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Q: fMRI studies on depression and suicidality ( Answered 5 out of 5 stars,   1 Comment )
Subject: fMRI studies on depression and suicidality
Category: Health > Conditions and Diseases
Asked by: road-ga
List Price: $50.00
Posted: 27 Sep 2003 20:24 PDT
Expires: 27 Oct 2003 19:24 PST
Question ID: 260874
Listing research centers and key findings in affective disorder fMRI
studies, what is presently being conducted on depression and

Request for Question Clarification by pafalafa-ga on 28 Sep 2003 04:20 PDT
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.


Clarification of Question by road-ga on 28 Sep 2003 05:48 PDT
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:

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

Thank you for your request for clarification

Clarification of Question by road-ga on 28 Sep 2003 05:55 PDT
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.

Subject: Re: fMRI studies on depression and suicidality
Answered By: pafalafa-ga on 28 Sep 2003 10:48 PDT
Rated:5 out of 5 stars
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.


search strategy:  Google search on [fmri depression (suicide OR


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

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.


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).


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.


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:

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.


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


Howard J. Aizenstein, M.D., Ph.D.

Principal Area of Research Interest: Cognitive neuroscience of
late-life depression and dementia using fMRI and computational

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.


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


 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


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.


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)

----- lec8-depression.rtf

Recent fMRI results support left frontal underactivity in depression
Neurochemistry of depression


"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.


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.


Relationships between Amygdala Volume and Activity during Emotional
Information Processing Tasks in Depressed and Never-Depressed
Individuals: An fMRI Investigation

Ann. N.Y. Acad. Sci. 2003; 985: 481-484. 


Brain Imaging Studies in Mood and Anxiety Disorders 
Special Emphasis on the Amygdala 

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.


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.


Subjective Memory Complaints and fMRI in Depression vs. AD


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.

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).


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]


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.


Seeing Our Feelings: Imaging Emotion in the Brain


You also may want to be aware of the fMRI Data Center site at:

which links to many fMRI studies, including those involving emotions,
although I did not see any specifically focused on depression or


Again, let me know if you need any additional information.
road-ga rated this answer:5 out of 5 stars
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.
Roadmind University Online

Subject: Re: fMRI studies on depression and suicidality
From: pafalafa-ga on 29 Sep 2003 09:39 PDT
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


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