Table 1.
Neuroimaging studies in depression in Parkinson's disease (PD)
| Study | Subjects | Sex (M/F) | H and Y (Mean ± SD) | Duration of PD (years) | UPDRS‐III | Imaging modality | Imaging analytical method | Diagnosis/measurement | Key findings |
|---|---|---|---|---|---|---|---|---|---|
| Ballanger et al. (2012) 11 |
4 dPDs 8 PDs 7 HCs |
4/0 6/2 5/2 |
No data |
4.5 ± 3.3 7.0 ± 3.0 |
27.3 ± 11.6 25.9 ± 4.5 |
[18F]MPPF PET | WB | DSM‐IV/BDI, MADRS |
HCs > dPDs: [18F]MPPF uptake in left dorsal anterior cingulate and orbitofrontal cortices, and right hippocampus and temporal cortex HCs > PDs: Bi. inferior frontal cortex and right ventral striatum and insula PDs > dPDs: Left hippocampus and superior temporal and orbitofrontal cortices and right insula |
| Bohnen et al. (2007) 12 |
12 PDs 6 PD‐Ds 10 HCs |
12/0 6/0 10/0 |
No data |
5.7 ± 4.1 3.8 ± 2.3 |
No data | [11C]PMP PET | ROI | CSDD | Inverse correlation between cortical cholinergic activity and depressive symptoms |
| Boileau et al. (2008) 13 |
7 dPDs 7 HCs |
4/3 4/3 |
1.71 ± 0.49 | 4 ± 2.9 | 21.1 ± 0.34 | [11C]DASB PET | ROI | DSM‐IV/ HAM‐D, IDS |
dPDs > HCs: [11C]DASB binding in dorsolateral and prefrontal cortices Positive correlation between [11C]DASB binding in the orbitofrontal cortex and depression |
| Ceravolo et al. (2013) 20 | 44 PDs | No data | No data | 1.14 ± 0.98 | 17.9 ± 7.7 | [123I]FP‐CIT SPECT | ROI | DSM‐IV‐TR/ HAM‐D, HAM‐A, BDI |
More depressed PDs > less depressed PDs: DAT binding in bi. caudate and putamen Positive correlation between depression and DAT binding bi. caudate and putamen |
| Felicio et al. (2010) 21 |
10 PDs 10 dPDs |
5/5 6/4 |
2.5 ± 0.4 2.2 ± 0.5 |
4.7 ± 2.2 4.0 ± 2.4 |
29.5 ± 10.6 26.3 ± 10.0 |
99mTc‐TRODAT‐1 SPECT | ROI | BDI | dPDs > PDs: DAT density in left caudate and right putamen |
| Guttman et al. (2007) 19 |
9 PDs 13 HCs |
7/2 5/8 |
2.56 ± 0.53 | 12.22 ± 3.73 | No data | [11C]DASB PET | ROI | HAM‐D, IDS | Inverse correlations between depression scores and [11C]DASB binding in putamen and insular and occipital cortices |
| Hesse et al. (2009) 22 |
110 PDs 20 dPDs 18 HCs |
59/51 13/17 8/10 |
1.6 ± 1.6 2.3 ± 0.9 |
3.1 ± 4.9 4.4 ± 4.5 |
28.6 ± 13.1 31.4 ± 13.7 |
[123I]FP‐CIT SPECT | ROI | DSM‐IV/BDI |
PDs > dPDs: [123I]FP‐CIT binding in striatum, thalamus, midbrain/brainstem HCs > dPDs without SSRI treatment: [123I]FP‐CIT binding in thalamus and midbrain |
| Huang et al. (2013) 14 |
26 PDs 12 HCs |
16/10 7/5 |
1–2.5 | 5.5 ± 0.7 | No data | [18F]FDG‐PET, T1‐weighted |
ROI (PET) WB (T1) |
BDI, BAI, AES |
Positive correlation between depression and metabolic elevations bi. amygdala No volumetric difference between HCs and PDs |
| Imamura et al. (2011) 23 |
22 PDs 16 minor dPDs 14 major dPDs 9 HCs |
10/12 7/9 12/24/5 |
2.98 ± 0.85 3.53 ± 0.96 3.32 ± 0.87 |
6.33 ± 4.81 6.77 ± 5.87 4.3 ± 3.4 |
22.3 ± 17.4 33.4 ± 18.5 26.7 ± 13.5 |
123I‐IMP SPECT | ROI | DSM‐IV/BDI | HCs > dPDs: rCBF in bi. PCC, hippocampus, cuneus, superior parietal and primary visual areas |
