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The effects of psychosocial stress on dopaminergic function and the acute stress response

  1. Michael AP Bloomfield  Is a corresponding author
  2. Robert A McCutcheon
  3. Matthew Kempton
  4. Tom P Freeman
  5. Oliver Howes  Is a corresponding author
  1. Imperial College London, United Kingdom
  2. University College London, United Kingdom
  3. Kings College London, United Kingdom
  4. NIHR University College London Hospitals Biomedical Research Centre, United Kingdom
  5. St Pancras Hospital, Camden and Islington NHS Foundation Trust, United Kingdom
  6. National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, United Kingdom
  7. University of Bath, United Kingdom
Research Article
Cite this article as: eLife 2019;8:e46797 doi: 10.7554/eLife.46797
4 figures, 4 tables and 2 additional files

Figures

Striatal dopamine synthesis capacity in Low Adversity (LA, n = 17) and High Adversity participants (HA, n = 17).

Dopamine synthesis capacity was significantly reduced in HA compared with LA (t32 = 2.27, p=0.03). Error bars indicate standard errors.

https://doi.org/10.7554/eLife.46797.003
The High Adversity group showed a heightened subjective response and a blunted physiological response.

Panel A shows subjective Threatened responses; Panels B (Cortisol) and C (Mean Arterial Blood Pressure) show physiological response. Data show mean (+ /- SEM).

https://doi.org/10.7554/eLife.46797.007
Correlations between striatal dopamine synthesis capacity and acute response to psychosocial stress.

(A) Whole striatal dopamine synthesis capacity was positively correlated with stress-induced threat in the Low Adversity group (r = 0.73, p=0.001) but not the High Adversity group (r = −0.03, p=0.934). (B). Whole striatal dopamine synthesis capacity was negatively correlated with stress-induced threat and mean arterial blood pressure in the Low Adversity group (r = −0.62, p=0.013) but not the High Adversity group (r = 0.23, p=0.395). Extreme bivariate outliers have been removed from the figures.

https://doi.org/10.7554/eLife.46797.008
Experimental procedures.

MIST, Montreal Imaging Stress Test; MAP, Mean Arterial Blood Pressure; VAS, visual analogue scale.

https://doi.org/10.7554/eLife.46797.009

Tables

Table 1
Sample characteristics and scan parameters
https://doi.org/10.7554/eLife.46797.002
Sample characteristicLA ( = 17)HA ( = 17)pa
Age, years [mean(SD)]27.6(7.8)29.2(7.2)0.54
Sex, nnine female, eight maleeight female, nine male1.00
Ethnicity, n17 WB4 BA, 1BB, 4 BC, 6 ME, 1 OE, 1 WB<0.001
Childhood Adversity
CTQ [mean(SD)]3.8(5.2)15.3(16.1)0.01
Parental loss (parental separation with loss of parental contact and/or death and/or going into foster care and/or being adopted) during childhood, n013<0.001
Childhood sexual abuse060.02
Adult Adversity
Number of adverse life events over last 6 months [mean(SD)]0.5 (0.9)2.6 (1.9)0.001
Life events score over last 6 months [mean(SD)]15.1 (37.0)72.3 (55.7)<0.01
Clinical Scores
BDI [mean(SD)]2.7 (3.8)6.5 (5.6)0.03
BAI [mean(SD)]4.8 (6.7)9.7 (10.2)0.11
IES-6 [mean(SD)]1.7 (2.3)7.7 (7.6)0.01
O-LIFE [mean(SD)]7.2 (6.5)13.1 (9.5)0.07
ASI [mean(SD)]5.7 (5.8)11.6 (7.5)0.02
Current Drug Usec,d
Tobacco cigarette smokers in last 3 months (n)three user, 14 non-usersfour users, 13 non-users1.00
Tobacco use in whole sample (cigarettes/day) [mean(SD)].4(1.5)1.7(3.6)0.19
Alcohol use in last 3 months (n)15 users, two non-users14 users, three non-users1.00
Alcohol use (UK alcohol units/week) [mean(SD)]10.2(9.0)7.0(8.9)0.30
Scan parameter
Injected dose (MBq) [mean(SD)]143.4(7.7)142.9(7.7)0.85
Specific activity (MBq/µmol) [mean(SD)]35.3(6.7)41.4(15.4)0.14
Whole striatal volume (mm3) [mean(SD)]16,842(5094)15,741(4,601)0.54
Associative striatal volume (mm3) [mean(SD)]10,460(3202)9771(2885)0.54
Limbic striatal volume (mm3) [mean(SD)]2005(610)1897(547)0.61
Sensorimotor striatal volume (mm3) [mean(SD)]4375(1314)4072(1189)0.51
  1. Abbreviations: ASI, Aberrant Salience Inventory; BA, black African; BAI; Beck Anxiety Inventory; BB, black British; BC, black Caribbean; BDI, Beck Depression Inventory; CTQ, Childhood Trauma Questionnaire; IES-6, Brief Impact of Events Scale;, mixed ethnicity; OE, other ethnicity; O-LIFE, Oxford-Liverpool Inventory of Feelings and Experiences; SEAT, Social Environment Assessment Tool; WB, White British.

