fMRI studies on depression and suicidality

March 10th, 2010
  • Listing research centers and key findings in affective disorder fMRI studies, what is presently being conducted on depression and suicidality?


  • Hello, and thank you for a very interesting question. There is actually a fair amount of research, it seems, that makes use of fMRI scans in the study of affective disorders, although research specifically focused on depression and suicide is still an emerging area without a deep base of existing literature. I have included below a fair number of links to research (sometimes completed, sometimes proposed) that uses fMRI in the study of depression and suicide, or closely-related emotional disturbances. These should bring you up to date on the state of the literature, as well as connect you to the institutions and individuals involved in such work. After you have looked over this list, let me know if there are any areas of work where you would like additional details. I'd be happy to continue working on this for you (you can even fMRI me to confirm my happiness!) if you feel you would like additional information beyond what I've already provided. Thanks again for your question, and best of luck with your work in this area. pafalafa-ga search strategy: Google search on [fmri depression (suicide OR suicidality)] ----- http://gpp.nih.gov/researchers/viewbook/Drevets_Wayne.html Mood and Anxiety Disorders Neuroimaging Assessing the Relationship Between Functional and Structural Imaging Abnormalities. Interactions between abnormalities of regional physiology, receptor pharmacology, grey matter volume are characterized in vivo in mood and anxiety disorders using PET, MRS, and fMRI technology. Abnormalities which suggest abnormalities of brain structure are pursued in post mortem neuropathological studies conducted in collaboration with anatomists/ neuropathologists to understand the histopathological correlates of imaging findings. Probing Dysfunction in Emotional Behavior Through Neurophysiological Mapping. Functional MRI (fMRI) and PET studies are performed in healthy humans and in subjects with mood and anxiety disorders to assess hemodynamic responses to neuropsychological tasks that probe elements of emotional expression, experience and regulation. These studies delineate the neurophysiological correlates of normal anxiety, fear, and sadness, and identify regions involved in inhibiting emotional responses to facilitate interpretation of regional differences between individuals with depressive or anxiety disorders and controls. They also aim to elucidate disorders of emotion regulation involved in the pathophysiology of mood and anxiety disorders. Assessing the Neuropharmacology of Emotional Behavior. PET and fMRI studies are conducted in healthy and mood disordered subjects to examine the effects of interventions such as natural reward, gonadal or adrenal steroids, or neurotransmitter antagonism/ depletion on central neurotransmitter release, neuroreceptor binding, and/or neurophysiolgical responses to emotion-related stimuli. ----- http://www.clinicaltrials.gov/ct/show/NCT00069225?order=28 Cerebral Structure and Function Before and After Pharmacological and Psychological Treatment for PTSD Posttraumatic stress disorder (PTSD) is characterized by intrusive recollections, avoidant behavior, anxiety and exaggerated fear response. The pathophysiology of PTSD is largely unknown. Neurophysiological testing in PTSD reveals deficits in memory and attention. Neuroimaging studies report increased amygdala and decreased anterior cingulated activation and reduced hippocampal volume. Clinical observations, psychophysiological measures and animal studies suggest that facilitated fear conditioning, delayed extinction, inescapable shock, sensitization and protracted habituation may contribute to the onset and persistence of PTSD. We propose to use fMRI and the psychophysiology lab to examine the effect of treatment with paroxetine and cognitive behavioral therapy on regional cerebral blood flow (rCBF) in brain regions conceivably involved in evolution and maintenance of PTSD: Amygdala, anterior cingulate and hippocampus. We will use emotional tasks that have elicited differences in perfusion or metabolism between patients with PTSD and trauma exposed and healthy subjects. Tasks performed in the fMRI will include 'masked' and 'unmasked' emotional faces paradigms and differential delay conditioning. Contextual fear provocation and eyeblink trace conditioning will be done in the psychophysiology lab. This evaluation will be performed before and after a 10-week period of treatment with paroxetine and a 10-session course of cognitive behavioral treatment (CBT). ----- http://www.drugabuse.gov/DirReports/DirRep901/DirectorReport3.html Functional Imaging of Neural Responses to Expectancy and Experience of Monetary Gains and Losses Dr. Hans Breiter and colleagues at the NMR Center of Massachusetts General Hospital used BOLD fMRI to map the brain areas activated during expectancy and delivery of monetary reward. These regions overlapped with the regions that were activated by cocaine infusions in a prior study by this investigator. Normal subjects