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An MRI Study of the Neurobiological Mechanisms of Change in the Psychotherapeutic Treatment of Panic Disorder Overview
This research study explores how the brain works in patients
with panic disorder and how this changes in response to psychotherapeutic
treatments. Subjects who have a current diagnosis of Panic Disorder and who
are currently participating in the Weill Cornell – University of
Pennsylvania NIMH-funded study of psychotherapy for panic disorder are
invited to participate. The purpose of the study is to use Magnetic
Resonance Imaging (MRI) technology to see which regions of the brain are
different in people with panic disorder and how these change during
treatment. Around 100 people are being asked to participate.
fMRI Studies of Social Interaction Overview
This research project looks to understand how the brain
works during social interactions. The purpose of this study is to use
Magnetic Resonance Imaging (MRI) technology to see which regions of the
brain are active as part of these interactions. Approximately 80 people are
being asked to participate for purposes of learning about the brain and
developing imaging techniques for understanding social processes.
Imaging Study for Persons in Psychoanalysis and a Control Group IRB Protocol: #4895, Bradley Peterson, PI
Overview Patients in psychoanalysis presumably experience a specific type of learning that focuses on internal psychological processes. This learning produces significantly greater self-regulation of affective states and behavior, greater creativity and awareness of internal mental states, and altered processes of representing the interaction between self and others. We hypothesize that our multimodal MR brain imaging study of patients in psychoanalysis will reveal neuroplastic changes in the brain structures that subserve self-regulatory functions as well as altered activation of self-regulatory circuits. We further hypothesize that educational learning differs from psychoanalytic learning and that educational learning will therefore not produce comparable changes in volume and activity in these areas. The groups of subjects who will participate in this study include: 1) Psychoanalytic candidates entering training before they begin psychoanalysis; 2) Patients entering psychoanalysis as training cases for psychoanalytic candidates; and 3) A control group matched for age, gender, and educational background, and in who are participating in an intense program of non-psychological educational experiences.
Genetics of Developmental Differences IRB Protocol: #5302, Bradley Peterson, PI
Overview The goal of this study is to collect samples of DNA from persons diagnosed with autism spectrum disorders (ASDs) and from their immediate biological family. We will then contribute those samples to two DNA repositories, one here at NYSPI and one at Rutgers University, for use in future studies of genetic abnormalities in autism spectrum disorders. Participants diagnosed with an ASD will be asked to provide a blood sample obtained through venipuncture or, in children younger than age 6, a saliva sample. Biological siblings and parents of participants will also be asked to provide a blood sample or, in children younger than age 6, a saliva sample. The biological samples that we collect will be split into two parts, one going into the DNA repository here at NYSPI and the other going to the Rutgers University Cell and DNA Repository (RUCDR) in Piscataway, New Jersey, for inclusion in the multi-site Simons Foundation Simplex Study. The Simons Simplex Collection is a research initiative through which collaborating scientists at thirteen sites in North America will collect DNA samples from families with just one child affected by an autism spectrum disorder and store the information in a central location. This valuable data will be available to leading scientists in the field to search for clues that will lead to important breakthroughs in the understanding and treatment of ASDs. By collecting biological samples from families on whom rich descriptive, phenotypic information is available scientists will be able to study the relation between genes and phenotype in ASDs, and this may lead to improved prevention and intervention for these disorders.
Comparison of Information Processing using Functional Neuroimaging and Virtual Reality Paradigms in Heightened Illness Concern, Obsessive- Compulsive Disorder, and Controls IRB Protocol: #5356, Kelli Harding, PI
Overview The primary objective of this study is to learn if patients with Heightened Illness Concern (HIC) compared to healthy controls will show functional abnormalities in certain brain regions when faced with memory tasks. The second objective is to see if patients with HIC differ significantly from patients with OCD in this respect. The third objective is to see if, within the HIC patients, persons expressing a great deal of bodily symptoms and persons with only a few bodily symptoms show functional brain differences. These objectives will be explored through the use of fMRI and virtual reality paradigms coupled with neuropsychological testing. This research is expected to result in data that will support the biological basis of HIC and support or contest whether HIC and OCD share a similar underlying biology.
