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Brain Imaging and Mental Illness 1

Running Head: Brain Imaging and Mental Illness

The Applications of Brain Imaging to the Diagnosis and Treatment of Mental Illnesses
Ellen E. Harrell
Glen Allen High School
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Introduction

Brain imaging as a tool to diagnose and treat mental illness has become exceedingly

controversial. While psychiatrists in the later twentieth century expected to be able to fully rely

on imaging to address mental illness by now, today’s diagnosis and treatment process largely

still relies on the methods of the past. The current diagnosis process for mental illness is based

off of patients’ answers to subjective diagnostic questions. The criteria for diagnosing mental

disorders, like depression, are loose. Such criteria lead to an over-diagnosis of some disorders

and an under-diagnosis of others, like unipolar depression and bipolar disorder respectively.

When mental disorders are misdiagnosed, patients are mistreated. The treatment plan for

someone with one disorder, like depression, is much different than for someone with another

disorder, like bipolar disorder. This places immense an immense amount of importance on

having a correct diagnosis in the first place. The idea behind brain imaging as a diagnostic tool

for mental illness is that if researchers can identify specific brain features unique to different

mental disorders that are absent in the general population, society could more accurately treat

patients.

The Stagnating Progress of Brain Imaging in Psychiatry

For decades, psychiatrists have been dreaming of transitioning to an imaging based

diagnosis process. The theory behind it is that imaging would enable a clear-cut diagnosis: one

based off of brain abnormalities rather than clusters of symptoms. It was expected that brain

imaging technology would have enabled faster diagnoses by present times. However, in 2005,

researchers had not come to a consensus about a tool that could be used for mental illness

evaluations (Carey, 2005). By this point, nearly three decades had already passed; the 1990’s had
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been dubbed the “Decade of the Brain” by scientists who hoped brain scans would “turn on the

lights in what had been a locked black box” (Carey, 2005). In the year 2005, nearly 500 imaging

studies were being published each year (Carey, 2005). Yet, the more imaging studies that were

conducted, the more obstacles were also discovered. Initially, it was thought that schizophrenia

could be identified by a loss of brain volume; studies demonstrated that those with schizophrenia

can “lose 5 to 10 percent of overall brain volume” over ten years (Carey, 2005). At the same

time, though, brain volume varies from person to person by “at least ten percent “(Carey, 2005).

Findings such as this one threaten the prospects of brain imaging as a diagnostic tool; there is

difficulty in distinguishing regular brain abnormalities from those that cause mental illness.

Other analyses and studies have supported this skepticism. While there are high hopes for

neuroimaging in mental illness diagnoses, there are problems associated with imaging itself that

make the process more difficult. In the meta-analysis “Addressing Reverse Interference in

Psychiatric Neuroimaging: Meta-analyses of Task Related Brain Activation in Common Mental

Disorders,” different regions of the brain were mapped in 537 fMRI studies (Sprooten et al.,

2017). These studies were of patients with a wide variety of disorders: “schizophrenia, bipolar

disorder, major depressive disorder, anxiety disorders, and obsessive compulsive disorder

(Sprooten et al., 2017). After looking at 21,427 patients, they found different regions of the brain

and their levels of activation to be associated with different mental disorders (Sprooten et al.,

2017). This finding does support using brain imaging to study mental disorders. However, they

also emphasized that different types of studies, such as region-of-interest studies (ROI studies),

resulted in “the over-representation of the amygdala and the caudate nucleus,” which did not

occur in “whole-brain studies” (Sprooten, et al.). In these whole-brain studies, the thalamus and

parahippocampal gyrus have been thought to be involved with mental illness, yet the widespread
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attribution of mental illness to the amygdala has stifled the research of these regions (Sprooten et

al., 2017). This finding signifies that mental illness research needs to analyze more than just

particular biomarkers in the brain; it must analyze the whole, not just the sum of its parts.

Misdiagnosis of Bipolar Disorder as Depression

Even though imaging might not be quite there yet, our current diagnostic process for

mental illness is arguably worse. Although the manual does get updated, the different versions of

the Diagnostic and Statistical Manual of Mental Disorders have proven themselves problematic.

To understand this, it is useful to analyze one misdiagnosis in particular: the misdiagnosis of

bipolar disorder as depression. In Dr. Tanvir Singh and Dr. Muhammed Rajput’s publication

“Misdiagnosis of Bipolar Disorder,” the prevalence of bipolar disorder is placed in context with

the misdiagnosis. It is estimated that 1.4 to 6.4 percent of people worldwide have bipolar

disorder, placing them at a risk of suicide twenty times higher than the general population (Singh

& Rajput, 2006). In 1994, bipolar disorder was found to be widely misdiagnosed, and a study in

2000 found that the misdiagnosis crisis had not improved since (Singh & Rajput, 2006). In a

National Depressive and Manic-Depressive Association survey, it was found that “69 percent of

patients are misdiagnosed initially and more than one-third remain misdiagnosed for 10 years or

more” (Singh & Rajput, 2006). Disturbingly, two different studies in 1999 and 2000 revealed

that “almost 40 percent of bipolar patients are initially diagnosed with unipolar depression”

(Singh & Rajput, 2006). With this information in mind, bipolar disorder is mistaken for

depression frequently, which results in the wrong medical treatment. This is giving a huge

proportion of people who are at a severe risk of suicide the wrong treatment. Much of this can be

attributed to the flawed diagnostic criteria of the DSM-IV. In diagnosing bipolar II disorder, it is
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required that a patient experiences a hypomanic state for a four day duration, whereas many

experts believe that hypomanic states only last for 1-3 days on average (Singh & Rajput, 2006).

