Brain SPECT Imaging: Uses and Benefits in Clinical Psychiatric Practice

By Daniel G. Amen, MD and Theodore Henderson, MD, PhD

Is it bipolar disorder or brain trauma? Depression or toxic exposure? Is my depressed patient’s brain overactive and needs a treatment to calm it down, or is it underactive and needs to be stimulated?  How would you ever know unless you actually looked?

Using brain SPECT imaging in clinical psychiatric practice is evidence-based. According to the AmericanCollege of Radiology1 and the European Association of Nuclear Medicine (EANM)2, brain SPECT imaging is indicated for evaluation of cerebral vascular disease, epilepsy, dementia, brain trauma, encephalitis, and movement disorders (common issues for psychiatrists). If psychiatrists only ordered SPECT for commonly accepted indications they would be ordering hundreds of thousands of scans each year. For example, depression, anxiety, personality changes, and attentional issues are common sequalae of brain injury3-6. Moreover, the EANM guidelines state, “SPECT can be useful in other indications such as psychiatric diseases (e.g. for follow-up of depression).

Yet, psychiatry remains the only medical specialty that rarely looks at the organ it treats. Cardiologists look … neurologists look… gastroenterologists look. All other medical specialists evaluate the organs they treat. Psychiatrists guess, which is holding our field back.

While the DSM-IV is the current gold standard for psychiatric diagnosis, its limitations are perhaps made most evident by the fact that treatment effectiveness rates, have shown little improvement from what they were in the 1970s, despite 40 years of randomized controlled trials (RCT) resulting in more than 130 FDA approved medications used in treating various DSM defined disorders. DePaulo7 summarized the results of the largest “effectiveness plus” studies ever conducted for bipolar disorder (STEP-BD), major depression (STAR*D), and antipsychotics (CATIE), “the three studies taken together, however, underline the suggestion that modern pharmacological treatments may be no more beneficial than older ones, despite their added cost.” Insel made similar observations, “The unfortunate reality is that current medications help too few people to get better and very few people to get well.” 8

We argue that the failure of these medications is not only due to their incomplete mechanisms of action, but also due to the poor identification of the underlying neurobiological mechanisms which they are intended to target. Identifying additional procedures to properly diagnose patients, and thereby better tailor their treatment, is critical to advancing psychiatric practice.

SPECT, used in combination with detailed clinical histories and mental status examinations, which is the method we have used for many years and thousands of patients, increases diagnostic certainty, reduces the number of medication trials, identifies unrecognized brain injury (whether traumatic or toxic), and improves patient compliance.

There is a rich basis in the medical literature for understanding the neurological processes underlying many psychiatric disorders. For example, patients with ADHD has been consistently demonstrated to have decreased perfusion in the orbital frontal cortex, lateral prefrontal cortex, and temporal lobes9-13. These findings are in contrast to those of bipolar disorder14, which can present with strongly overlapping symptoms making clinical differentiation challenging. Likewise, depression and dementia can present with overlapping symptoms in the elderly. However, functional neuroimaging can differentiate these disorders. Studies of Alzheimer’s using perfusion SPECT followed over a longitudinal clinical course and/or histopathology demonstrate a sensitivity in the range of 82-96% and a specificity in the range of 84-89%15-16 and can be clearly distinguished from depression17,18. Deep brain stimulation can be effective in treatment-resistant depression, but this surgical intervention is not attempted without confirming the underlying neurological process of overactive subgenual anterior cingulate gyrus19.

In a recent study20, seven board certified psychiatrists evaluated 109 patient files that included clinical histories and mental status exams, without the SPECT images, and gave diagnoses and treatment recommendations. They were then given the SPECT data. The scans changed the initial diagnoses or treatment recommendations in 79% of cases. Twenty-two percent showed an unexpected brain trauma, 22% had unexpected toxicity, and 60% showed new targets for medications.

These findings are consistent with Borghesani et al.21 who found that SPECT confirmed, clarified, or contradicted initial clinical diagnosis in greater than 80% of patients with possible dementia. “Neuroimaging was useful even if it only confirmed the diagnosis … Seeing the disease process increased diagnostic confidence and clinician’s ability to explain symptoms to patients and families … Images have a special resonance for patients/families, grounding symptoms in observable brain changes.”

