PMID- 24385130
OWN - NLM
STAT- MEDLINE
DCOM- 20141215
LR  - 20211021
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 39
IP  - 6
DP  - 2014 May
TI  - Stress-induced dopamine response in subjects at clinical high risk for 
      schizophrenia with and without concurrent cannabis use.
PG  - 1479-89
LID - 10.1038/npp.2013.347 [doi]
AB  - Research on the environmental risk factors for schizophrenia has focused on 
      either psychosocial stress or drug exposure, with limited investigation of their 
      interaction. A heightened dopaminergic stress response in patients with 
      schizophrenia and individuals at clinical high risk (CHR) supports the 
      dopaminergic sensitization hypothesis. Cannabis is believed to contribute to the 
      development of schizophrenia, possibly through a cross-sensitization with stress. 
      Twelve CHR and 12 cannabis-using CHR (CHR-CU, 11 dependent) subjects underwent 
      [(11)C]-(+)-PHNO positron emission tomography scans, while performing a 
      Sensorimotor Control Task (SMCT) and a stress condition (Montreal Imaging Stress 
      task). The simplified reference tissue model was used to obtain binding potential 
      relative to non-displaceable binding (BPND) in the whole striatum, its functional 
      subdivisions (limbic striatum (LST), associative striatum (AST), and sensorimotor 
      striatum (SMST)), globus pallidus (GP), and substantia nigra (SN). Changes in 
      BPND, reflecting alterations in synaptic dopamine (DA) levels, were tested with 
      analysis of variance. SMCT BPND was not significantly different between groups in 
      any brain region (p>0.21). Although stress elicited a significant reduction in 
      BPND in the CHR group, CHR-CU group exhibited an increase in BPND. Stress-induced 
      changes in regional BPND between CHR-CU and CHR were significantly different in 
      AST (p<0.001), LST (p=0.007), SMST (p=0.002), SN (p=0.021), and whole striatum 
      (p=0.001), with trend level in the GP (p=0.099). All subjects experienced an 
      increase in positive (attenuated) psychotic symptoms (p=0.001) following the 
      stress task. Our results suggest altered DA stress reactivity in CHR subjects who 
      concurrently use cannabis, as compared with CHR subjects. Our finding does not 
      support the cross-sensitization hypothesis, which posits greater dopaminergic 
      reactivity to stress in CHR cannabis users, but adds to the growing body of 
      literature showing reduced DA (stress) response in addiction.
FAU - Mizrahi, Romina
AU  - Mizrahi R
AD  - 1] PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] 
      Faculty of Medicine, Division of Brain and Therapeutics, Department of 
      Psychiatry, University of Toronto, Toronto, ON, Canada.
FAU - Kenk, Miran
AU  - Kenk M
AD  - PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
FAU - Suridjan, Ivonne
AU  - Suridjan I
AD  - PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
FAU - Boileau, Isabelle
AU  - Boileau I
AD  - 1] PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] 
      Faculty of Medicine, Division of Brain and Therapeutics, Department of 
      Psychiatry, University of Toronto, Toronto, ON, Canada.
FAU - George, Tony P
AU  - George TP
AD  - Faculty of Medicine, Division of Brain and Therapeutics, Department of 
      Psychiatry, University of Toronto, Toronto, ON, Canada.
FAU - McKenzie, Kwame
AU  - McKenzie K
AD  - Faculty of Medicine, Division of Brain and Therapeutics, Department of 
      Psychiatry, University of Toronto, Toronto, ON, Canada.
FAU - Wilson, Alan A
AU  - Wilson AA
AD  - 1] PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] 
      Faculty of Medicine, Division of Brain and Therapeutics, Department of 
      Psychiatry, University of Toronto, Toronto, ON, Canada.
FAU - Houle, Sylvain
AU  - Houle S
AD  - 1] PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] 
      Faculty of Medicine, Division of Brain and Therapeutics, Department of 
      Psychiatry, University of Toronto, Toronto, ON, Canada.
FAU - Rusjan, Pablo
AU  - Rusjan P
AD  - PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131224
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Brain/diagnostic imaging/*metabolism
MH  - Brain Mapping
MH  - Dopamine/*metabolism
MH  - Female
MH  - Humans
MH  - Male
MH  - Marijuana Abuse/*metabolism
MH  - Neuropsychological Tests
MH  - Positron-Emission Tomography
MH  - Prodromal Symptoms
MH  - Psychiatric Status Rating Scales
MH  - Psychotic Disorders/psychology
MH  - Risk
MH  - Schizophrenia/*epidemiology
MH  - Signal Processing, Computer-Assisted
MH  - Stress, Psychological/*metabolism/psychology
MH  - Young Adult
PMC - PMC3988552
EDAT- 2014/01/05 06:00
MHDA- 2014/12/17 06:00
PMCR- 2015/05/01
CRDT- 2014/01/04 06:00
PHST- 2013/07/19 00:00 [received]
PHST- 2013/11/26 00:00 [revised]
PHST- 2013/11/30 00:00 [accepted]
PHST- 2014/01/04 06:00 [entrez]
PHST- 2014/01/05 06:00 [pubmed]
PHST- 2014/12/17 06:00 [medline]
PHST- 2015/05/01 00:00 [pmc-release]
AID - npp2013347 [pii]
AID - 10.1038/npp.2013.347 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2014 May;39(6):1479-89. doi: 10.1038/npp.2013.347. Epub 
      2013 Dec 24.