    a Independent-samples t-tests for variables with normal data distributions; Mann-Whitney U tests for variables with non-normal data distributions; χ2-tests for dichotomous variables.

  2. bGroups were compared on a dichotomised ethnicity variable (white British vs ethnic minority).

    c 1 UK alcohol unit = 10 mL (~7.88 g) alcohol.

Table 2
[18F]-DOPA Kicer (min−1) by group
https://doi.org/10.7554/eLife.46797.004
VOILA ( = 17)HA ( = 17)Group comparisonsaEffect size
Mean(SD)Mean(SD)tdfp(Cohen’s D)
STR0.0133(0.0014)0.0124(0.0013)2.27320.030.80
AST0.0133(0.0011)0.0124(0.0010)2.28320.030.81
LST0.0140(0.0015)0.0128(0.0010)2.69320.010.95
SMST0.0132(0.0013)0.0125(0.0011)1.17320.100.41
  1. Abbreviations: AST, associative striatum; LST, limbic striatum; Kicer, influx rate constant; SMST, sensorimotor striatum; STR, whole striatum; VOI, volume of interest.

    a Independent-samples t-tests.

Table 3
Baseline stress reactivity in Low Adversity (LA) and High Adversity (HA) groups at prior to acute psychosocial stress challenge
https://doi.org/10.7554/eLife.46797.005
MeasureLA ( = 17)HA ( = 17)Group comparisonsEffect size
Mean(SD)Mean(SD)tdfP(Cohen’s D)
Threatened (mm)6.75(15.52)4.58(6.00)0.46260.650.18
Cortisol (U/mL)3.93(2.74)5.12(3.54)1.08300.290.38
Amylase (U/mL)178.42(173.83)92.79(53.13)1.83300.070.67
MAP (mmHg)89.67(9.45)90.38(9.63)0.21290.840.07
  1. Abbreviations: HA, high adversity; LA, low adversity; MAP, mean arterial pressure.

Table 4
Acute response to psychosocial stress challenge in Low Adversity (LA) and High Adversity (HA) groups
https://doi.org/10.7554/eLife.46797.006
MeasureLA ( = 17)HA ( = 17)Group comparisonsEffect size
Mean(SD)Mean(SD)tdfp(Cohen’s D)
Threatened (AUC)191.25(587.99)780.83(764.33)2.31260.040.86
Cortisol (AUC)122.34(156.49)11.75(166.14)1.94300.060.69
Amylase (AUC)1616.67(5750.66)1015.84(2740.24)0.37300.720.13
MAP (AUC)153.30(90.04)79.31(92.09)2.26290.030.81
  1. Abbreviations: HA, high adversity; LA, low adversity; MAP, mean arterial pressure.

Data availability

The raw data from this study are available on written request to the Chief Investigator. This restriction is due to sensitive data on human research participants. Processed data files for Figures 1 and 2, and table 2 are provided in Source data 1.

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