Duloxetine for Chronic Depression: A double-Blind Study IRB Protocol: #4967, David Hellerstein, PI
Overview The primary goal of this project is to study the tolerability, dosing, and efficacy of duloxetine in chronically depressed outpatients in three phases of treatment over a 22 week period. In addition, a subset of patients will be enrolled into an MRI substudy in which analyses of brain structure and functioning will be performed both before medication treatment begins and after the first phase of medication treatment. Patients who respond to Duloxetine will have a third MRI at the end of the third phase of treatment. MR imaging of patients with chronic depression will shed light on brain structure, function, neurotransmitter levels, and neuronal fiber tracts in relation to treatment with medication or placebo. We believe that this should also add very significantly to our understanding of chronic depression by relating the effects of medication on brain structure, function and connectivity.
Multimodal CNS Imaging of Prematurely Born Infants IRB Protocol: #5304, Bradley Peterson, PI
Overview The goal of this study is to define the effects of prematurity (delivery at gestational ages < 30 weeks) on brain structure, blood flow, neurometabolite concentrations, and neuroelectric functioning, and to assess how well the identified abnormalities in brain structure and function in the neonatal period predict neurodevelopmental outcome in early childhood. Imaging measures will include anatomical MRI, Diffusion Tensor Imaging (DTI), Magnetic Resonance Spectroscopy (MRS), and regional cerebral blood flow using perfusion imaging. Acquisition of precise, quantitative measures of brain structure and function using a combination of imaging techniques will provide knowledge of the neural bases of the adverse consequences of preterm birth on brain development in this population of preterm infants.
The Neural Bases of Repetitive Behaviors IRB protocol: #5642, Bradley Peterson, PI Overview This 5-year longitudinal imaging study aims to identify the neural bases of the repetitive behaviors of Tourette Syndrome (TS), Obsessive Compulsive Disorder (OCD), Attention-Deficit/Hyperactivity Disorder (ADHD) and Stuttering. Repetitive behaviors such as tic symptoms and stuttering, and the pediatric-onset form of OCD and ADHD, arise most often in young children, and our previous cross-sectional imaging findings suggest that the brain often attenuates these symptoms through the mechanisms of activity-dependent neural plasticity. We are interested in studying these compensatory systems longitudinally in children with TS, OCD, ADHD, and most importantly, Stuttering. During this 5-year study, we will use anatomical MRI, diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and fMRI methodologies with 50 children with TS, 50 children with ADHD, 35 children with Stuttering, 35 children with OCD, and 50 healthy controls. We will follow these subjects for 5 years, conducting psychological tests, diagnostic interviews, and scanning them in a 3 Tesla MRI Scanner at baseline and once annually until the end of Year 5. This study will greatly increase our understanding of the origins of repetitive behaviors and neural compensation in the central nervous system, and it will help to identify neural systems that could lead to future treatments of childhood neuropsychiatric disorders. For more information about this study, visit the study website: http://stutteringresearchcolumbiany.blogspot.com/ |
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MRI Studies of the Brain in Health and Illness IRB Protocol: #5321R, Bradley Peterson, PI
Overview This study will use functional MR brain imaging (fMRI) to understand better the neurobiology of neuropsychiatric disorders such as Tourette’s syndrome, Obsessive-Compulsive Disorder (OCD), Attention Deficit Hyperactivity Disorder (ADHD), anxiety disorders (DSM-IV defined Generalized Anxiety, Separation Anxiety, and Panic Disorders, as well as Social Phobia or Simple Phobia but not claustrophobia), substance use disorders (DSM-IV cocaine dependence, cannabis dependence, opioid dependence, alcohol dependence), pathological gambling, and affective illness (DSM-IV defined major depressive and bipolar disorders) or disruptive behavior disorders (DSM-IV defined Conduct, Oppositional Defiant, and Disruptive Behavior Disorders NOS). Clinical experience has shown that people with a serious neuropsychiatric disorder suffer most not from their primary diagnostic symptoms, but from their difficulties with impulse control, hyperactivity, inattention, and response inhibition. These problems cut across most diagnostic domains and are amongst the most frequent causes for clinical referral. By understanding the neural dysfunction involved in these disorders, we will be better able to design and assess the effects of new therapeutics. All study procedures are conducted on-site at the New York State Psychiatric Institute. |
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Genetic Studies of Brain Structure and Function IRB Protocol: #5018, Bradley Peterson, PI
Overview The objective of this study is to add a genetic component to Dr. Peterson’s imaging studies. The goal is to add the collection of DNA to our protocols in order to examine correlates between brain structure and function and DNA. We want to collect a DNA sample from siblings, parents, or other first-degree relatives of participants with the goal of incorporating into our studies a Haplotype Relative Risk (HRR) assessment of genetic risk for psychopathology in the proband. We are interested in collecting blood samples for DNA extraction from participants in our imaging protocols, as an extension of those studies. Those who do not want to provide a blood sample will be given the option of providing a sample of saliva using a mouth rinse and a cheek swab. This genetic data, combined with the brain imaging data and a comprehensive repository of clinical profiles, could make this a unique data set for studying the genetic underpinnings of brain structure and function. |
