- Email: [email protected]
633. The Self and Susceptibility: The Role of the Medial Prefrontal Cortex in Addiction Comorbidity
Biological Psychiatry
Friday Abstracts
Background: Since Emil Kraepelin’s conceptualization of endogenous psychoses as dementia praecox and manic depression the separation between primary psychotic disorders and primary affective disorders has been much debated. Methods: We conducted a systematic review of case-control studies contrasting magnetic resonance imaging studies in schizophrenia and bipolar disorder. A literature search in PubMed of studies published between January 2005 and December 2016 was conducted. Results: 50 structural, 29 functional, 7 magnetic resonance spectroscopy, and 8 combined imaging and genetic studies were deemed eligible for systematic review. Structural neuroimaging studies suggest white matter integrity deficits that are consistent across the psychosis spectrum, while gray matter reductions appear more widespread in schizophrenia compared to bipolar disorder. Spectroscopy studies in cortical gray matter report evidence of decreased neuronal integrity in both disorders. Functional neuroimaging studies typically report similar functional architecture of brain networks in healthy controls and patients across the psychosis spectrum, but find differential extent of alterations in task related activation and resting state connectivity between illnesses. The very limited imaging-genetic literature suggests a relationship between psychosis risk genes and brain structure, and possible gene by diagnosis interaction effects on functional imaging markers. Conclusions: While the existing literature suggests some shared and some distinct neural markers in across schizophrenia and bipolar disorder, it will be imperative to conduct large, well designed, multi-modal neuroimaging studies in medication-naïve first episode patients that will be followed longitudinally over the course of their illness in an effort to advance our understanding of disease mechanisms. Supported By: National Institute of Mental Health (R01MH102951, ACL; K23MH106683, NVK). Keywords: Schizophrenia, Schizoaffective disorder, Bipolar disorder, Magnetic resonance spectroscopy, Functional magnetic resonance imaging, Diffusion tensor imaging, gray matter, white matter, resting state
632. Combining Neuro-Imaging and Non-Invasive Brain Stimulation for Clinical Intervention in Alcohol Use Disorder Yuclyn Camchong, Liliana Goelkel, Bryon Mueller, Angus W MacDonald III, Kelvin Lim, and Matt Kushner The University of Minnesota Background: New interventions are needed to improve high relapse rates in alcohol use disorder (AUD). We have neuroimaging evidence showing that individuals with AUD with long-term abstinence have higher resting functional connectivity (FC) in a network including prefrontal cortex, thalamus and nucleus accumbens than those with short-term abstinence. Low FC in this network during early abstinence predicts subsequent relapse. Literature shows that thalamus-prefrontal FC can be enhanced with transcranial direct current stimulation (tDCS). Methods: We investigated whether thalamus-prefrontal FC can be enhanced in AUD with a double-blind longitudinal study design. Intervention: 10 cognitive training sessions combined
S256
with either sham-tDCS or active-tDCS (anode on left dorsolateral prefrontal cortex). Rest fMRI data was collected pre- and post-intervention. Two AUD subjects undergoing active tDCS were compared to two AUD subjects undergoing sham tDCS. Preprocessing used FSL-FEAT and Melodic-ICA denoising. We hypothesized that individuals assigned to receive stimulation on left dorsolateral prefrontal cortex would show increases in thalamus-prefrontal FC when compared to individuals assigned to receive sham-tDCS. Results: Preliminary analyses examining FC between left thalamus and left dorsolateral prefrontal cortex showed that subjects assigned to active-tDCS had a significant withingroup FC increase (t520.87, p50.037) while subjects assigned to sham-tDCS did not (t50.27, p50.832). Group x Time effects was eta-square η250.116 Conclusions: These pilot data suggest tDCS can improve thalamocortical connectivity. Larger sample size and treatment outcome information will provide crucial evidence supporting the therapeutic use of interventions targeting both cognitive and underlying neural mechanisms that support abstinence. Supported By: CTSI (Clinical and Translational Science Institute) Keywords: Alcohol Use Disorder, Neuromodulation, Neuroimaging, Functional connectivity, intervention
