Dean Carson is Consulting Assistant Professor in the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine and Director of Scientific and Clinical Operations at Trigemina, Inc. He received his PhD in neuropharmacology from the University of Sydney, Australia and completed postdoctoral training in pediatric psychopharmacology at Stanford University. He has over 10 years experience in CNS drug development and his research expertise includes the use of preclinical behavioral and neurobiological models to identify novel drug targets for a broad range of CNS indications (autism, anxiety, addiction, pain). He is also highly experienced in regulatory affairs, clinical trial protocol design, and clinical operations for Phase I and II clinical trials in both pediatric and adult CNS indications. With over 20 peer-reviewed scientific articles in high impact journals, published abstracts, and book chapters he has a strong international reputation for conducting innovative translational research.
Honors & Awards
Bass Pediatric Scholar, Lucile Packard Children's Hospital (2014-2015)
Meixner Translational Science Postdoctoral Fellowship, Autism Speaks (2012-2014)
Dean of Medicine's Postdoctoral Fellowship, Stanford University School of Medicine (2012)
Mosbacher Postdoctoral Fellowship, Autism Center, Stanford University (2011)
Biomedical Postgraduate Research Scholarship, National Health & Medical Research Council, Australia (2010-2011)
Royston George Booker Scholarship, University of Sydney, Australia (2009)
PHD, University of Sydney, Australia, Neuropharmacology (2012)
BSc, University of New South Wales, Australia, Psychology/Behavioral Neuroscience (2007)
Dean Carson. "United States Patent 2482835 THERAPY AND PREVENTION OF PROBLEM DRINKING", Iain Stewart Mcgregor, Dean Samuel Carson, Adam John Guastella, Michael Thomas Bowen, Aug 8, 0175
- Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism PLOS ONE 2015; 10 (7)
Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism.
2015; 10 (7)
Brain arginine vasopressin (AVP) critically regulates normative social behavior in mammals, and experimental disruption of the AVP signaling pathway produces social impairments in rodent models. We therefore hypothesized that AVP signaling deficits may contribute to social impairments in children with autism spectrum disorder (ASD). Since blood measures (which are far easier to obtain than brain measures) of AVP are most meaningful if they are related to brain AVP activity, Study 1 tested the relationship between AVP concentrations in concomitantly collected blood and CSF samples from children and adults (N = 28) undergoing clinical procedures. Study 2 tested whether blood AVP concentrations: 1) differed between children with ASD (N = 57), their ASD discordant siblings (N = 47), and neurotypical controls (N = 55); and 2) predicted social functioning (using the NEPSY-II Theory of Mind and Affect Recognition tasks and the Social Responsiveness Scale) in this large, well-characterized child cohort. Blood AVP concentrations significantly and positively predicted CSF AVP concentrations (F1,26 = 7.17, r = 0.46, p = 0.0127) in Study 1. In Study 2, blood AVP concentrations did not differ between groups or by sex, but significantly and positively predicted Theory of Mind performance, specifically in children with ASD, but not in non-ASD children (F1,144 = 5.83, p = 0.017). Blood AVP concentrations can be used: 1) as a surrogate for brain AVP activity in humans; and 2) as a robust biomarker of theory of mind ability in children with ASD. These findings also suggest that AVP biology may be a promising therapeutic target by which to improve social cognition in individuals with ASD.