Such strict criteria prevents patients from getting individualized care, as mental disorders are

certainly not as clear-cut as one would hope.

Biomarkers of Bipolar Disorder and Depression

Where the DSM-IV criteria is failing to distinguish bipolar disorder and unipolar

depression, neuroimaging is showing promise. While these studies are in their earliest stages,

studies are aiming to identify different endophenotypic markers of bipolar disorder that would

distinguish it from unipolar depression (Keener & Phillips, 2009). These endophenotypic

markers could be linked to findings in MRI, positron emission tomography (PET), and diffusion

tensor imaging (DTI) studies (Keener & Phillips, 2009). If such markers were found, they would

allow individuals who are at risk for bipolar disorder to be diagnosed early prior to the illnesses’

onset (Keener & Phillips, 2009). In Dr. Matthew Keener and Dr. Mary Phillips’s “Neuroimaging

in Bipolar Disorder: A Critical Review of Findings,” it was found that adults with bipolar

disorder have enlarged amygdalae (Keener & Phillips, 2009). This differs with the finding that

adolescents with bipolar disorder have smaller amygdalae (Keener & Phillips, 2009). It also must

be noted that these studies specifically focused on bipolar I disorder, and studies on bipolar II

disorder are lagging behind (Keener & Phillips, 2009). The study concludes that neuroimaging is

useful in identifying the endophenotypic markers associated with bipolar disorder, and that

future studies should focus on neural systems associated with emotional regulation (Keener &

Phillips, 2009).
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While endophenotypic markers can be found in bipolar disorder, research is also

developing biomarkers with depression. As in a publication by Drysdale et al., depression “is not

a unitary disease…” (Drysdale, et al., 2017). This disorder has been found to have four distinct

types (Drysdale, et al., 2017). According to this article, depression can be identified by its

pathways in the limbic system and in the frontostriatal circuits; in each different type of

depression, there is dysfunction (Drysdale, et al., 2017). Although symptoms overlap among the

four types, these different types have specific biomarkers in the brain (Drysdale, et al., 2017). In

these studies, it was found that “[c]lustering patients...enabled the development of diagnostic

classifiers (biomarkers) with high sensitivity and specificity…” meaning that depression can be

identified in this manner statistically (Drysdale, et al., 2017). If this is the case, depression can

more easily be differentiated from other disorders, like bipolar disorder, perhaps leading to better

diagnoses.

Conclusion

Seeing the flaws in the diagnosis process in context with the emerging results of

neuroimaging, it can best be inferred that neuroimaging should play a role in the future of mental

illness diagnoses. The questions of when and how of course lingers, but in this moment, the

focus needs to be on consolidating the research. More meta-analyses need to take place, and they

need to be applied to clinical practice, as Dr. Daniel Amen is doing. Clinical trials must take

place to see how accurate the studies are cumulatively. Most importantly, research must begin to

be added up, so that doctors can best understand their patients situation’s in a timely manner. The

DSM’s will only get so good from version to version, and it would be best if we could focus

most on imaging. Therefore, neuroimaging should not be immediately used to diagnose and treat
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mental illness, but seeing the stagnation of our current diagnostic system alongside the progress

in neuroimaging, a shift needs to begin to occur.


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References

Carey, B. (18 Oct. 2005). Can brain scans see depression? The New York Times.

Retrieved from http://www.nytimes.com/2005/10/18/health/psychology/can-

Brain-scans-see-depression.html

Drysdale, A. T., Grosenick, L., Downar, J., Dunlop, K., Mansouri, F., Meng, Y., … Liston, C.

(2017). Erratum: Resting-state connectivity biomarkers define neurophysiological

subtypes of depression. Nat Med, 23(2): 264. doi: 10.1038/nm0217-264d.

Keener, M. T. & Phillips, M. L. (2009). Neuroimaging in Bipolar Disorder: A critical review of

current findings. Curr Psychiatry Rep. 9(6) 512-520. Retrieved from

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686113/

Sprooten E., Rasgon A., Goodman M., Carlin A., Leibu E, Lee W. H., & Frangou S. (2017).

Addressing reverse inference in psychiatric neuroimaging: Meta-analyses of task-related

brain activation in common mental disorders. Human Brain Mapping PMID: 28067006

Singh, T., & Rajput, M. (2006). Misdiagnosis of Bipolar Disorder. Psychiatry (Edgemont),

3(10), 57-63. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945875/

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