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A Magnetic Resonance Imaging Study of Children and Adults with Autism Spectrum Disorder IRB Protocol: #4994, Bradley Peterson, PI
Overview Individuals with an Autism Spectrum Disorder have specific delays and deviance in social, communicative, and cognitive development that are typically manifested within the first few years of life. Although often associated with mental retardation, the disturbances in these domains are both qualitatively distinct from and quantitatively disproportionate to the mental age (IQ) of the individual who exhibits them. One aim of this study is to characterize better, through Magnetic Resonance Imaging (MRI), brain regions and the tissue types and fiber tracts that contribute to abnormal brain growth in persons with Autism Spectrum Disorder (ASD), which includes such disorders as: Autistic Disorder, Asperger’s Disorder, or Pervasive Developmental Disorder - Not Otherwise Specified, with an onset in childhood. Another goal is to compare cognitive performance (memory, language, visual-spatial perception, attention, social judgment, and logical sequencing) with MRI findings in higher functioning individuals with ASD. Substudy: "Assessment of Receptive Prosody in Individuals with Autism" IRB Protocol: #4994, Bradley Peterson, PI
Overview Autism Spectrum Disorder (ASD) manifests itself in the first few years of life and has been defined as a triad of delays and disturbances in the social, communicative, and cognitive domains. While deficits in communication due to language impairments are central to our understanding of ASD, the extent to which language function is associated to the abnormalities seen in the social domain remains unclear. Thus, understanding the association between ASD and prosody - a language function that serves a highly social purpose, would be useful. More specifically, prosody is a general term used to describe the melody of speech, and refers to the supra-segmental acoustic features used by a speaker to facilitate a variety of communicative functions including linguistic (e.g. whether an utterance is a statement, question, or command), affective (e.g., emotional state), and pragmatic (e.g., humor or sarcasm). The primary aim of this study is to assess the ability of individuals with ASD to use and understand both linguistic and social prosody. A secondary goal of this study is to profile prosodic ability across measures of IQ, attention, expressive and receptive language, and non-verbal emotion comprehension
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Research on Atypical Development (ROAD) Database Study IRB Protocol: #4459, Agnes Whittaker, PI
Overview The purpose of this study is to build a computerized database that will include information on neurological, developmental and behavioral problems in children. The database will be used by researchers to test ideas about how neurological problems, as seen on brain imaging and in laboratory tests, are related to developmental and behavioral problems in children. This research aims to improve recognition and treatment of neurological, developmental and behavioral problems in children. Participants will be patients and their families who have been referred to the Pediatric Neurology Service (PNS) at the Columbia-Presbyterian Hospital for a neurological evaluation. The research staff for this study will assess the patient’s current developmental and behavioral functioning, and they will abstract relevant information from records of past evaluations. They will link the information anonymously in an electronic database to the patient’s neurological work-up in the PNS. The neurological work-up typically includes the neurological exam and any genetic, metabolic and brain imaging tests that have been completed, have been scheduled or will be scheduled by the pediatric neurologist working with the patient and family in the PNS. Some of the doctors conducting this study may also be involved in the patient’s care, but if the patient and/or family decide not to participate, the patient’s care will not be changed in any way. We expect that 200 or more patients in the PNS and their parents will participate in this project. |
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Cognitive Performance in High Functioning Individuals with Autism Spectrum
Disorder IRB Protocol #4888, Bradley Peterson, PI
Overview The goal of this study is to obtain research measures of cognitive performance (learning, memory, language, visual-spatial perception, attention, social judgment and logical sequencing) in high functioning individuals with Autism Spectrum Disorder (ASD), and relate these measures to brain imaging scans (Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy data) collected for clinical purposes. Examination of these relations may lead to better understanding of underlying brain mechanisms related to autism spectrum disorders. Participants in this study (ROAD 2) will be recruited from the Research on Atypical Development (ROAD) Database Study (ROAD I protocol #4459). Potential recruits must have a diagnosis of ASD (Asperger’s Disorder, Autistic Disorder or Pervasive Developmental Disorder, Not Otherwise Specified), a recent (within last year) tested IQ >70, as well as a Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy scan (MRI/MRS) that was obtained for clinical purposes as part of their evaluation in Pediatric Neurology (PNS) or the Developmental Neuropsychiatry Program (DNP). Some of the doctors conducting this study may also be involved in the patient’s care, but if the patient and/or family decide not to participate, the patient’s care will not be changed in any way. We expect that 100 patients from the ROAD I will participate in this study (ROAD 2). |