View details for DOI 10.1371/journal.pone.0132224
View details for PubMedID 26200852
- Plasma vasopressin concentrations positively predict cerebrospinal fluid vasopressin concentrations in human neonates PEPTIDES 2014; 61: 12-16
Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2014; 111 (33): 12258-12263
The neuropeptide oxytocin (OXT) and its receptor (OXTR) regulate social functioning in animals and humans. Initial clinical research suggests that dysregulated plasma OXT concentrations and/or OXTR SNPs may be biomarkers of social impairments in autism spectrum disorder (ASD). We do not know, however, whether OXT dysregulation is unique to ASD or whether OXT biology influences social functioning more generally, thus contributing to, but not causing, ASD phenotypes. To distinguish between these possibilities, we tested in a child ASD cohort, which included unaffected siblings and unrelated neurotypical controls (ages 3-12 y; n = 193), whether plasma OXT concentrations and OXTR SNPs (i) interact to produce ASD phenotypes, (ii) exert differential phenotypic effects in ASD vs. non-ASD children, or (iii) have similar phenotypic effects independent of disease status. In the largest cohort tested to date, we found no evidence to support the OXT deficit hypothesis of ASD. Rather, OXT concentrations strongly and positively predicted theory of mind and social communication performance in all groups. Furthermore, OXT concentrations showed significant heritability between ASD-discordant siblings (h(2) = 85.5%); a heritability estimate on par with that of height in humans. Finally, carriers of the "G" allele of rs53576 showed impaired affect recognition performance and carriers of the "A" allele of rs2254298 exhibited greater global social impairments in all groups. These findings indicate that OXT biology is not uniquely associated with ASD, but instead exerts independent, additive, and highly heritable influences on individual differences in human social functioning, including the severe social impairments which characterize ASD.
View details for DOI 10.1073/pnas.1402236111
View details for Web of Science ID 000340438800080
View details for PubMedID 25092315
Plasma oxytocin concentrations are lower in depressed vs. healthy control women and are independent of cortisol
JOURNAL OF PSYCHIATRIC RESEARCH
2014; 51: 30-36
The neuropeptide oxytocin (OT) promotes social behavior and attenuates stress responsivity in mammals. Recent clinical evidence suggests OT concentrations may be dysregulated in major depression. This study extends previous research by testing whether: 1) OT concentrations vary systematically in depressive disorders with and without hypercortisolemia, 2) gender differences in OT concentrations are observed in depressed vs. healthy control participants, and 3) OT concentrations are predictive of clinical phenotypes. Plasma OT concentrations of psychotic major depressive (PMD; n = 14: 10 female, 4 male), non-psychotic major depressive (NPMD; n = 17: 12 female, 5 male), and non-depressed, healthy control (n = 19: 11 female, 8 male) participants were assayed at 2000, 2400, 0400, and 0800 h. Plasma cortisol concentrations were quantified at 2300 h, and clinical phenotypes were determined. As expected, PMD participants, compared to NPMD and healthy control participants, showed higher plasma cortisol concentrations. Although both depressed groups showed similar OT concentrations, a significant interaction effect between group and gender was observed. Specifically, depressed females exhibited lower mean OT concentrations than depressed males. Further, depressed vs. healthy control female participants exhibited lower mean OT concentrations, whereas depressed vs. healthy control male participants showed a trend in the opposite direction. OT concentrations were also predictive of desirability, drug dependence, and compulsivity scores as measured by the Million Clinical Multiaxial Inventory-III. All findings were independent of cortisol. These data suggest that OT signaling may provide a mechanism by which to better understand female-biased risk to develop depressive disorders and that plasma OT concentrations may be a useful biomarker of certain clinical phenotypes.
View details for DOI 10.1016/j.jpsychires.2013.12.012
View details for Web of Science ID 000332909500004
View details for PubMedID 24405552
Lithium carbonate in the management of cannabis withdrawal: a randomized placebo-controlled trial in an inpatient setting.
