TY - JOUR
T1 - Stress-induced cortical dopamine response is altered in subjects at clinical high risk for psychosis using cannabis
AU - Schifani, Christin
AU - Pruessner, Jens
AU - Tseng, Huai Hsuan
AU - Rao, Naren
AU - Tagore, Abanti
AU - Wilson, Alan A.
AU - Houle, Sylvain
AU - Rusjan, Pablo M.
AU - Mizrahi, Romina
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Stress and cannabis use are risk factors for the development of psychosis. We have previously shown that subjects at clinical high risk for psychosis (CHR) exhibit a higher striatal dopamine response to stress compared with healthy volunteers (HV), with chronic cannabis use blunting this response. However, it is unknown if this abnormal dopamine response extends to the prefrontal cortex (PFC). Here, we investigated dorsolateral PFC (dlPFC) and medial PFC (mPFC) dopamine release using [11C]FLB457 positron emission tomography (PET) and a validated stress task. Thirty-three participants completed two PET scans (14 CHR without cannabis use, eight CHR regular cannabis users [CHR-CUs] and 11 HV) while performing a Sensory Motor Control Task (control scan) and the Montreal Imaging Stress Task (stress scan). Stress-induced dopamine release (ΔBPND) was defined as percent change in D2/3 receptor binding potential between both scans using a novel correction for injected mass of [11C]FLB457. ΔBPND was significantly different between groups in mPFC (F(2,30) = 5.40,.010), with CHR-CUs exhibiting lower ΔBPND compared with CHR (.008). Similarly, salivary cortisol response (ΔAUCI) was significantly lower in CHR-CU compared with CHR (F(2,29) = 5.08,.013; post hoc.018) and positively associated with ΔBPND. Furthermore, CHR-CUs had higher attenuated psychotic symptoms than CHR following the stress task, which were negatively associated with ΔBPND. Length of cannabis use was negatively associated with ΔBPND in mPFC when controlling for current cannabis use. Given the global trend to legalize cannabis, this study is important as it highlights the effects of regular cannabis use on cortical dopamine function in high-risk youth.
AB - Stress and cannabis use are risk factors for the development of psychosis. We have previously shown that subjects at clinical high risk for psychosis (CHR) exhibit a higher striatal dopamine response to stress compared with healthy volunteers (HV), with chronic cannabis use blunting this response. However, it is unknown if this abnormal dopamine response extends to the prefrontal cortex (PFC). Here, we investigated dorsolateral PFC (dlPFC) and medial PFC (mPFC) dopamine release using [11C]FLB457 positron emission tomography (PET) and a validated stress task. Thirty-three participants completed two PET scans (14 CHR without cannabis use, eight CHR regular cannabis users [CHR-CUs] and 11 HV) while performing a Sensory Motor Control Task (control scan) and the Montreal Imaging Stress Task (stress scan). Stress-induced dopamine release (ΔBPND) was defined as percent change in D2/3 receptor binding potential between both scans using a novel correction for injected mass of [11C]FLB457. ΔBPND was significantly different between groups in mPFC (F(2,30) = 5.40,.010), with CHR-CUs exhibiting lower ΔBPND compared with CHR (.008). Similarly, salivary cortisol response (ΔAUCI) was significantly lower in CHR-CU compared with CHR (F(2,29) = 5.08,.013; post hoc.018) and positively associated with ΔBPND. Furthermore, CHR-CUs had higher attenuated psychotic symptoms than CHR following the stress task, which were negatively associated with ΔBPND. Length of cannabis use was negatively associated with ΔBPND in mPFC when controlling for current cannabis use. Given the global trend to legalize cannabis, this study is important as it highlights the effects of regular cannabis use on cortical dopamine function in high-risk youth.
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U2 - 10.1111/adb.12812
DO - 10.1111/adb.12812
M3 - Article
C2 - 31389139
AN - SCOPUS:85070502925
VL - 25
JO - Addiction Biology
JF - Addiction Biology
SN - 1355-6215
IS - 4
M1 - e12812
ER -