633. The Self and Susceptibility: The Role of the Medial Prefrontal Cortex in Addiction Comorbidity Bradford Martins1, Ricardo Caceda1, Josh Cisler2, Clinton Kilts1, and G. Andrew James1 University of Arkansas for Medical Sciences, 2University of Wisconsin Madison
1
Background: Individuals with drug use disorders (DUD) cooccurring with other psychiatric disorders have poorer treatment outcomes than individuals without co-occurring disorders. Based upon prior research relating medial prefrontal cortex (MPFC) and dorsolateral prefrontal cortex (DLPFC) function and structure with resilience against and susceptibility to DUD and other forms of psychopathology, we hypothesized that these regions would also be associated with the degree of susceptibility for childhood trauma-exposed men and women to develop comorbid DUD. Methods: A sample of adults with childhood maltreatment (n579) was divided into the following groups based on DSM-IV psychiatric diagnoses and drug use history: no current or past psychiatric disorders (resilient, used as a trauma control sample), DUD only, MDD/PTSD only, and comorbid DUD with MDD/PTSD. Using a 200-node functional brain atlas, robust regression identified differences in ACC and/or DLPFC restingstate functional connectivity (FC) between groups. These grouplevel FC differences were then related to individual differences in psychiatric symptomatology, trauma history, and self-schema using Spearman’s correlation followed by elastic net regression. Bootstrapped mediation analyses were then performed on the comorbid and DUD subgroups to further explore the relationship between trauma, FC, and negative self-schema. Results: Increased VMPFC–hippocampal FC was found to mediate the relationship between physical neglect and
Biological Psychiatry May 15, 2017; 81:S140–S276 www.sobp.org/journal
Biological Psychiatry
Friday Abstracts
negative self-schema traits (Pessimism, Self-Criticism, and Indecisiveness) in the comorbid subgroup. Conclusions: Our findings suggest that comorbidity is not a simple conglomeration of DUD and other psychopathology, but involves unique neural processing in MPFC networks related to self-representation that are altered by childhood trauma. Supported By: T32DA022981 Keywords: Addiction, Resting state fMRI, Comorbidity, Childhood Trauma, Resilience
634. Cognitive Neurostimulation of the Dopaminergic Midbrain with Real Time fMRI Neurofeedback Training: A Novel Treatment Approach for Cocaine Addiction? Matthias Kirschner1, Ronald Sladky2, Philipp Stämpfli2, Elisabeth Jehli2, Martina Hodel2, Etna Engeli1, Lea Hulka1, Frank Scharnowski2, Markus Baumgartner3, Erich Seifritz2, James Sulzer4, Boris B. Quednow5, and Marcus Herdener1
Keywords: real-time fMRI neurofeedback, Dopaminergic circutry, cocaine addiction, functional imaging, Reward Learning
635. The Influence of Intelligence, Cortical Thickness, Surface Area, and White Matter Connectivity on Child Sexual Abuse Behavior by Pedophiles Tristram Lett1, Sebastian Mohnke2, Till Amelung2, Eva Brandl2, Kolja Schiltz3, Alexander Pohl4, Hannah Gerwinn4, Christian Kärgel5, Claudia Massau5, Gilian Tenbergen6, Matthias Wittfoth7, Jonas Kneer7, Klaus Beier2, Martin Walter8, Jorge Ponseti4, Tillmann Kruger7, Boris Schiffer5, and Henrik Walter2 Charite Universitatsmedizin Berlin, 2Charité Universitätsmedizin Berlin, 3Psychiatric Hospital of the University of Munich, Germany, 4Kiel University, Medical School, Germany, 5University of Duisburg-Essen, Germany, 6State University of New York at Oswego, 7Hannover Medical School, Hannover, Germany, 8Department of Psychiatry, Otto von Guericke University
1
1