viewed one of three stimuli, each of which generated a specific expectancy regarding monetary gains or losses. The stimuli consisted of a circle divided into three equal segments and a spinning arrow. In one stimulus, the 'good' stimulus, two of the three parts denoted a monetary gain, with the third part denoting a zero outcome. A second stimulus was 'bad' in that two segments predicted a monetary loss, with the third segment again having a zero outcome. The third stimulus had one gain segment, one loss segment, and a zero segment. Brain images were obtained during the expectancy phase while the arrow was spinning and during the outcome phase when the arrow pointed to one of the segments. A widespread brain network was activated during both the expectancy and outcome phases, including regions of the orbitofrontal cortex, ventral striatum, and extended amygdala. In addition, expectancies determined the neural responses to identical outcomes. In the context of the 'good' spinner, an outcome of $0 represented a relative loss (absence of gain), and there was a marked decrease in the BOLD signal to a $0 outcome, similar to an actual monetary loss. But in the context of the 'bad' spinner, a $0 outcome represented a relative gain (absence of loss), and there was a marked increase in the BOLD signal, similar to an actual monetary gain. These data show that the response to reward in these ventral striatal regions are not driven by the presence and absolute magnitude of the reward, but rather by cognitively driven expectancies anticipated outcomes. Breiter, H.C. et al., Functional imaging of neural responses to expectancy and experience of monetary gains and losses. Neuron, 30, pp. 619-639, 2001. ----- http://www.nimh.nih.gov/ncdeu/abstracts2003/ncdeu2096.cfm Functional Brain Magnetic Resonance Imaging (fMRI) Study of Problem-Solving and Hope in Healthy Volunteers Introduction: Using PET technology, reduced prefrontal cortical brain metabolism was recently reported in suicide attempters (versus non-attempters) following the administration of a serotonin-releasing agent (fenfluramine). Neuropsychological tests in depressed suicide attempters versus non-attempters have identified significantly reduced problem-solving / strategic thinking / verbal fluency in depressed suicide attempters, suggesting that frontal cortical dysfunction is associated with depression with suicidal features. We used an fMRI executive reasoning and future-thinking paradigm in healthy volunteers to analyse brain circuits that may be involved in thought processes related to problem-solving and future thinking as a model for studying the suicidal brain. ----- NIH maintains an entire facility devoted to fMRI research, whichis described here: http://fmrif.nimh.nih.gov/public/research/index_html/view The Genetics of Mental Disease In this work Ahmad Hariri, a post-doctoral fellow working in the Cognitive Brain Disorders Branch, showed that a polymorphism in the human serotonin transporter gene, SLC6A4, is associated with greater activity in the amygdala when individuals with this allele view fearful stimuli. The figure below illustrates this finding by comparing the BOLD response (measured with the 3 Tesla FMRIF scanner) between two groups of subjects, one of whom had the modified allele and the others who did not. This result is notable since it provides a link between the increased fear and anxiety reported and measured physiologically in individuals who are born with this allele and other members of the public. Such genetically driven variation in the function of the serotonin transporter function and subsequent amygdala activity may contribute to the abnormalities of the serotonergic system in depression and suicide. This combination of functional mapping and genetic analysis is likely to be a potent tool in our understanding of the neurobiology of mental illness. ----- www.cdc.gov/nceh/veterans/vet_hlth_actvy.pdf Cognitive Function and Symptom Patterns in Gulf War VeteransIn November 1997, CDC funded a study by the Boston University School of Public Health toexamine potential reasons for the memory and thinking problems reported by Gulf War veterans.In one component of this study, functional magnetic resonance imaging (fMRI) was used toexamine possible differences in brain activation patterns within specific areas of the brain. GulfWar veterans and their non-deployed peers with differing levels of symptoms were compared. Inanother component of this study, Danish armed forces personnel were tested to determinewhether they are experiencing the same types of memory and thinking problems reported byU.S. troops who participated in the Gulf War. www.cdc.gov/nceh/veterans/vet_hlth_actvy.pdf ----- http://www.wpic.pitt.edu/research/ResearchDay/Sessions_Geriatrics.htm Howard J. Aizenstein, M.D., Ph.D. Principal Area of Research Interest: Cognitive neuroscience of late-life depression and dementia using fMRI and computational modeling Depression in late-life is common and is associated a high variability in treatment response. A number of investigators have suggested that comorbid Alzheimer's disease and cerebrovascular disease (CVD) contribute significantly to the etiology of