The effect of apomorphine on regional cerebral blood flow in schizophrenia

Daniel, DG; Kf, Berman; Dr, Weinberger

doi:10.1176/jnp.1.4.377

Cited by 56 publications

(1 citation statement)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation has been posited to explain the decreased activation of the PFC during cognitive testing in schizophrenia patients. Indeed, the degree of dlPFC activation in patients performing a working memory task is correlated with decreased cerebrospinal concentrations of dopamine metabolites (Weinberger et al, 1988), and a nonselective dopamine agonist can increase frontal activity in the brains of patients performing similar tasks (Daniel et al, 1989, Dolan et al, 1995). However, in these original studies it was unclear whether the decreased metabolites were indeed originating from the-cortex or from other brain structures.…”

Section: Beyond Symptoms: the Biology Of Schizophreniamentioning

confidence: 99%

Using human brain imaging studies as a guide toward animal models of schizophrenia

2016

View full text Add to dashboard Cite

Schizophrenia is a heterogeneous and poorly understood mental disorder that is presently defined solely by its behavioral symptoms. Advances in genetic, epidemiological and brain imaging techniques in the past half century, however, have significantly advanced our understanding of the underlying biology of the disorder. In spite of these advances clinical research remains limited in its power to establish the causal relationships that link etiology with pathophysiology and symptoms. In this context, animal models provide an important tool for causally testing hypotheses about biological processes postulated to be disrupted in the disorder. While animal models can exploit a variety of entry points towards the study of schizophrenia, here we describe an approach that seeks to closely approximate functional alterations observed with brain imaging techniques in patients. By modeling these intermediate pathophysiological alterations in animals, this approach offers an opportunity to (1) tightly link a single functional brain abnormality with its behavioral consequences, and (2) to determine whether a single pathophysiology can causally produce alterations in other brain areas that have been described in patients. In this review we first summarize a selection of well-replicated biological abnormalities described in the schizophrenia literature. We then provide examples of animal models that were studied in the context of patient imaging findings describing enhanced striatal dopamine D2 receptor function, alterations in thalamo-prefrontal circuit function, and metabolic hyperfunction of the hippocampus. Lastly, we discuss the implications of findings from these animal models for our present understanding of schizophrenia, and consider key unanswered questions for future research in animal models and human patients.

show abstract

Section: Beyond Symptoms: the Biology Of Schizophreniamentioning

confidence: 99%

Using human brain imaging studies as a guide toward animal models of schizophrenia

2016

View full text Add to dashboard Cite

show abstract

Brain Morphology and Schizophrenia

Breier

Boyer

Elkashef

et al. 1992

Arch Gen Psychiatry

474

View full text Add to dashboard Cite

Dopaminergic modulation of cortical function in patients with Parkinson's disease

Mattay

Tessitore

Callicott

et al. 2002

Annals of Neurology

378

233

View full text Add to dashboard Cite

Patients with idiopathic Parkinson's disease suffer not only from classic motor symptoms, but from deficits in cognitive function, primarily those subserved by the prefrontal cortex as well. The aim of the current study was to investigate the modulatory effects of dopaminergic therapy on neural systems subserving working memory and motor function in patients with Parkinson's disease. Ten patients with stage I and II Parkinson's disease were studied with functional magnetic resonance imaging, during a relatively hypodopaminergic state (ie, 12 hours after a last dose of dopamimetic treatment), and again during a dopamine-replete state. Functional magnetic resonance imaging was performed under three conditions: a working memory task, a cued sensorimotor task and rest. Consistent with prior data, the cortical motor regions activated during the motor task showed greater activation during the dopamine-replete state; however, the cortical regions subserving working memory displayed greater activation during the hypodopaminergic state. Interestingly, the increase in cortical activation during the working memory task in the hypodopaminergic state positively correlated with errors in task performance, and the increased activation in the cortical motor regions during the dopamine-replete state was positively correlated with improvement in motor function. These results support evidence from basic research that dopamine modulates cortical networks subserving working memory and motor function via two distinct mechanisms: nigrostriatal projections facilitate motor function indirectly via thalamic projections to motor cortices, whereas the mesocortical dopaminergic system facilitates working memory function via direct inputs to prefrontal cortex. The results are also consistent with evidence that the hypodopaminergic state is associated with decreased efficiency of prefrontal cortical information processing and that dopaminergic therapy improves the physiological efficiency of this region.

show abstract

The effect of apomorphine on regional cerebral blood flow in schizophrenia

Cited by 56 publications

References 37 publications

Using human brain imaging studies as a guide toward animal models of schizophrenia

Using human brain imaging studies as a guide toward animal models of schizophrenia

Brain Morphology and Schizophrenia

Dopaminergic modulation of cortical function in patients with Parkinson's disease

Contact Info

Product

Resources

About