- Email: [email protected]
P.4.b.006 Aberrant resting-state functional connectivity in panic disorder patients
P.4.b. Anxiety disorders and anxiolytics − Anxiety disorders (basic) diagnosis of GAD. All patients were assessed using the Structured Clinical Interview for DSM-IV. The presence of panic attacks was assessed and characterized by the type of panic attack. A GAD panic attack was defined as one which occurs strictly within the context of GAD type worrying. Subjects also completed a battery of self-report symptom severity measures. Demographic correlates, diagnoses and symptom severity scales scores were examined and compared. Results: The sample was 73.2% female, with a mean age of 33.7±13.1 years. The mean CGI-S score was 3.9±0.6 years. Forty-seven percent of the sample also met criteria for lifetime panic disorder±agoraphobia. Twenty-one percent reported having GAD panic attacks; 22% reported situationally predisposed attacks; 16% reported situationally bound attacks and 39% reported having spontaneous panic attacks. Fifty percent of those with GAD panic attacks (10% of the total sample) reported having no other types of panic attacks. Anxiety Sensitivity Index scores were lower in subjects whose only panic attacks were GAD panic attacks (27.3±13.0 vs. 38.9±14.0, p < 0.01). In addition, those with GAD panic attacks were less likely to have obsessive compulsive disorder (34.6% vs. 49.5%, p < 0.05) than subjects who did not report having GAD panic attacks. Conclusions: Approximately 1 in 5 GAD patients reported experiencing panic attacks in response to GAD type worry. Individuals with GAD panic attacks did not appear meaningfully different in terms of demographic characteristics, comorbid diagnoses or symptom severity from individuals with GAD without. However, lower ASI scores in this group indicate that individuals with GAD panic attacks are much less fearful of their symptoms than those with Panic Disorder. GAD panic attacks may be more like situationally bound attacks, a premise partially supported by work by Brown and colleagues who found that GAD was most strongly related to negative affect and was inversely related to autonomic arousal. [3] Future studies may examine whether the presence of panic attacks in GAD have implications for diagnostic classification, course of illness and response to treatment. References [1] Liebowitz, M.R., Klein, D.F., 1981 Differential diagnosis and treatment of panic attacks and phobic states. Ann Rev Med 32, 583–599. [2] Liebowitz, M.R., Fyer, A.J., Chapter 2, “Diagnosis and Clinical Course of Panic Disorder with and without Agoraphobia”, in Treatment of Panic Disorder; Wolfe B and Maser JD, editors. American Psychiatric Press Inc; Washington DC, 1994. [3] Brown, T.A., Chorpita, B.F., Barlow, D.H., 1998 Structural relationships among dimensions of the DSM-IV anxiety disorders and mood disorders and dimensions of negative affect, positive affect and autonomic arousal. J Abnormal Psych 107(2), 179–192.
