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Principal Investigator: Milissa L Kaufman
Organization: MCLEAN HOSPITAL
Fiscal Year: 2024
Award: $761,347
Funding agency: National Institute of Mental Health
Dissociative symptoms in traumatized individuals are common, debilitating, and costly; however, little is
known about how its biological mechanisms interact with PTSD treatment. Traumatic dissociation broadly
encompasses a range of distinct, yet clinically interrelated symptoms: depersonalization, derealization,
amnesia, numbing, flashbacks, passive influence phenomena, and identity disturbances. Either alone or in
various combinations, these symptoms serve as diagnostic criteria and commonly associated features across
multiple psychiatric disorders. Traumatic dissociation is also associated with significant personal and societal
burden. Traumatized individuals with dissociative symptoms typically have co-occurring psychiatric conditions,
high rates of self-destructive behaviors and suicidality, and are disproportionate treatment utilizers. In addition,
they are at increased risk for attrition, non-response and relapse following treatment interventions. Despite the
significant and disabling nature of traumatic dissociative symptoms, little is known about the neurobiology of
these processes and targeted interventions do not exist.
PTSD treatment studies have neither looked at neural intermediate phenotypes of dissociation, nor how
these are associated with psychophysiological and digital phenotypes. Compared to clinical symptom
measures, these biological and in-the-moment digital markers of dissociation may more robustly map onto the
underlying core aspects of the disorder differentiating dissociation subtypes following childhood and adult
trauma. We propose to build upon our prior Exploratory R21 to now capture longitudinal multimodal phenotype
data related to dissociation, pre-, post- and during PTSD treatment modalities that include empirically-derived,
exposure-based components.
The goals of this study will be 1) to understand the differential biomarkers that map onto dissociative
symptoms, and 2) to understand how these biomarkers may best predict trajectory of response to empirically
based standard-of-care treatments. For each of these Aims, we will collect Neuroimaging, Physiology, and
Digital Phenotyping data, applying computational modeling with multimodal data to provide machine-learning
based, unbiased predictive models of dissociative intermediate phenotypes at baseline and longitudinally. This
naturalistic study will allow us to map the biology of dissociation, and importantly, the change in dissociative
symptoms and underlying biomarkers over time, using naturalistic evidenced-based treatment for PTSD in 130
treatment-seeking patients with PTSD, and a range of dissociative symptoms.
Successful completion of these Aims will provide a novel and powerful understanding of the biological
markers of dissociation subtypes following trauma exposure, and will identify biological mechanisms for
understanding and treating PTSD with dissociation.
Terms: <21+ years old><Adult><Adult Human><After Care><After-Treatment><Aftercare><Amnesia><Amnesia-Memory Loss><Anterior><Arousal><Attention><Behavioral><Biological><Biological Markers><Biology><Brain><Brain Nervous System><Brain region><Childhood><Clinical><Clinical Trials><Complex><Computer Models><Computerized Models><Data><Depersonalization><Derealizations><Diagnosis><Digital biomarker><Dimensions><Disabling><Disease><Disorder><Dissociation><Dorsal><Ecological momentary assessment><Emotional><Encephalon><Environment><Equipment and supply inventories><Evidence based treatment><Exhibits><Fear><Fright><Future><Goals><History><Image><Individual><Intervention><Intervention Strategies><Inventory><Learning><Loss of Sensation><MR Imaging><MR Tomography><MRI><MRIs><Machine Learning><Magnetic Resonance Imaging><Maps><Measures><Medial><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Mental disorders><Mental health disorders><Modality><Modeling><NMR Imaging><NMR Tomography><Nature><Neurobiology><Nuclear Magnetic Resonance Imaging><Numbness><PTSD><Participant><Pathologic><Patient Self-Report><Patients><Phase><Phenotype><Physiologic><Physiologic Psychology><Physiological><Physiological Psychology><Physiology><Post-Traumatic Neuroses><Post-Traumatic Stress Disorders><Posttraumatic Neuroses><Prefrontal Cortex><Process><Psychiatric Disease><Psychiatric Disorder><Psychometrics><Psychophysiological><Psychophysiology><Recording of previous events><Recovery><Reflex><Reflex action><Refractory><Regulation><Relapse><Rest><Risk><Role><Self Destructive Behavior><Self-Report><Sinus Arrhythmia><Symptoms><System><Time><Trauma><Work><Zeugmatography><adolescent trauma><adulthood><bio-markers><biologic><biologic marker><biomarker><childhood trauma><clinical care><computational modeling><computational models><computer based models><computer based prediction><computerized modeling><cost><debilitating symptom><diagnostic criteria><digital><digital assessment><digital marker><digital phenotyping><emotion regulation><emotional regulation><exposure to trauma><heart rate variability><histories><imaging><interventional strategy><machine based learning><mental illness><multi-modal data><multi-modal datasets><multi-modality><multimodal data><multimodal datasets><multimodality><neural><neural imaging><neuro-imaging><neurobiological><neuroimaging><neurological imaging><novel><pediatric><pediatric trauma><phenotypic data><physiopsychology><post treatment><post-trauma stress disorder><posttrauma stress disorder><predictive modeling><psychiatric illness><psycho-physiological><psychological disorder><respiratory><response><skills><social role><standard of care><suicidal><suicidality><targeted biomarker><targeted drug trials><targeted pharmaceutical trials><targeted therapy trials><targeted treatment trials><trauma exposure><trauma in children><traumatic neurosis>