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Jennifer C. Britton Ph.D,
S. Evelyn Stewart M.D,
William D.S. Killgore Ph.D,
Isabelle M. Rosso Ph.D,
Lauren M. Price B.A,
Andrea L. Gold M.S,
Daniel S. Pine M.D,
Sabine Wilhelm Ph.D,
Michael A. Jenike M.D,
Scott L. Rauch M.D,
Jennifer C. Britton,
S. Evelyn Stewart,
William D.S. Killgore,
Isabelle M. Rosso,
Lauren M. Price,
Andrea L. Gold,
Daniel S. Pine,
Sabine Wilhelm,
Michael A. Jenike, Scott L. Rauch
[show abstract]
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ABSTRACT: Background: Exaggerated amygdala activation to threatening faces has been detected in adults and children with anxiety disorders, compared to healthy comparison (HC) subjects. However, the profile of amygdala activation in response to facial expressions in obsessive–compulsive disorder (OCD) may be a distinguishing feature; a prior study found that compared with healthy adults, adults with OCD exhibited less amygdala activation to emotional and neutral faces, relative to fixation [Cannistraro et al. (2004). Biological Psychiatry 56:916–920]. Methods: In the current event-related functional magnetic resonance imaging (fMRI) study, a pediatric OCD sample (N=12) and a HC sample (N=17) performed a gender discrimination task while viewing emotional faces (happy, fearful, disgusted) and neutral faces. Results: Compared to the HC group, the OCD group showed less amygdala/hippocampus activation in all emotion and neutral conditions relative to fixation. Conclusions: Like previous reports in adult OCD, pediatric OCD may have a distinct neural profile from other anxiety disorders, with respect to amygdala activation in response to emotional stimuli that are not disorder specific. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc.
Depression and Anxiety 06/2010; 27(7):643 - 651. · 4.18 Impact Factor
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ABSTRACT: In DSM-III, DSM-III-R, and DSM-IV, obsessive-compulsive disorder (OCD) was classified as an anxiety disorder. In ICD-10, OCD is classified separately from the anxiety disorders, although within the same larger category as anxiety disorders (as one of the "neurotic, stress-related, and somatoform disorders"). Ongoing advances in our understanding of OCD and other anxiety disorders have raised the question of whether OCD should continue to be classified with the anxiety disorders in DSM-V. This review presents a number of options and preliminary recommendations to be considered for DSM-V. Evidence is reviewed for retaining OCD in the category of anxiety disorders, and for moving OCD to a separate category of obsessive-compulsive (OC)-spectrum disorders, if such a category is included in DSM-V. Our preliminary recommendation is that OCD be retained in the category of anxiety disorders but that this category also includes OC-spectrum disorders along with OCD. If this change is made, the name of this category should be changed to reflect this proposed change.
Depression and Anxiety 06/2010; 27(6):495-506. · 4.18 Impact Factor
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Katharine A. Phillips M.D,
Ph.D Dan J. Stein M.D,
Scott L Rauch M.D,
Eric Hollander M.D,
Brian A. Fallon M.D,
Arthur Barsky M.D,
Naomi Fineberg M.D,
David Mataix-Cols Ph.D,
Ph.D. Ygor Arzeno Ferrão M.D,
Sanjaya Saxena M.D, [......],
David Mataix‐Cols,
Ygor Arzeno Ferrão,
Sanjaya Saxena,
Sabine Wilhelm,
Megan M. Kelly,
Lee Anna Clark,
Anthony Pinto,
O. Joseph Bienvenu,
Joanne Farrow,
James Leckman
[show abstract]
[hide abstract]
ABSTRACT: The obsessive–compulsive (OC) spectrum has been discussed in the literature for two decades. Proponents of this concept propose that certain disorders characterized by repetitive thoughts and/or behaviors are related to obsessive–compulsive disorder (OCD), and suggest that such disorders be grouped together in the same category (i.e. grouping, or “chapter”) in DSM. This article addresses this topic and presents options and preliminary recommendations to be considered for DSM-V. The article builds upon and extends prior reviews of this topic that were prepared for and discussed at a DSM-V Research Planning Conference on Obsessive–Compulsive Spectrum Disorders held in 2006. Our preliminary recommendation is that an OC-spectrum grouping of disorders be included in DSM-V. Furthermore, we preliminarily recommend that consideration be given to including this group of disorders within a larger supraordinate category of “Anxiety and Obsessive–Compulsive Spectrum Disorders.” These preliminary recommendations must be evaluated in light of recommendations for, and constraints upon, the overall structure of DSM-V. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc.
