Neanderthal‐derived genetic variation in living humans relates to schizophrenia diagnosis, to psychotic symptom severity, and to dopamine synthesis

Author(s):  
Michael D. Gregory ◽  
Daniel P. Eisenberg ◽  
Madeline Hamborg ◽  
J. Shane Kippenhan ◽  
Philip Kohn ◽  
...  
2016 ◽  
Vol 46 (16) ◽  
pp. 3383-3395 ◽  
Author(s):  
M. A. P. Bloomfield ◽  
E. Mouchlianitis ◽  
C. J. A. Morgan ◽  
T. P. Freeman ◽  
H. V. Curran ◽  
...  

BackgroundCannabis is a widely used drug associated with increased risk for psychosis. The dopamine hypothesis of psychosis postulates that altered salience processing leads to psychosis. We therefore tested the hypothesis that cannabis users exhibit aberrant salience and explored the relationship between aberrant salience and dopamine synthesis capacity.MethodWe tested 17 cannabis users and 17 age- and sex-matched non-user controls using the Salience Attribution Test, a probabilistic reward-learning task. Within users, cannabis-induced psychotic symptoms were measured with the Psychotomimetic States Inventory. Dopamine synthesis capacity, indexed as the influx rate constant Kicer, was measured in 10 users and six controls with 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine positron emission tomography.ResultsThere was no significant difference in aberrant salience between the groups [F1,32 = 1.12, p = 0.30 (implicit); F1,32 = 1.09, p = 0.30 (explicit)]. Within users there was a significant positive relationship between cannabis-induced psychotic symptom severity and explicit aberrant salience scores (r = 0.61, p = 0.04) and there was a significant association between cannabis dependency/abuse status and high implicit aberrant salience scores (F1,15 = 5.8, p = 0.03). Within controls, implicit aberrant salience was inversely correlated with whole striatal dopamine synthesis capacity (r = −0.91, p = 0.01), whereas this relationship was non-significant within users (difference between correlations: Z = −2.05, p = 0.04).ConclusionsAberrant salience is positively associated with cannabis-induced psychotic symptom severity, but is not seen in cannabis users overall. This is consistent with the hypothesis that the link between cannabis use and psychosis involves alterations in salience processing. Longitudinal studies are needed to determine whether these cognitive abnormalities are pre-existing or caused by long-term cannabis use.


2011 ◽  
Vol 39 (2) ◽  
pp. 330-338 ◽  
Author(s):  
J. L. Roffman ◽  
D. G. Brohawn ◽  
A. Z. Nitenson ◽  
E. A. Macklin ◽  
J. W. Smoller ◽  
...  

2019 ◽  
Vol 85 (10) ◽  
pp. S129
Author(s):  
Michael Gregory ◽  
Daniel Eisenberg ◽  
J. Shane Kippenhan ◽  
Philip Kohn ◽  
Karen Berman

2021 ◽  
Author(s):  
Kristina Sabaroedin ◽  
Adeel Razi ◽  
Sidhant Chopra ◽  
Nancy Tran ◽  
Andrii Pozaruk ◽  
...  

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. Here, we used spectral dynamic causal modelling (DCM) of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naive first-episode psychosis (FEP) patients and 23 controls and an independent sample of 36 patients with established schizophrenia (SCZ) patients and 100 controls. We found that midbrain and thalamic connectivity were implicated across both patient groups. Dysconnectivity in FEP patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in SCZ patients. In another independent sample of 33 healthy individuals who underwent concurrent fMRI and [18F]DOPA positron emission tomography, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits as those associated with psychotic symptom severity in patients. Our findings thus indicate that subcortical dysconnectivity is salient in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signaling are closely related to striatal dopamine synthesis capacity, which is a robust risk marker for psychosis.


2006 ◽  
Vol 189 (2) ◽  
pp. 137-143 ◽  
Author(s):  
L. Hides ◽  
S. Dawe ◽  
D. J. Kavanagh ◽  
R. M. Young

BackgroundCannabis use appears to exacerbate psychotic symptoms and increase risk of psychotic relapse. However, the relative contribution of cannabis use compared with other risk factors is unclear. The influence of psychotic symptoms on cannabis use has received little attention.AimsTo examine the influence of cannabis use on psychotic symptom relapse and the influence of psychotic symptom severity on relapse in cannabis use in the 6 months following hospital admission.MethodAt baseline, 84 participants with recent-onset psychosis were assessed and 81 were followed up weekly for 6 months, using telephone and face-to-face interviews.ResultsA higher frequency of cannabis use was predictive of psychotic relapse, after controlling for medication adherence, other substance use and duration of untreated psychosis. An increase in psychotic symptoms was predictive of relapse to cannabis use, and medication adherence reduced cannabis relapse risk.ConclusionsThe relationship between cannabis use and psychosis may be bidirectional, highlighting the need for early intervention programmes to target cannabis use and psychotic symptom severity in this population.


2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Michael J C Bray ◽  
Bhanu Sharma ◽  
Julia Cottrelle ◽  
Matthew E Peters ◽  
Mark Bayley ◽  
...  

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