Fig. 10.1
Differences in brain FDOPA uptake between Parkinson’s disease patients with impulse control disorders compared to Parkinson’s disease patients without behavioral or mood disorders. Statistical pseudo-T map of the voxel-wise group comparison is shown. Red-yellow color shows regions with higher binding in patients with impulse control disorders (Courtesy of Dr. J. Joutsa)
Dopaminergic PET and SPECT studies therefore indicate that striatal dopamine release may be greater in PD patients with repetitive behavioral disorders compared to control PD patients, reflecting supersensitized dopaminergic mesolimbic system to rewards and reward-related cues. The findings concerning baseline dopamine D2 receptor binding are still inconclusive, as are studies focusing on presynaptic function (DAT and FDOPA).
10.4.2 Other Tracers
Brain perfusion studies in PD ICDs have provided partially conflicting results. A SPECT study using ECD for rCBF measurement has shown increased resting perfusion in the right hemisphere including the orbitofrontal cortex, the hippocampus, the amygdala, the insula, and the ventral pallidum in PD patients with pathological gambling (11 PD gamblers vs. 40 PD controls vs. 29 healthy controls) (Cilia et al. 2008). Cilia et al. further studied 15 PD patients with pathological gambling, 15 PD controls, and 15 healthy controls. Gambling severity (SOGS score) correlated negatively with rCBF in several brain regions such as the right ventrolateral prefrontal cortex, right anterior cingulate cortex, right posterior cingulate cortex, bilateral insula, and the left striatum (more severe symptoms associated with lower perfusion). The region with the highest level of significance was the right ventrolateral prefrontal cortex. The authors suggested that this region may have a role in risk-taking behaviors (Cilia et al. 2011). However, the authors also reported positive correlations between SOGS scores and resting state rCBF in the left fusiform gyrus and the cerebellum.
The same group also studied seven PD patients with pathological gambling and seven control patients with [15O]H2O using the same stimulus as in their [11C]raclopride study (simulated card game, mostly the same patients as in the previous study) (Steeves et al. 2009; van Eimeren et al. 2010). The patients were scanned before and after subcutaneous administration of apomorphine. Interestingly, the variant of the task (financial/neutral) did not influence rCBF. The main finding was the effect of apomorphine: in gamblers, the drug decreased rCBF in regions such as the orbitofrontal cortex and the rostral cingulate zone, whereas in controls, the effect was the opposite. As the authors point out, the sample size is relatively small and limits the generalizability of these results.
10.5 Personality Changes in Parkinson’s Disease
It has been claimed that PD could be associated with a specific, possibly premorbid personality type. The “parkinsonian personality” has been described as introverted, quiet, morally rigid, serious, stoic, industrious, inflexible, and punctual. PD patients have been claimed to have less novelty seeking behavior, which is considered a personality trait primarily modulated by dopamine, but a systematic review of the literature has shown that existing studies are mostly insufficient and prospective personality data is needed (Ishihara and Brayne 2006). A later large follow-up study of more than 7000 individuals, followed over four decades, indicated that novelty seeking and introversion do not predict the long-term risk of Parkinson’s disease (Arabia et al. 2010).
Although the first PET study with nine PD patients using FDOPA indicated that the striatal dopaminergic function may be associated with novelty seeking (Menza et al. 1995), a later study with 47 patients failed to show significant correlations between striatal FDOPA uptake and novelty seeking (Kaasinen et al. 2001). However, studies in both healthy controls (Suhara et al. 2001) and PD patients (Kaasinen et al. 2004) indicate that dopamine D2 receptor binding potential in the insular cortex (as measured with [11C]FLB 457) may be negatively associated with novelty seeking scores. The combined results suggest that the novelty seeking trait may relate to specific insular dopaminergic function, not to the level of the dopaminergic activity per se.
Although novelty seeking does not seem to correlate well with striatal dopamine function in PD, caudate FDOPA uptake seems to be related to harm avoidance, a personality trait arguably associated more with serotonin function and anxiety-related behavioral responses (Kaasinen et al. 2001).
Also other personality characteristics, apart from novelty seeking, have been studied in PD with neuroimaging. FDG-PET study about “honesty” in patients with PD has been performed (resting state glucose metabolism in 32 patients with PD and 20 healthy controls). Patients with PD had difficulties in telling lies as compared to controls, and this difficulty of making deceptive responses was correlated to prefrontal hypometabolism (Abe et al. 2009).
10.6 Conclusions
The great majority of studies concerning neuroimaging and PD psychiatric complications have been published during the last 5 years. The research area is new and the results are mostly preliminary. There is still considerable variation in published results and studies with apparently comparable methodology may show contradictory findings. The variation in the results could reflect the interindividual variation and complexity of the psychiatric phenomenon. In addition, the scales that are used to measure psychiatric symptoms differ from study to study. For instance, depression has been measured with several different scales. The disease severity and the stage of the overall disease (early unmedicated de novo vs. moderate medicated non-fluctuating vs. advanced with motor fluctuations and cognitive defect) is another factor, which seems to greatly affect the results. It is also possible that the apparently contradictory results reflect different stages in the development of psychiatric complications in PD and are a demonstration of a continuum from a compensatory upregulation to end-stage downregulation of neurotransmission. Finally, the statistical power in some pilot studies can be questioned.
Even with the limitations, and the limited number of studies, the combined results demonstrate the feasibility of functional neuroimaging in PD psychiatry. The studies show that both baseline neurotransmission and treatment response can be investigated. As larger confirmatory studies are performed, the method may prove to be a useful tool to monitor neurotransmission in clinical drug trials for psychiatric complications in PD.
References
Abe N, Fujii T, Hirayama K, Takeda A, Hosokai Y, Ishioka T, Nishio Y, Suzuki K, Itoyama Y, Takahashi S, Fukuda H, Mori E (2009) Do parkinsonian patients have trouble telling lies? The neurobiological basis of deceptive behaviour. Brain 132:1386–1395PubMedCentralPubMedCrossRef
Arabia G, Grossardt BR, Colligan RC, Bower JH, Maraganore DM, Ahlskog JE, Geda YE, Rocca WA (2010) Novelty seeking and introversion do not predict the long-term risk of Parkinson disease. Neurology 75:349–357PubMedCentralPubMedCrossRef
Cropley VL, Fujita M, Bara-Jimenez W, Brown AK, Zhang XY, Sangare J, Herscovitch P, Pike VW, Hallett M, Nathan PJ, Innis RB (2008) Pre- and post-synaptic dopamine imaging and its relation with frontostriatal cognitive function in Parkinson disease: PET studies with [11C]NNC 112 and [18F]FDOPA. Psychiatry Res 163:171–182PubMedCrossRef
Felicio AC, Moriyama TS, Godeiro-Junior C, Shih MC, Hoexter MQ, Borges V, Silva SM, Amaro-Junior E, Andrade LA, Ferraz HB, Bressan RA (2010) Higher dopamine transporter density in Parkinson’s disease patients with depression. Psychopharmacology (Berl) 211:27–31CrossRef
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