late-life depression (LLD), and may account for some of the variability in treatment response. These etiologic mechanisms are distinguished by their effects on implicit and explicit learning, and on the underlying frontostriatal circuits implicated in these tasks. Thus, investigations of the frontostriatal system using implicit and explicit learning offer promise in characterizing LLD phenotypes, and thus in predicting treatment response. In this presentation I will review our recent fMRI studies of implicit and explicit learning, which engage components of the frontostriatal circuit. I will review two studies in healthy young controls, which identify distinct prefrontal and subcortical roles in learning. I will also present preliminary results from an ongoing study of implicit and explicit sequence learning in the elderly and LLD. The results of the normative work support theories of distinct and complementary implicit and explicit systems for the learning of both categories and sequences. ----- http://www.wpic.pitt.edu/research/City/Grants/GrantDebellis3.htm Anatomical and Functional Magnetic Resonance Imaging (MRI) Studies in Child & Adolescent Posttraumatic Stress Disorder, P.I., Michael De Bellis, M.D. Posttraumatic stress disorder (PTSD) in childhood has psychopathological and developmental consequences. Studies of PTSD in adult humans suggest that high levels of cortisol and catecholamines associated with stress have neurotoxic effects on the brain. Traumatic events such as childhood maltreatment are associated with stress system dysregulation, may be associated with structural brain changes, and may cause disruption of the prefrontal cortical - limbic circuit and result in characteristic deficits on tasks that require attention (or failure of inhibition of irrelevant stimuli). Completed investigations from the 1995 NARSAD Young Investigator Award show that maltreated children with PTSD who had high rates of subsequent and co-morbid affective disorder showed stress system dysregulation. These subjects also evidenced structural brain changes. It is hypothesized that maltreated children with PTSD and affective co-morbidity may have structural changes that result in disruption of the prefrontal cortical - limbic circuit and result in characteristic deficits on tasks that require intact inhibitory processes. Deficits in inhibitory attentional processes may lead to impulsivity and result in failure of affect regulation, suicidal thoughts and self destructive behaviors. In this protocol, measures of anatomical and functional magnetic resonance imaging (fMRI) of the brain will be utilized. Thus it is hypothesized that maltreated children with PTSD and affective co-morbidity may have structural changes that result in disruption of the prefrontal cortical - limbic circuit and result in characteristic deficits on tasks that require attention (inhibition of irrelevant stimuli) and concentration than PTSD only and healthy control children. ----- http://www.psychiatry.wustl.edu/Department/Faculty/department_faculty_research_interest.htm Sheline Y, MD: 1) structural brain changes associated with major depression; 2) PET and fMRI studies of brain function in major depression, particularly in relation to treatment response ----- http://www.wjh.harvard.edu/psych/epp.html Pizzagalli, Diego. Diego A. Pizzagalli received his M.S. (1995) and Ph.D. (1998) from the University of Zurich, Switzerland. In 1999, his interest in affective neuroscience led him to join the Psychology Department at the University of Wisconsin, Madison as a post-doctoral fellow, and later as an Associate Scientist. The main goal of his research is to investigate the brain mechanisms underlying affective processing in normal individuals and subjects with affective disorders (e.g. depression). Past and ongoing work has relied on various functional neuroimaging techniques (electroencephalogram, EEG; functional magnetic resonance imaging, fMRI; and positron emission tomography, PET) to investigate: (a) the functional neuroanatomy of depression; (b) brain substrates of individual differences in affective style and vulnerability to affective disorders; and (c) brain mechanisms of affective processing (e.g. face perception) and learning (e.g. Pavlovian conditioning). In general, both the spatial (“Which brain regions are involved?”) and temporal (“When in the information processing flow do processes occur?”) aspects of brain mechanisms underlying affect and affective disorders have attracted his attention. Dr. Pizzagalli will join the Harvard faculty in July 2002. ----- http://psyphz.psych.wisc.edu/front/lab%20articles/2002/Depression.pdf ANTERIOR CINGULATE CORTEX IN DEPRESSION: THE FINDINGS In major depression, decreasedACC activation relative to controls has been repeatedly reported. In single photon emission computed tomography studies, decreased regional cerebral blood flow in the left (Curran et al. 1993, Mayberg et al. 1994) or right (Ito et al. 1996) ACC has been found in medicated depressed unipolar patients compared with controls. Decreased ACC activation has been replicated with positron emission tomography (PET) (Bench et al. 1992, Drevets et al. 1997, George et al. 