Dopamine Function in Cigarette Smokers: An [18F]-DOPA PET Study

Bloomfield, Michael; Pepper, Fiona; Egerton, Alice; Demjaha, Arsime; Tomasi, Giampaolo; Mouchlianitis, Elias; Maximen, Levi; Veronese, Mattia; Turkheimer, Federico; Selvaraj, Sudhakar; Howes, Oliver

doi:10.1038/npp.2014.87

Cited by 45 publications

(38 citation statements)

References 58 publications

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“…First, being a smoker may interfere with memory consolidation or retrieval and/or related discrimination processes, possibly via nicotinergic or dopaminergic mechanisms (Fu et al, 2007;Kutlu and Gould, 2015;Subramaniyan and Dani, 2015). Although several studies found alterations of dopaminergic functioning in smokers (Bloomfield et al, 2014;Cosgrove et al, 2015;Rademacher et al, 2015), there is evidence that dopamine is involved in the consolidation of safety memories to inhibit the return of fear responses (Haaker et al, 2013(Haaker et al, , 2015a. Second, maintained smoking habits (Winkler et al, 2011) and a persistent conditioned fear response in safe contexts might be due to an common underling deficit in flexibly adjusting learned associations.…”

Section: Discussionmentioning

confidence: 99%

Where There is Smoke There is Fear—Impaired Contextual Inhibition of Conditioned Fear in Smokers

Haaker

Lonsdorf

Schümann

et al. 2017

Neuropsychopharmacol

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The odds-ratio of smoking is elevated in populations with neuropsychiatric diseases, in particular in the highly prevalent diagnoses of post-traumatic stress and anxiety disorders. Yet, the association between smoking and a key dimensional phenotype of these disorders-maladaptive deficits in fear learning and fear inhibition-is unclear. We therefore investigated acquisition and memory of fear and fear inhibition in healthy smoking and non-smoking participants (N=349, 22% smokers). We employed a well validated paradigm of context-dependent fear and safety learning (day 1) including a memory retrieval on day 2. During fear learning, a geometrical shape was associated with an aversive electrical stimulation (classical fear conditioning, in danger context) and fear responses were extinguished within another context (extinction learning, in safe context). On day 2, the conditioned stimuli were presented again in both contexts, without any aversive stimulation. Autonomic physiological measurements of skin conductance responses as well as subjective evaluations of fear and expectancy of the aversive stimulation were acquired. We found that impairment of fear inhibition (extinction) in the safe context during learning (day 1) was associated with the amount of pack-years in smokers. During retrieval of fear memories (day 2), smokers showed an impairment of contextual (safety context-related) fear inhibition as compared with non-smokers. These effects were found in physiological as well as subjective measures of fear. We provide initial evidence that smokers as compared with non-smokers show an impairment of fear inhibition. We propose that smokers have a deficit in integrating contextual signs of safety, which is a hallmark of post-traumatic stress and anxiety disorders.

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Section: Discussionmentioning

confidence: 99%

Where There is Smoke There is Fear—Impaired Contextual Inhibition of Conditioned Fear in Smokers

Haaker

Lonsdorf

Schümann

et al. 2017

Neuropsychopharmacol

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“…PET imaging acquisition and analysis All participants received a PET scan to index dopamine synthesis capacity at baseline. Subjects were asked not to eat or drink (except water), and refrain from alcohol for 12 h prior to scan and not to smoke for 2 h prior to the scan [40]. Imaging data were obtained on a Siemens Biograph 6 HiRez PET scanner (Siemens, Erlangen, Germany) in three-dimensional mode.…”

Section: Clinical Measuresmentioning

confidence: 99%

Glutamatergic and dopaminergic function and the relationship to outcome in people at clinical high risk of psychosis: a multi-modal PET-magnetic resonance brain imaging study

Howes

Bonoldi

McCutcheon

et al. 2019

Neuropsychopharmacol.

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Preclinical models of psychosis propose that hippocampal glutamatergic neuron hyperactivity drives increased striatal dopaminergic activity, which underlies the development of psychotic symptoms. The aim of this study was to examine the relationship between hippocampal glutamate and subcortical dopaminergic function in people at clinical high risk for psychosis, and to assess the association with the development of psychotic symptoms. 1 H-MRS was used to measure hippocampal glutamate concentrations, and 18 F-DOPA PET was used to measure dopamine synthesis capacity in 70 subjects (51 people at clinical high risk for psychosis and 19 healthy controls). Clinical assessments were undertaken at baseline and follow-up (median 15 months). Striatal dopamine synthesis capacity predicted the worsening of psychotic symptoms at follow-up (r = 0.35; p < 0.05), but not transition to a psychotic disorder (p = 0.22), and was not significantly related to hippocampal glutamate concentration (p = 0.13). There were no differences in either glutamate (p = 0.5) or dopamine (p = 0.5) measures in the total patient group relative to controls. Striatal dopamine synthesis capacity at presentation predicts the subsequent worsening of sub-clinical total and psychotic symptoms, consistent with a role for dopamine in the development of psychotic symptoms, but is not strongly linked to hippocampal glutamate concentrations.

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“…PET image analysis was conducted as previously described (Bloomfield et al, 2014). Interframe correction for head movement during the scan was performed by denoising the nonattenuation-corrected dynamic images using a level 2, order 64 Battle-Lemarie wavelet filter.…”

Section: Image Analysismentioning

confidence: 99%

Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [18F]DOPA PET Study

Kim

Howes

Veronese

et al. 2016

Neuropsychopharmacol

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Some patients with schizophrenia show poor response to first-line antipsychotic treatments and this is termed treatment-resistant schizophrenia. The differential response to first-line antipsychotic drugs may reflect a different underlying neurobiology. Indeed, a previous study found dopamine synthesis capacity was significantly lower in patients with treatment-resistant schizophrenia. However, in this study, the treatment-resistant patients were highly symptomatic, whereas the responsive patients showed no or minimal symptoms. The study could not distinguish whether this was a trait effect or reflected the difference in symptom levels. Thus, we aimed to test whether dopaminergic function is altered in patients with a history of treatment resistance to first-line drugs relative to treatment responders when both groups are matched for symptom severity levels by recruiting treatment-resistant patients currently showed low symptom severity with the clozapine treatment. Healthy controls (n=12), patients treated with clozapine (n=12) who had not responded to first-line antipsychotics, and patients who had responded to first-line antipsychotics (n=12) were recruited. Participants were matched for age and sex and symptomatic severity level in patient groups. Participants' dopamine synthesis capacity was measured by using [F]DOPA PET. We found that patients treated with clozapine show lower dopamine synthesis capacity than patients who have responded to first-line treatment (Cohen's d=0.9191 (whole striatum), 0.7781 (associative striatum), 1.0344 (limbic striatum), and 1.0189 (sensorimotor striatum) in line with the hypothesis that the dopaminergic function is linked to treatment response. This suggests that a different neurobiology may underlie treatment-resistant schizophrenia and that dopamine synthesis capacity may be a useful biomarker to predict treatment responsiveness.

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Dopamine Function in Cigarette Smokers: An [18F]-DOPA PET Study

Cited by 45 publications

References 58 publications

Where There is Smoke There is Fear—Impaired Contextual Inhibition of Conditioned Fear in Smokers

Where There is Smoke There is Fear—Impaired Contextual Inhibition of Conditioned Fear in Smokers

Glutamatergic and dopaminergic function and the relationship to outcome in people at clinical high risk of psychosis: a multi-modal PET-magnetic resonance brain imaging study

Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [18F]DOPA PET Study

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