Noradrenergic Overactivity in Chronic Schizophrenia: Evidence Based on Cerebrospinal Fluid Noradrenaline and Cyclic Nucleotide Concentrations

Gomes, U.C.R.; Shanley, B. C.; Potgieter, L.; Roux, JN

doi:10.1192/bjp.137.4.346

Cited by 88 publications

(16 citation statements)

References 17 publications

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“…A number of subsequent postmortem studies detected increased levels of noradrenaline in the brains of schizophrenic patients – in particular, in tissue from those patients with paranoid schizophrenia [54–56]. Consistent with these findings, the levels of noradrenaline and its metabolites in the cerebrospinal fluid (CSF) and plasma of patients with schizophrenia were found to be elevated, and paranoid schizophrenic patients (when examined) were found to be affected to a greater extent than other subjects [57–60]. van Kammen et al .…”

Section: Discussionmentioning

confidence: 85%

The locus coeruleus in schizophrenia: a postmortem study of noradrenergic neurones

Craven¹,

Priddle²,

Crow³

et al. 2005

Neuropathology Appl Neurobio

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Despite evidence for an abnormality of noradrenergic function in schizophrenia, it remains unclear whether the number of noradrenergic neurones is normal in patients with the disorder. In postmortem, formalin-fixed tissue from 15 schizophrenic patients and 18 controls matched for age and gender, we made estimates of the number and size of tyrosine-hydroxylase-immunoreactive cells in the locus coeruleus (LC). No significant difference was detected between these groups in the cross-sectional area or diameter of immunoreactive cell profiles. Profile number was not significantly affected by gender, side of the brainstem (left or right), postmortem interval or time in formalin; however, the levels of immunoreaction product (optical density) correlated significantly with our profile counts, which were lower on average in the schizophrenic group. When optical density was included as a covariate in our comparison (a repeated-measures analysis of variance) of schizophrenic and control cases, we found no difference between these groups in the number of neurones counted. An age-related decrease in profile number was detected, but no effect of age on our estimates of cell size was apparent. Our results highlight the importance of accounting for potential confounding variables, including variations in the quality of immunostaining, in investigations of this type. The findings presented here concur with previous studies suggesting that noradrenergic dysfunction in schizophrenia is not associated with an anatomical abnormality at the level of the LC.

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Section: Discussionmentioning

confidence: 85%

The locus coeruleus in schizophrenia: a postmortem study of noradrenergic neurones

Craven¹,

Priddle²,

Crow³

et al. 2005

Neuropathology Appl Neurobio

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show abstract

“…Schizophrenia is often considered the prime example of these diseases; however, Tourette syndrome and post-traumatic stress disorder (PTSD) are also reliably associated with disrupted PPI Castellanos et al, 1996;Grillon et al, 1996;Swerdlow, 2001). These disorders are well known to be responsive to NE-based drugs and potentially involve dysregulation of the NE system (Bhidayasiri, 2005;Breier et al, 1990;Gay et al, 1989;Gomes et al, 1980;Leckman et al, 1995;Sandyk, 1986). Therefore, it is possible that increased NE signaling at a1-and b-receptors in regions such as posterior mPFC, NAccSh, BNST, BLA, and MD-thalamus could contribute to the pathophysiology of these psychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

Discrete Forebrain Neuronal Networks Supporting Noradrenergic Regulation of Sensorimotor Gating

Alsene

Rajbhandari

Ramaker

et al. 2011

Neuropsychopharmacol

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Prepulse inhibition (PPI) refers to the reduction in the startle response when a startling stimulus is preceded by a weak prestimulus, and is an endophenotype of deficient sensorimotor gating in several neuropsychiatric disorders. Emerging evidence suggests that norepinephrine (NE) regulates PPI, however, the circuitry involved is unknown. We found recently that stimulation of the locus coeruleus (LC), the primary source of NE to the forebrain, induces a PPI deficit that is a result of downstream NE release. Hence, this study sought to identify LC-innervated forebrain regions that mediate this effect. Separate groups of male Sprague-Dawley rats received a cocktail solution of the a1-NE receptor agonist phenylephrine plus the b-receptor agonist isoproterenol (equal parts of each; 0, 3, 10, and 30 mg) into subregions of the medial prefrontal cortex (mPFC), nucleus accumbens (NAcc), extended amygdala, mediodorsal thalamus (MD-thalamus), or the dorsal hippocampus (DH) before PPI testing. NE agonist infusion into the posterior mPFC, NAcc shell, bed nucleus of the stria terminalis, basolateral amygdala, and the MD-thalamus disrupted PPI, with particularly strong effects in MD-thalamus. Sites in which NE receptor stimulation did not disrupt PPI (anterior mPFC, NAcc core, central amygdala, and DH) did support PPI disruptions with the dopamine D2 receptor agonist quinpirole (0, 10 mg). This pattern reveals new pathways in the regulation of PPI, and suggests that NE transmission within distinct thalamocortical and ventral forebrain networks may subserve the sensorimotor gating deficits that are seen in disorders such as schizophrenia, Tourette syndrome, and post-traumatic stress disorder.

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“…Elevated concentrations of norepinephrine have been detected postmortem in limbic forebrain (Farley et al 1978;Bird et al 1979;Hornykiewicz 1986) in schizophrenic subjects as compared to control subjects. An elevation of norepinephrine in the cerebrospinal fluid of schizophrenics compared to controls has also been reported (Gomes et al 1980;Lake et al 1980;Sternberg et al 1981;Van Kammen et al 1989). Interestingly, measures of noradrenergic activity seem to be good indicators and/or predictors of the state of disease and its outcome (Hornykiewicz 1982(Hornykiewicz , 1986Van Kammen and Kelley 1991).…”

mentioning

confidence: 80%

Brain Noradrenergic Receptors in Major Depression and Schizophrenia

Klimek

Rajkowska

Luker

et al. 1999

Neuropsychopharmacology

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Noradrenergic Overactivity in Chronic Schizophrenia: Evidence Based on Cerebrospinal Fluid Noradrenaline and Cyclic Nucleotide Concentrations

Cited by 88 publications

References 17 publications

The locus coeruleus in schizophrenia: a postmortem study of noradrenergic neurones

The locus coeruleus in schizophrenia: a postmortem study of noradrenergic neurones

Discrete Forebrain Neuronal Networks Supporting Noradrenergic Regulation of Sensorimotor Gating

Brain Noradrenergic Receptors in Major Depression and Schizophrenia

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