SPECT digs deep to parse heterogeneity of depression

For the most part, deciding which medication to give someone suffering from depression is a blind choice. If the first one doesn't work, a second is tried, and so on. SPECT imaging shows promise, however, of being able to highlight cerebral biomarkers that may help clinicians not only choose the right medication but also monitor its effectiveness.

It is well documented that depression sufferers have decreased regional cerebral blood flow (rCBF). What is not fully understood is how specific patterns of decreased blood flow can predict therapeutic efficacy.

Using SPECT imaging, Dr. Holger Brockmann and colleagues from the University of Bonn in Germany examined whether cerebral biomarkers were present at baseline for responders to pharmacotherapy.

Researchers evaluated 93 patients with major depression using SPECT with technetium-99m hexamethylpropyleneamine oxime (HMPAO). Subjects were imaged before treatment and four weeks following pharmacotherapy with citalopram, a selective serotonin reuptake inhibitor, or SSRI (J Nucl Med 2007;48[Supp 2]:262P).

Compared with the nonresponders (49), the responders showed significantly greater rCBF before treatment in a widespread region encompassing prefrontal and anterior/perigenual cingulate regions.

"Most notably, this effect was independent of the initial depression score and may thus be a helpful clinical marker in patients with major depression," said Brockmann, a nuclear medicine physician.

In another Tc-99 HMPAO SPECT study, Dr. Yoav Kohn and colleagues from Hadassah-Hebrew University Medical Center in Jerusalem found that rCBF deficits in depression largely normalized in patients who responded to pharmacotherapy (see figure) but decreased in patients who responded to electroconvulsive therapy.

The decreased rCBF in those treated with electroconvulsive therapy is consistent with the hypothesis that inhibitory processes act to terminate the seizure, according to the study. Researchers concluded that the increased perfusion in the medicated subjects is related to the change in clinical status rather than being the effect of medication per se. Medications included SSRIs and tricyclic antidepressants, or TACs (J Nucl Med 2007;48[8]:1273-1278).

"Clinical psychiatry is based almost solely on subjective observer-based judgment. Our findings suggest that objective imaging evaluations could support subjective clinical decisions," said senior investigator Dr. Omer Bonne, an associate professor of psychiatry.

Dr. Daniel Amen has found that SPECT imaging can differentiate between several subtypes of depression. Amen is CEO and medical director of the Amen Clinics, which he claims has amassed the world's largest database of brain SPECT scans related to behavioral problems. People with decreased prefrontal cortex activity and increased deep limbic system activity, for example, respond best to either dopaminergic (i.e., Wellbutrin) or noradrenergic (TACs such as Elavil) intervention.

Those with increased anterior cingulate, thalamus, and basal ganglia activity, often respond best to the SSRIs, such as Prozac. Those with decreased prefrontal cortex activity with increased or decreased temporal lobe activity often do worse on SSRIs but respond favorably to anticonvulsants. Perhaps the best benefit of SPECT, according to Amen, is that it can enhance compliance and diminish stigma because the patient can actually see the changes in the brain.