1997, Kumar et al. 1993) and fMRI (Beauregard et al. 1998) techniques. ----- www.owlnet.rice.edu/~psyc332/lecturenotes/ lec8-depression.rtf Recent fMRI results support left frontal underactivity in depression Neurochemistry of depression ----- http://hcpc.uth.tmc.edu/research.htm "Cognitive Activated Functional MRI of the Brain" Joel Steinberg, M.D. et al Study population: Adult inpatients with confirmed Axis I psychiatric disorder. Using functional magnetic resonance imaging, (fMRI), the functional brain activation in patients with psychiatric disorders will be compared with those who are healthy. A simple computer "game" the Continuous Performance Test (CPT) will be performed by subjects during the fMRI. ----- http://serendip.brynmawr.edu/sci_cult/mentalhealth/treatments.html Pictures of the Mind: fMRI and Mood Disorders, December 22, 2001 Selective serotonin re-uptake inhibitors may help patients suffering from such distinct illnesses as major depression and obsessive-compulsive disorder. ----- http://www.annalsnyas.org/cgi/collection/suicide Relationships between Amygdala Volume and Activity during Emotional Information Processing Tasks in Depressed and Never-Depressed Individuals: An fMRI Investigation GREG J. SIEGLE, ROMA O. KONECKY, MICHAEL E. THASE, and CAMERON S. CARTER Ann. N.Y. Acad. Sci. 2003; 985: 481-484. ----- http://www.annalsnyas.org/cgi/content/abstract/985/1/370 Brain Imaging Studies in Mood and Anxiety Disorders Special Emphasis on the Amygdala AMIT ANAND and ANANTHA SHEKHAR Department of Psychiatry, Indiana University School of Medicine, University Hospital, Indianapolis, Indiana 46202, USA Ann. N.Y. Acad. Sci. 985: 370-388 (2003). Human studies attempting to elucidate brain functioning in health and disease are crucial for our understanding of neuropsychiatric disorders. In the past, scientists relied heavily on neurological lesion studies to understand the functional roles of brain areas. In the last few decades, brain imaging research has made it possible to investigate the molecular and synaptic neuronal events as well as the functioning of neuronal networks in vivo, in patients with neuropsychiatric illnesses. In this context, the functional role of the amygdala has been a focus of neuroimaging studies by leading researchers. Several of these researchers presented papers at a conference, entitled The Amygdala in Brain Function: Basic and Clinical Approaches, that provided the basis for this volume. These papers follow this review in the current volume. The present paper briefly summarizes the highlights of the different presentations, focusing on the functional diversity of the amygdala and its role in different neuropsychiatric disorders; reviews the various brain imaging technologies currently available; and discusses the major findings on the pathophysiology and treatment of depression, bipolar disorder, and anxiety disorders. ----- http://www.afsp.org/research/grants03.htm Michael S. McCloskey, Ph.D. (Mentor: Emil F. Coccaro, M.D.), Functional Magnetic Resonance Imaging of Emotional Information Processing among Borderline Personality Disordered Patients With and Without Past Suicide Attempts The proposed study will look for differences in areas of brain activation between people with and without a history of past suicide attempts when looking at emotional stimuli (e.g. sad, happy, neutral, or fearful faces). A group of individuals with Borderline Personality Disorder, a psychiatric disorder associated with an increased risk of suicide, will be asked to look at emotional faces while a functional Magnetic Resonance Imaging (fMRI) machine is used to determine what area of their brain are more or less active. Half of the individuals with Borderline Personality Disorder will have a history of past suicide attempts and half will have no history of past suicide attempts. Areas of brain activation for individuals with and without past suicide attempts will be examined to see if individuals with a history of suicide attempts exhibit different patterns of brain activation as compared to individuals without any history of suicidal behavior when exposed to emotional information. If it is found that the brains of individuals with a history of suicide attempts do respond differently to emotional stimuli, fMRI could be used to assist in an assessment of suicide risk, allowing for earlier and better-targeted intervention. Furthermore, these results would suggest specific area of focus for both psychotherapy (emotional information processing) and medication-based (the areas of abnormal brain activation) interventions. ----- neurology.jwatch.org/misc/jwneuro_index_2002.pdf Subjective Memory Complaints and fMRI in Depression vs. AD ----- http://www.ktgf.org/fellow.html The Neurobiology of Positive Affect in Childhood Depression Although childhood depression is often considered a disorder of increased negative affect, poor regulation of positive affect is also an important feature. Low mood and difficulty obtaining pleasure from experiences are central symptoms. In fact, emotion-based theories of psychopathology posit that depression is characterized primarily by dysregulation in positive affect systems. This claim has been