Preclinical studies suggest that lithium carbonate (lithium) can reduce precipitated cannabinoid withdrawal in rats by stimulating release of the neuropeptide oxytocin, while two open-label studies indicate lithium may ameliorate cannabis withdrawal symptoms in humans.This study was conducted to examine the efficacy and safety of lithium in the inpatient management of cannabis withdrawal and to determine whether lithium affects plasma oxytocin and the rate of elimination of plasma cannabinoids during abstinence.Treatment-seeking cannabis-dependent adults (n = 38) were admitted for 8 days to an inpatient withdrawal unit and randomized to either oral lithium (500 mg) or placebo given twice a day under double-blind randomized controlled trial (RCT) conditions. Primary outcomes included withdrawal severity [cannabis withdrawal scale (CWS)], rates of detoxification completion, and adverse events. Plasma cannabinoids, plasma oxytocin and serum lithium levels were measured repeatedly over admission. Follow-up research interviews were conducted at 14, 30, and 90 days postdischarge.Lithium did not significantly affect total CWS scores relative to placebo, although it significantly reduced individual symptoms of "loss of appetite," "stomach aches," and "nightmares/strange dreams." No significant group differences were found in treatment retention or adverse events. Lithium did not increase plasma oxytocin levels nor influence the rate of elimination of cannabinoids. Both placebo- and lithium-treated participants showed reduced levels of cannabis use (verified by urinalysis) and improved health and psychosocial outcomes at 30- and 90-day follow-up relative to pretreatment baselines.Despite the strong rationale for the present study, the efficacy of lithium over placebo in the management of cannabis withdrawal was not demonstrated.
View details for DOI 10.1007/s00213-014-3611-5
View details for PubMedID 24880749
Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children.
The neuropeptide oxytocin (OXT) exerts anxiolytic and prosocial effects in the central nervous system of rodents. A number of recent studies have attempted to translate these findings by investigating the relationships between peripheral (e.g., blood, urinary and salivary) OXT concentrations and behavioral functioning in humans. Although peripheral samples are easy to obtain in humans, whether peripheral OXT measures are functionally related to central OXT activity remains unclear. To investigate a possible relationship, we quantified OXT concentrations in concomitantly collected cerebrospinal fluid (CSF) and blood samples from child and adult patients undergoing clinically indicated lumbar punctures or other CSF-related procedures. Anxiety scores were obtained in a subset of child participants whose parents completed psychometric assessments. Findings from this study indicate that plasma OXT concentrations significantly and positively predict CSF OXT concentrations (r=0.56, P=0.0064, N=27). Moreover, both plasma (r=-0.92, P=0.0262, N=10) and CSF (r=-0.91, P=0.0335, N=10) OXT concentrations significantly and negatively predicted trait anxiety scores, consistent with the preclinical literature. Importantly, plasma OXT concentrations significantly and positively (r=0.96, P=0.0115, N=10) predicted CSF OXT concentrations in the subset of child participants who provided behavioral data. This study provides the first empirical support for the use of blood measures of OXT as a surrogate for central OXT activity, validated in the context of behavioral functioning. These preliminary findings also suggest that impaired OXT signaling may be a biomarker of anxiety in humans, and a potential target for therapeutic development in individuals with anxiety disorders.Molecular Psychiatry advance online publication, 4 November 2014; doi:10.1038/mp.2014.132.
View details for DOI 10.1038/mp.2014.132
View details for PubMedID 25349162
- Oxytocin treatment for amphetamine-induced social impairments. The Journal of neuroscience : the official journal of the Society for Neuroscience 2014; 34 (44): 14503-5
- Commentary on Heinzerling et al. (2014): A growing methamphetamine dependence therapeutics graveyard. Addiction (Abingdon, England) 2014; 109 (11): 1887-8
A brief history of oxytocin and its role in modulating psychostimulant effects
JOURNAL OF PSYCHOPHARMACOLOGY
2013; 27 (3): 231-247
Over the past century, the polypeptide oxytocin has played an important role in medicine with major highlights including the identification of its involvement in parturition and the milk let-down reflex. Oxytocin is now implicated in an extensive range of psychological phenomena including reward and memory processes and has been investigated as a treatment for several psychiatric disorders including addiction, anxiety, autism, and schizophrenia. In this review, we first provide an historical overview of oxytocin and describe key aspects of its physiological activity. We then outline some pharmacological limitations in this field of research before highlighting the role of oxytocin in a wide range of behavioral and neuronal processes. Finally, we review evidence for a modulatory role of oxytocin with regard to psychostimulant effects. Key findings suggest that oxytocin attenuates a broad number of cocaine and methamphetamine induced behaviors and associated neuronal activity in rodents. Evidence also outlines a role for oxytocin in the prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in both rodents and humans. Clinical trials should now investigate the effectiveness of oxytocin as a novel intervention for psychostimulant addiction and should aim to determine its specific role in the therapeutic properties of MDMA that are currently being investigated.