| Matsui et al. (2006) 24 |
18 PDs 22 dPDs |
5/17 2/20 |
3.2 ± 0.4 3.3 ± 0.5 |
8.8 ± 5.8 10.5 ± 6.8 |
28.9 ± 15.7 38.4 ± 15.3 |
123I‐IMP SPECT | ROI | DSM‐IV/ HAM‐D | PDs > dPDs: Perfusion in left superior and inferior frontal gyri |
| Mayberg et al. (1990) 15 |
4 PDs 5 dPDs 6 HCs |
4/0 3/2 4/2 |
≤3 |
8.5 ± 4 7.2 ± 2 |
No data | [18F]FDG‐PET | ROI | DSM‐III/ HAM‐D |
HCs and PDs > dPDs: Metabolic activity in caudate and orbital‐inferior frontal area Inverse correlation between metabolism in orbital‐inferior frontal area and depression scores |
| Mentis et al. (2002) 16 |
15 PDs 14 HCs |
No data | 3.3 ± 0.9 | No data | No data | [18F]FDG‐PET | WB | BDI |
In PDs, inverse correlation between depression and metabolism in lateral/medial frontal, ACC, orbitofrontal cortex Positive correlation between depression and metabolism in cerebellum |
| Pålhagen et al. (2009) 25 |
11 dPDs 14 PDs 12 MDs |
6/5 8/6 7/5 |
2.2 ± 0.4 1.8 ± 0.4 |
9.7 ± 4.7 6.9 ± 2.4 |
24.9 ± 10.8 22.6 ± 10.1 |
HMPAO SPECT | ROI | DSM‐III–IV/ HAM‐D, MADRS |
dPDs vs. MDs: ↑ rCBF in right frontal and left frontoparietal regions; ↓ rCBF in right preoccipital region dPDs + PDs vs. MDs: ↓ rCBF in bi. preoccipital regions and occipital lobe dPDs vs. PDs: ↑ rCBF in bi. frontoparietal areas, right dorsolateral and left anterior frontal areas dPDs + MDs vs. PDs: ↑ rCBF in right dorsolateral frontal area |
| Politis et al. (2010) 18 |
10 dPDs 24 PDs 10 HCs |
6/4 20/4 8/2 |
3.1 ± 0.6 2.5 ± 0.8 |
10.3 ± 9.1 8.6 ± 4.5 |
81.9 ± 16.3 61.2 ± 18.5 |
[11C]DASB PET | ROI | DSM‐IV/ HAM‐D, BDI |
dPDs and HCs > PDs: Serotonergic binding in amygdala, hypothalamus, caudal raphe nuclei and PCC HCs > dPDs: Serotonergic binding in ACC, caudate nucleus, insula, prefrontal cortex, putamen, rostral raphe nuclei, thalamus and ventral striatum |
| Rektorova et al. (2008) 26 | 20 PDs | 10/10 | No data | 5.6 ± 3.5 | 20.9 ± 10.8 | [123I]FP‐CIT SPECT | ROI | MADRS |
Inverse correlation between depression scores and DAT availability in bi. striatum and putamen, left striatum and putamen → depression |
| Remy et al. (2005) 17 |
8 dPDs 12 PDs 7 HCs |
5/3 9/3 |
1–3.5 1–3.5 |
3.1 ± 1.8 4.9 ± 2.6 |
24.3 ± 11.2 23.3 ± 6.7 |
[11C]RTI‐32 PET | ROI | BDI, AES, STAS |
HCs > PDs + dPDs: Binding value in bi. caudate, putamen, ventral striatum and substantia nigra HCs > dPDs: Binding value in ACC, thalamus PDs > dPDs: Binding value in bi. thalamus and locus coeruleus ACC, right amygdala and left ventral striatum Inverse correlation between depression and binding value in left ventral striatum |
| Vriend et al. (2014) 27 | 100 PDs | 61/39 | 2.08 ± 0.64 | 3.5 ± 4.4 | 23.6 ± 11.5 | [123I]FP‐CIT SPECT | ROI | BDI | Inverse correlation between depression and DAT binding |
| Weintraub et al. (2005) 28 |
76 PDs 46 HCs |
57/19 24/22 |
No data | 7.5 ± 5.5 | No data | 99mTc‐ TRODAT‐1 SPECT | ROI | POMS, STAS | Inverse correlation between depression and DAT availability in left anterior putamen |
| Wu et al. (2011) 29 |
17 PDs 13 MDs 10 HCs |
9/8 7/6 5/5 |
