Functional Magnetic Resonance Imaging Investigation of the Amphetamine Sensitization Model of Schizophrenia in Healthy Male Volunteers

O’Daly, Owen; Joyce, Daniel; Stephan, Klaas Ε.; Murray, Robin M.; Shergill, Sukhwinder S.

doi:10.1001/archgenpsychiatry.2011.3

Cited by 28 publications

(29 citation statements)

References 114 publications

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“…The measurement and analysis of these data have been presented in detail elsewhere [70]. Here, we provide a brief summary of these results for completeness.…”

Section: Methodsmentioning

confidence: 97%

“…We anticipated behavioural (subjective) sensitization to amphetamine to mirror previous findings [62]–[65], including enhanced amphetamine-like experience, amphetamine-induced euphoria (ARCI-MBG), profile of mood states activity-vigour, alertness and attentiveness and positive affect as well as sensitization of resting eye-blink rate [70]. These hypotheses were tested using a Group × Administration/Session repeated measures analysis of variance (rmANOVA) for each dependent variable, using a level of significance of p<0.05 with Greenhouse-Geisser correction.…”

Section: Methodsmentioning

confidence: 97%

“…The data reported here is from the same participants as in our previous paper [70] but salient details will be repeated here in brief. Twenty-two right handed male volunteers (age 30.8 years +/−8.5 years), were recruited and assigned to receive either four oral doses of dexamphetamine (20mg), or four doses of a placebo, following a procedure (albeit with a fixed dose across all participants) previously shown to produce dopaminergic sensitization in humans [65].…”

Section: Methodsmentioning

confidence: 99%

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Amphetamine Sensitization Alters Reward Processing in the Human Striatum and Amygdala

et al. 2014

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Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS) has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD) signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.

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“…The measurement and analysis of these data have been presented in detail elsewhere [70]. Here, we provide a brief summary of these results for completeness.…”

Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

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Amphetamine Sensitization Alters Reward Processing in the Human Striatum and Amygdala

et al. 2014

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“…No authoritative cause for any primary deficit in the auditory cortices has yet been proposed. Finally not all studies on AVH have included non-hallucinating patient populations, which raises a question on the specificity of any detected abnormalities [67]. …”

Section: The Neurocognitive Modelsmentioning

confidence: 99%

Mechanisms Underlying Auditory Hallucinations—Understanding Perception without Stimulus

Tracy

Shergill

2013

Brain Sciences

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Auditory verbal hallucinations (AVH) are a common phenomenon, occurring in the “healthy” population as well as in several mental illnesses, most notably schizophrenia. Current thinking supports a spectrum conceptualisation of AVH: several neurocognitive hypotheses of AVH have been proposed, including the “feed-forward” model of failure to provide appropriate information to somatosensory cortices so that stimuli appear unbidden, and an “aberrant memory model” implicating deficient memory processes. Neuroimaging and connectivity studies are in broad agreement with these with a general dysconnectivity between frontotemporal regions involved in language, memory and salience properties. Disappointingly many AVH remain resistant to standard treatments and persist for many years. There is a need to develop novel therapies to augment existing pharmacological and psychological therapies: transcranial magnetic stimulation has emerged as a potential treatment, though more recent clinical data has been less encouraging. Our understanding of AVH remains incomplete though much progress has been made in recent years. We herein provide a broad overview and review of this.

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“…These effects may become stronger with continued stimulant exposure due to a process of sensitisation (O'Daly et al, 2011;Wang et al, 2010;PelegRaibstein et al, 2009;Featherstone et al, 2007;Ujike and Sato, 2004;Curran et al, 2004;Ujike, 2002;Hermens et al, 2009) Despite these overlaps, there were consistent differences in the associations of stimulant use disorders and cannabis use disorders. In all groups, cannabis use disorders were most common in people in their late teens and early twenties and were strongly associated with male gender and rural location.…”

Section: Summary Findingsmentioning

confidence: 99%

Stimulant use disorders and psychosis: prevalence, correlates and impacts

Sara¹

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Functional Magnetic Resonance Imaging Investigation of the Amphetamine Sensitization Model of Schizophrenia in Healthy Male Volunteers

Cited by 28 publications

References 114 publications

Amphetamine Sensitization Alters Reward Processing in the Human Striatum and Amygdala

Amphetamine Sensitization Alters Reward Processing in the Human Striatum and Amygdala

Mechanisms Underlying Auditory Hallucinations—Understanding Perception without Stimulus

Stimulant use disorders and psychosis: prevalence, correlates and impacts

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