Studies of Catecholamine Metabolism in Schizophrenia/Psychosis-II

Maas, James W.; Contreras, Salvador; Miller, Alexander L.; Berman, Nancy; Bowden, Charles L.; Javors, Martin A.; Seleshi, Ermias; Weintraub, Susan E

doi:10.1038/npp.1993.12

Cited by 12 publications

(6 citation statements)

References 27 publications

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“…In this regard, it is noteworthy that the knockdown of DISC1 can cause reductions in mitochondrial MAO-A activity. MAO-A has been considered to be involved in human psychopathologies, including schizophrenia, because of its activity in the catabolic pathway of biogenic amines, including dopamine (34). Down-regulation of MAO-A by compromised functioning of the DISC1-Mitofilin complex, which is likely to cause up-regulated monoamine contents in monoaminergic neurons, may help explain the cellular basis underlying schizophreniaassociated neurochemical disturbances.…”

Section: Discussionmentioning

confidence: 99%

Disrupted-in-schizophrenia 1 (DISC1) plays essential roles in mitochondria in collaboration with Mitofilin

Park

Jeong

Lee

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

137

121

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Disrupted-in-schizophrenia 1 (DISC1) has emerged as a schizophrenia-susceptibility gene affecting various neuronal functions. In this study, we characterized Mitofilin, a mitochondrial inner membrane protein, as a mediator of the mitochondrial function of DISC1. A fraction of DISC1 was localized to the inside of mitochondria and directly interacts with Mitofilin. A reduction in DISC1 function induced mitochondrial dysfunction, evidenced by decreased mitochondrial NADH dehydrogenase activities, reduced cellular ATP contents, and perturbed mitochondrial Ca 2+ dynamics. In addition, deficiencies in DISC1 and Mitofilin induced a reduction in mitochondrial monoamine oxidase-A activity. The mitochondrial dysfunctions evoked by the deficiency of DISC1 were partially phenocopied by an overexpression of truncated DISC1 that is associated with schizophrenia in human. DISC1 deficiencies induced the ubiquitination of Mitofilin, suggesting that DISC1 is critical for the stability of Mitofilin. Finally, the mitochondrial dysfunction induced by DISC1 deficiency was partially reversed by coexpression of Mitofilin, confirming a functional link between DISC1 and Mitofilin for the normal mitochondrial function. According to these results, we propose that DISC1 plays essential roles for mitochondrial function in collaboration with a mitochondrial interacting partner, Mitofilin.IMMT | mitochondrial dysfunctions | hyperdopaminergia | calcium buffering | psychiatric disorders

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Section: Discussionmentioning

confidence: 99%

Disrupted-in-schizophrenia 1 (DISC1) plays essential roles in mitochondria in collaboration with Mitofilin

Park

Jeong

Lee

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

137

121

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“…In terms of NE's role in schizophrenia, there have been reports that schizophrenia symptoms are correlated with MHPG (e.g., Kaneko et al 1992;Maas et al 1993). Changes in CSF NE have been reported to help predict relapse in people with chronic schizophrenia (van Kammen et al 1994).…”

Section: Discussionmentioning

confidence: 99%

Postmortem studies in schizophrenia

Harrison

2000

Dialogues in Clinical Neuroscience

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For over a century, postmortem studies have played a central part in the search for the structural and biochemical pathology of schizophrenia. However, for most of this time, little progress has been made. Recently, the situation has begun to change, helped by the emergence of more powerful methodologies and research designs, and by the availability of brain imaging to provide complementary information. As a result, it can now be clearly concluded that there are structural cerebral abnormalities in schizophrenia that are intrinsic to the disorder. The neuropathological process is not primarily degenerative, but involves a change in the normal cytoarchitecture of the brain, probably originating in development. Neurochemically, there is postmortem evidence for alterations in several transmitter systems including dopamine, glutamate, serotonin, and γ-aminobutyric acid (GABA). The cardinal findings are reviewed here, together with a consideration of the conceptual and methodological issues that face postmortem studies of schizophrenia.