supported by research with adults but it has not yet been addressed in studies with children. Dr. Forbes' research addresses the regulation and dysregulation of positive affect and the processing of reward in childhood depression. Her research project will use an fMRI strategy to measure patterns of brain activation, with a guiding hypothesis that childhood depression is associated with dysregulation of positive affect. Specific hypotheses are that in comparison with control children, children with depression 1) will exhibit decreased brain activity during the anticipation of reward but not after obtaining reward; and 2) will exhibit poor flexibility in responding to reward-related stimuli. Thus, Dr. Forbes' research examines both the importance of dysregulation of positive affect in childhood depression and the neural bases for that dysregulation. ----- http://www.bpchildresearch.org/about/scientists.html Hilary Blumberg, M.D. Dr. Hilary Blumberg is an Assistant Professor of Psychiatry at the Yale University School of Medicine. Her specialty is the study of abnormalities in the brain circuits that underlie bipolar disorder using brain scanning technologies such as functional magnetic resonance imaging (fMRI). ----- http://www.fmri.org/pdfs/Brody.pdf Regional Brain Metabolic Changes in Patients With Major Depression Treated With Either Paroxetine or Interpersonal Therapy Background: In functional brain imaging studies of major depressive disorder (MDD), regional abnormalities have been most commonly found in prefrontal cortex, anterior cingulate gyrus, and temporal lobe. We examined baseline regional metabolic abnormalities and metabolic changes from pretreatment to posttreatment in subjects with MDD. We also performed a preliminary comparison of regional changes with 2 distinct forms of treatment (paroxetine and interpersonal psychotherapy). [NOTE: This entire site is devoted to fMRI research] ----- http://www.pennhealth.com/health_info/tips/depression/new_research.html Advanced brain imaging techniques Advanced brain imaging techniques, such as single photon emission computed tomography (SPECT), proton emission tomography (PET) and an advanced type of MRI known as functional magenetic resonance imaging (fMRI) are being used to study the anatomy and physiology of depressed patients in greater detail than ever before. At the present time, however, these neuroimaging techniques are only research tools. They have not been developed to the point where they can be used clinically to diagnose depression. ----- http://www.mental-health-matters.com/articles/article.php?artID=333 Seeing Our Feelings: Imaging Emotion in the Brain ----- You also may want to be aware of the fMRI Data Center site at: http://www.fmridc.org/index.html which links to many fMRI studies, including those involving emotions, although I did not see any specifically focused on depression or suicide. ----- Again, let me know if you need any additional information.


  • Your search for research on the suicidal brain was thorough and well done. I will contact the centers doing this type of research and will ask more questions that I know you can answer very well. Thank you, Robert Roerich, M.D. Founder Roadmind University Online http://www.roadmind.com


  • Sorry not to answer your question more directly: Yes, a list of studies of this topic, many with links to abstracts would be very helpful, in addition to the clarification I have already posted. Regards


  • Thanks for the kind rating, and I'm glad to hear that this information met your needs. Looking forward to seeing you back here one of these days... pafalafa-ga


  • Are you looking for a list of studies of this topic, many with links to abstracts? If this is not your preference, could you please explain in a bit more detail what type of answer would best meet your needs. Thank you. pafalafa-ga


  • I am an independent clinical psychiatric researcher studying new methods of assessing for undiagnosed depression and suicidality. Present standards rely on direct clinical interview and psychological testing to determine patient mental status. A respect for scientific opinion requires that I explore this arena with scientific tools that can be quantified. fMRI studies offer this option, but research may not be looking in the right places because of study topic prejudice. A list of websites, researchers, study centers that focus on using the fMRI to explore emotion would be helpful. Here is an example of one that studies cognition and memory: http://memory.wustl.edu/ Recognizing beforehand that fMRI studies on people who have actually committed suicide is not possible, any study that focuses on severely depressed people would be the most helpful. A specific fMRI pattern may be detectable in suicidal people, if only researchers knew that they were truly and presently suicidal. Ethical considerations and a duty to safeguard research subjects is key in a proposed study of this nature. The scenario is such: a good tool exists but knowledge is lacking, knowledge exists but a good tool to use is beyond my present reach. Thank you for your request for clarification







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