Center for Addictive Disorders, University Hospital of Psychiatry Zurich, Switzerland, 2Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Switzerland, 3Institute of Forensic Medicine, University of Zurich, Switzerland, 4Department of Robotics, Biomechanics and Neuroscience, University of Texas, 5Neuropsychopharmacology and Brain Imaging, University Hospital of Psychiatry Zurich, Switzerland Background: Cocaine addiction is associated with dysfunction of the dopaminergic reward circuit and reinforcement learning. However, it is unknown if cocaine users can actively self-regulate neural activity or even learn to improve self-regulation capabilities in the substantia nigra/ventral tegmental area complex (SN/ VTA). Real-time fMRI (rtfMRI) neurofeedback training (NFBT) is a promising method enhancing the ability to self-regulate neural activity with positive mental imagery in the dopaminergic reward system. For the first time, we tested this non-invasive cognitive neurostimulation method in cocaine users (CUs) to evaluate its potential as novel treatment approach. Methods: 24 CUs 29 healthy controls (HC) performed a rtfMRI block design task in sessions with or without visual feedback of neural activity in the SN/VTA. In the active condition, we instructed participants to voluntary up-regulate the activity in SN/VTA by recalling non-drug related rewarding scenes. In the neutral condition no active imagery was performed. Results: Both groups were able to self-activate SN/VTA activity and other reward coding regions e.g. hippocampus, nucleus accumbens and orbitofrontal cortex (FWE corrected p,0.05). Furthermore, both groups improved this self-regulation ability with rtfMRI NFBT (F56.74, p,0.01), but no effect of group was observed (F50.22, p,0.639536). Conclusions: Cocaine users are able to actively self-regulate neural activity in the dopaminergic reward system and to improve this ability with rtfMRI NFBT. To elucidate the potential of rtfMRI NFBT as non-invasive treatment strategy future research should focus on the impact of cognitive neurostimulation with neurofeedback on clinical outcome in cocaine addiction. Supported By: Hartmann Mueller Foundation Zurich
Background: Pedophilia is a heterogeneous disorder for which the neurobiological correlates are not well established. In particular, there are no biological markers identifying individuals with high risk to commit sexual abuse of children. Methods: Pedophiles who have committed child sexual offense (P1CSO; N573), pedophiles who have not committed child sexual offense (P-CSO; N577), and healthy controls (HC; N5133) were assessed via full scale IQ performance, and multimodal structural neuroimaging measures including: cortical thickness (CT), surface area (SA), and white matter fractional anisotropy (FA), and on IQ performance. Cortex-wise mediation analysis used to assess the relationships among brain structure, IQ and child sexual abuse behavior. Results: Lower IQ performance was strongly associated with P1CSO (P1CSO vs P-CSO: χ2516.1, P56.0x10-6; P1CSO vs HC: χ2510.7, P50.0011). P1CSO had lower CT in the right motor cortex (PFWE-corrected,0.05), had strong reductions in SA spanning the bilateral frontal, temporal, cingulate, and insula regions (PFWE-corrected ,0.05). P1CSO had lower FA particularly in the corpus callosum (PFWE-corrected,0.05). The relationship between SAnd P1CSO was significantly mediated by IQ with particularly in the prefrontal and anterior insular cortices (PFWE-corrected,0.05). Conclusions: This study demonstrates that, among pedophiles, converging neurobiological findings in P1CSO including lower IQ performance, cortical thickness, surface area, and FA with near identical neuroanatomical differences between P1CSO and HC. Further, IQ potentially mediates abuse by pedophiles via aberrant SA, whereas the CT and FA associations were independent of IQ differences. These findings suggest aberrant neuroanatomy and lower intelligence as a potential core feature underlying child sexual abuse behavior by pedophiles. Supported By: CIHR, BMBF Keywords: Pedophilia, Cortical Thickness, Cortical surface area, Diffusion Tensor Imaging (DTI), Mediation Analysis
