Sierra Pacific Mental Illness Research

Palo Alto, CA, United States

Sierra Pacific Mental Illness Research

Palo Alto, CA, United States
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Korgaonkar M.S.,University of Sydney | Grieve S.M.,University of Sydney | Grieve S.M.,Brain Resource | Etkin A.,Stanford University | And 5 more authors.
Neuropsychopharmacology | Year: 2013

Functional neuroimaging studies have implicated dysregulation of prefrontal circuits in major depressive disorder (MDD), and these circuits are a viable target for predicting treatment outcomes. However, because of the heterogeneity of tasks and samples used in studies to date, it is unclear whether the central dysfunction is one of prefrontal hyperreactivity or hyporeactivity. We used a standardized battery of tasks and protocols for functional magnetic resonance imaging, to identify the common vs the specific prefrontal circuits engaged by these tasks in the same 30 outpatients with MDD compared with 30 matched, healthy control participants, recruited as part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D). Reflecting cognitive neuroscience theory and established evidence, the battery included cognitive tasks designed to assess functions of selective attention, sustained attention-working memory and response inhibition, and emotion tasks to assess explicit conscious and implicit nonconscious viewing of facial emotion. MDD participants were distinguished by a distinctive biosignature of: hypoactivation of the dorsolateral prefrontal cortex during working memory updating and during conscious negative emotion processing; hyperactivation of the dorsomedial prefrontal cortex during working memory and response inhibition cognitive tasks and hypoactivation of the dorsomedial prefrontal during conscious processing of positive emotion. These results show that the use of standardized tasks in the same participants provides a way to tease out prefrontal circuitry dysfunction related to cognitive and emotional functions, and not to methodological or sample variations. These findings provide the frame of reference for identifying prefrontal biomarker predictors of treatment outcomes in MDD. © 2013 American College of Neuropsychopharmacology. All rights reserved.


Trockel M.,Sierra Pacific Mental Illness Research | Trockel M.,Stanford University | Karlin B.E.,Health-U | Karlin B.E.,Education Development Center Inc. | And 6 more authors.
Sleep | Year: 2015

Objective: To examine the effects of cognitive behavioral therapy for insomnia (CBT-I) on suicidal ideation among Veterans with insomnia. Design: Longitudinal data collected in the course of an uncontrolled evaluation of a large-scale CBT-I training program. Setting: Outpatient and residential treatment facilities. Participants: Four hundred five Veterans presenting for treatment of insomnia. Interventions: Cognitive behavioral therapy for insomnia. Measurement and Results: At baseline, 32% of patients, compared with 21% at final assessment, endorsed some level of suicidal ideation [χ2(df = 1) = 125; P < 0.001]. After adjusting for demographic variables and baseline insomnia severity, each 7-point decrease in Insomnia Severity Index score achieved during CBT-I treatment was associated with a 65% (odds ratio = 0.35; 95% confidence intervals = 0.24 to 0.52) reduction in odds of suicidal ideation. The effect of change in insomnia severity on change in depression severity was also significant. After controlling for change in depression severity and other variables in the model, the effect of change in insomnia severity on change in suicidal ideation remained significant. Conclusion: This evaluation of the largest dissemination of cognitive behavioral therapy for insomnia (CBT-I) in the United States found a clinically meaningful reduction in suicidal ideation among Veterans receiving CBT-I. The mechanisms by which effective treatment of insomnia with CBT-I reduces suicide risk are unknown and warrant investigation. The current results may have significant public health implications for preventing suicide among Veterans.


Karlin B.E.,Health-U | Brown G.K.,Veterans Integrated Service Network 4 Mental Illness Research | Brown G.K.,University of Pennsylvania | Trockel M.,Stanford University | And 4 more authors.
Journal of Consulting and Clinical Psychology | Year: 2012

