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      Methamphetamine-Associated Psychosis

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          Abstract

          Methamphetamine (METH) is a frequent drug of abuse in U.S. populations and commonly associated with psychosis. This may be a factor in frequent criminal justice referrals and lengthy treatment required by METH users. Persecutory delusions and auditory hallucinations are the most consistent symptoms of METH-associated psychosis (MAP). MAP has largely been studied in Asian populations and risk factors have varied across studies. Duration, frequency and amount of use as well as sexual abuse, family history, other substance use, and co-occurring personality and mood disorders are risk factors for MAP. MAP may be unique with its long duration of psychosis and recurrence without relapse to METH. Seven candidate genes have been identified that may be associated with MAP. Six of these genes are also associated with susceptibility, symptoms, or treatment of schizophrenia and most are linked to glutamatergic neurotransmission. Animal studies of pre-pulse inhibition, attenuation of social interaction, and stereotypy and alterations in locomotion are used to study MAP in rodents. Employing various models, rodent studies have identified neuroanatomical and neurochemical changes associated with METH use. Throughout this review, we identify key gaps in our understanding of MAP and suggest potential directions for future research.

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          Most cited references172

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          Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus.

          The suprachiasmatic nucleus (SCN) controls the circadian rhythm of physiological and behavioural processes in mammals. Here we show that prokineticin 2 (PK2), a cysteine-rich secreted protein, functions as an output molecule from the SCN circadian clock. PK2 messenger RNA is rhythmically expressed in the SCN, and the phase of PK2 rhythm is responsive to light entrainment. Molecular and genetic studies have revealed that PK2 is a gene that is controlled by a circadian clock (clock-controlled). Receptor for PK2 (PKR2) is abundantly expressed in major target nuclei of the SCN output pathway. Inhibition of nocturnal locomotor activity in rats by intracerebroventricular delivery of recombinant PK2 during subjective night, when the endogenous PK2 mRNA level is low, further supports the hypothesis that PK2 is an output molecule that transmits behavioural circadian rhythm. The high expression of PKR2 mRNA within the SCN and the positive feedback of PK2 on its own transcription through activation of PKR2 suggest that PK2 may also function locally within the SCN to synchronize output.
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            Methamphetamine toxicity and messengers of death.

            Methamphetamine (METH) is an illicit psychostimulant that is widely abused in the world. Several lines of evidence suggest that chronic METH abuse leads to neurodegenerative changes in the human brain. These include damage to dopamine and serotonin axons, loss of gray matter accompanied by hypertrophy of the white matter and microgliosis in different brain areas. In the present review, we summarize data on the animal models of METH neurotoxicity which include degeneration of monoaminergic terminals and neuronal apoptosis. In addition, we discuss molecular and cellular bases of METH-induced neuropathologies. The accumulated evidence indicates that multiple events, including oxidative stress, excitotoxicity, hyperthermia, neuroinflammatory responses, mitochondrial dysfunction, and endoplasmic reticulum stress converge to mediate METH-induced terminal degeneration and neuronal apoptosis. When taken together, these findings suggest that pharmacological strategies geared towards the prevention and treatment of the deleterious effects of this drug will need to attack the various pathways that form the substrates of METH toxicity.
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              Cannabis use and psychosis: a longitudinal population-based study.

              J. VAN OS (2002)
              Cannabis use may increase the risk of psychotic disorders and result in a poor prognosis for those with an established vulnerability to psychosis. A 3-year follow-up (1997-1999) is reported of a general population of 4,045 psychosis-free persons and of 59 subjects in the Netherlands with a baseline diagnosis of psychotic disorder. Substance use was assessed at baseline, 1-year follow-up, and 3-year follow-up. Baseline cannabis use predicted the presence at follow-up of any level of psychotic symptoms (adjusted odds ratio (OR) = 2.76, 95% confidence interval (CI): 1.18, 6.47), as well as a severe level of psychotic symptoms (OR = 24.17, 95% CI: 5.44, 107.46), and clinician assessment of the need for care for psychotic symptoms (OR = 12.01, 95% CI: 2.24, 64.34). The effect of baseline cannabis use was stronger than the effect at 1-year and 3-year follow-up, and more than 50% of the psychosis diagnoses could be attributed to cannabis use. On the additive scale, the effect of cannabis use was much stronger in those with a baseline diagnosis of psychotic disorder (risk difference, 54.7%) than in those without (risk difference, 2.2%; p for interaction = 0.001). Results confirm previous suggestions that cannabis use increases the risk of both the incidence of psychosis in psychosis-free persons and a poor prognosis for those with an established vulnerability to psychotic disorder.
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                Author and article information

                Contributors
                kathleen.grant2@va.gov
                Journal
                J Neuroimmune Pharmacol
                Journal of Neuroimmune Pharmacology
                Springer US (Boston )
                1557-1890
                1557-1904
                5 July 2011
                5 July 2011
                March 2012
                : 7
                : 1
                : 113-139
                Affiliations
                [1 ]Department of Internal Medicine, VA Nebraska-Western Iowa Health Care System, University of Nebraska Medical Center, Omaha, NE 68198-5300 USA
                [2 ]Departments of Internal Medicine and Epidemiology, VA Nebraska-Western Iowa Health Care System, University of Nebraska Medical Center, Omaha, NE 68198–5910 USA
                [3 ]Department of Environmental, Agricultural & Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198–5910 USA
                [4 ]Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198–5880 USA
                [5 ]Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588–0308 USA
                Article
                9288
                10.1007/s11481-011-9288-1
                3280383
                21728034
                401923f5-55c8-4bb2-89dc-a02d6bbc8b6a
                © The Author(s) 2011
                History
                : 6 May 2011
                : 21 June 2011
                Categories
                Invited Review
                Custom metadata
                © Springer Science+Business Media, LLC 2012

                Pharmacology & Pharmaceutical medicine
                psychotic symptoms,schizophrenia,drug addiction,methamphetamine,substance use disorder,candidate genes

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