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Increased cortical excitability in human MDMA users
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CPDD 77th Annual Meeting Abstracts (2015) / Drug and Alcohol Dependence 156 (2015) e2–e101
Sex differences in effects of trait impulsivity on vulnerability to substance dependence Ayca Coskunpinar 3,∗ , Jasmin Vassileva 2 , Eileen Martin 1 1
Psychiatry, Rush University Medical Center, Chicago, IL, United States 2 Virginia Commonwealth University, Richmond, VA, United States 3 Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States Aims: Trait level impulsivity is a core feature of addictive processes. Research with non-clinical populations suggests that different components of impulsivity are most prominent among men (sensation seeking: SS) and women (negative urgency: NU). This study investigated potential sex differences in the relationship between sensation seeking, negative urgency and substance use among 271 participants with substance use disorders (SUDs). Methods: 139 men and 132 women completed the UPPS-P Impulsive Behavior Scale as part of a larger study of sex differences in neurocognition and drug dependence. DSM-IV TR diagnoses were obtained using the SCID-Substance Abuse Module. All subjects were verified abstinent by toxicology screening. Results: As predicted, men scored significantly higher on the SS (p = .02) (Cohen’s d = 0.50) while NU scores were significantly higher for women (p < .001) (Cohen’s d = 0.3). Among women, higher NU scores were significantly associated with past alcohol dependence, p = .01. By contrast, higher SS scores were significantly associated with cocaine dependence among men, p = .004. These results were unchanged when controlling for depression. Conclusions: NU is an index of behavioral dyscontrol triggered by negative affect and SS is the tendency and openness to try new and exciting activities that vary in danger level. NU had a significant positive relationship with past alcohol dependence only for women and this effect could not be attributed to nonspecific effects of psychological distress, while SS was significantly associated with cocaine dependence, but only among men. These findings suggest that specific components of impulsivity interact with vulnerability to substance use disorders differently among men and women and that effective prevention and treatment strategies for alcohol and cocaine dependence may benefit from sex and substance specific tailoring. Financial support: Supported by the National Institute on Drug Abuse R01 DA12828. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.1053 Increased cortical excitability in human MDMA users Ronald Cowan 1,∗ , Mary Dietrich 1 , Joseph Kim 2 , David Zald 2 1 Psychiatric Neuroimaging Program, Vanderbilt University, Nashville, TN, United States 2 Psychology, Vanderbilt University, Nashville, TN, United States
Aims: MDMA produces serotonergic axon toxicity in animal models. Human recreational MDMA users have reduced serotonin in cortex. Serotonin is mainly inhibitory in cortex; therefore we posited that MDMA users would have increased cortical excitability. We measured cortical excitability using transcranial magnetic stimulation (TMS) in the primary visual and primary motor cortices of MDMA users and non-MDMA exposed control subjects.
Methods: We enrolled 16 MDMA users and 16 non-MDMA exposed control subjects (age was 22.3 ± 2.3 years). All were free from drug use for 2 weeks, verified by repeated urine drug screening. A T1-weighted structural MRI scan was obtained and the TMS coil was stereotactically positioned using each subject’s structural scan. We used a Magstim 2T Rapid stimulator (Magstim Company, UK) peak discharge = 1.8 kV; 70-mm figure-eight) to deliver cortical excitation. For visual cortex, we positioned the coil to allow evocation of the phosphene within 2◦ of the fovea; coil location was about 2 cm above the inion. Coil intensity was set at 90% intensity to yield a phosphene with eyes closed or motor twitch of the dorsal interosseous muscle of the right hand. TMS intensity was then reduced to 54% intensity and adjusted upward until the individual was able to detect the phosphene threshold or motor twitch generation on 75% of trials. Results: MDMA users had increased cortical excitability (as indexed by lower TMS stimulation thresholds). Mean TMS threshold for visual system was 66.67 ± 6.72% for MDMA users and 75.31 ± 10.56% for controls (p = 0.012). Mean TMS threshold for motor system was 63.43 ± 7.90% for MDMA users and 73.75 ± 8.06% for controls (p = 0.001). Greater lifetime MDMA use was significantly associated with increased cortical excitability (reduced TMS threshold) for the visual system (rs = −0.82; p < 0.001) but not for motor threshold (rs = −0.15; p = 0.575). Conclusions: MDMA users have increased cortical excitability. This finding is consistent with the predicted consequences of MDMA-induced serotonin neurotoxicity. Financial support: NIDA DA033341;Vanderbilt CTSA TR000445. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.1054 Shared and distinct neural mechanisms of inhibitory control in individuals with a history of a substance use disorder and depression Natania A. Crane 1,∗ , Laura Gabriel 1 , Kortni K. Meyers 2 , Anne L. Weldon 1 , Michelle T. Kassel 1 , Robin J. Mermelstein 1 , Jon-Kar Zubieta 2 , Scott A. Langenecker 1 1 2
