Owen Gareth O鈥橠aly, MSc, PhD; Daniel Joyce, PhD; Klaas Enno Stephan, MD, Dr med, PhD; et al.
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Arch Gen Psychiatry. 2011;68(6):545-554. doi:10.1001/archgenpsychiatry.2011.3
ContextRecent work suggests that the amphetamine sensitization model of schizophrenia can safely be induced in healthy volunteers and is associated both with behavioral and dopaminergic hypersensitivity to amphetamine. However, the effects of a sensitization on brain function remain unclear.ObjectiveTo assess the impact of a sensitizing dosage regimen of dextroamphetamine on human cortical functioning and cognition.DesignRandomized, double-blind, parallel-groups design using pharmacological functional magnetic resonance imaging.SettingThe neuroimaging research unit at the Institute of Psychiatry, King's College London, London, England.ParticipantsHealthy male volunteers (n聽=聽22).InterventionsDextroamphetamine (20 mg) or placebo administration at 4 testing sessions, using a dosage regimen shown to induce sensitization (ie, 3 doses administered with a 48-hour interdose interval and a final dose after a 2-week washout period).Main Outcome MeasuresSensitization was characterized by enhanced subjective response to the drug, changes in behavioral performance (reaction time and accuracy), and functional magnetic resonance imaging measurements of brain activity during an N-back working memory task.ResultsSensitization was associated with more rapid responding during the performance of an intermediate-load working memory challenge. During a high-load cognitive challenge, sensitization did not produce performance deficits, but functional magnetic resonance imaging showed hyperactivity of the dorsolateral prefrontal cortex and aberrant recruitment of the superior temporal gyrus, caudate nucleus, and thalamus. Furthermore, the change in striatal activity was negatively correlated with the enhanced subjective effects of the drug, whereas prefrontal hyperactivity was positively correlated with sensitized measures of alertness.ConclusionsThese transient load-dependent abnormalities of frontal and temporal activity induced by amphetamine sensitization support neuroimaging findings in schizophrenic patients, implying that amphetamine sensitization may help to bridge pathophysiological theories of schizophrenia that focus on pharmacological (dopaminergic) and cognitive mechanisms, respectively.
David Erritzoe, MD, PhD; Vibe G. Frokjaer, MD, PhD; Klaus K. Holst, MSc; et al.
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Arch Gen Psychiatry. 2011;68(6):562-576. doi:10.1001/archgenpsychiatry.2011.56
Katherine E. Watkins, MD, MSHS; Sarah B. Hunter, PhD; Kimberly A. Hepner, PhD; et al.
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Arch Gen Psychiatry. 2011;68(6):577-584. doi:10.1001/archgenpsychiatry.2011.53
Roger T. Webb, PhD; Ping Qin, PhD; Hanne Stevens, MSc; et al.
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Arch Gen Psychiatry. 2011;68(6):591-599. doi:10.1001/archgenpsychiatry.2011.7
ContextPrevious research has focused on suicide among male prisoners and ex-prisoners, but little is known about risk in the wider offender population.ObjectiveTo examine suicide risk over 3 decades among all people processed by a national criminal justice system.DesignNested case-control study.SettingThe whole Danish population.ParticipantsInterlinked national registers identified all adult suicides during 1981 to 2006 according to any criminal justice system contact since 1980. Exposure was defined according to history of criminal justice adjudication, up to and including each subject's last judicial verdict before suicide (or date of matching for controls). There were 27聽219 suicides and 524聽899 controls matched on age, sex, and time, ie, controls were alive when their matched case died.Main Outcome MeasureSuicide.ResultsMore than a third of all male cases had a criminal justice history, but relative risk against the general population was higher for women than men. Independent effects linked with criminal justice exposure persisted with confounder adjustment. Suicide risk was markedly elevated with custodial sentencing, but the strongest effects were with sentencing to psychiatric treatment and with charges conditionally withdrawn. Risk was raised even in people with a criminal justice history but without custodial sentences or guilty verdicts. It was especially high with recent or frequent contact and in people charged with violent offenses.ConclusionsWe examined a section of society in which major health and social problems frequently coexist including offending, psychopathology, and suicidal behavior. The need for developing more far-reaching national suicide prevention strategies is indicated. In particular, improved mental health service provision is needed for all people in contact with the criminal justice system, including those not found guilty and those not given custodial sentences. Our findings also suggest that public services should be better coordinated to tackle co-occurring health and social problems more effectively.
Patrick J. Brown, PhD; D. P. Devanand, MD; Xinhua Liu, PhD; et al.
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Arch Gen Psychiatry. 2011;68(6):617-626. doi:10.1001/archgenpsychiatry.2011.57
Yuhua Bao, PhD; George S. Alexopoulos, MD; Lawrence P. Casalino, MD, PhD; et al.
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Arch Gen Psychiatry. 2011;68(6):627-636. doi:10.1001/archgenpsychiatry.2011.55
Alessandra C. Iervolino, PhD; Fruhling V. Rijsdijk, PhD; Lynn Cherkas, DPhil; et al.
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Arch Gen Psychiatry. 2011;68(6):637-644. doi:10.1001/archgenpsychiatry.2011.54