View details for DOI 10.1177/0269881112473788
View details for Web of Science ID 000316907400001
View details for PubMedID 23348754
Preliminary Evidence for Lowered Basal Cortisol in a Naturalistic Sample of Methamphetamine Polydrug Users
EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY
2012; 20 (6): 497-503
The effects of chronic methamphetamine use on neuroendocrine functioning in humans are largely undocumented. Here we assessed basal plasma oxytocin, arginine vasopressin, and cortisol levels in a naturalistic sample of methamphetamine polydrug users (n = 12) compared with controls matched for age, gender, education, occupation status, and marital status (n = 17). All of the methamphetamine users tested positive for blood methamphetamine and/or its main metabolite, amphetamine. Other drugs of abuse were detected in a small number of methamphetamine users (MDMA [3,4-methylenedioxy-N-methylamphetamine; n = 2], THC [delta-9-tetrahydrocannabinol; n = 2]). Almost half of the methamphetamine users reported using methamphetamine intravenously, and others smoked or ingested the drug. Methamphetamine users had significantly lower basal plasma cortisol (p = .025), but similar basal plasma oxytocin and arginine vasopressin levels compared with controls. Basal plasma oxytocin was positively correlated (p = .011), with basal plasma arginine vasopressin in controls, but not in methamphetamine users. Methamphetamine users reported higher rates of psychiatric symptoms including substance use disorders, impulsivity, and positive, negative, manic, and disorientation symptoms compared with controls. Psychiatric symptoms were not related to neuroendocrine functioning in either group. These results provide preliminary evidence for lowered basal cortisol levels in methamphetamine polydrug users and encourage further research in to the effects of methamphetamine on neuroendocrine functioning in humans using more highly controlled experimental research designs.
View details for DOI 10.1037/a0029976
View details for Web of Science ID 000312170700008
View details for PubMedID 23066858
Adolescent Oxytocin Exposure Causes Persistent Reductions in Anxiety and Alcohol Consumption and Enhances Sociability in Rats
2011; 6 (11)
Previous studies have suggested that administration of oxytocin (OT) can have modulatory effects on social and anxiety-like behavior in mammals that may endure beyond the time of acute OT administration. The current study examined whether repeated administration of OT to male Wistar rats (n?=?48) during a key developmental epoch (early adolescence) altered their physiology and behavior in later-life. Group housed rats were given intraperitoneal injections of either 1 mg/kg OT or vehicle during early adolescence (post natal-days [PND] 33-42). OT treatment caused a transient inhibition of body weight gain that recovered quickly after the cessation of treatment. At PND 50, the rats pre-treated with OT displayed less anxiety-like behavior on the emergence test, while at PND 55 they showed greater levels of social interaction. A subgroup of OT pre-treated rats examined at PND 63 showed a strong trend towards increased plasma OT levels, and also displayed significantly increased OT receptor mRNA in the hypothalamus. Rats pre-treated with OT and their controls showed similar induction of beer intake in daily 70 min test sessions (PND 63 onwards) in which the alcohol concentration of beer was gradually increased across days from 0.44% to 4.44%. However, when given ad libitum access to beer in their home cages from PND 72 onwards (early adulthood), consumption of beer but not water was significantly less in the OT pre-treated rats. A "booster" shot of OT (1 mg/kg) given after 25 days of ad libitum access to beer had a strong acute inhibitory effect on beer intake without affecting water intake. Overall these results suggest that exogenous OT administered during adolescence can have subtle yet enduring effects on anxiety, sociability and the motivation to consume alcohol. Such effects may reflect the inherent neuroplasticity of brain OT systems and a feed-forward effect whereby exogenous OT upregulates endogenous OT systems.