Depression and Anxiety 05/2010; 27(6):528 - 555. · 4.18 Impact Factor
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James F Leckman,
Damiaan Denys,
H Blair Simpson,
David Mataix-Cols,
Eric Hollander,
Sanjaya Saxena,
Euripedes C Miguel, Scott L Rauch,
Wayne K Goodman,
Katharine A Phillips,
Dan J Stein
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ABSTRACT: Since the publication of the DSM-IV in 1994, research on obsessive-compulsive disorder (OCD) has continued to expand. It is timely to reconsider the nosology of this disorder, assessing whether changes to diagnostic criteria as well as subtypes and specifiers may improve diagnostic validity and clinical utility.
The existing criteria were evaluated. Key issues were identified. Electronic databases of PubMed, ScienceDirect, and PsycINFO were searched for relevant studies.
This review presents a number of options and preliminary recommendations to be considered for DSM-V. These include: (1) clarifying and simplifying the definition of obsessions and compulsions (criterion A); (2) possibly deleting the requirement that people recognize that their obsessions or compulsions are excessive or unreasonable (criterion B); (3) rethinking the clinical significance criterion (criterion C) and, in the interim, possibly adjusting what is considered "time-consuming" for OCD; (4) listing additional disorders to help with the differential diagnosis (criterion D); (5) rethinking the medical exclusion criterion (criterion E) and clarifying what is meant by a "general medical condition"; (6) revising the specifiers (i.e., clarifying that OCD can involve a range of insight, in addition to "poor insight," and adding "tic-related OCD"); and (7) highlighting in the DSM-V text important clinical features of OCD that are not currently mentioned in the criteria (e.g., the major symptom dimensions).
A number of changes to the existing diagnostic criteria for OCD are proposed. These proposed criteria may change as the DSM-V process progresses.
Depression and Anxiety 03/2010; 27(6):507-27. · 4.18 Impact Factor
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ABSTRACT: Bipolar disorder is characterized by recurrent episodes of depression and/or mania along with interepisodic mood symptoms that interfere with psychosocial functioning. Despite periods of symptomatic recovery, individuals with bipolar disorder often continue to experience impairments in psychosocial functioning, particularly occupational functioning. Two determinants of psychosocial functioning of euthymic (neither fully depressed nor manic) individuals with bipolar disorder are residual depressive symptoms and cognitive impairment (i.e., difficulties with executive functioning, attention, and memory). The present study explored whether a new cognitive remediation (CR) treatment designed to treat residual depressive symptoms and, for the first time to the best of our knowledge, address cognitive impairment would be associated with improvement in psychosocial functioning in individuals with bipolar disorder. Following a neuropsychological and clinical assessment 18 individuals with DSM-IV bipolar disorder were treated with 14 individual sessions of CR. Results indicated that at the end of treatment, as well as at the 3-months follow-up, patients showed lower residual depressive symptoms, and increased occupational, as well as overall psychosocial functioning. Pretreatment neuropsychological impairment predicted treatment response. Improvements in executive functioning were associated with improvements in occupational functioning. These findings suggest that treating residual depressive symptoms and cognitive impairment may be an avenue to improving occupational and overall functioning in individuals with bipolar disorder.
CNS Neuroscience & Therapeutics 11/2009; 16(5):298-307. · 4.44 Impact Factor
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ABSTRACT: This article reviews current issues in the diagnosis and treatment of obsessive-compulsive disorder (OCD). The introduction of the selective serotonin reuptake inhibitors and of cognitive-behavioral therapy were significant advances for treating OCD. Nevertheless, there is a need to improve awareness of OCD and its management, and to develop novel approaches to treatment-refractory patients. Although the diagnostic criteria for OCD have remained unchanged for some time, there are several areas where potential modification may be useful. There is a growing evidence base on OCD symptom dimensions and subtyping, and it is timely to consider incorporating some of these emerging data into diagnostic classification systems.
The Psychiatric clinics of North America 10/2009; 32(3):665-85. · 1.87 Impact Factor
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ABSTRACT: Recent neuroimaging research has revealed functional abnormalities in the anterior cingulate cortex, amygdala, and hippocampus in individuals with posttraumatic stress disorder (PTSD).