How does SPECT change psychiatric diagnosis and treatment?  What can SPECT scan tell clinicians and patients that they cannot obtain through history, mental status examinations, physical examinations or neuropsychological testing?

1. SPECT teaches you to ask better questions. Dr. Harold Bursztajn from Harvard says, “SPECT doesn’t give you the answer, it teaches you to ask better questions.”  It helps to understand the underlying physiology of disorders.

2. SPECT helps to prevent mistakes, such as stimulating an overactive brain or calming a brain that is already low in activity. With SPECT, in complex or treatment resistant cases, there are often unexpected findings that may be contributing to problems, such as inflammation, trauma, or toxicity.

3. SPECT aids in the diagnosis and treatment of substance abusers. It helps to break denial (hard to be in denial when you see a “toxic” looking scan). It also increases compliance, helps to understand co-morbidity, and can be useful in drug education.

4. SPECT helps to subtype psychiatric illnesses. Giving someone the diagnosis of depression is like giving them the diagnosis of chest pain. There are too many causes, which is one of the reasons antidepressant studies have such poor outcomes. It is not that our medications are ineffective, it is that we are not tailoring the treatment to the type of brain each patient possesses. Brockman demonstrated SPECT’s usefulness in choosing between treatments for depression22.

5. SPECT increases compliance as patients can see they have a problem.

6. SPECT helps families as they begin to see problems as medical not moral. It decreases shame, guilt, stigma, and self-loathing, and increases forgiveness and compassion. We have nothing else in psychiatry that is this powerful or this immediate.

Often, a careful clinical evaluation can accurately diagnose many psychiatric disorders. SPECT’s best use is in complex or treatment-resistant cases. Withholding imaging in unclear cases does an injustice to our patients and can harm them. Multiple trials of ineffective or inappropriate medications, delays in identifying comorbid conditions, targeting the wrong neurobiological process of a psychiatric symptom (treating anxious inattention with a stimulant), and the delay in recovery are expensive and dangerous.

For example, adults labeled as “personality disordered” often on SPECT can show temporal lobe dysfunction23,24, frontal lobe trauma or dysfunction25,26, brain toxicity27,28, or findings consistent with ADHD29. Children who present with rage outbursts30 commonly show temporal lobe abnormalities31, OCD32, bipolar disorder30,33, ADHD30,33, brain trauma34 or toxicity35.

Below we’ve listed the arguments posed against SPECT in clinical practice by our colleagues at the recent APA debate and, in parentheses, our brief response.

1. SPECT is not standard of care. (What innovation is? Deep brain stimulation was considered radical at one point. Its use also is rooted in the recognized value of functional neuroimaging.)

2. There is a cost to doing scans. (We argue that it is much more expensive and potentially lethal to have an ineffectively treated psychiatric disorder or multiple failed treatment trials).

3. There is radiation with the scans. (The radiation level is about 640 mRems which is roughly1.5 times the annual background radiation for Denver, Colorado36,37. The dose is less than that of most CT scans36. Ernst and colleagues reviewed this issue extensively and concluded that radiation exposures of this level are not significantly harmful38.

4. There is not enough research. (There are numerous, and a wide range of studies demonstrating SPECT’s usefulness in a number of diagnoses.)

5. Our work with tens of thousands of patients is “anecdotal.” (We have published more than 40 peer-reviewed studies on SPECT in psychiatry.)

6. SPECT is not ready, and it should be left in the hands of researchers. (We believe this is a disturbing argument, as it aims to withhold a useful medical procedure to patients who could benefit from it now.)

At the debate we referenced a 1993 study presented at the APA by Drs. Sam Mehr and Tom Jaeger from Creighton University on 100 bipolar teenagers. Fifty were scanned on the day of admission, fifty were never scanned. The average length of stay in the “never scanned” group was 44 days. The average length of stay in the scanned group was 17 days, which was a significant cost savings, consistent with our experience.

By not using functional imaging routinely in clinical practice we hurt patients and their families, we diminish our profession, and patients are mislabeled and mistreated. We believe that soon it will be malpractice not to order functional imaging in complex cases.




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