presents a developmental approach that understands behavioral problems as the result of intentions, values and goals that need to be taken in full consideration and that are usually legitimate, even though carried out in ways that prove dysfunctional for both the young person and society. In other words, we consider antisocial behaviors as maladaptive responses to legitimate developmental tasks, a deviant way of meeting positive goals and taking control of one’s life. In the program we describe, a developmental understanding is combined with a psychoanalytically informed perspective on treatment and delivered in multi-modal terms. It has been carried out in Italy for the past 20 years, with positive outcomes, both in private practice and within the juvenile justice services. 
Mícheál de Barra, PhD
Lecturer in Psychology
Brunel University London
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Disgust has been called the "intuitive microbiologist" - it tracks the sources of infection in our environment. But so far, there has been little attempt to link the sources of disgust to the sources of infectious disease in a comprehensive way. So we developed a method for developing stimuli based on a random sample illness.
We basically asked ourselves what the kinds of cues that might be associated with that kind of disease risk and asked people to rate disgust responses. The main motive for this was to contribute to a debate in the literature about if there are "kinds of disgust" and if so, how many. I results were a little ambiguous there I'm afraid.
Dr. Ryerson[/caption]
Christopher J. Ryerson, M.D.
Assistant Professor
Centre for Heart Lung Innovation
University of British Columbia
Vancouver, Canada
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: A new Idiopathic pulmonary fibrosis (IPF) mortality analysis presented at the American Thoracic Society’s 2018 annual conference suggests that treatment with nintedanib may be associated with reduced risk of death in patients with the rare lung disease idiopathic pulmonary fibrosis (IPF).
Pooled data from the two Phase II INPULSIS trials and the Phase II TOMORROW study compared the number of deaths observed versus the number predicted based on GAP stage over one year. GAP stage is used to predict IPF prognosis and is based on gender, age and lung function (as measured by forced vital capacity [FVC] decline predicted and DLco % predicted). Higher stages of GAP are associated with an increased risk of death.
Across the population in the analysis (n=1,228), there were fewer deaths observed in each treatment group than predicted based on GAP stage at baseline (nintedanib: 42 vs. 89.9; placebo: 41 vs. 64.2). In the treated group, the number of observed deaths was 46.7% of the number predicted based on GAP stage, while in the placebo group the number of observed deaths was 63.9% of the number predicted. Based on these observations, the analysis suggests that nintedanib may be associated with a 26.8% relative reduction in the risk of death compared with placebo over one year. 
Dr. Jerusalem[/caption]
Dr. Guy Jerusalem, MD, PhD
CHU Sart Tilman Liege and Liege University
Liege, Belgium
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: BOLERO-6 was conducted to fulfill postapproval regulatory commitments to the FDA and EMA to estimate treatment benefit with EVE + EXE vs EVE alone or CAP for ER+, HER2− ABC that had progressed on an NSAI. Everolimus plus exemestane has not previously been compared with everolimus alone or capecitabine in a randomized setting.Data describing everolimus alone are limited to a single phase 2 study of just 19 patients. Thus, the FDA deemed it important to ascertain the efficacy of everolimus alone for ER+ breast cancer, and to determine the contribution of exemestane to combination therapy with everolimus. Capecitabine is often the first chemotherapeutic agent given for ER+ breast cancer that has progressed on anti-estrogen therapy. It has a reported PFS of 4.1–7.9 months among patients with HER2-negative advanced breast cancer. However, it has a different safety profile to everolimus or exemestane, and a comparison of endocrine-based combination therapy with single-agent chemotherapy was yet to be conducted.
The median PFS with EVE + EXE (8.4 months) was consistent with BOLERO-2 (7.8 months), and compared to EVE alone here (6.8 months) corresponded to an estimated 26% reduction of risk of disease progression or death (HR 0.74).
A numerical median PFS difference was observed for CAP over EVE + EXE (9.6 vs 8.4 months), which may be attributed to various baseline characteristics favoring CAP and potential informative censoring. The median PFS with capacitabine was longer than expected based on previous trials. Interpretation of the results of BOLERO-6 must consider the limited sample size and open-label design. 