Dopamine and neuropsychological impairment during depression

Evidence suggests that a pattern of specific neuropsychological impairment (SNI) during major depressive episodes (MDE) is associated with decreased striatal synaptic dopamine. The main aspects of this SNI are slowed movement speed and poor performance on the interference part of the stroop test. The aim of our study is to confirm that extracellular dopamine is low during MDE with SNI. By combining [ 11C] raclopride Positron Emission Tomography (PET) with a dopamine depletion paradigm a method of assessing extracellular dopamine levels is now available in humans. [ 11C] raclopride is a selective dopamine D2 receptor (D2 R) radiotracer that labels D2 Rs void of endogenous dopamine. The application of the reversible tyrosine hydroxylase inhibitor a-methyl-para- tyrosine (AMPT) leads to a vigorous, transient depletion of extracellular dopamine followed by an increase in D 2 R binding potential (D2 RBP) measured by [ 11C] raclopride PET. Dopamine levels during baseline release can be estimated by comparing [ 11C] raclopride binding to D2 R at baseline and after rapid dopamine depletion (DD). In this study extracellular dopamine concentration before and after DD will be compared in three groups: MDE with SNI, MDE with no SNI and healthy subjects. SNI will be quantified using the finger tapping test, FTT, (motor slowing) and the stroop interference test (divided attention). Our hypothesis is that during MDE with SNI, elevated D2 RBP that will not increase much after DD will be found reflecting a chronically low extracellular dopamine which cannot be lowered much more. During MDE with no SNI, a normal D2 RBP will occur that will increase substantially after DD reflecting a near normal extracellular dopamine which can be lowered much more. If SNI in MDE truly represents low extracellular dopamine, it can be easily identified by clinicians using the FTT and the stroop test. Then it may be possible to specifically target SNI. To our knowledge there are no treatments aimed towards the SNI found during MDE. Such treatments may be useful in raising response rates to antidepressants and reducing residual symptoms for patients with MDE.