Biological Psychiatry May 15, 2017; 81:S140–S276 www.sobp.org/journal
S257
Friday Abstracts
Background: Since Emil Kraepelin’s conceptualization of endogenous psychoses as dementia praecox and manic depression the separation between primary psychotic disorders and primary affective disorders has been much debated. Methods: We conducted a systematic review of case-control studies contrasting magnetic resonance imaging studies in schizophrenia and bipolar disorder. A literature search in PubMed of studies published between January 2005 and December 2016 was conducted. Results: 50 structural, 29 functional, 7 magnetic resonance spectroscopy, and 8 combined imaging and genetic studies were deemed eligible for systematic review. Structural neuroimaging studies suggest white matter integrity deficits that are consistent across the psychosis spectrum, while gray matter reductions appear more widespread in schizophrenia compared to bipolar disorder. Spectroscopy studies in cortical gray matter report evidence of decreased neuronal integrity in both disorders. Functional neuroimaging studies typically report similar functional architecture of brain networks in healthy controls and patients across the psychosis spectrum, but find differential extent of alterations in task related activation and resting state connectivity between illnesses. The very limited imaging-genetic literature suggests a relationship between psychosis risk genes and brain structure, and possible gene by diagnosis interaction effects on functional imaging markers. Conclusions: While the existing literature suggests some shared and some distinct neural markers in across schizophrenia and bipolar disorder, it will be imperative to conduct large, well designed, multi-modal neuroimaging studies in medication-naïve first episode patients that will be followed longitudinally over the course of their illness in an effort to advance our understanding of disease mechanisms. Supported By: National Institute of Mental Health (R01MH102951, ACL; K23MH106683, NVK). Keywords: Schizophrenia, Schizoaffective disorder, Bipolar disorder, Magnetic resonance spectroscopy, Functional magnetic resonance imaging, Diffusion tensor imaging, gray matter, white matter, resting state
632. Combining Neuro-Imaging and Non-Invasive Brain Stimulation for Clinical Intervention in Alcohol Use Disorder Yuclyn Camchong, Liliana Goelkel, Bryon Mueller, Angus W MacDonald III, Kelvin Lim, and Matt Kushner The University of Minnesota Background: New interventions are needed to improve high relapse rates in alcohol use disorder (AUD). We have neuroimaging evidence showing that individuals with AUD with long-term abstinence have higher resting functional connectivity (FC) in a network including prefrontal cortex, thalamus and nucleus accumbens than those with short-term abstinence. Low FC in this network during early abstinence predicts subsequent relapse. Literature shows that thalamus-prefrontal FC can be enhanced with transcranial direct current stimulation (tDCS). Methods: We investigated whether thalamus-prefrontal FC can be enhanced in AUD with a double-blind longitudinal study design. Intervention: 10 cognitive training sessions combined
S256
with either sham-tDCS or active-tDCS (anode on left dorsolateral prefrontal cortex). Rest fMRI data was collected pre- and post-intervention. Two AUD subjects undergoing active tDCS were compared to two AUD subjects undergoing sham tDCS. Preprocessing used FSL-FEAT and Melodic-ICA denoising. We hypothesized that individuals assigned to receive stimulation on left dorsolateral prefrontal cortex would show increases in thalamus-prefrontal FC when compared to individuals assigned to receive sham-tDCS. Results: Preliminary analyses examining FC between left thalamus and left dorsolateral prefrontal cortex showed that subjects assigned to active-tDCS had a significant withingroup FC increase (t520.87, p50.037) while subjects assigned to sham-tDCS did not (t50.27, p50.832). Group x Time effects was eta-square η250.116 Conclusions: These pilot data suggest tDCS can improve thalamocortical connectivity. Larger sample size and treatment outcome information will provide crucial evidence supporting the therapeutic use of interventions targeting both cognitive and underlying neural mechanisms that support abstinence. Supported By: CTSI (Clinical and Translational Science Institute) Keywords: Alcohol Use Disorder, Neuromodulation, Neuroimaging, Functional connectivity, intervention