UIC, Chicago, IL, United States UM, Ann Arbor, MI, United States
Aims: Substance Use Disorders (SUD) and Major Depressive Disorder (MDD) often co-occur, leading to poor functional and cognitive outcomes. However, little is known about the shared and distinct neural mechanisms of SUD and MDD. This study examined how a past history of SUD (hSUD) and active MDD impacts neural processing during inhibitory control (IC). Methods: Six hSUD individuals, 14 hSUD + MDD, 22 MDD, and 37 healthy controls (HC), free of potential confounds, completed the Parametric Go/No-Go Task (PGNG) during fMRI. The PGNG is a measure of IC including commission trials. Results: hSUD performed more poorly on IC than hSUD + MDD and HC, with no group differences in Go accuracy. MDD and hSUD + MDD had slower reaction time on the task than nonMDD. During commissions, hSUD had greater BOLD activation compared to all other groups in the right dorsolateral prefrontal cortex (rDLPFC). On the other hand, during commissions, hSUD had less BOLD activation compared to all other groups in the right insula/inferior frontal gyrus (rI/IFG). In addition, HC had greater activation in rostral anterior cingulate cortex (rACC) relative to all other groups during commissions. Conclusions: Our results provide preliminary evidence that SUD and MDD have some distinct, as well as some shared neural
CPDD 77th Annual Meeting Abstracts (2015) / Drug and Alcohol Dependence 156 (2015) e2–e101
Sex differences in effects of trait impulsivity on vulnerability to substance dependence Ayca Coskunpinar 3,∗ , Jasmin Vassileva 2 , Eileen Martin 1 1
Psychiatry, Rush University Medical Center, Chicago, IL, United States 2 Virginia Commonwealth University, Richmond, VA, United States 3 Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States Aims: Trait level impulsivity is a core feature of addictive processes. Research with non-clinical populations suggests that different components of impulsivity are most prominent among men (sensation seeking: SS) and women (negative urgency: NU). This study investigated potential sex differences in the relationship between sensation seeking, negative urgency and substance use among 271 participants with substance use disorders (SUDs). Methods: 139 men and 132 women completed the UPPS-P Impulsive Behavior Scale as part of a larger study of sex differences in neurocognition and drug dependence. DSM-IV TR diagnoses were obtained using the SCID-Substance Abuse Module. All subjects were verified abstinent by toxicology screening. Results: As predicted, men scored significantly higher on the SS (p = .02) (Cohen’s d = 0.50) while NU scores were significantly higher for women (p < .001) (Cohen’s d = 0.3). Among women, higher NU scores were significantly associated with past alcohol dependence, p = .01. By contrast, higher SS scores were significantly associated with cocaine dependence among men, p = .004. These results were unchanged when controlling for depression. Conclusions: NU is an index of behavioral dyscontrol triggered by negative affect and SS is the tendency and openness to try new and exciting activities that vary in danger level. NU had a significant positive relationship with past alcohol dependence only for women and this effect could not be attributed to nonspecific effects of psychological distress, while SS was significantly associated with cocaine dependence, but only among men. These findings suggest that specific components of impulsivity interact with vulnerability to substance use disorders differently among men and women and that effective prevention and treatment strategies for alcohol and cocaine dependence may benefit from sex and substance specific tailoring. Financial support: Supported by the National Institute on Drug Abuse R01 DA12828. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.1053 Increased cortical excitability in human MDMA users Ronald Cowan 1,∗ , Mary Dietrich 1 , Joseph Kim 2 , David Zald 2 1 Psychiatric Neuroimaging Program, Vanderbilt University, Nashville, TN, United States 2 Psychology, Vanderbilt University, Nashville, TN, United States
Aims: MDMA produces serotonergic axon toxicity in animal models. Human recreational MDMA users have reduced serotonin in cortex. Serotonin is mainly inhibitory in cortex; therefore we posited that MDMA users would have increased cortical excitability. We measured cortical excitability using transcranial magnetic stimulation (TMS) in the primary visual and primary motor cortices of MDMA users and non-MDMA exposed control subjects.