Objective: The Department of Veterans Affairs (VA) health care system is nationally disseminating and implementing cognitive behavioral therapy for depression (CBT-D). The current article evaluates therapist and patient-level outcomes associated with national training in and implementation of CBT-D in the VA health care system. Method: Therapist competencies were assessed with the Cognitive Therapy Rating Scale (CTRS). Patient outcomes were assessed with the Beck Depression Inventory-II and the World Health Organization Quality of Life-BREF. Therapeutic alliance was assessed with the Working Alliance Inventory-Short Revised. Two-hundred twenty-one therapists have received training, and 356 veteran patients have received treatment through the VA CBT-D Training Program. Results: Of therapists who have participated in the program, 182 (82%) completed all training requirements and achieved competency, reflected by a score of 40 on the CTRS. Of 356 patients, nearly 70% completed 10 or more sessions or improved sufficiently to stop therapy before the 10th session. Mean depression scores decreased by approximately 40% from initial to later treatment phase. Effect sizes of changes ranged from d = 0.39 to d = 0.74 for quality of life and from d = 0.47 to d = 0.66 for therapeutic alliance measures. Conclusion: National training in and implementation of CBT-D within the VA health care system is associated with significant, positive therapist training outcomes, as evidenced by increases in CBT core competencies. The implementation of the protocol by newly trained CBT-D therapists is associated with significantly improved patient outcomes, as evidenced by large decreases in depression and improvements in quality of life. © 2012 American Psychological Association.


Chen A.C.,Stanford University | Chen A.C.,Sierra Pacific Mental Illness Research | Etkin A.,Stanford University | Etkin A.,Sierra Pacific Mental Illness Research
Neuropsychopharmacology | Year: 2013

Anxiety disorders are a diverse group of clinical states. Post-traumatic stress disorder (PTSD) and generalized anxiety disorder (GAD), eg, share elevated anxiety symptoms, but differ with respect to fear-related memory dysregulation. As the hippocampus is implicated in both general anxiety and fear memory, it may be an important brain locus for mapping the similarities and differences among anxiety disorders. Anxiety and fear also functionally associate with different subdivisions of the hippocampus along its longitudinal axis: the human posterior (rodent dorsal) hippocampus is involved in memory, through connectivity with the medial prefrontal-medial parietal default-mode network, whereas the anterior (rodent ventral) hippocampus is involved in anxiety, through connectivity with limbic-prefrontal circuits. We examined whether differential hippocampal network functioning may help account for similarities and differences in symptoms in PTSD and GAD. Network-sensitive functional magnetic resonance imaging-based resting-state intrinsic connectivity methods, along with task-based assessment of posterior hippocampal/default-mode network function, were used. As predicted, in healthy subjects resting-state connectivity dissociated between posterior hippocampal connectivity with the default-mode network, and anterior hippocampal connectivity to limbic-prefrontal circuitry. The posterior hippocampus and the associated default-mode network, across both resting-state connectivity and task-based measures, were perturbed in PTSD relative to each of the other groups. By contrast, we found only modest support for similarly blunted anterior hippocampal connectivity across both patient groups. These findings provide new insights into the neural circuit-level dysfunctions that account for similar vs different features of two major anxiety disorders, through a translational framework built on animal work and carefully selected clinical disorders.


Etkin A.,Stanford University | Etkin A.,Sierra Pacific Mental Illness Research | Schatzberg A.F.,Stanford University | Schatzberg A.F.,Sierra Pacific Mental Illness Research
American Journal of Psychiatry | Year: 2011

Objective: Anxiety and depressive disorders are both associated with abnormalities in the processing and regulation of emotion. However, little is known about the similarities and differences between anxiety and depression at the neural level. The authors examined emotional conflict processing using a salient stimulus associated with observable and interpretable behavioral outcomes and with activation in limbic and prefrontal regions implicated in anxiety and depression. Method: Thirty-two healthy comparison subjects, 18 patients with generalized anxiety disorder only, 14 patients with major depression only, and 25 patients with comorbid generalized anxiety disorder and major depression were studied using functional MRI while they performed an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect label words. The authors used behavioral and neural measures to compare trial-by-trial changes in conflict regulation, a test of implicit regulation of emotional processing.Results: Behavioral data indicated that only patients with generalized anxiety (i.e., the anxiety-only and comorbid groups) failed to implicitly regulate emotional conflict. By contrast, deficits in activation and connectivity of the ventral anterior cingulate and amygdala, areas previously implicated in regulating emotional conflict, were found in all patient groups. Depression- only patients, however, compensated for this deficit by also activating the left and right anterior lateral prefrontal cortices, in which activity was correlated with behavioral evidence of successful implicit regulation, thus mediating the disorderspecificity of the behavioral phenotype. Conclusions: These data support the existence of a common abnormality in anxiety and depression in the ventral cingulate and the amygdala, which may be related to a shared genetic etiology. Compensatory engagement of cognitive control circuitry in depression illustrates how the complex nature of psychopathology arises from the interaction of deficits and compensation, all of which can occur at an implicit level.