View details for DOI 10.1371/journal.pone.0027237
View details for Web of Science ID 000297555400028
View details for PubMedID 22110618
Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus
2010; 15 (4): 448-463
Recent preclinical evidence indicates that the neuropeptide oxytocin may have potential in the treatment of drug dependence and drug withdrawal. Oxytocin reduces methamphetamine self-administration, conditioned place preference and hyperactivity in rodents. However, it is unclear how oxytocin acts in the brain to produce such effects. The present study examined how patterns of neural activation produced by methamphetamine were modified by co-administered oxytocin. Male Sprague-Dawley rats were pretreated with either 2 mg/kg oxytocin (IP) or saline and then injected with either 2 mg/kg methamphetamine (IP) or saline. After injection, locomotor activity was measured for 80 minutes prior to perfusion. As in previous studies, co-administered oxytocin significantly reduced methamphetamine-induced behaviors. Strikingly, oxytocin significantly reduced methamphetamine-induced Fos expression in two regions of the basal ganglia: the subthalamic nucleus and the nucleus accumbens core. The subthalamic nucleus is of particular interest given emerging evidence for this structure in compulsive, addiction-relevant behaviors. When administered alone, oxytocin increased Fos expression in several regions, most notably in the oxytocin-synthesizing neurons of the supraoptic nucleus and paraventricular nucleus of the hypothalamus. This provides new evidence for central actions of peripheral oxytocin and suggests a self-stimulation effect of exogenous oxytocin on its own hypothalamic circuitry. Overall, these results give further insight into the way in which oxytocin might moderate compulsive behaviors and demonstrate the capacity of peripherally administered oxytocin to induce widespread central effects.
View details for DOI 10.1111/j.1369-1600.2010.00247.x
View details for Web of Science ID 000282634400008
View details for PubMedID 20731630
Intranasal Arginine Vasopressin Enhances the Encoding of Happy and Angry Faces in Humans
2010; 67 (12): 1220-1222
Arginine vasopressin (AVP) has a complex but crucial role in social behavior. In nonhuman mammals it facilitates social recognition and bonding while also promoting defensive, aggressive, and territorial behaviors. There has been little research in humans exploring its effect on social cognition, including the encoding of social memories.In a double-blind, randomized, placebo-controlled, between-subject design, we administered AVP (20 IU) or a placebo intranasally to 48 healthy human male volunteers and then presented 54 happy, angry, or neutral human faces. Participants returned the following day to make "remember", "know", or "new" judgments for a mix of 108 new and previously seen faces.Participants who were administered AVP were more likely to make know judgments for previously seen happy and angry faces in comparison with neutral human faces. Arginine vasopressin did not influence judgments for faces that had not been presented previously.Administration of AVP to male humans enhances the encoding of both happy and angry social information to make this more memorable. Results suggest that AVP could facilitate both bonding and aggressive related behaviors in humans by enhancing the encoding of positive and negative social cues within everyday interactions.