No data | 1.17 ± 0.5 | No data | 99mTc‐ TRODAT‐1 SPECT | ROI | CCMD‐3, DSM‐IV/ HAM‐D | HCs and MDs > PDs: Dopaminergic availability in bi. striatum |
| Qamhawi et al. (2015) 30 |
345 PDs 56 SWEDDs 185 HCs |
231/114 40/16 126/59 |
1.5 ± 0.5 1.4 ± 0.5 |
0.53 ± 0.5 |
19.6 ± 8.9 12.5 ± 6.8 |
[123I]FP‐CIT SPECT | ROI | GDS | No significant relationship between depression and raphe specific binding ratio |
| Becker et al. (1997) 43 |
30 HCs 13 dPDs 17 PDs |
24/6 11/2 14/3 |
2–4 (PDs + dPDs) |
9.7 ± 5.8 (PDs + dPDs) |
27.7 ± 13.1 | TCS | ROI |
CGI HAM‐D |
HCs + PDs > dPDs: Raphe echogenicity Inverse correlation between raphe echogenicity and depression severity |
| Berg et al. (1999) 48 |
31 patients (20dPDs 11 PDs) |
16/15 | 2.58 ± 0.76 | 6.6 (1–17) | No UPDRS, but CURS = 35.1 (16–50) |
TCS T2‐weighted |
ROI | DSM‐IV/ HAM‐D, BDI |
dPDs > PDs: More hyperintense in mesencephalic midline Higher T2 values in pontine midline, but lower in mesencephalic midline Decreased echogenicity in mesencephalic midline |
| Walter et al. (2007) 44 |
55 HCs 55 MDs 45 PDs 45 dPDs |
27/28 11/44 23/22 23/22 |
No data |
7.4 ± 6.4 8.1 ± 6.4 |
32.4 ± 20.7 34.1 ± 18.5 |
TCS | ROI | DSM‐IV/BDI, HAM‐D |
HCs + PDs > MDs + dPDs: Echogenicity in brainstem dPDs: Hyperechogenicity in substantia nigra, hypoechogenicity in brainstem raphe |
| Cardoso et al. (2009) 46 |
20 dPDs 16 PDs |
20/0 16/0 |
2.5 ± 0.6 2.3 ± 0.3 |
11.2 ± 6.9 10.2 ± 4.3 |
36.7 ± 12.2 32.8 ± 8.74 |
T1‐weighted task FMRI |
ROI (T1) WB (FMRI) |
DSM‐IV/ HAM‐D |
Structural (volume): dPDs > PDs: Bi. mediodorsal thalamic nucleis Functional (activity): PDs > dPDs: Bi. dorsomedial prefrontal cortices and middle cingulate gyri; left mediodorsal thalamus |
| Feldmann et al. (2008) 31 |
23 dPDs 27 PDs 16 HCs |
dPDs + PDs: 30/20 9/7 |
2.7 ± 0.4 2.7 ± 0.4 |
9.9 ± 5.2 11.2 ± 5.9 |
35.1 ± 9.3 33.6 ± 8.8 |
T1‐weighted | WB | MADRS |
No difference between HCs and PDs and between HCs and dPDs PDs > dPDs: Left orbitofrontal inferior gyrus and rectus; right temporal superior pole and rectus Inverse relationship between depression scores and grey matter volumes in bi. orbitofrontal and right temporal and limbic regions in dPDs |
| Kostić et al. (2010) 32 |
24 PDs 16 dPDs 26 HCs |
13/11 8/8 14/12 |
2 (1–3) 2 (1–3) |
5 (1–19) 6 (1–14) |
19 (10–35) 23 (4–36) |
T1‐weighted |
WB | HAM‐D |
HCs > PDs + dPDs: GM in right ACC and insula; left middle frontal and angular PDs > dPDs: WM in right ACC and inferior orbitofrontal region PDs + dPDs: inverse correlation between WM volume in right inferior orbitofrontal region and depression scores |
| van Mierlo et al. (2015) 33 |
67 PDs |
43/24 | 2.1 ± 0.6 | 2.95 ± 3.39 | 23.27 ± 10.56 | T1‐weighted | WB, followed by ROI | BDI | Inverse correlation between depression and bi. hippocampus and right amygdalar volume |
| Huang et al. (2014) 34 |
15 dPDs 15 PDs |
9/6 9/6 |
2.7 ± 0.8 2.5 ± 1 |
5.3 ± 4.8 4.2 ± 4.0 |
54.6 ± 23.7 45.3 ± 26.1 |
DTI | WB | HAM‐D |