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P.4.b.006 Aberrant resting-state functional connectivity in panic disorder patients N. van der Wee1 ° , N. Pannekoek1 , I. Veer2 , M.J. van Tol3 , L. Demenescu4 , A. Aleman4 , D. Veltman5 , F. Zitman6 , 1 Leiden University Medical Center, Leiden S. Rombouts7 . Institute for Brain and Cognition/Department of Psychiatry B1-P, Leiden, The Netherlands; 2 Leiden University Medical Center, Leiden Instiute for Brain and Cognition/Department of Radiology B1-P, Leiden, The Netherlands; 3 Leiden University Medical Center, Leiden Instiute for Brain and Cognition/Department of Psychiatry B1-P, Leiden, The Netherlands; 4 University Groningen, BCN Neuroimaging Center, Groningen, The Netherlands; 5 VU Medical Center, Department of Psychiatry, Amsterdam, The Netherlands; 6 Leiden University Medical Center, Department of Psychiatry, Leiden, The Netherlands; 7 Leiden University Medical Center, Leiden Institute for Brain and Cognition Department of Radiology, Leiden, The Netherlands Introduction: Panic Disorder (PD) is characterized by recurrent unexpected panic attacks, followed by persistent concerns about additional attacks, worrying about their consequences, and behaviour change resulting from the attacks. The underlying neurobiology of PD has still not been fully elucidated. Neuroimaging studies thus far have shown abnormalities in various brain areas, particularly reporting the amygdala, insula and anterior cingulate cortex (ACC) [1]. These regions are key-players within the neural circuitry dedicated to the processing and evaluation of emotions and bodily states. Resting-state fMRI has become an important tool to map such circuits in the human brain. However, no study yet has focused on resting-state functional connectivity (RSFC) in PD. In this study we employed seed-based RSFC analysis using the amygdala and dorsal ACC (dACC) as seed regions to examine functional connectivity in PD in brain networks dedicated to the processing and regulation of emotions. Methods: 3.0 Tesla fMRI data from 11 patients with PD without psychiatric comorbidity were selected from the Netherlands Study of Depression and Anxiety, with 11 subsequently age, gender, and education pair-wise matched healthy controls. Patients were diagnosed with panic disorder by the DSM-IV-based Composite International Diagnostic Interview, lifetime version 2.1. All data were preprocessed and analysed using FEAT, part of FSL. Bilateral amygdala and dACC masks were created in standard space and registered to the individual resting-state data sets to extract the mean time series from each mask. These time series were used as regressor in a general linear model together with motion, white matter, CSF and global signal as confound regressors to calculate individual RSFC maps for each of the seeds. Between groups differences were assessed using a mixedeffects analysis (cluster-forming z>2.3, corrected p < 0.05). Results: PD patients demonstrated increased negative RSFC between the right amygdala and the bilateral precuneus and lateral occipital cortex compared with healthy controls. Separate investigation of the left dACC showed increased positive connectivity in healthy controls with the bilateral frontal pole and superior frontal gyrus when compared to PD patients. PD patients showed greater positive left dorsal anterior cingulate connectivity than healthy controls with the bilateral superior parietal lobule, postcentral gyrus, and precentral gyrus, and with the right ACC. Finally, PD patients exhibited increased negative right dACC with the right superior parietal lobule, while healthy controls showed greater positive connectivity with lateral occipital cortex, postcentral gyrus, and precentral gyrus.
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P.4.b. Anxiety disorders and anxiolytics − Anxiety disorders (basic)
Conclusion: PD patients showed aberrant RSFC between areas involved in emotional processing, autobiographical memory, and self-referential thought, which has not been shown in PD previously. Our findings of this heightened functional connectivity in PD patients could further extend functional neuroanatomical models of panic disorder by implementing the role of the precuneus, which is thus far a missing structure in existing models [2,3]. References [1] Damsa C., Kosel, M., Moussally, J., 2009 Current status of brain imaging in anxiety disorders. Current Opinion in Psychiatry 22, 96– 110. [2] Clark D.M., Salkovskis, P.M., Ost, L.G., Breitholtz, E., Koehler, K.A., Westling, B.E., Jeavons, A., Gelder, M., 1997 Misinterpretation of body sensations in panic disorder. Journal of Consulting and Clinical Psychology, 65, 203–213. [3] Gorman J.M., Kent, J.M., Sullivan, G.M., Coplan, J.D., 2000 Neuroanatomical hypothesis of panic disorder, revised. American Journal of Psychiatry 157, 493–505.