Eftekhari A.,National Center for PTSD | Ruzek J.I.,National Center for PTSD | Crowley J.J.,National Center for PTSD | Rosen C.S.,National Center for PTSD | And 2 more authors.
JAMA Psychiatry | Year: 2013

IMPORTANCE: Posttraumatic stress disorder (PTSD) is a pervasive and often debilitating condition that affects many individuals in the general population and military service members. Effective treatments for PTSD are greatly needed for both veterans returning from Iraq and Afghanistan and veterans of other eras. Prolonged exposure (PE) therapy has been shown to be highly efficacious in clinical trials involving women with noncombat trauma, but there are limited data on its effectiveness in real-world clinical practice settings and with veterans. OBJECTIVE: To evaluate the effectiveness of PE as implemented with veterans with PTSD in a large health care system. DESIGN, SETTING, AND PARTICIPANTS: This evaluation included 1931 veterans treated by 804 clinicians participating in the Department of Veterans Affairs (VA) PE Training Program. After completing a 4-day experiential PE training workshop, clinicians implemented PE (while receiving consultation) with a minimum of 2 veteran patients who had a primary diagnosis of PTSD. MAIN OUTCOMES AND MEASURES: Changes in PTSD and depression symptoms were assessed with the PTSD Checklist and the Beck Depression Inventory II, measured at baseline and at the final treatment session. Multiple and single imputation were used to estimate the posttest scores of patients who left treatment before completing 8 sessions. Demographic predictors of treatment dropout were also examined. RESULTS: Intent-to-treat analyses indicate that PE is effective in reducing symptoms of both PTSD (pre-post d = 0.87) and depression (pre-post d = 0.66), with effect sizes comparable to those reported in previous efficacy trials. The proportion of patients screening positive for PTSD on the PTSD Checklist decreased from 87.6%to 46.2%. CONCLUSIONS: Clinically significant reductions in PTSD symptoms were achieved among male and female veterans of all war eras and veterans with combat-related and non-combat-related PTSD. Results also indicate that PE is effective in reducing depression symptoms, even though depression is not a direct target of the treatment.


Jahshan C.,Sierra Pacific Mental Illness Research | Jahshan C.,University of California at Los Angeles | Wynn J.K.,Sierra Pacific Mental Illness Research | Wynn J.K.,University of California at Los Angeles | And 2 more authors.
Schizophrenia Research | Year: 2013

Patients with schizophrenia have well-established deficits in their ability to identify emotion from facial expression and tone of voice. In the visual modality, there is strong evidence that basic processing deficits contribute to impaired facial affect recognition in schizophrenia. However, few studies have examined the auditory modality for mechanisms underlying affective prosody identification. In this study, we explored links between different stages of auditory processing, using event-related potentials (ERPs), and affective prosody detection in schizophrenia. Thirty-six schizophrenia patients and 18 healthy control subjects received tasks of affective prosody, facial emotion identification, and tone matching, as well as two auditory oddball paradigms, one passive for mismatch negativity (MMN) and one active for P300. Patients had significantly reduced MMN and P300 amplitudes, impaired auditory and visual emotion recognition, and poorer tone matching performance, relative to healthy controls. Correlations between ERP and behavioral measures within the patient group revealed significant associations between affective prosody recognition and both MMN and P300 amplitudes. These relationships were modality specific, as MMN and P300 did not correlate with facial emotion recognition. The two ERP waves accounted for 49% of the variance in affective prosody in a regression analysis. Our results support previous suggestions of a relationship between basic auditory processing abnormalities and affective prosody dysfunction in schizophrenia, and indicate that both relatively automatic pre-attentive processes (MMN) and later attention-dependent processes (P300) are involved with accurate auditory emotion identification. These findings provide support for bottom-up (e.g., perceptually based) cognitive remediation approaches. © 2012 .


