Negative symptoms in schizophrenia

Callicott, J. H., Bertolino, A., Egan, M. F. et al. Selective relationship between prefrontal N-acetylaspartate measures and negative symptoms in schizophrenia. Am. J. Psychiatry 157 1646-1651,2000. 

Psychedelics (LSD) and other psy-chotomimetics such as mescaline and psilocybin can induce states of altered awareness, or induce hallucinations and anxiety, probably mediated by 5-HT2A receptors. Overactivity of these receptors may also play a role in the genesis of negative symptoms in schizophrenia (p. 238) and sleep disturbances. 

Murphy BP, Chung YC, Park TW, McGorry PD. Pharmacological treatment of primary negative symptoms in schizophrenia a systematic review. Schizoph Res 2006 88(l-3) 5-25. 

Abnormalities of the glutamate system have also been documented in neuropsychiatric disorders. For example, compounds such as PCP and ketamine, which block the NMDA receptor, can induce psychotic symptoms. By contrast, compounds such as d-cycloserine or glycine, which increase NMDA receptor function via the glycine binding site, can decrease psychotic and/or negative symptoms in schizophrenia (Farber et ah, 1999 Goff et ah, 1999, Fleresco-Levy et ah, 1999). 

T. Shioiri, T. Kato, T. Inubushi, J. Murashita and S. Takahashi, Correlations of phos-phomonoesters measured by phosphorus-31 magnetic resonance spectroscopy in the frontal lobes and negative symptoms in schizophrenia. Psychiatry Res., 1994, 55, 223-235. 

Meltzer HY, Zureick JL. Negative symptoms in schizophrenia a target for new drug development. Psychopharmacoi Ser 1989 7 68-77. 

Negative symptoms in schizophrenia can be either primary or secondary (Fig. 10—3). Primary negative symptoms are considered to be those that are core to primary deficits of schizophrenia itself. Other core deficits of schizophrenia that may manifest themselves as negative symptoms may be those associated with or thought to be secondary to the positive symptoms of psychosis. Other negative symptoms are considered to be secondary to extrapyramidal symptoms (EPS), especially those... 

FIGURE 10—3. Negative symptoms in schizophrenia can either be a primary deficit of the illness (1° deficit) or secondary to depression (2° to dep), secondary to extrapyramidal symptoms (2° to EPS), secondary to environmental deprivation, or even secondary to positive symptoms (2° to pos sxs) in schizophrenia. 

FIGURE 11—27. The mesocortical dopamine pathway may mediate deficits in cognitive functioning and negative symptoms in schizophrenia because of a relative deficiency in dopamine, due either to a primary deficiency or to various secondary causes, such as serotonin excess. In either case, blockade of 5HT2A receptors with an atypical antipsychotic should lead to dopamine release, which could compensate for the dopamine deficiency and improve negative and cognitive symptoms. 

Duinkerke SJ, Botter PA, Jansen AA, van Dongen PA, van Haaften AJ, Boom AJ, van Laarhoven JH, Busard HL (1993) Ritanserin, a selective 5-ht2/lc antagonist, and negative symptoms in schizophrenia. A placebo-controlled double-blind trial. Br J Psychiatry... 

Tandon R, DeQuardo JR, Goodson J, Mann NA, Greden JF. 1992. Effect of anticholinergics on positive and negative symptoms in schizophrenia. Psychopharmacol Bull 28 297-302. 

Buchanan RW, Javitt DC, Marder SR, Schooler NR, Gold JM, et al. 2007. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST) The efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry 164 1593-1602. 

Javitt DC, Zylberman I, Zukin SR, Heresco-Levy U, Lindenmayer JP. 1994. Amelioration of negative symptoms in schizophrenia by glycine. Am J Psychiatry... 

Dysbindin genotype and negative symptoms in schizophrenia. Am J Psychiatry 163 532-534. 

Eaton WW, Thara R, Federman B, Melton B, Liang KY. 1995. Structure and course of positive and negative symptoms in schizophrenia. Arch Gen Psychiatry 52 127-134. 

Heresco-Levy U, Javitt DC. 2004. Comparative effects of glycine and D-cycloserine on persistent negative symptoms in schizophrenia A retrospective analysis. Schizophr Res 66 89-96. 

Andreason NC. 1982. Negative symptoms in schizophrenia Definition and reliability. Arch Gen Psychiatry 39 784-788. 

Coyle JT, Tsai G. 2004. The NMDA receptor glycine modula-troy site A therapeutic target for improving cognition and reducing negative symptoms in schizophrenia. Psychopharmacology 174(1) 32-38. 

Goff DC, Bottiglieri T, Arning E, Shih V, Freudenreich O, et al. 2004. Folate, homocysteine, and negative symptoms in schizophrenia. Am J Psychiatry 161(9) 1705-1708. 

Patkar AA, Gopalakrishnan R, Lundy A, Leone FT, Certa KM, et al. 2002. Relationship between tobacco smoking and positive and negative symptoms in schizophrenia. J Nerv Ment Dis 190(9) 604-610. 

Yasui-Furukori N, Kondo T, Mihara K, Inoue Y, Kaneko S. Fluvoxamine dose-dependent interaction and the effects on negative symptoms in schizophrenia. Psychopharmacology 2004 171 223-7. 

Low dose activating actions may be beneficial for negative symptoms in schizophrenia... 

The question arises whether 5-HT2A antagonism per se may be sufficient to treat positive as well as negative symptoms in schizophrenia without causing EPS. 

Cazorla P, Mackle M, Zhao J, Ha X, Szegedi A. Safety and tolerabflity of switching to asenapine from other antipsychotic agents pooled results from two randomized multicenter trials in stable patients with persistent negative symptoms in schizophrenia. Neuropsychiatr Dis Treat 2012 8 247-57. 

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