P.4.b.007 Resting-state fMRI in social phobia patients N. van der Wee1 ° , N. Pannekoek1 , I. Veer2 , M.J. van Tol3 , L. Demenescu4 , A. Aleman4 , D. Veltman5 , F. Zitman6 , 1 Leiden University Medical Center, Leiden S. Rombouts2 . Institute for Brain and Cognition/Department of Psychiatry B1-P, Leiden, The Netherlands; 2 Leiden University Medical Center, Leiden Institute for Brain and Cognition/Department of Radiology, Leiden, The Netherlands; 3 Leiden University Medical Center, Leiden Institute for Brain and Cognition/Department of Psychiatry, Leiden, The Netherlands; 4 University of Groningen, BCN Neuroimaging Center, Groningen, The Netherlands; 5 VU Medical Center, Department of Psychiatry, Amsterdam, The Netherlands; 6 Leiden University Medical Center, Department of Psychiatry, Leiden, The Netherlands Purpose of the study: Social phobia (SP) is a common anxiety disorder, yet much still remains to be elucidated about the neurobiology of this illness. Neuroimaging techniques have proved to be helpful in this. Thus far, the most common finding from functional imaging studies is increased activity in limbic regions, with predominance of the amygdala. Additional observations of alterations in regions in the prefrontal and medial temporal cortex show that much still needs to be investigated in future studies of social anxiety disorder [1]. Recent resting-state (RS) studies identified several RS networks that were altered in SP patients, including the salience network and a limbic network [2,3]. However, the patients studied were young [2] or had psychiatric comorbidity [3]. Our aim is to further elucidate the RS connectivity in SP using a region-of-interest approach focusing on areas in the limbic system and the salience network in a group of SP patients of varied age and without psychiatric comorbidity, using seed regions of interest in the amygdala and dorsal anterior cingulate cortex (dACC). The authors expect to find altered resting-state connectivity of these areas. The default mode network (DMN) is altered in many diseases, such as depression, schizophrenia, and Alzheimer’s Disease. We include the DMN in our analysis to investigate its connectivity in SP, with a seed in the ventral ACC (vACC). Methods: 3.0 Tesla fMRI data from 19 patients with SP and from 19 age, gender, and education pair-wise matched healthy controls were available from the Netherlands Study of Depression and Anxiety MRI study. Patients were diagnosed with SP using the DSM-IV-based Composite International Diagnostic Interview, lifetime version 2.1. Severity of anxiety symptoms was measured
with the Dutch version of the Beck Anxiety Inventory. Regions of interest were created in standard space using the Harvard-Oxford Cortical and Subcortical Structural Atlases in FSL. Image processing and analysis were performed using statistical parametric mapping with a mixed-effects model in FSL. Group differences were assessed within the context of a general linear model with significance set at p < 0.05, cluster corrected. Results: No group differences were found between patients and controls in amygdala connectivity. Combining bilateral dorsal anterior cingulate in one analysis showed increased positive connectivity in SP patients with bilateral posterior cingulate cortex and precuneus. Both groups showed DMN activity, and increased positive connectivity was found in healthy controls with the bilateral posterior cingulate and precuneus. Conclusion: Taking previous literature into account [1,2,3], our finding that the amygdala shows no significantly different connectivity between SP patients and healthy controls is unexpected. However, the increased dACC connectivity in SP patients is in line with previous research suggesting altered ACC connectivity in anxiety disorders [1,2]. Finally, DMN connectivity is, as it is in many diseases, aberrant in SP. Our findings advance the knowledge on effective connectivity networks associated with the amygdala in SP and more in general the neural rest circuitry underlying SP. References [1] Freitas-Ferrari, M.C., Hallak, J.E., Trzesniak, C., Filho, A.S., Machadode-Sousa, J.P., Chagas, M.H., Nardi, A.E., Crippa, J.A., 2010 Neuroimaging in social anxiety disorder: a systematic review of the literature. Progress in neuro-psychopharmacology & biological psychiatry 34, 565–580. [2] Liao, W., Qiu, C., Gentili, C., Walter, M., Pan, Z., Ding, J., Zhang, W., Gong, Q., Chen, H., 2010 Altered effective connectivity network of the amygdala in social anxiety disorder: a resting-state FMRI study. PLoS One 12, e15238. [3] Hahn, A., Stein, P., Windischberger, C., Weissenbacher, A., Spindelegger, C., Moser, E., Kasper, S., Lanzenberger, R., 2011 Reduced restingstate functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder. Neuroimage, [Epub ahead of print].