PDs > dPDs: FA in left uncinate fasciculus, superior and inferior longitudinal fasciculi, anterior thalamic radiation and forceps minor dPDs: Inverse correlation between depression and FA in left deep temporal cortex No difference or correlation was found in mean diffusivity |
| Li et al. (2010) 35 |
14 dPDs 18 PDs |
4/10 10/8 |
1.96 ± 0.99 1.83 ± 0.75 |
6.29 ± 5.51 5.67 ± 2.57 |
39.04 ± 22.28 33.83 ± 15.09 |
DTI | ROI | DSM‐IV/ HAM‐D |
PDs > dPDs: FA in bi. mediodorsal thalamic areas Inverse correlations between depression and FA in bi. mediodorsal thalamic areas |
| Matsui et al. (2007) 36 |
14 dPDs 14 PDs |
2/12 4/10 |
3.1 ± 0.4 3.1 ± 0.4 |
8.8 ± 5.2 7.4 ± 5.1 |
34.9 ± 14.7 27.4 ± 14.1 |
DTI | ROI | HAM‐D |
PDs > dPDs: FA in bi. ACC No difference or correlation was found in mean diffusivity |
| Surdhar et al. (2012) 45 |
6 dPDs6 PDs 6 HCs |
5/1 5/1 5/1 |
No data | No data |
16.67 ± 11.6 11.83 ± 2.5 |
T1‐weighted DTI |
ROI | GDS |
No FA difference in corpus callosum and uncinate fasciculus HCs > dPDs: GM volume in bi. amygdala |
| Huang et al. (2015) 47 |
19 dPDs 28 HCs |
10/9 9/19 |
2.6 ± 0.7 2.3 ± 1.0 |
5.2 ± 4.8 4.6 ± 5.0 |
57.7 ± 22.4 50.8 ± 22.4 |
T1‐weighted RS‐FMRI |
ROI | HAM‐D |
Structural (volume): No difference between groups in amygdala Functional (activity): dPDs > HCs and PDs: Left amygdala regional cerebral functional activity PDs + dPDs: Positive correlation between depression scores and left amygdala PDs > dPDs: Connectivity between right amygdala and frontoparietal areas dPDs: Inverse correlation between functional connectivity of right amygdala with right middle frontal gyrus and depression |
| Hu et al. (2015) 37 |
20 dPDs 39 PDs 41 HCs |
9/11 26/13 20/21 |
1.4 ± 0.6 1.72 ± 0.64 |
5.35 ± 2.82 6.5 ± 3.54 |
27.65 ± 13.17 28.21 ± 13.17 |
RS‐FMRI | ROI | DSM‐V/ HAM‐D |
dPDs > PDs: Connectivity between left amygdala and bi. mediodorsal thalamus and between right amygdala and left superior temporal and calcarine gyri dPDs vs. HCs: ↑ connectivity between left amygdala and bi. mediodorsal thalamus; ↓ connectivity between left amygdala and left putamen, inferior frontal gyrus and right cerebellum; ↓ connectivity between right amygdala and left rectus, inferior orbitofrontal gyrus and right putamen |
| Lou et al. (2015) 38 |
17 dPDs 17 PDs 17 HCs |
8/9 9/8 9/8 |
2.71 ± 0.25 2.62 ± 0.28 |
No data |
44.06 ± 12.34 40.47 ± 9.19 |
RS‐FMRI | WB | DSM‐IV/ HAM‐D |
PDs > dPDs: Connectivity in left dorsolateral prefrontal cortex and right superior temporal gyrus dPDs > PDs: Connectivity in right PCC HCs > dPDs: Connectivity in bi. frontal, temporal and parietal regions and left insula Inverse correlation between depression and PCC |
| Luo et al. (2014) 42 |
29 dPDs 30 PDs 30 HCs |
14/15 15/15 15/15 |
1.79 ± 0.62 1.73 ± 0.58 |
1.98 ± 1.64 2.12 ± 1.30 |
28.34 ± 16.9 26.83 ± 12.44 |
RS‐FMRI | WB followed by ROI | DSM‐IV/ HAM‐D |
dPDs > PDs and HCs: Regional cerebral function in left orbitofrontal area PDs + dPDs: Positive correlation between depression and regional cerebral function in left orbitofrontal cortex HCs > PDs > dPDs: Connectivity in the prefrontal−limbic network |