To determine whether resting functional abnormalities found in PTSD are acquired characteristics or familial risk factors.
Cross-sectional design including identical twins discordant for trauma exposure.
Academic medical center.
Combat-exposed veterans with PTSD (n = 14) and their identical co-twins not exposed to combat (n = 14) as well as combat-exposed veterans without PTSD (n = 19) and their identical co-twins not exposed to combat (n = 19).
We used positron emission tomography and fluorodeoxyglucose 18 to examine resting regional cerebral metabolic rate for glucose (rCMRglu).
Veterans with PTSD and their co-twins had significantly higher resting rCMRglu in the dorsal anterior cingulate cortex/midcingulate cortex (dACC/MCC) compared with veterans without PTSD and their co-twins. Resting rCMRglu in the dACC/MCC in unexposed co-twins was positively correlated with combat exposure severity, PTSD symptom severity, and alcohol use in their exposed twins.
Enhanced resting metabolic activity in the dACC/MCC appears to represent a familial risk factor for developing PTSD after exposure to psychological trauma.
Archives of general psychiatry 10/2009; 66(10):1099-107. · 12.26 Impact Factor
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ABSTRACT: A clinical characteristic of posttraumatic stress disorder (PTSD) is persistently elevated fear responses to stimuli associated with the traumatic event. The objective herein is to determine whether extinction of fear responses is impaired in PTSD and whether such impairment is related to dysfunctional activation of brain regions known to be involved in fear extinction, viz., amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC), and dorsal anterior cingulate cortex (dACC).
Sixteen individuals diagnosed with PTSD and 15 trauma-exposed non-PTSD control subjects underwent a 2-day fear conditioning and extinction protocol in a 3-T functional magnetic resonance imaging scanner. Conditioning and extinction training were conducted on day 1. Extinction recall (or extinction memory) test was conducted on day 2 (extinguished conditioned stimuli presented in the absence of shock). Skin conductance response (SCR) was scored throughout the experiment as an index of the conditioned response.
The SCR data revealed no significant differences between groups during acquisition and extinction of conditioned fear on day 1. On day 2, however, PTSD subjects showed impaired recall of extinction memory. Analysis of functional magnetic resonance imaging data showed greater amygdala activation in the PTSD group during day 1 extinction learning. During extinction recall, lesser activation in hippocampus and vmPFC and greater activation in dACC were observed in the PTSD group. The magnitude of extinction memory across all subjects was correlated with activation of hippocampus and vmPFC during extinction recall testing.
These findings support the hypothesis that fear extinction is impaired in PTSD. They further suggest that dysfunctional activation in brain structures that mediate fear extinction learning, and especially its recall, underlie this impairment.
Biological psychiatry 09/2009; 66(12):1075-82. · 8.93 Impact Factor
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ABSTRACT: Psychiatric neurosurgery, specifically stereotactic ablation, has continued since the 1940s, mainly at a few centers in Europe and the US. Since the late 1990s, the resurgence of interest in this field has been remarkable; reports of both lesion procedures and the newer technique of deep brain stimulation (DBS) have increased rapidly. In early 2009, the US FDA granted limited humanitarian approval for DBS for otherwise intractable obsessive-compulsive disorder (OCD), the first such approval for a psychiatric illness. Several factors explain the emergence of DBS and continued small-scale use of refined lesion procedures. DBS and stereotactic ablation have been successful and widely used for movement disorders. There remains an unmet clinical need: current drug and behavioral treatments offer limited benefit to some seriously ill people. Understandings of the neurocircuitry underlying psychopathology and the response to treatment, while still works in progress, are much enhanced. Here, we review modern lesion procedures and DBS for OCD in the context of neurocircuitry. A key issue is that clinical benefit can be obtained after surgeries targeting different brain structures. This fits well with anatomical models, in which circuits connecting orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), basal ganglia, and thalamus are central to OCD pathophysiology and treatment response. As in movement disorders, dedicated interdisciplinary teams, here led by psychiatrists, are required to implement these procedures and maintain care for patients so treated. Available data, although limited, support the promise of stereotactic ablation or DBS in carefully selected patients. Benefit in such cases appears not to be confined to obsessions and compulsions, but includes changes in affective state. Caution is imperative, and key issues in long-term management of psychiatric neurosurgery patients deserve focused attention. DBS and contemporary ablation also present different patterns of potential benefits and burdens. Translational research to elucidate how targeting specific nodes in putative OCD circuitry might lead to therapeutic gains is accelerating in tandem with clinical use.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 09/2009; 35(1):317-36. · 6.99 Impact Factor
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ABSTRACT: A cardinal feature of schizophrenia is the poor comprehension, or misinterpretation, of the emotional meaning of social interactions and events, which can sometimes take the form of a persecutory delusion. It has been shown that the comprehension of the emotional meaning of the social world involves a midline paralimbic cortical network. However, the function of this network during emotional appraisals in patients with schizophrenia is not well understood. In this study, hemodynamic responses were measured in 14 patients with schizophrenia and 18 healthy subjects during the evaluation of descriptions of social situations with negative, positive, and neutral affective valence. The healthy and schizophrenia groups displayed opposite patterns of responses to emotional and neutral social situations within the medial prefrontal and posterior cingulate cortices--healthy participants showed greater activity to the emotional compared to the neutral situations, while patients exhibited greater responses to the neutral compared to the emotional situations. Moreover, the magnitude of the response within bilateral cingulate gyri to the neutral social stimuli predicted delusion severity in the patients with schizophrenia. These findings suggest that impaired functioning of cortical midline structures in schizophrenia may underlie faulty interpretations of social events, contributing to delusion formation.