P.4.b.008 Aberrant fronto-cingulate activation in obsessive-compulsive disorder is related to task complexity in a working memory task G. Wagner1 ° , K. Koch1 , C. Schachtzabel1 , G. Peikert1 , C.C. Schultz1 , H. Sauer1 , R.G. Schl¨osser1 . 1 Jena University Hospital, Department of Psychiatry, Jena, Germany Objectives: Besides clinical characteristics, such as obsessive thoughts and compulsive behavior most patients with OCD display distinct and often disabling cognitive disturbances. Studies with OCD patients have revealed deficits in several executive domains such as response inhibition, cognitive reversal learning or cognitive shifting ability. Furthermore, evidence showing OCD patients to be impaired in verbal or spatial working memory (WM) tasks is increasing. Poor inhibition of interfering thoughts has been discussed as one critical factor causing cognitive impairments especially in the working memory domain [1]. These memory deficits, in turn, may produce characteristic symptoms like frequent checking and increased error monitoring found in many patients with OCD. Surprisingly few studies have specifically investigated the neural correlates of working memory in OCD patients. However, findings regarding the underlying neural substrates are heterogeneous. Moreover, the influence of cognitive
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P.4.b.006 Aberrant resting-state functional connectivity in panic disorder patients N. van der Wee1 ° , N. Pannekoek1 , I. Veer2 , M.J. van Tol3 , L. Demenescu4 , A. Aleman4 , D. Veltman5 , F. Zitman6 , 1 Leiden University Medical Center, Leiden S. Rombouts7 . Institute for Brain and Cognition/Department of Psychiatry B1-P, Leiden, The Netherlands; 2 Leiden University Medical Center, Leiden Instiute for Brain and Cognition/Department of Radiology B1-P, Leiden, The Netherlands; 3 Leiden University Medical Center, Leiden Instiute for Brain and Cognition/Department of Psychiatry B1-P, Leiden, The Netherlands; 4 University Groningen, BCN Neuroimaging Center, Groningen, The Netherlands; 5 VU Medical Center, Department of Psychiatry, Amsterdam, The Netherlands; 6 Leiden University Medical Center, Department of Psychiatry, Leiden, The Netherlands; 7 Leiden University Medical Center, Leiden Institute for Brain and Cognition Department of Radiology, Leiden, The Netherlands Introduction: Panic Disorder (PD) is characterized by recurrent unexpected panic attacks, followed by persistent concerns about additional attacks, worrying about their consequences, and behaviour change resulting from the attacks. The underlying neurobiology of PD has still not been fully elucidated. Neuroimaging studies thus far have shown abnormalities in various brain areas, particularly reporting the amygdala, insula and anterior cingulate cortex (ACC) [1]. These regions are key-players within the neural circuitry dedicated to the processing and evaluation of emotions and bodily states. Resting-state fMRI has become an important tool to map such circuits in the human brain. However, no study yet has focused on resting-state functional connectivity (RSFC) in PD. In this study we employed seed-based RSFC analysis using the amygdala and dorsal ACC (dACC) as seed regions to examine functional connectivity in PD in brain networks dedicated to the processing and regulation of emotions. Methods: 3.0 Tesla fMRI data from 11 patients with PD without psychiatric comorbidity were selected from the Netherlands Study of Depression and Anxiety, with 11 subsequently age, gender, and education pair-wise matched healthy controls. Patients were diagnosed with panic disorder by the DSM-IV-based Composite International Diagnostic Interview, lifetime version 2.1. All data were preprocessed and analysed using FEAT, part of FSL. Bilateral amygdala and dACC masks were created in standard space and registered to the individual resting-state data sets to extract the mean time series from each mask. These time series were used as regressor in a general linear model together with motion, white matter, CSF and global signal as confound regressors to calculate individual RSFC maps for each of the seeds. Between groups differences were assessed using a mixedeffects analysis (cluster-forming z>2.3, corrected p < 0.05). Results: PD patients demonstrated increased negative RSFC between the right amygdala and the bilateral precuneus and lateral occipital cortex compared with healthy controls. Separate investigation of the left dACC showed increased positive connectivity in healthy controls with the bilateral frontal pole and superior frontal gyrus when compared to PD patients. PD patients showed greater positive left dorsal anterior cingulate connectivity than healthy controls with the bilateral superior parietal lobule, postcentral gyrus, and precentral gyrus, and with the right ACC. Finally, PD patients exhibited increased negative right dACC with the right superior parietal lobule, while healthy controls showed greater positive connectivity with lateral occipital cortex, postcentral gyrus, and precentral gyrus.