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MRI Studies of Adolescents and Adults with Bipolar Disorder IRB Protocol: #4890, Bradley Peterson, PI
Overview This study will use functional magnetic resonance brain imaging (fMRI) to better understand the neural basis of Bipolar Disorder (BD), particularly the neural determinants of switches in affective state. During this 5-year study, we will use fMRI methodologies to identify trait- and state-related disturbances in brain structure and function in 60 adolescents with BD and 60 healthy controls. We will follow these subjects for 5 years, conducting psychological tests, diagnostic interviews, and scanning them in a 3 Tesla MRI Scanner at baseline, during switches in affective state, and at the end of Year 5. We will ascertain switches in affective state by conducting monthly telephone calls to the BD participants during which will we will conduct three short assessments and provide recommendations for accessing social services in their neighborhood if they so wish. By better understanding the neural basis of BD, specifically how the brain changes during switches in affective state, we believe that this research could lead to future treatments for BD. |
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MRI Studies of the Effects of Environmental Toxins on CNS Development IRB Protocol: #5128
*Currently recruiting ages 4-6 Overview We will use various forms of magnetic resonance imaging (MRI) to detect differences between the brains of children who have been exposed prenatally to environmental toxins and normal control subjects. We hypothesize that abnormalities will be found in the volume of the entire brain and particularly in higher order, heteromodal association cortices (e.g., the frontal and temporal cortices); in the anatomical connectivity between brain in these regions; and in their neurochemical concentrations. Our imaging findings will be analyzed in conjunction with outcomes of neurodevelopmental testing. All subjects will be recruited from the population of participants in the “Mothers and Newborns Study” at the Center for Children’s Environmental Health. The Principal Investigator of the “Mothers and Newborns Study,” Dr. Frederica Perera, has been following inner city children who were exposed in utero to various environmental toxins since these children were born. |
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Children at High and Low Risk for Depression IRB Protocol: #4506, Myrna Weissman & Bradley Peterson, Co-PIs
Overview The overall aim of this study has been to understand the long term temporal sequence and familial patterns of mood and other disorders from childhood to adulthood in offspring at high and low risk for depression. The basic design is one of families at high and low risk for depression based on the depression status of the original sample (1st generation, the grandparents). Dr. Myrna Weissman has followed this sample of families over 4 waves of assessments. The last wave began in 12/98, 17 years after the initial assessment. This study which includes MRI is Wave 5. The sample now includes 3 generations (grandparents, parents, and grandchildren). Our previous findings in the offspring (2nd generation (now the parents)) showed both cross-sectionally and longitudinally that the offspring of depressed grandparents were at high risk (3-fold increase) for major depression. Their depression began early, often at puberty, and was preceded by prepubertal onset anxiety. The results for the 3rd generation (the grandchildren) again shows that the grandchildren in the high risk group (i.e., at least one depressed grandparent) are at increased risk of mood and anxiety disorders. These consistent findings across the generations lead directly to this new study which focuses on understanding the brain based correlates of familial depression. A new aim of the current proposal is to define the neural correlates of familial risk for depression in subjects in the 2nd and 3rd generations of this cohort using anatomical and functional MRI. This sample is uniquely valuable for identifying the neural correlates of familial risk because the study of high-risk populations prior to the onset of illness is likely to be the best way to distinguish cause from compensatory effect in neurobiological studies, and because psychiatric diagnoses established prospectively and across generations will provide the greatest possible confidence in the assessment of multi-generational familial risk. In addition, the availability of MRI data will provide us with the opportunity to understand better the underlying basis, in terms of brain structure and function, of the electrophysiological abnormalities identified in the last cyclic of funding. Dr. Weissman is also collecting blood samples from the families being followed in Wave 5. The goal is to add the collection of DNA to the imaging data in order to examine correlates between brain structure and function and DNA. We want to collect a DNA sample from participants with the goal of incorporating into our studies a Haplotype Relative Risk (HRR) assessment of genetic risk for psychopathology in the proband. This genetic data, combined with the brain imaging data and a comprehensive repository of clinical profiles, could make this a unique data set for studying the genetic underpinnings of brain structure and function. |