Schizophrenia Bulletin 08/2009; 37(1):164-76. · 8.80 Impact Factor
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ABSTRACT: Emotional interference tasks may be useful in probing anterior cingulate cortex (ACC) function to understand abnormal attentional study in individuals with specific phobia.
In a 3 T functional MRI study, individuals with specific phobias of the animal subtype (SAP, n=12) and healthy comparison (HC) adults (n=12) completed an event-related emotional counting Stroop task. Individuals were presented phobia-related, negative, and neutral words and were instructed to report via button press the number of words displayed on each trial.
Compared to the HC group, the SAP group exhibited greater rostral ACC activation (i.e., greater response to phobia-related words than neutral words). In this same contrast, HCs exhibited greater right amygdala and posterior insula activations as well as greater thalamic deactivation than the SAP group. Both groups exhibited anterior cingulate, dorsomedial prefrontal cortex, inferior frontal gyrus/insula, and amygdala activations as well as thalamic deactivation. Psychophysiological interaction analysis highlighted a network of activation in these regions in response to phobia-related words in the SAP group.
Taken together, these findings implicate a circuit of dysfunction, which is linked to attention abnormalities in individuals with SAP.
Depression and Anxiety 06/2009; 26(9):796-805. · 4.18 Impact Factor
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Antonia Vitalo,
Jonathan Fricchione,
Monica Casali,
Yevgeny Berdichevsky,
Elizabeth A Hoge, Scott L Rauch,
Francois Berthiaume,
Martin L Yarmush,
Herbert Benson,
Gregory L Fricchione,
John B Levine
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ABSTRACT: Environmental enrichment (EE) fosters attachment behavior through its effect on brain oxytocin levels in the hippocampus and other brain regions, which in turn modulate the hypothalamic-pituitary axis (HPA). Social isolation and other stressors negatively impact physical healing through their effect on the HPA. Therefore, we reasoned that: 1) provision of a rat EE (nest building with Nestlets) would improve wound healing in rats undergoing stress due to isolation rearing and 2) that oxytocin would have a similar beneficial effect on wound healing.
In the first two experiments, we provided isolation reared rats with either EE or oxytocin and compared their wound healing to group reared rats and isolation reared rats that did not receive Nestlets or oxytocin. In the third experiment, we examined the effect of Nestlets on open field locomotion and immediate early gene (IEG) expression. We found that isolation reared rats treated with Nestlets a) healed significantly better than without Nestlets, 2) healed at a similar rate to rats treated with oxytocin, 3) had decreased hyperactivity in the open field test, and 4) had normalized IEG expression in brain hippocampus.
This study shows that when an EE strategy or oxytocin is given to isolation reared rats, the peripheral stress response, as measured by burn injury healing, is decreased. The findings indicate an association between the effect of nest making on wound healing and administration of the pro-bonding hormone oxytocin. Further elucidation of this animal model should lead to improved understanding of how EE strategies can ameliorate poor wound healing and other symptoms that result from isolation stress.
