Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging

Smucny, Jason; Tregellas, Jason R.

doi:10.1177/0269881117705071

Cited by 19 publications

(9 citation statements)

References 159 publications

(193 reference statements)

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“…The effects of nicotine, cannabinoids and psychostimulants mirrors what is observed in clinical literature, e.g. nicotine improves attention and processing speed in individuals with schizophrenia [203,204], cannabis worsens schizophrenia symptoms and clinical prognosis [205], CBD has antipsychotic-like effects [206], and there is recent evidence of increased susceptibility to effects of amphetamine on sensorimotor gating in schizophrenia [207]. Importantly, this provides predictive validity to these models, and facilitates the use of these models to better understand brain changes associ- ated with drug susceptibility.…”

Section: Interim Summarysupporting

confidence: 58%

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

Menne

Chesworth

2020

Neuroanatomy and Behaviour

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Schizophrenia is a severe psychiatric disorder which is worsened substantially by substance abuse/addiction. Substance abuse affects nearly 50% of individuals with schizophrenia, extends across several drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants) and worsens overall functioning of patients. Prominent theories explaining schizophrenia and addiction comorbidity include the primary addiction hypothesis (i.e. schizophrenia susceptibility primes drug reward circuits, increasing drug addiction risk following drug exposure), the two-hit hypothesis (i.e. drug abuse and other genetic and/or environmental risk factors contribute to schizophrenia development) and the self-medication hypothesis (i.e. drug use alleviates schizophrenia symptoms). Animal models can be used to evaluate the utility and validity of these theories. Since this literature was last reviewed by Ng and colleagues in 2013 [Neurosci Biobehav Rev, 37(5)], significant advances have been made to our understanding of schizophrenia and substance abuse comorbidity. Here we review advances in the field since 2013, focussing on two key questions: 1) Does schizophrenia susceptibility increase susceptibility to drug addiction (assessing the primary addiction hypothesis), and 2) Do abused drugs exacerbate or ameliorate schizophrenia symptoms (assessing the two-hit hypothesis and the self-medication hypothesis). We addressed these questions using data from several schizophrenia preclinical models (e.g. genetic, lesion, neurodevelopmental, pharmacological) across drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants). We conclude that addiction-like behaviour is present in several preclinical schizophrenia models, and drugs of abuse can exacerbate but also ameliorate schizophrenia-relevant behaviours. These behavioural changes are associated with altered receptor system function (e.g. dopaminergic, glutamatergic, GABAergic) critically implicated in schizophrenia and addiction pathology.

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Section: Interim Summarysupporting

confidence: 58%

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

Menne

Chesworth

2020

Neuroanatomy and Behaviour

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“…33 Occipital cortex may be the neurobiological basis of visual processing defects in the early stage of schizophrenia. 34 In conclusion, the function and structure of occipital lobe may also be related to schizophrenia, which appears in the early course of schizophrenia and persists throughout the course of the disease.…”

Section: Specific Imaging Abnormal Markersmentioning

confidence: 90%

Regional Homogeneity Brain Alterations in Schizophrenia: An Activation Likelihood Estimation Meta-Analysis

Qiu

Zhang

et al. 2021

Psychiatry Investig

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Objective Resting state functional magnetic resonance imaging (rsfMRI) provides a lot of evidence for local abnormal brain activity in schizophrenia, but the results are not consistent. Our aim is to find out the consistent abnormal brain regions of the patients with schizophrenia by using regional homogeneity (ReHo), and indirectly understand the degree of brain damage of the patients with drug-naive first episode schizophrenia (Dn-FES) and chronic schizophrenia. Methods We performed the experiment by activation likelihood estimation (ALE) software to analysis the differences between people with schizophrenia group (all schizophrenia group and chronic schizophrenia group) and healthy controls. Results Thirteen functional imaging studies were included in quantitative meta-analysis. All schizophrenia group showed decreased ReHo in bilateral precentral gyrus (PreCG) and left middle occipital gyrus (MOG), and increased ReHo in bilateral superior frontal gyrus (SFG) and right insula. Chronic schizophrenia group showed decreased ReHo in bilateral MOG, right fusiform gyrus, left PreCG, left cerebellum, right precuneus, left medial frontal gyrus and left anterior cingulate cortex (ACC). No significant increased brain areas were found in patients with chronic schizophrenia. Conclusion Our findings suggest that patients with chronic schizophrenia have more extensive brain damage than FES, which may contribute to our understanding of the progressive pathophysiology of schizophrenia.

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“…Several of these efforts have emphasized the α7 subtype of nAChRs due to the preponderance of patients with schizophrenia who self-medicate with nicotine to manage cognitive and negative symptoms and the side effects of antipsychotic medications [( 28), but see (29)]. This hypothesis is built on evidence that nicotinic receptor signaling is fundamentally decreased in individuals experiencing schizophrenia, and thus patients are using the most readily available method for pharmacologically targeting this system in an attempt to restore signaling to appropriate levels (30).…”

Section: Introductionmentioning

confidence: 99%

Effects of 7.5% Carbon Dioxide and Nicotine Administration on Latent Inhibition

et al. 2021

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Stratified medicine approaches have potential to improve the efficacy of drug development for schizophrenia and other psychiatric conditions, as they have for oncology. Latent inhibition is a candidate biomarker as it demonstrates differential sensitivity to key symptoms and neurobiological abnormalities associated with schizophrenia. The aims of this research were to evaluate whether a novel latent inhibition task that is not confounded by alternative learning effects such as learned irrelevance, is sensitive to (1) an in-direct model relevant to psychosis [using 7.5% carbon dioxide (CO2) inhalations to induce dopamine release via somatic anxiety] and (2) a pro-cognitive pharmacological manipulation (via nicotine administration) for the treatment of cognitive impairment associated with schizophrenia. Experiment 1 used a 7.5% CO2 challenge as a model of anxiety-induced dopamine release to evaluate the sensitivity of latent inhibition during CO2 gas inhalation, compared to the inhalation of medical air. Experiment 2 examined the effect of 2 mg nicotine administration vs. placebo on latent inhibition to evaluate its sensitivity to a potential pro-cognitive drug treatment. Inhalation of 7.5% CO2 raised self-report and physiological measures of anxiety and impaired latent inhibition, relative to a medical air control; whereas administration of 2 mg nicotine, demonstrated increased latent inhibition relative to placebo control. Here, two complementary experimental studies suggest latent inhibition is modified by manipulations that are relevant to the detection and treatment of schizophrenia. These results suggest that this latent inhibition task merits further investigation in the context of neurobiological sub-groups suitable for novel treatment strategies.

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Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging

Cited by 19 publications

References 159 publications

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

Regional Homogeneity Brain Alterations in Schizophrenia: An Activation Likelihood Estimation Meta-Analysis

Effects of 7.5% Carbon Dioxide and Nicotine Administration on Latent Inhibition

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