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MRI Studies of Infants Exposed Prenatally to Drugs of Abuse IRB Protocol: #4693, Bradley Peterson, PI
Overview The aim of this project is to define the effects of drugs of abuse on brain structure and metabolite concentrations, as well as their behavioral correlates, in infants and children who have in-utero exposure to drugs of abuse. We will obtain high-resolution anatomical MRI, magnetic resonance spectroscopy (MRS), and Diffusion Tensor Imaging (DTI) scans in 225 newborn infants exposed to drugs of abuse during fetal development (45 exposed to opiates, 45 exposed to cocaine, 45 exposed to methamphetamine, 45 exposed to marijuana) and 45 matched, unexposed newborn controls. We will measure and compare regional brain volumes, metabolite levels, and white matter fiber pathways across groups of exposed and unexposed infants and determine the physical, neurological, motor, and cognitive development of these infants until age 36 months. We will then determine whether brain MRI measures at birth correlate with differential neurodevelopmental outcome across the 4 groups of newborns. We will also attempt to acquire follow-up scans of the infants at 2, 4, 6, 9, 12, 18, 24, and 36 months to monitor disturbances in postnatal brain development (however, only the baseline scan is required for participation). This data will be correlated with the first MRI measures as well as with the behavioral data gathered during the three years of the study. This study promises to define the consequences of prenatal exposure to cocaine, methamphetamine, marijuana, and opiates on brain structure and metabolite concentrations. Defining these consequences will in turn help to identify the pathophysiological mediators and suggest possible prevention and early intervention strategies. |
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World Trade Center Evacuee Child Study IRB Protocol: #4838, Christina Hoven, PI
Overview This study was initially designed to finalize instrument selection and
identify the best field methodologies to sample, contact, recruit and
assess (in 2005) a representative sample of World Trade Center (WTC)
evacuees and their children, and to determine their willingness to
participate in a longitudinal study about familial transmission of trauma.
At this time, the proposed Pilot Study is completed, and the CDC-NYC-Dept.
of Health and Mental Hygiene Registry of all persons in and around the WTC
on 9/11 has been completed. All aspects of the pilot study were intended
to inform the final study, described below. |
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An fMRI Study of Self-Regulation in Patients with Bulimia Nervosa IRB Protocol #4396, Rachel Marsh, PI
Overview The long-term objective of our research is to use functional MR brain imaging (fMRI) to understand better the neural circuitry involved in self-regulation. The conceptual construct of self-regulation reflects broad classes of psychosocial functioning involving a higher level of CNS organization, including attentional processes, executive functions, impulse control, and memory systems. This study will be part of our ongoing effort to characterize the similarities and differences of many neuropsychiatric conditions involving the dysfunction of these higher-order, self-regulatory systems. The other disorders we are studying include Tourette’s syndrome, Obsessive-Compulsive Disorder (OCD), Attention Deficit Hyperactivity Disorder (ADHD), affective illnesses, and anxiety disorders. We now propose to study subjects with a history of bulimia nervosa (BN) using the same experiments and procedures that we have used in the study of ADHD, OCD and TS subjects. |
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MRI Studies of Affect Bradley Peterson, PI Overview The study aims to identify neurological substrates for the dimensions predicted by the circumplex model of affect. The circumplex model posits two fundamental dimensions which underscore all affective experience: valence (pleasure/displeasure) and arousal. (Russel, J.A., 1980; Russell, J.A., & Feldman Barrett, L.,1999). This model of emotion has been replicated through multiple lines of inquiry including factor analytic and scaling procedures of emotional terms and facial expressions (Kring, A.M., et al. 2003; Russell, J.A., 1980; Schlosberg, H., 1952). Studies investigating subjects' self-reports of affective experience have yielded similar results (Feldman Barrett, L., & Russell, J.A. 1998; Watson, D. & Tellegen, A. 1985). However, relatively few studies have used functional imaging (fMRI) to investigate the neurological substrates predicted by the circumplex model. We will attempt this by parametrically correlating subjects' affective ratings of various probes with the concurrent imaging characteristics. Our hypothesis is that as emotional arousal and valence increase, image intensity in specific neuroanatomical sites will also increase. Furthermore, we will demonstrate that this mechanism is consistent when subjects are experiencing affective states, assessing the affective states of others (based on facial cues), and linguistically, as subjects assess the affective content of words. Finally, we will investigate the utility of physiologic measures to independently corroborate the affective state of subjects. Specifically, facial EMG readings and the galvanic skin reaction (GSR) will be assessed as physiologic correlates of emotional valence and arousal. |