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“…It should be underscored that negative symptoms of schizophrenia such as poverty of speech, flattened affect and psychomotor retardation are not associated with hypersensitivity of mesocorticolimbic DA activity (see [195] for review) or panic. It should be considered that mesocorticolimbic hypersensitivity might follow from the chronic neuroleptic regimens employed to attenuate delusions and hallucinations [196]. Typically, delusions, hallucinations and phobic avoidance assessed by the Minnesota Multiphasic Personality Inventory (MMPI), Clinical General Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS) [157,159,195,196] are exacerbated over the course of the illness.…”

Section: Dopamine and Cholecystokinin In The Mesocorticolimbic Systemmentioning

confidence: 99%

“…It should be considered that mesocorticolimbic hypersensitivity might follow from the chronic neuroleptic regimens employed to attenuate delusions and hallucinations [196]. Typically, delusions, hallucinations and phobic avoidance assessed by the Minnesota Multiphasic Personality Inventory (MMPI), Clinical General Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS) [157,159,195,196] are exacerbated over the course of the illness. The gradual exacerbation of schizophrenic symptoms has prompted suggestion that conditioning and/or sensitization of mesocorticolimbic DA (see [181,[197][198][199] for review of mesocorticolimbic DA and cognition; c.f.…”

Section: Dopamine and Cholecystokinin In The Mesocorticolimbic Systemmentioning

confidence: 99%

“…It is interesting, however, that postmortem CCK determinations in brain tissue have verified patterns of CCK activity within specific brain sites associated with positive and negative symptoms of schizophrenia. On the one hand, positive symptoms of schizophrenia, precipitated by increased DA activity [195,196,216,217], are associated with a greater reduction in frontal cortex CCK mRNA compared to the temporal cortex. On the other hand, negative symptoms of schizophrenia are associated with reduced CCK mRNA in the temporal cortex, amygdala and hippocampus [215].…”

Section: Dopamine and Cholecystokinin In The Mesocorticolimbic Systemmentioning

confidence: 99%

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The Myth of Panic Spontaneity: Consideration of Behavioral and Neurochemical Sensitization

Hebb¹,

Anger²,

Mendella³

et al. 2007

TOPJ

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Panic disorder is characterized by a progression of panic symptom severity with repeated attacks. Repeated panic episodes evoke heightened anticipatory anxiety, phobic avoidance and are typically associated with comorbid symptoms of depression. Due to the heterogeneity of the disorder, reliable neurochemical correlates attending panic have not been identified. However, variable neuropeptide interfacing with major and minor transmitter systems may modulate individual vulnerability to panic and account for variable panic profiles. The extensive colocalization of cholecystokinin (CCK) with other neurotransmitters, including dopamine (DA), enkephalin (ENK) and GABA, in specific central sites may influence various aspects of anxiety and panic. The behavioral correlates attending panic likely follow from variable neurochemical release and conditioning/sensitization. Clinicians maintain that recurrent panic attacks are spontaneous (unexpected, uncued) and fail to acknowledge the wealth of information implicating a prominent role for stressful life events in panic. Conditioning and sensitization of both behavior (e.g., fear-motivated) and neurochemical events (e.g., DA and CCK) in response to uncontrollable stressors parallel the diverse heterogeneity of panic amongst clinical samples. Cholecystokinin-4, pentagastrin, lactate acid, and CO 2 induce panic attacks that are dependent on subjective history, expectancy measures and panic profiles. Panic disorder is associated with chronic illness and familial sick-role modeling exacerbates the course of the illness. The current review outlines the evidence in support of a conditioning/sensitization model for panic, a model that may explain the variable efficacies of pharmacological interventions.

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Studies of Catecholamine Metabolism in Schizophrenia/Psychosis-II

Cited by 12 publications

References 27 publications

Disrupted-in-schizophrenia 1 (DISC1) plays essential roles in mitochondria in collaboration with Mitofilin

Disrupted-in-schizophrenia 1 (DISC1) plays essential roles in mitochondria in collaboration with Mitofilin

Postmortem studies in schizophrenia

The Myth of Panic Spontaneity: Consideration of Behavioral and Neurochemical Sensitization

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