Etkin A.,Stanford University | Gyurak A.,Stanford University | Gyurak A.,Sierra Pacific Mental Illness Research | O'Hara R.,Stanford University
Dialogues in Clinical Neuroscience | Year: 2013

Deficits in brain networks that support cognitive regulatory functions are prevalent in many psychiatric disorders. Findings across neuropsychology and neuroimaging point to broad-based impairments that cross traditional diagnostic boundaries. These dysfunctions are largely separate from the classical symptoms of the disorders, and manifest in regulatory problems in both traditional cognitive and emotional domains. As such, they relate to the capacity of patients to engage effectively in their daily lives and activity, often persist even in the face of symptomatically effective treatment, and are poorly targeted by current treatments. Advances in cognitive neuroscience now allow us to ground an understanding of these cognitive regulatory deficits in the function and interaction of key brain networks. This emerging neurobiological understanding furthermore points to several promising routes for novel neuroscience-informed treatments targeted more specifically at improving cognitive function in a range of psychiatric disorders. © 2013, AICH-Servier Research Group.


Marusak H.A.,Wayne State University | Martin K.R.,Wayne State University | Etkin A.,Stanford University | Etkin A.,Sierra Pacific Mental Illness Research | Thomason M.E.,Wayne State University
Neuropsychopharmacology | Year: 2015

Early-life trauma is one of the strongest risk factors for later emotional psychopathology. Although research in adults highlights that childhood trauma predicts deficits in emotion regulation that persist decades later, it is unknown whether neural and behavioral changes that may precipitate illness are evident during formative, developmental years. This study examined whether automatic regulation of emotional conflict is perturbed in a high-risk urban sample of trauma-exposed children and adolescents. A total of 14 trauma-exposed and 16 age-, sex-, and IQ-matched comparison youth underwent functional MRI while performing an emotional conflict task that involved categorizing facial affect while ignoring an overlying emotion word. Engagement of the conflict regulation system was evaluated at neural and behavioral levels. Results showed that trauma-exposed youth failed to dampen dorsolateral prefrontal cortex activity and engage amygdala-pregenual cingulate inhibitory circuitry during the regulation of emotional conflict, and were less able to regulate emotional conflict. In addition, trauma-exposed youth showed greater conflict-related amygdala reactivity that was associated with diminished levels of trait reward sensitivity. These data point to a trauma-related deficit in automatic regulation of emotional processing, and increase in sensitivity to emotional conflict in neural systems implicated in threat detection. Aberrant amygdala response to emotional conflict was related to diminished reward sensitivity that is emerging as a critical stress-susceptibility trait that may contribute to the emergence of mental illness during adolescence. These results suggest that deficits in conflict regulation for emotional material may underlie heightened risk for psychopathology in individuals that endure early-life trauma. © 2015 American College of Neuropsychopharmacology. All rights reserved.


Sze J.A.,San Francisco Medical Center | Goodkind M.S.,Sierra Pacific Mental Illness Research | Goodkind M.S.,Stanford University | Gyurak A.,Stanford University | Levenson R.W.,University of California at Berkeley
Psychology and Aging | Year: 2012

Past studies on emotion recognition and aging have found evidence of age-related decline when emotion recognition was assessed by having participants detect single emotions depicted in static images of full or partial (e.g., eye region) faces. These tests afford good experimental control but do not capture the dynamic nature of real-world emotion recognition, which is often characterized by continuous emotional judgments and dynamic multimodal stimuli. Research suggests that older adults often perform better under conditions that better mimic real-world social contexts. We assessed emotion recognition in young, middle-aged, and older adults using two traditional methods (single emotion judgments of static images of faces and eyes) and an additional method in which participants made continuous emotion judgments of dynamic, multimodal stimuli (videotaped interactions between young, middle-aged, and older couples). Results revealed an Age × Test interaction. Largely consistent with prior research, we found some evidence that older adults performed worse than young adults when judging single emotions from images of faces (for sad and disgust faces only) and eyes (for older eyes only), with middle-aged adults falling in between. In contrast, older adults did better than young adults on the test involving continuous emotion judgments of dyadic interactions, with middle-aged adults falling in between. In tests in which target stimuli differed in age, emotion recognition was not facilitated by an age match between participant and target. These findings are discussed in terms of theoretical and methodological implications for the study of aging and emotional processing. © 2012 American Psychological Association.

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