PLoS ONE 02/2009; 4(5):e5523. · 4.09 Impact Factor
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ABSTRACT: To examine the effects of sleep on fear conditioning, extinction, extinction recall, and generalization of extinction recall in healthy humans.
During the Conditioning phase, a mild, 0.5-sec shock followed conditioned stimuli (CS+s), which consisted of 2 differently colored lamps. A third lamp color was interspersed but never reinforced (CS-). Immediately after Conditioning, one CS+ was extinguished (CS+E) by presentation without shocks (Extinction phase). The other CS+ went unextinguished (CS+U). Twelve hours later, following continuous normal daytime waking (Wake group, N=27) or an equal interval containing a normal night's sleep (Sleep group, N=26), conditioned responses (CRs) to all CSs were measured (Extinction Recall phase). It was hypothesized that the Sleep versus Wake group would show greater extinction recall and/or generalization of extinction recall from the CS+E to the CS+U.
Academic medical center.
Paid normal volunteers.
Square-root transformed skin conductance response (SCR) measured conditioned responding. During Extinction Recall, the Group (Wake or Sleep) x CS+ Type (CS+E or CS+U) interaction was significant (P = 0.04). SCRs to the CS+E did not differ between groups, whereas SCRs to the CS+U were significantly smaller in the Sleep group. Additionally, SCRs were significantly larger to the CS+U than CS+E in the Wake but not the Sleep group.
After sleep, extinction memory generalized from an extinguished conditioned stimulus to a similarly conditioned but unextinguished stimulus. Clinically, adequate sleep may promote generalization of extinction memory from specific stimuli treated during exposure therapy to similar stimuli later encountered in vivo.
Sleep 02/2009; 32(1):19-26. · 5.05 Impact Factor
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ABSTRACT: Verbal learning and strategic processing deficits are common sequelae of traumatic brain injury (TBI); however, the neurophysiological mechanisms underlying such deficits remain poorly understood.
We performed functional magnetic resonance imaging (fMRI) in 25 individuals with chronic TBI (>1 year after injury) and 20 matched healthy controls. Subjects were scanned while encoding word lists, with free recall and recognition assessed after each scanning run. To vary the strategic processing load, participants learned semantically unrelated words (Unrelated condition), semantically related words under null instruction conditions (Spontaneous condition), and semantically related words following training on the use of a semantic clustering strategy (Directed condition).
Behavioral performance on recall, recognition, and semantic clustering improved significantly as follows: Unrelated < Spontaneous < Directed. Individuals with TBI exhibited impaired yet parallel behavioral performance relative to control participants. The fMRI measures of brain activity during verbal encoding revealed decreased activity in participants with TBI relative to controls in left dorsolateral prefrontal cortex (DLPFC; BA 9) and in a region spanning the left angular and supramarginal gyri (BA 39/40). Functional connectivity analysis revealed evidence of a functional-but not anatomical-breakdown in the connectivity between the DLPFC and other regions specifically when participants with TBI were directed to use the semantic encoding strategy.
After TBI, the DLPFC appears to be decoupled from other active brain regions specifically when strategic control is required. We hypothesize that approaches designed to help re-couple DLPFC under such conditions may aid TBI cognitive rehabilitation.
Neurorehabilitation and neural repair 01/2009; 23(3):226-36. · 4.49 Impact Factor
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ABSTRACT: Functional magnetic resonance imaging (fMRI) studies have documented abnormalities in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex in bipolar disorder in the context of working memory tasks. It is increasingly recognized that DLPFC regions play a role in mood regulation and the integration of emotion and cognition. The purpose of the present study was to investigate with fMRI the interaction between acute sadness and working memory functioning in individuals with bipolar disorder.
Nine depressed individuals with DSM-IV bipolar I disorder (BP-I) and 17 healthy control participants matched for age, gender, education, and IQ completed a 2-back working memory paradigm under no mood induction, neutral state, or acute sadness conditions while undergoing fMRI scanning. Functional MRI data were analyzed with SPM2 using a random-effects model.
Behaviorally, BP-I subjects performed equally well as control participants on the 2-back working memory paradigm. Compared to control participants, individuals with BP-I were characterized by more sadness-specific activation increases in the left DLPFC (BA 9/46) and left dorsal anterior cingulate (dACC).
Our study documents sadness-specific abnormalities in the left DLPFC and dACC in bipolar disorder that suggest difficulties in the integration of emotion (sadness) and cognition. These preliminary findings require further corroboration with larger sample sizes of medication-free subjects.
