Dataset Information

Neural Responses to Smoking Cues in Schizophrenia.

ABSTRACT: The high prevalence of nicotine dependence contributes to excess mortality in schizophrenia. Cue reactivity, or the encounter of drug-related cues or contexts, triggers craving, drug-seeking, and relapse. Prior functional magnetic resonance imaging (fMRI) research indicates that individuals with schizophrenia have blunted neural responses to rewarding stimuli in association with more severe negative symptoms. The objectives of this study are to determine if smokers with schizophrenia have altered neural reactivity to smoking cues compared with non-psychiatrically ill smokers and to evaluate the influence of negative symptoms on cue reactivity. Twenty smokers with schizophrenia and 19 control smokers underwent fMRI while viewing smoking-related and neutral cues. The primary analysis was group comparison of Smoking-Neutral contrast using whole-brain analysis (Pcorrected < .05). Smokers with schizophrenia had significantly greater baseline carbon monoxide levels and longer duration of smoking, suggesting more nicotine use. While both groups had greater brain reactivity to smoking vs neutral cues, smokers with schizophrenia had significantly decreased cue reactivity (Smoking-Neutral) compared to controls in bilateral frontal midline regions. There were significant negative correlations between negative symptoms and frontal midline reactivity. Despite greater nicotine use, smokers with schizophrenia exhibited decreased smoking cue-induced neural reactivity in frontal midline regions, suggesting that increased smoking and low cessation rates in schizophrenia are not primarily driven by responses to smoking-related cues. The finding of negative correlations between cue reactivity and negative symptoms is consistent with previous research demonstrating decreased neural responses to rewarding cues, particularly in patients with negative symptoms.

SUBMITTER: Moran LV

PROVIDER: S-EPMC5890466 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Neural Responses to Smoking Cues in Schizophrenia.

Moran Lauren V LV Betts Jennifer M JM Ongur Dost D Janes Amy C AC

Schizophrenia bulletin 20180401 3

The high prevalence of nicotine dependence contributes to excess mortality in schizophrenia. Cue reactivity, or the encounter of drug-related cues or contexts, triggers craving, drug-seeking, and relapse. Prior functional magnetic resonance imaging (fMRI) research indicates that individuals with schizophrenia have blunted neural responses to rewarding stimuli in association with more severe negative symptoms. The objectives of this study are to determine if smokers with schizophrenia have altere ...[more]

PMID: 29106683

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Project description:CONTEXT Abnormalities in associative memory processes, such as Pavlovian fear conditioning and extinction, have been observed in schizophrenia. The retrieval of fear extinction memories (safety signals) may be particularly affected; although schizophrenic patients can extinguish conditioned fear, they show a deficit in retrieving fear extinction memories after a delay. The neurobiological basis of this abnormality is unknown, but clues have emerged from studies in rodents and humans demonstrating that the ventromedial prefrontal cortex (vmPFC) is a key mediator of extinction memory retrieval. OBJECTIVE To measure autonomic and neural responses during the acquisition and extinction of conditioned fear and the delayed recall of fear and extinction memories in patients with schizophrenia and healthy control participants. DESIGN Cross-sectional case control, functional magnetic resonance imaging study. SETTING Academic medical center. PARTICIPANTS Twenty schizophrenic patients and 17 healthy control participants demographically matched to the patient group. MAIN OUTCOME MEASURES Skin conductance and blood oxygen level-dependent responses. RESULTS During fear conditioning, schizophrenic patients showed blunted autonomic responses and abnormal blood oxygen level-dependent responses, relative to control participants, within the posterior cingulate gyrus, hippocampus, and other regions. Several of these abnormalities were linked to negative symptoms. During extinction learning, patients with schizophrenia and control participants showed comparable autonomic and neural responses. Twenty-four hours after the learning phases, the control subjects exhibited decreased fear and increased vmPFC responses in the extinction (safe) context as expected, indicating successful retention of the extinction memory. In contrast, the schizophrenic patients showed inappropriately elevated fear and poor vmPFC responses in the safe context. CONCLUSION Failure of extinction memory retrieval in schizophrenia is associated with vmPFC dysfunction. In future studies, abnormalities in fear learning and extinction recall may serve as quantitative phenotypes that can be linked to genetic, symptom, or outcome profiles in schizophrenia and those at risk for the disorder.

Project description:ImportanceAlthough chronic relapse is a characteristic of addiction to stimulants, conventional measures (eg, clinical, demographic, and self-report) do not robustly identify which individuals are most vulnerable to relapse.ObjectivesTo test whether drug cues are associated with increased mesolimbic neural activity in patients undergoing treatment for stimulant use disorder and whether this activity is associated with risk for subsequent relapse.Design, setting, and participantsThis prospective cohort study of 76 participants included a control group for baseline group comparisons. Veteran patients (n = 36) with stimulant use disorders were recruited from a 28-day residential treatment program at the Veterans Affairs Palo Alto Health Care System. Healthy controls (n = 40) were recruited from the surrounding community. Baseline data were collected between September 21, 2015, and January 26, 2018, from patients and healthy controls using functional magnetic resonance imaging during a performance of a reward cue task. Patients' stimulant use was subsequently assessed after treatment discharge (at approximately 1, 3, and 6 months) to assess relapse outcomes.Main outcomes and measuresPrimary measures included neural responses to drug and food cues in estimated mesolimbic volumes of interest, including the medial prefrontal cortex, nucleus accumbens (NAcc), and ventral tegmental area. The primary outcome variable was relapse (defined as any stimulant use), assessed both dichotomously (3 months after discharge) and continuously (days to relapse). Brain activity measures were contrasted between groups to validate neural measures of drug cue reactivity, which were then used to estimate relapse outcomes of patients.ResultsRelative to controls (n = 40; 16 women and 24 men; mean [SD] age, 32.0 [11.6] years), patients (n = 36; 2 women and 34 men; mean [SD] age, 43.4 [13.3] years) showed increased mesolimbic activity in response to drug cues (medial prefrontal cortex, t74 = 2.90, P = .005, Cohen d = 0.66; NAcc, t74 = 2.39, P = .02, Cohen d = 0.54; and ventral tegmental area, t74 = 4.04, P < .001, Cohen d = 0.92). In patients, increased drug cue response in the NAcc (but not other volumes of interest) was associated with time to relapse months later (Cox proportional hazards regression hazard ratio, 2.30; 95% CI, 1.40-3.79). After controlling for age, NAcc response to drug cues classified relapsers (12 patients; 1 woman and 11 men; mean [SD] age, 49.3 [14.1] years) and abstainers (21 patients; 1 woman and 20 men; mean [SD] age, 39.3 [12.3] years) at 3 months with 75.8% classification accuracy. Model comparison further indicated that NAcc responses to drug cues were associated with relapse above and beyond estimations of relapse according to conventional measures.Conclusions and relevanceResponses in the NAcc to stimulant cues appear to be associated with relapse in humans. Identification of neural markers may eventually help target interventions to the most vulnerable individuals.

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Neural Responses to Smoking Cues in Schizophrenia.

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Neural Responses to Smoking Cues in Schizophrenia.

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