633. The Self and Susceptibility: The Role of the Medial Prefrontal Cortex in Addiction Comorbidity Bradford Martins1, Ricardo Caceda1, Josh Cisler2, Clinton Kilts1, and G. Andrew James1 University of Arkansas for Medical Sciences, 2University of Wisconsin Madison
1
Background: Individuals with drug use disorders (DUD) cooccurring with other psychiatric disorders have poorer treatment outcomes than individuals without co-occurring disorders. Based upon prior research relating medial prefrontal cortex (MPFC) and dorsolateral prefrontal cortex (DLPFC) function and structure with resilience against and susceptibility to DUD and other forms of psychopathology, we hypothesized that these regions would also be associated with the degree of susceptibility for childhood trauma-exposed men and women to develop comorbid DUD. Methods: A sample of adults with childhood maltreatment (n579) was divided into the following groups based on DSM-IV psychiatric diagnoses and drug use history: no current or past psychiatric disorders (resilient, used as a trauma control sample), DUD only, MDD/PTSD only, and comorbid DUD with MDD/PTSD. Using a 200-node functional brain atlas, robust regression identified differences in ACC and/or DLPFC restingstate functional connectivity (FC) between groups. These grouplevel FC differences were then related to individual differences in psychiatric symptomatology, trauma history, and self-schema using Spearman’s correlation followed by elastic net regression. Bootstrapped mediation analyses were then performed on the comorbid and DUD subgroups to further explore the relationship between trauma, FC, and negative self-schema. Results: Increased VMPFC–hippocampal FC was found to mediate the relationship between physical neglect and
Biological Psychiatry May 15, 2017; 81:S140–S276 www.sobp.org/journal
Biological Psychiatry
Friday Abstracts
negative self-schema traits (Pessimism, Self-Criticism, and Indecisiveness) in the comorbid subgroup. Conclusions: Our findings suggest that comorbidity is not a simple conglomeration of DUD and other psychopathology, but involves unique neural processing in MPFC networks related to self-representation that are altered by childhood trauma. Supported By: T32DA022981 Keywords: Addiction, Resting state fMRI, Comorbidity, Childhood Trauma, Resilience
634. Cognitive Neurostimulation of the Dopaminergic Midbrain with Real Time fMRI Neurofeedback Training: A Novel Treatment Approach for Cocaine Addiction? Matthias Kirschner1, Ronald Sladky2, Philipp Stämpfli2, Elisabeth Jehli2, Martina Hodel2, Etna Engeli1, Lea Hulka1, Frank Scharnowski2, Markus Baumgartner3, Erich Seifritz2, James Sulzer4, Boris B. Quednow5, and Marcus Herdener1
Keywords: real-time fMRI neurofeedback, Dopaminergic circutry, cocaine addiction, functional imaging, Reward Learning
635. The Influence of Intelligence, Cortical Thickness, Surface Area, and White Matter Connectivity on Child Sexual Abuse Behavior by Pedophiles Tristram Lett1, Sebastian Mohnke2, Till Amelung2, Eva Brandl2, Kolja Schiltz3, Alexander Pohl4, Hannah Gerwinn4, Christian Kärgel5, Claudia Massau5, Gilian Tenbergen6, Matthias Wittfoth7, Jonas Kneer7, Klaus Beier2, Martin Walter8, Jorge Ponseti4, Tillmann Kruger7, Boris Schiffer5, and Henrik Walter2 Charite Universitatsmedizin Berlin, 2Charité Universitätsmedizin Berlin, 3Psychiatric Hospital of the University of Munich, Germany, 4Kiel University, Medical School, Germany, 5University of Duisburg-Essen, Germany, 6State University of New York at Oswego, 7Hannover Medical School, Hannover, Germany, 8Department of Psychiatry, Otto von Guericke University
1
1