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P.4.b. Anxiety disorders and anxiolytics − Anxiety disorders (basic)
Conclusion: PD patients showed aberrant RSFC between areas involved in emotional processing, autobiographical memory, and self-referential thought, which has not been shown in PD previously. Our findings of this heightened functional connectivity in PD patients could further extend functional neuroanatomical models of panic disorder by implementing the role of the precuneus, which is thus far a missing structure in existing models [2,3]. References [1] Damsa C., Kosel, M., Moussally, J., 2009 Current status of brain imaging in anxiety disorders. Current Opinion in Psychiatry 22, 96– 110. [2] Clark D.M., Salkovskis, P.M., Ost, L.G., Breitholtz, E., Koehler, K.A., Westling, B.E., Jeavons, A., Gelder, M., 1997 Misinterpretation of body sensations in panic disorder. Journal of Consulting and Clinical Psychology, 65, 203–213. [3] Gorman J.M., Kent, J.M., Sullivan, G.M., Coplan, J.D., 2000 Neuroanatomical hypothesis of panic disorder, revised. American Journal of Psychiatry 157, 493–505.
P.4.b.007 Resting-state fMRI in social phobia patients N. van der Wee1 ° , N. Pannekoek1 , I. Veer2 , M.J. van Tol3 , L. Demenescu4 , A. Aleman4 , D. Veltman5 , F. Zitman6 , 1 Leiden University Medical Center, Leiden S. Rombouts2 . Institute for Brain and Cognition/Department of Psychiatry B1-P, Leiden, The Netherlands; 2 Leiden University Medical Center, Leiden Institute for Brain and Cognition/Department of Radiology, Leiden, The Netherlands; 3 Leiden University Medical Center, Leiden Institute for Brain and Cognition/Department of Psychiatry, Leiden, The Netherlands; 4 University of Groningen, BCN Neuroimaging Center, Groningen, The Netherlands; 5 VU Medical Center, Department of Psychiatry, Amsterdam, The Netherlands; 6 Leiden University Medical Center, Department of Psychiatry, Leiden, The Netherlands Purpose of the study: Social phobia (SP) is a common anxiety disorder, yet much still remains to be elucidated about the neurobiology of this illness. Neuroimaging techniques have proved to be helpful in this. Thus far, the most common finding from functional imaging studies is increased activity in limbic regions, with predominance of the amygdala. Additional observations of alterations in regions in the prefrontal and medial temporal cortex show that much still needs to be investigated in future studies of social anxiety disorder [1]. Recent resting-state (RS) studies identified several RS networks that were altered in SP patients, including the salience network and a limbic network [2,3]. However, the patients studied were young [2] or had psychiatric comorbidity [3]. Our aim is to further elucidate the RS connectivity in SP using a region-of-interest approach focusing on areas in the limbic system and the salience network in a group of SP patients of varied age and without psychiatric comorbidity, using seed regions of interest in the amygdala and dorsal anterior cingulate cortex (dACC). The authors expect to find altered resting-state connectivity of these areas. The default mode network (DMN) is altered in many diseases, such as depression, schizophrenia, and Alzheimer’s Disease. We include the DMN in our analysis to investigate its connectivity in SP, with a seed in the ventral ACC (vACC). Methods: 3.0 Tesla fMRI data from 19 patients with SP and from 19 age, gender, and education pair-wise matched healthy controls were available from the Netherlands Study of Depression and Anxiety MRI study. Patients were diagnosed with SP using the DSM-IV-based Composite International Diagnostic Interview, lifetime version 2.1. Severity of anxiety symptoms was measured
