An evaluation of the role of the noradrenergic system in the neurobiology of depression: a review

Redmond, A. M.; Leonard, Brian E.

doi:10.1002/(sici)1099-1077(199709/10)12:5<407::aid-hup918>3.0.co;2-1

Cited by 25 publications

(14 citation statements)

References 214 publications

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“…An involvement of alpha 2 -ARs in the regulation of attention is further suggested by the finding that methylphenidate (Ritalin, the non-amphetamine stimulant that is used to treat children with Attention Deficit Hyperactivity Disorder) affects neuronal activity in the LC (Ishimatsu et al 2002). Administration of the antagonist yohimbine which results in increased LC firing, induced anxiety-like behavior in rats and monkeys (Redmond and Leonard 1997). Last but not least, brain alpha 2 -AR changes have been proposed to be involved in the etiology of depression (see below).…”

Section: Alpha 2 -Adrenoceptorsmentioning

confidence: 99%

Perturbations in brain monoamine systems during stress

2003

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Monoamines modulate the activity of many neurons and there is evidence that a balanced synthesis of central nervous monoamines is a prerequisite for normal brain functioning. Stress accelerates both release and turnover of brain monoamines and the resulting fluctuations in concentrations affect various parameters within neurotransmitter systems. Acute stress leads to only transient alterations in monoamine systems so that homeostasis can be restored, in contrast, chronic stress accompanied by repetitive and/or prolonged stimulation of monoaminergic neurons can induce a long-lasting imbalance in central nervous neurotransmitter systems. Accordingly, stress-induced changes in brain monoamine systems are suspected to contribute to psychiatric diseases such as depression. The present paper gives a short overview of stress effects on brain monoamines and their receptors.

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Section: Alpha 2 -Adrenoceptorsmentioning

confidence: 99%

Perturbations in brain monoamine systems during stress

2003

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“…Stress‐induced changes in the brain noradrenergic system have been suspected to contribute to psychopathologies such as depression (Redmond & Leonard, 1997) and it has been hypothesized that either an increase (Weiss & Simson, 1988) or a decrease in noradrenergic activity (Anisman & Zacharko, 1990) might be responsible for depressive symptoms. Among the components of the brain's noradrenergic system that are affected by stress are α 2 ‐adrenoceptors (α 2 ‐AR) that are known to modulate neuronal activity (Aghajanian & Vandermaelen, 1982; Williams et al ., 1985; Starke, 1987; Limbird, 1988; Boehm, 1999).…”

Section: Introductionmentioning

confidence: 99%

α_2A and α_2C‐adrenoceptor regulation in the brain: α_2A changes persist after chronic stress

Flügge

Kampen

Meyer

et al. 2003

Eur J of Neuroscience

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Stress-induced activation of the central nervous noradrenergic system has been suspected to induce depressive disorders. As episodes of depression often occur some time after a stress experience we investigated whether stress-induced changes in the alpha2-adrenoceptor (alpha2-AR) system persist throughout a post-stress recovery period. Brains of male tree shrews were analysed after 44 days of chronic psychosocial stress and after a subsequent 10-day recovery period. Expression of RNA for alpha2A and alpha2C-adrenoceptors was quantified by in situ hybridization, and receptor binding was determined by in vitro receptor autoradiography. Activities of the sympathetic nervous system and of the hypothalamo-pituitary-adrenal axis were increased during chronic stress but normalized during recovery. Alpha2A-AR RNA in the glutamatergic neurons of the lateral reticular nucleus was elevated significantly after stress and after recovery (by 29% and 17%). In the dorsal motor nucleus of the vagus, subtype A expression was enhanced after recovery (by 33%). In the locus coeruleus, subtype A autoreceptor expression was not changed significantly. Subtype C expression in the caudate nucleus and putamen was elevated by stress (by 5 and 4%, respectively) but normalized during recovery. Quantification of 3H-RX821002 binding revealed receptor upregulation during stress and/or recovery. Our data therefore show: (i) that chronic psychosocial stress differentially regulates expression of alpha2-adrenoceptor subtypes A and C; (ii) that subtype A heteroreceptor expression is persistently upregulated whereas (iii), subtype C upregulation is only transient. The present findings coincide with post mortem studies in depressed patients revealing upregulation of alpha2A-ARs.

