The Synaptic Hypothesis of Schizophrenia

Frankle, W. Gordon; Lerma, Juan; Laruelle, Marc

doi:10.1016/s0896-6273(03)00423-9

Cited by 160 publications

(111 citation statements)

References 42 publications

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“…Evidence for synaptic dysfunction in psychiatric disorders Expression changes in many synaptic-associated proteins such as synaptophysin, complexin I and II, synaptosomal-associated protein (SNAP)-25 and syntaxin (for example Eastwood et al, 43 Sawada et al, 44 Owen et al 45 and Frankle et al 46 ) have been found in schizophrenia. In addition, these protein changes are in keeping with synaptic-associated roles for many of the recently described candidate genes for schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

“…23 Indeed, synaptic disturbance in schizophrenia is well described, involving both the pre-and postsynaptic machinery, and is considered a characteristic feature of this complex disorder. [24][25][26][27] However, mRNA may not be the most reliable method to use in order to gain insight into the underlying pathophysiology of schizophrenia, where abnormalities in gene function may or may not affect downstream protein expression. 28,29 To approach this issue, proteomic techniques have been used, on a complementary basis, to investigate the underlying molecular abnormalities in the cortex in schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

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Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

et al. 2007

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There is evidence for both similarity and distinction in the presentation and molecular characterization of schizophrenia and bipolar disorder. In this study, we characterized protein abnormalities in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder using two-dimensional gel electrophoresis. Tissue samples were obtained from 35 individuals with schizophrenia, 35 with bipolar disorder and 35 controls. Eleven protein spots in schizophrenia and 48 in bipolar disorder were found to be differentially expressed (P < 0.01) in comparison to controls, with 7 additional spots found to be altered in both diseases. Using mass spectrometry, 15 schizophrenia-associated proteins and 51 bipolar disorder-associated proteins were identified. The functional groups most affected included synaptic proteins (7 of the 15) in schizophrenia and metabolic or mitochondrial-associated proteins (25 of the 51) in bipolar disorder. Six of seven synaptic-associated proteins abnormally expressed in bipolar disorder were isoforms of the septin family, while two septin protein spots were also significantly differentially expressed in schizophrenia. This finding represented the largest number of abnormalities from one protein family. All septin protein spots were upregulated in disease in comparison to controls. This study provides further characterization of the synaptic pathology present in schizophrenia and of the metabolic dysfunction observed in bipolar disorder. In addition, our study has provided strong evidence implicating the septin protein family of proteins in psychiatric disorders for the first time.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

et al. 2007

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“…[78][79][80] Converging evidence suggests that schizophrenia may be related to altered connectivity between brain regions, especially at the level of the synapse. 81 There are numerous proteins involved in regulating and maintaining synaptic integrity. One such protein is Reelin (RELN), synthesized by GABA interneurons, and thought to be involved in maintaining dendritic spine density and function in neighboring pyramidal cells.…”

Section: Mrna Stabilitymentioning

confidence: 99%

Expanding the ‘central dogma’: the regulatory role of nonprotein coding genes and implications for the genetic liability to schizophrenia

2004

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“…Neuroimaging data and post-mortem studies have shown that N-acetylaspartate (NAA), a marker of neuronal integrity, is decreased in first episode and nevermedicated patients (Bertolino and Weinberger, 1999;Nudmamud et al, 2003). Based on these neuropathological changes, investigators have conceptualized schizophrenia as a disease of functional "dysconnectivity" (Weinberger et al, 1992;Friston and Frith, 1995;McGlashan and Hoffman, 2000), or a "disorder of the synapse" (Mirnics et al, 2001;Frankle et al, 2003) affecting the machinery of the synapse (Harrison and Eastwood, 2001;Honer and Young, 2004).…”

Section: Introductionmentioning

confidence: 99%

Serotonin and Schizophrenia

Quednow

Geyer

Halberstadt

2010

Handbook of Behavioral Neuroscience

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Although the serotonin hypothesis of schizophrenia is one of the oldest neurochemical hypotheses on the pathogenesis of this disease, it is still highly topical. The concept of how the serotonin system is involved in the origin and progress of schizophrenia has considerably changed over the past decades. Therefore, the present work will give an overview about the development and the current directions of the serotonin hypothesis of schizophrenia. In this regard, we will discuss the phenomenology of hallucinogenic drug action, model psychosis and translational research, post-mortem studies on receptors and transporters, imaging studies, antipsychotic drug action, neuroendocrine challenge studies, platelet and cerebrospinal fluid data, genetic association studies, developmental aspects, and the cross-talk between the glutamate and the serotonin system. In sum, there are several lines of evidence suggesting that the serotonin system plays a major role in the pathogenesis of at least a subpopulation of schizophrenia patients. Further studies are needed to better characterize patients whose psychotic symptoms are suspected to have a serotonergic origin. Serotonin and Schizophrenia AbstractAlthough the serotonin hypothesis of schizophrenia is one of the oldest neurochemical hypotheses on the pathogenesis of this disease, it is still highly topical. The concept of how the serotonin system is involved in the origin and progress of schizophrenia has considerably changed over the past decades.Therefore, the present work will give an overview about the development and the current directions of the serotonin hypothesis of schizophrenia. In this regard, we will discuss the phenomenology of hallucinogenic drug action, model psychosis and translational research, post-mortem studies on receptors and transporters, imaging studies, antipsychotic drug action, neuroendocrine challenge studies, platelet and cerebrospinal fluid data, genetic association studies, developmental aspects, and the cross-talk between the glutamate and the serotonin system. In sum, there are several lines of evidence suggesting that the serotonin system plays a major role in the pathogenesis of at least a subpopulation of schizophrenia patients. Further studies are needed to better characterize patients whose psychotic symptoms are suspected to have a serotonergic origin.3

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The Synaptic Hypothesis of Schizophrenia

Cited by 160 publications

References 42 publications

Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

Expanding the ‘central dogma’: the regulatory role of nonprotein coding genes and implications for the genetic liability to schizophrenia

Serotonin and Schizophrenia

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