Bipolar Disorders 01/2009; 10(8):928-42. · 5.29 Impact Factor
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Antonia Vitalo,
Jonathan Fricchione,
Monica Casali,
Yevgeny Berdichevsky,
Elizabeth A Hoge, Scott L Rauch,
Francois Berthiaume,
Martin L Yarmush,
Herbert Benson,
Gregory L Fricchione,
John B Levine
[show abstract]
[hide abstract]
ABSTRACT: Background: Environmental enrichment (EE) fosters attachment behavior through its effect on brain oxytocin levels in the hippocampus and other brain regions, which in turn modulate the hypothalamic-pituitary axis (HPA). Social isolation and other stressors negatively impact physical healing through their effect on the HPA. Therefore, we reasoned that: 1) provision of a rat EE (nest building with NestletsH) would improve wound healing in rats undergoing stress due to isolation rearing and 2) that oxytocin would have a similar beneficial effect on wound healing. Methodology/Principal Findings: In the first two experiments, we provided isolation reared rats with either EE or oxytocin and compared their wound healing to group reared rats and isolation reared rats that did not receive Nestlets or oxytocin. In the third experiment, we examined the effect of Nestlets on open field locomotion and immediate early gene (IEG) expression. We found that isolation reared rats treated with Nestlets a) healed significantly better than without Nestlets, 2) healed at a similar rate to rats treated with oxytocin, 3) had decreased hyperactivity in the open field test, and 4) had normalized IEG expression in brain hippocampus. Conclusions/Significance: This study shows that when an EE strategy or oxytocin is given to isolation reared rats, the peripheral stress response, as measured by burn injury healing, is decreased. The findings indicate an association between the effect of nest making on wound healing and administration of the pro-bonding hormone oxytocin. Further elucidation of this animal model should lead to improved understanding of how EE strategies can ameliorate poor wound healing and other symptoms that result from isolation stress.
PLoS ONE 01/2009; 4. · 4.09 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Schizophrenia is associated with abnormalities in emotional processing and social cognition, which might result from disruption of the underlying neural mechanism(s) governing emotional learning and memory. To investigate this possibility, we measured the acquisition and extinction of conditioned fear responses and delayed recall of extinction in schizophrenia and control subjects.
Twenty-eight schizophrenia and 18 demographically matched control subjects underwent a 2-day fear conditioning, extinction learning, and extinction recall procedure, in which skin conductance response (SCR) magnitude was used as the index of conditioned responses.
During fear acquisition, 83% of the control subjects and 57% of the patients showed autonomic responsivity ("responders"), and the patients showed larger SCRs to the stimulus that was not paired with the unconditioned stimulus (CS-) than the control subjects. Within the responder group, there was no difference between the patients and control subjects in levels of extinction learning; however, the schizophrenia patients showed significant impairment, relative to the control subjects, in context-dependent recall of the extinction memory. In addition, delusion severity in the patients correlated with baseline skin conductance levels.
These data are consistent with prior evidence for a heightened neural response to innocuous stimuli in schizophrenia and elevated arousal levels in psychosis. The finding of deficient extinction recall in schizophrenia patients who showed intact extinction learning suggests that schizophrenia is associated with a disturbance in the neural processes supporting emotional memory.
Biological psychiatry 12/2008; 65(6):455-63. · 8.93 Impact Factor
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Donald A Malone,
Darin D Dougherty,
Ali R Rezai,
Linda L Carpenter,
Gerhard M Friehs,
Emad N Eskandar, Scott L Rauch,
Steven A Rasmussen,
Andre G Machado,
Cynthia S Kubu,
Audrey R Tyrka,
Lawrence H Price,
Paul H Stypulkowski,
Jonathon E Giftakis,
Mark T Rise,
Paul F Malloy,
Stephen P Salloway,
Benjamin D Greenberg
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ABSTRACT: We investigated the use of deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) for treatment refractory depression.
Fifteen patients with chronic, severe, highly refractory depression received open-label DBS at three collaborating clinical sites. Electrodes were implanted bilaterally in the VC/VS region. Stimulation was titrated to therapeutic benefit and the absence of adverse effects. All patients received continuous stimulation and were followed for a minimum of 6 months to longer than 4 years. Outcome measures included the Hamilton Depression Rating Scale-24 item (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Global Assessment of Function Scale (GAF).