| Sheng et al. (2014) 39 |
20 dPDs 21 PDs 25 HCs |
13/8 13/7 16/9 |
2.1 ± 0.75 1.95 ± 0.63 |
3.4 ± 1.7 4.0 ± 2.4 |
39.4 ± 10.8 43.8 ± 8.2 |
RS‐FMRI | WB followed by ROI | DSM‐IV/ HAM‐D |
dPDs vs. PDs: Regional activity: ↑ in left middle frontal gyrus and right inferior frontal gyrus; ↓ in left amygdala and bi. lingual gyri dPDs vs. PDs: Connectivity: ↓ within prefrontal−limbic system and ↑ in prefrontal cortex and lingual gyrus |
| Skidmore et al. (2013) 40 | 15 PDs | 12/3 | No data | No data | 37 ± 13 | RS‐FMRI | WB | HAM‐D, LARS |
Positive correlation between depression and regional cerebral function in bi. cunei and cerebellums, right subgenual cingulate, lateral geniculate and mesial frontal gyrus Depression was predicted by functional activity signal in right subgenual cingulate |
| Wen et al. (2013) 41 |
17 dPDs 16 PDs 21 HCs |
7/10 8/8 13/8 |
2.1 ± 1.9 1.5 ± 1 |
6.4 ± 5.4 5.6 ± 7.4 |
42. ±46 33.8 ± 24.2 |
RS‐FMRI | WB | DSM‐IV/ HAM‐D |
dPDs vs. PDs: ↑ Regional cerebral function in bi. (mostly right) frontal areas, including ACC and dorsolateral prefrontal cortex and left temporal lobe; ↓ regional cerebral function in bi. cerebellum dPDs vs. HCs: ↑ Bi. temporal and parietal regions and left inferior frontal gyrus; ↓ bi. caudate and precuneus, right frontal, superior temporal and thalamic areas Positive correlation between depression and regional cerebral function in the dorsolateral prefrontal cortex |
ACC, anterior cingulated cortex; AES, Apathy Evaluation Scale; ALFF, amplitude of low frequency function; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; bi., bilateral; CCMD‐3, Chinese Classification of Mental Disorders version 3; CGI, clinical global impression; CSDD, Cornell Scale for Depression in Dementia; CURS, Columbia University Rating Scale; DAT, dopamine transporter; dPDs, PD patients with depression; DSM‐IV, ‐IV‐TR, ‐III, and ‐V, Diagnostic and Statistical Manual of Mental Disorders, 4th, 4th‐TR, 3rd, and 5th editions; DTI, diffusion tensor imaging; FA, fractional anisotropy; GDS, Geriatric Depression Scale; GM, grey matter; HAM‐A, Hamilton Anxiety Scale; HAM‐D, Hamilton Depression Scale; H and Y, Hoehn and Yahr scale; HCs, healthy controls; IDS, Inventory of Depressive Symptomatology; LARS, Lille Apathy Rating Scale; MADRS, Montgomery Asberg Depression Rating Scale; MD, patients with major depression; PCC, posterior cingulate cortex; PDs, patients with PD alone; PD‐Ds, patients with PD and dementia; PET, positron emission tomography; POMS, Profile of Mood States; rCBF, regional cerebral blood flow; ROI, region of interest; RS‐FMRI, resting state functional magnetic resonance imaging; SPECT, single‐photon emission computed tomography; STAS, State–Trait Anxiety Scale; SWEDD, patients with scans without evident dopaminergic deficits; TCS, transcranial sonography; UPDRS‐III, Unified Parkinson's Disease Rating Scale III; WB, whole brain; WM, white matter.