with the Dutch version of the Beck Anxiety Inventory. Regions of interest were created in standard space using the Harvard-Oxford Cortical and Subcortical Structural Atlases in FSL. Image processing and analysis were performed using statistical parametric mapping with a mixed-effects model in FSL. Group differences were assessed within the context of a general linear model with significance set at p < 0.05, cluster corrected. Results: No group differences were found between patients and controls in amygdala connectivity. Combining bilateral dorsal anterior cingulate in one analysis showed increased positive connectivity in SP patients with bilateral posterior cingulate cortex and precuneus. Both groups showed DMN activity, and increased positive connectivity was found in healthy controls with the bilateral posterior cingulate and precuneus. Conclusion: Taking previous literature into account [1,2,3], our finding that the amygdala shows no significantly different connectivity between SP patients and healthy controls is unexpected. However, the increased dACC connectivity in SP patients is in line with previous research suggesting altered ACC connectivity in anxiety disorders [1,2]. Finally, DMN connectivity is, as it is in many diseases, aberrant in SP. Our findings advance the knowledge on effective connectivity networks associated with the amygdala in SP and more in general the neural rest circuitry underlying SP. References [1] Freitas-Ferrari, M.C., Hallak, J.E., Trzesniak, C., Filho, A.S., Machadode-Sousa, J.P., Chagas, M.H., Nardi, A.E., Crippa, J.A., 2010 Neuroimaging in social anxiety disorder: a systematic review of the literature. Progress in neuro-psychopharmacology & biological psychiatry 34, 565–580. [2] Liao, W., Qiu, C., Gentili, C., Walter, M., Pan, Z., Ding, J., Zhang, W., Gong, Q., Chen, H., 2010 Altered effective connectivity network of the amygdala in social anxiety disorder: a resting-state FMRI study. PLoS One 12, e15238. [3] Hahn, A., Stein, P., Windischberger, C., Weissenbacher, A., Spindelegger, C., Moser, E., Kasper, S., Lanzenberger, R., 2011 Reduced restingstate functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder. Neuroimage, [Epub ahead of print].
P.4.b.008 Aberrant fronto-cingulate activation in obsessive-compulsive disorder is related to task complexity in a working memory task G. Wagner1 ° , K. Koch1 , C. Schachtzabel1 , G. Peikert1 , C.C. Schultz1 , H. Sauer1 , R.G. Schl¨osser1 . 1 Jena University Hospital, Department of Psychiatry, Jena, Germany Objectives: Besides clinical characteristics, such as obsessive thoughts and compulsive behavior most patients with OCD display distinct and often disabling cognitive disturbances. Studies with OCD patients have revealed deficits in several executive domains such as response inhibition, cognitive reversal learning or cognitive shifting ability. Furthermore, evidence showing OCD patients to be impaired in verbal or spatial working memory (WM) tasks is increasing. Poor inhibition of interfering thoughts has been discussed as one critical factor causing cognitive impairments especially in the working memory domain [1]. These memory deficits, in turn, may produce characteristic symptoms like frequent checking and increased error monitoring found in many patients with OCD. Surprisingly few studies have specifically investigated the neural correlates of working memory in OCD patients. However, findings regarding the underlying neural substrates are heterogeneous. Moreover, the influence of cognitive