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“…In fact, ECT influences neurotrophin expression even more than antidepressants, corresponding to its higher efficacy as a treatment for depression. 19 The exact mechanisms by which antidepressants influence BDNF expression are difficult to discern, because CREB is influenced by more than one intracellular signalling cascade. 62 Owing to this complexity, novel antidepressants are being developed that are aimed specifically at the cAMP pathway, a major intracellular cascade that controls CREB.…”

Section: The Neurotrophin Hypothesis Of Depressionmentioning

confidence: 99%

Sleep Pathologies in Depression and the Clinical Utility of Polysomnography

Sculthorpe

Douglass

2010

Can J Psychiatry

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Abnormal sleep accompanies many psychiatric conditions, but has long been recognized as a particularly conspicuous feature of affective disorders. More than a mere epiphenomenon, the powerful link between sleep and mood regulation is most dramatically demonstrated by the high efficacy of sleep deprivation in alleviating depression. Indeed, the sleep abnormalities that accompany depression may be due to the same neuropathologies that are responsible for its mood and cognitive symptoms. This powerful link between sleep and mood regulation makes polysomnography (PSG) a useful window into the underlying pathophysiology of depression, yet it is underused, particularly in clinical diagnosis. Recent depression research has emphasized the importance of establishing biologically relevant subtypes of depression with treatment specificity and prognostic value. PSG measures, among other biological markers, may be of importance in establishing these subtypes. Two subtypes of depression that appear to have robust biological differences, the melancholic and atypical subtypes, have recently been shown to have different sleep profiles that can aid in differential diagnosis. Further, routine use of PSG in the workup of a depressed patient would minimize the chances of misdiagnosis in those suffering from primary sleep disorders such as sleep apnea, which can present secondary mood symptoms resembling depression. Increased use of PSG in clinical psychiatric practice would enlarge the body of data available for defining new depressive subtypes in the future. It would also serve an immediate purpose in the separation of atypical, compared with melancholic, depression, and the differential diagnosis of depression from primary sleep disorders.Can J Psychiatry. 2010;55(7):413-421. Clinical Implications· PSG measures are gaining increasing importance in the differential diagnosis of depressive subtypes, particularly atypical, compared with melancholic, depression. · PSG measures obtained in the clinic need to be modernized and standardized to increase their sensitivity to neurobiological changes. · Depression is highly comorbid with primary sleep disorders; PSG should be routinely employed to prevent misdiagnosis. Limitations· Research investigating the relations between depressive subtypes and sleep abnormalities using modern measures is at an early stage. · There has been a general lack of standardization in PSG measures, which reduces the ability to compare results between different laboratories and (or) clinics. · Sleep laboratory-based PSG assessments introduce scheduling and compliance issues with patients, and may delay (but improve) diagnosis.

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An evaluation of the role of the noradrenergic system in the neurobiology of depression: a review

Cited by 25 publications

References 214 publications

Perturbations in brain monoamine systems during stress

Perturbations in brain monoamine systems during stress

α_2A and α_2C‐adrenoceptor regulation in the brain: α_2A changes persist after chronic stress

Sleep Pathologies in Depression and the Clinical Utility of Polysomnography

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An evaluation of the role of the noradrenergic system in the neurobiology of depression: a review

Cited by 25 publications

References 214 publications

Perturbations in brain monoamine systems during stress

Perturbations in brain monoamine systems during stress

α2A and α2C‐adrenoceptor regulation in the brain: α2A changes persist after chronic stress

Sleep Pathologies in Depression and the Clinical Utility of Polysomnography

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Product

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α_2A and α_2C‐adrenoceptor regulation in the brain: α_2A changes persist after chronic stress