View details for DOI 10.1016/j.biopsych.2010.03.014
View details for Web of Science ID 000279205800016
View details for PubMedID 20447617
Oxytocin decreases methamphetamine self-ad ministration, methamphetamine hyperactivity, and relapse to methamphetamine-seeking behaviour in rats
2010; 58 (1): 38-43
There is emerging evidence that the neuropeptide oxytocin may be utilised as a treatment for various psychopathologies, including drug addictions. Here we used an animal model to assess whether oxytocin might be effective in the treatment of methamphetamine addiction. Sprague-Dawley rats were trained to lever press to intravenously self-administer methamphetamine under a progressive ratio schedule of reinforcement. Once responding had stabilised, one group of rats received escalating doses of oxytocin (0.001, 0.01, 0.1, 0.3, 1 mg/kg) administered intraperitoneally (IP) prior to daily self-administration tests, while other rats received vehicle. After these tests, lever-pressing was extinguished and the ability of methamphetamine primes (IP, 1 mg/kg) to reinstate responding was studied with and without co-administration of oxytocin (IP, 0.3 and 1 mg/kg). Results showed that oxytocin dose-dependently reduced responding for intravenous methamphetamine with an almost complete absence of responding at the highest oxytocin dose (1 mg/kg). Hyperactivity during methamphetamine self-administration was also dose-dependently reduced by oxytocin. Oxytocin (1 but not 0.3 mg/kg) also reduced the ability of methamphetamine to reinstate methamphetamine-seeking behaviour. In separate tests, oxytocin (IP, 0.3 and 1 mg/kg) robustly decreased the hyperactivity and rearing induced by methamphetamine challenge (IP, 1 mg/kg), producing activity levels similar to control animals. This study suggests that oxytocin may have a powerful inhibitory effect on the motivation to consume methamphetamine and on hyperactivity associated with acute methamphetamine intoxication. These results point to the potential utility of human trials of oxytocin as a therapeutic treatment for methamphetamine addiction.
View details for DOI 10.1016/j.neuropharm.2009.06.018
View details for Web of Science ID 000273051700006
View details for PubMedID 19560473
A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder
2009; 34 (6): 917-923
In humans, oxytocin nasal administration reduces social-threat perception and improves processes involved in communication and the encoding of positive social cues. The aim of this study was to determine whether oxytocin given as an adjunct to exposure therapy improves treatment for social anxiety disorder (SAD) as indicated by a comprehensive set of symptom outcome measures. In a randomized, double-blind, placebo-controlled trial, we administered 24 IU of oxytocin or a placebo in combination with exposure therapy to twenty-five participants who met primary diagnosis for SAD. Participants administered with oxytocin showed improved positive evaluations of appearance and speech performance as exposure treatment sessions progressed. These effects did not generalize to improve overall treatment outcome from exposure therapy. Participants who received oxytocin or placebo reported similar levels of symptom reduction following treatment across symptom severity, dysfunctional cognition, and life-impairment measures. This study shows that the administration of oxytocin improves mental representations of self, following exposure therapy. These effects may be either short term or situation specific. Future research is now needed to determine whether oxytocin can enhance treatment outcomes for SAD when used with greater frequency, with a wider variety of social learning experiences, and in conjunction with interventions that more specifically target change in broader dysfunctional cognitions.
View details for DOI 10.1016/j.psyneuen.2009.01.005
View details for Web of Science ID 000266398800014
View details for PubMedID 19246160
Does oxytocin influence the early detection of angry and happy faces?
2009; 34 (2): 220-225
Oxytocin has a crucial role in social behaviour, although its effects on social cognition are not fully understood. Past research shows that oxytocin enhances encoding and conceptual recognition of positive social stimuli over social-threat stimuli. In this study, we evaluated whether oxytocin modified responses to positive and threatening social stimuli at an earlier perceptual stage of processing using the visual search task. In a double-blind, randomized, placebo-controlled, between-subject design, oxytocin (24 IU) or a placebo was administered to 104 healthy volunteers. Participants returned to complete the visual search paradigm 45min later. Results showed that angry faces were detected more efficiently than happy faces. Participants also gazed longer and more frequently toward angry faces. Oxytocin did not, however, influence response time, accuracy, or gaze toward angry or happy faces, even when participants were separated into high- and low-social anxiety. The results of this study suggest that oxytocin may not influence the detection of positive and threatening social stimuli at early perceptual levels of processing. Oxytocin may have greater influence in altering the cognitive processing of social valence at more conceptual and elaborate levels of processing.
View details for DOI 10.1016/j.psyneuen.2008.09.001
View details for Web of Science ID 000263431300007
View details for PubMedID 18848401