Significant improvements in depressive symptoms were observed during DBS treatment. Mean HDRS scores declined from 33.1 at baseline to 17.5 at 6 months and 14.3 at last follow-up. Similar improvements were seen with the MADRS (34.8, 17.9, and 15.7, respectively) and the GAF (43.4, 55.5, and 61.8, respectively). Responder rates with the HDRS were 40% at 6 months and 53.3% at last follow-up (MADRS: 46.7% and 53.3%, respectively). Remission rates were 20% at 6 months and 40% at last follow-up with the HDRS (MADRS: 26.6% and 33.3%, respectively). The DBS was well-tolerated in this group.
Deep brain stimulation of the VC/VS offers promise for the treatment of refractory major depression.
Biological psychiatry 11/2008; 65(4):267-75. · 8.93 Impact Factor
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Jack F Samuels,
O Joseph Bienvenu,
Anthony Pinto,
Dennis L Murphy,
John Piacentini, Scott L Rauch,
Abby J Fyer,
Marco A Grados,
Benjamin D Greenberg,
James A Knowles,
James T McCracken,
Bernadette Cullen,
Mark A Riddle,
Steven A Rasmussen,
David L Pauls,
Kung-Yee Liang,
Rudolf Hoehn-Saric,
Ann E Pulver,
Gerald Nestadt
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ABSTRACT: Little is known about whether the clinical correlates of hoarding behavior are different in men and women with obsessive-compulsive disorder (OCD). In the current study, we evaluated the association of hoarding with categories of obsessions and compulsions, psychiatric disorders, personality dimensions, and other clinical characteristics separately in 151 men and 358 women with OCD who were examined during the OCD Collaborative Genetics Study. We found that, among men but not women, hoarding was associated with aggressive, sexual, and religious obsessions and checking compulsions. In men, hoarding was associated with generalized anxiety disorder and tics whereas, among women, hoarding was associated with social phobia, post-traumatic stress disorder, body dysmorphic disorder, nail biting, and skin picking. In women but not men, hoarding was associated with schizotypal and dependent personality disorder dimensions, and with low conscientiousness. These findings indicate that specific clinical correlates of hoarding in OCD are different in men and women and may reflect sex-specific differences in the course, expression, and/or etiology of hoarding behavior in OCD.
Behaviour research and therapy 10/2008; 46(9):1040-6. · 3.00 Impact Factor
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Anthony Pinto,
Benjamin D Greenberg,
Marco A Grados,
O Joseph Bienvenu,
Jack F Samuels,
Dennis L Murphy,
Gregor Hasler,
Robert L Stout, Scott L Rauch,
Yin Y Shugart, [......],
James T McCracken,
John Piacentini,
Ying Wang,
Virginia L Willour,
Bernadette Cullen,
Kung-Yee Liang,
Rudolf Hoehn-Saric,
Mark A Riddle,
Steven A Rasmussen,
Gerald Nestadt
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[hide abstract]
ABSTRACT: Despite progress in identifying homogeneous subphenotypes of obsessive-compulsive disorder (OCD) through factor analysis of the Yale Brown Obsessive-Compulsive Scale Symptom Checklist (YBOCS-SC), prior solutions have been limited by a reliance on presupposed symptom categories rather than discrete symptoms. Furthermore, there have been few attempts to evaluate the familiality of OCD symptom dimensions. The purpose of this study was to extend prior work by this collaborative group in category-based dimensions by conducting the first-ever exploratory dichotomous factor analysis using individual OCD symptoms, comparing these results to a refined category-level solution, and testing the familiality of derived factors. Participants were 485 adults in the six-site OCD Collaborative Genetics Study, diagnosed with lifetime OCD using semi-structured interviews. YBOCS-SC data were factor analyzed at both the individual item and symptom category levels. Factor score intraclass correlations were calculated using a subsample of 145 independent affected sib pairs. The item- and category-level factor analyses yielded nearly identical 5-factor solutions. While significant sib-sib associations were found for four of the five factors, Hoarding and Taboo Thoughts were the most robustly familial (r ICC>or=0.2). This report presents considerable converging evidence for a five-factor structural model of OCD symptoms, including separate factor analyses employing individual symptoms and symptom categories, as well as sibling concordance. The results support investigation of this multidimensional model in OCD genetic linkage studies.
Psychiatry Research 08/2008; 160(1):83-93. · 2.52 Impact Factor