Methods: We enrolled 16 MDMA users and 16 non-MDMA exposed control subjects (age was 22.3 ± 2.3 years). All were free from drug use for 2 weeks, verified by repeated urine drug screening. A T1-weighted structural MRI scan was obtained and the TMS coil was stereotactically positioned using each subject’s structural scan. We used a Magstim 2T Rapid stimulator (Magstim Company, UK) peak discharge = 1.8 kV; 70-mm figure-eight) to deliver cortical excitation. For visual cortex, we positioned the coil to allow evocation of the phosphene within 2◦ of the fovea; coil location was about 2 cm above the inion. Coil intensity was set at 90% intensity to yield a phosphene with eyes closed or motor twitch of the dorsal interosseous muscle of the right hand. TMS intensity was then reduced to 54% intensity and adjusted upward until the individual was able to detect the phosphene threshold or motor twitch generation on 75% of trials. Results: MDMA users had increased cortical excitability (as indexed by lower TMS stimulation thresholds). Mean TMS threshold for visual system was 66.67 ± 6.72% for MDMA users and 75.31 ± 10.56% for controls (p = 0.012). Mean TMS threshold for motor system was 63.43 ± 7.90% for MDMA users and 73.75 ± 8.06% for controls (p = 0.001). Greater lifetime MDMA use was significantly associated with increased cortical excitability (reduced TMS threshold) for the visual system (rs = −0.82; p < 0.001) but not for motor threshold (rs = −0.15; p = 0.575). Conclusions: MDMA users have increased cortical excitability. This finding is consistent with the predicted consequences of MDMA-induced serotonin neurotoxicity. Financial support: NIDA DA033341;Vanderbilt CTSA TR000445. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.1054 Shared and distinct neural mechanisms of inhibitory control in individuals with a history of a substance use disorder and depression Natania A. Crane 1,∗ , Laura Gabriel 1 , Kortni K. Meyers 2 , Anne L. Weldon 1 , Michelle T. Kassel 1 , Robin J. Mermelstein 1 , Jon-Kar Zubieta 2 , Scott A. Langenecker 1 1 2
UIC, Chicago, IL, United States UM, Ann Arbor, MI, United States
Aims: Substance Use Disorders (SUD) and Major Depressive Disorder (MDD) often co-occur, leading to poor functional and cognitive outcomes. However, little is known about the shared and distinct neural mechanisms of SUD and MDD. This study examined how a past history of SUD (hSUD) and active MDD impacts neural processing during inhibitory control (IC). Methods: Six hSUD individuals, 14 hSUD + MDD, 22 MDD, and 37 healthy controls (HC), free of potential confounds, completed the Parametric Go/No-Go Task (PGNG) during fMRI. The PGNG is a measure of IC including commission trials. Results: hSUD performed more poorly on IC than hSUD + MDD and HC, with no group differences in Go accuracy. MDD and hSUD + MDD had slower reaction time on the task than nonMDD. During commissions, hSUD had greater BOLD activation compared to all other groups in the right dorsolateral prefrontal cortex (rDLPFC). On the other hand, during commissions, hSUD had less BOLD activation compared to all other groups in the right insula/inferior frontal gyrus (rI/IFG). In addition, HC had greater activation in rostral anterior cingulate cortex (rACC) relative to all other groups during commissions. Conclusions: Our results provide preliminary evidence that SUD and MDD have some distinct, as well as some shared neural