Center for Addictive Disorders, University Hospital of Psychiatry Zurich, Switzerland, 2Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Switzerland, 3Institute of Forensic Medicine, University of Zurich, Switzerland, 4Department of Robotics, Biomechanics and Neuroscience, University of Texas, 5Neuropsychopharmacology and Brain Imaging, University Hospital of Psychiatry Zurich, Switzerland Background: Cocaine addiction is associated with dysfunction of the dopaminergic reward circuit and reinforcement learning. However, it is unknown if cocaine users can actively self-regulate neural activity or even learn to improve self-regulation capabilities in the substantia nigra/ventral tegmental area complex (SN/ VTA). Real-time fMRI (rtfMRI) neurofeedback training (NFBT) is a promising method enhancing the ability to self-regulate neural activity with positive mental imagery in the dopaminergic reward system. For the first time, we tested this non-invasive cognitive neurostimulation method in cocaine users (CUs) to evaluate its potential as novel treatment approach. Methods: 24 CUs 29 healthy controls (HC) performed a rtfMRI block design task in sessions with or without visual feedback of neural activity in the SN/VTA. In the active condition, we instructed participants to voluntary up-regulate the activity in SN/VTA by recalling non-drug related rewarding scenes. In the neutral condition no active imagery was performed. Results: Both groups were able to self-activate SN/VTA activity and other reward coding regions e.g. hippocampus, nucleus accumbens and orbitofrontal cortex (FWE corrected p,0.05). Furthermore, both groups improved this self-regulation ability with rtfMRI NFBT (F56.74, p,0.01), but no effect of group was observed (F50.22, p,0.639536). Conclusions: Cocaine users are able to actively self-regulate neural activity in the dopaminergic reward system and to improve this ability with rtfMRI NFBT. To elucidate the potential of rtfMRI NFBT as non-invasive treatment strategy future research should focus on the impact of cognitive neurostimulation with neurofeedback on clinical outcome in cocaine addiction. Supported By: Hartmann Mueller Foundation Zurich
Background: Pedophilia is a heterogeneous disorder for which the neurobiological correlates are not well established. In particular, there are no biological markers identifying individuals with high risk to commit sexual abuse of children. Methods: Pedophiles who have committed child sexual offense (P1CSO; N573), pedophiles who have not committed child sexual offense (P-CSO; N577), and healthy controls (HC; N5133) were assessed via full scale IQ performance, and multimodal structural neuroimaging measures including: cortical thickness (CT), surface area (SA), and white matter fractional anisotropy (FA), and on IQ performance. Cortex-wise mediation analysis used to assess the relationships among brain structure, IQ and child sexual abuse behavior. Results: Lower IQ performance was strongly associated with P1CSO (P1CSO vs P-CSO: χ2516.1, P56.0x10-6; P1CSO vs HC: χ2510.7, P50.0011). P1CSO had lower CT in the right motor cortex (PFWE-corrected,0.05), had strong reductions in SA spanning the bilateral frontal, temporal, cingulate, and insula regions (PFWE-corrected ,0.05). P1CSO had lower FA particularly in the corpus callosum (PFWE-corrected,0.05). The relationship between SAnd P1CSO was significantly mediated by IQ with particularly in the prefrontal and anterior insular cortices (PFWE-corrected,0.05). Conclusions: This study demonstrates that, among pedophiles, converging neurobiological findings in P1CSO including lower IQ performance, cortical thickness, surface area, and FA with near identical neuroanatomical differences between P1CSO and HC. Further, IQ potentially mediates abuse by pedophiles via aberrant SA, whereas the CT and FA associations were independent of IQ differences. These findings suggest aberrant neuroanatomy and lower intelligence as a potential core feature underlying child sexual abuse behavior by pedophiles. Supported By: CIHR, BMBF Keywords: Pedophilia, Cortical Thickness, Cortical surface area, Diffusion Tensor Imaging (DTI), Mediation Analysis
Biological Psychiatry May 15, 2017; 81:S140–S276 www.sobp.org/journal
S257