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Neurobiology of depression: an integrated view of key findings.

Maletic V, Robinson M, Oakes T, Iyengar S, Ball SG, Russell J - Int. J. Clin. Pract. (2007)

Bottom Line: In patients with MDD, alterations in the dynamic patterns of activity among these structures have profound implications for the pathogenesis of this illness.Antidepressant pharmacotherapy is associated with restoration of the underlying physiology.Clinicians are advised to intervene with MDD using an early, comprehensive treatment approach that has remission as the goal.

View Article: PubMed Central - PubMed

Affiliation: School of Medicine, University of South Carolina, Greer, SC 29650, USA. vmaletic@bellsouth.net

ABSTRACT

Aims: The objectives of the present review were to summarise the key findings from the clinical literature regarding the neurobiology of major depressive disorder (MDD) and their implications for maximising treatment outcomes. Several neuroanatomical structures in the prefrontal and limbic areas of the brain are involved in affective regulation. In patients with MDD, alterations in the dynamic patterns of activity among these structures have profound implications for the pathogenesis of this illness.

Discussion: The present work reviews the evidence for the progressive nature of MDD along with associated changes in neuroanatomical structure and function, especially for the hippocampus. The role of glucocorticoids, inflammatory cytokines and brain-derived growth factors are discussed as mediators of these pathological alterations. From this integrated model, the role of antidepressant therapy in restoring normative processes is examined along with additional treatment guidelines.

Conclusion: Major depressive disorder is an illness with significant neurobiological consequences involving structural, functional and molecular alterations in several areas of the brain. Antidepressant pharmacotherapy is associated with restoration of the underlying physiology. Clinicians are advised to intervene with MDD using an early, comprehensive treatment approach that has remission as the goal.

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Related in: MedlinePlus

Antidepressant therapy is associated with restoring normative processes. Treatment with various selective serotonin antidepressant treatments and serotonergic noradrenergic reuptake inhibitors resulted in increases in serum brain-derived neurotrophic factor (BDNF) for patients with MDD to levels comparable that were observed with healthy controls. Reprinted with copyright permission from ref. no. (66)
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Related In: Results  -  Collection


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fig04: Antidepressant therapy is associated with restoring normative processes. Treatment with various selective serotonin antidepressant treatments and serotonergic noradrenergic reuptake inhibitors resulted in increases in serum brain-derived neurotrophic factor (BDNF) for patients with MDD to levels comparable that were observed with healthy controls. Reprinted with copyright permission from ref. no. (66)

Mentions: The effect of increasing monoamine levels (dopamine, 5-HT and NE) on BDNF and growth factors may be one mechanism that produces the antidepressant response. Preclinical study of rat brain cells has demonstrated that monoamenergic activity (NE, 5-HT) upregulates BDNF synthesis in astrocytes (62). Clinically, successful treatment with antidepressants results in normalisation of serum BDNF level, which is considered an indirect measure of cortical BDNF activity. Support for the relationship between serum and cortical BDNF levels has been derived from correlations in animal studies as well as findings that serum BDNF passes the blood–brain barrier and reflects stored and circulating BDNF in humans (63, 64). In a study of 10 patients who were treated for 12 weeks with a dual reuptake inhibitor, improvement in depressive symptoms was correlated with increases in BDNF levels, and the BDNF levels of remitted patients had normalised to the same level observed in healthy controls (65). Response to various SSRI and 5-HT noradrenalin reuptake inhibitors (SNRI) treatments has been similarly associated with restoration of normative BDNF values (66) (Figure 4). Postmortem analysis of brain tissue has shown that subjects who had been treated with an antidepressant at time of death had greater hippocampal BDNF expression as measured by immunoreactivity than did untreated subjects with mood disorders (67).


Neurobiology of depression: an integrated view of key findings.

Maletic V, Robinson M, Oakes T, Iyengar S, Ball SG, Russell J - Int. J. Clin. Pract. (2007)

Antidepressant therapy is associated with restoring normative processes. Treatment with various selective serotonin antidepressant treatments and serotonergic noradrenergic reuptake inhibitors resulted in increases in serum brain-derived neurotrophic factor (BDNF) for patients with MDD to levels comparable that were observed with healthy controls. Reprinted with copyright permission from ref. no. (66)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2228409&req=5

fig04: Antidepressant therapy is associated with restoring normative processes. Treatment with various selective serotonin antidepressant treatments and serotonergic noradrenergic reuptake inhibitors resulted in increases in serum brain-derived neurotrophic factor (BDNF) for patients with MDD to levels comparable that were observed with healthy controls. Reprinted with copyright permission from ref. no. (66)
Mentions: The effect of increasing monoamine levels (dopamine, 5-HT and NE) on BDNF and growth factors may be one mechanism that produces the antidepressant response. Preclinical study of rat brain cells has demonstrated that monoamenergic activity (NE, 5-HT) upregulates BDNF synthesis in astrocytes (62). Clinically, successful treatment with antidepressants results in normalisation of serum BDNF level, which is considered an indirect measure of cortical BDNF activity. Support for the relationship between serum and cortical BDNF levels has been derived from correlations in animal studies as well as findings that serum BDNF passes the blood–brain barrier and reflects stored and circulating BDNF in humans (63, 64). In a study of 10 patients who were treated for 12 weeks with a dual reuptake inhibitor, improvement in depressive symptoms was correlated with increases in BDNF levels, and the BDNF levels of remitted patients had normalised to the same level observed in healthy controls (65). Response to various SSRI and 5-HT noradrenalin reuptake inhibitors (SNRI) treatments has been similarly associated with restoration of normative BDNF values (66) (Figure 4). Postmortem analysis of brain tissue has shown that subjects who had been treated with an antidepressant at time of death had greater hippocampal BDNF expression as measured by immunoreactivity than did untreated subjects with mood disorders (67).

Bottom Line: In patients with MDD, alterations in the dynamic patterns of activity among these structures have profound implications for the pathogenesis of this illness.Antidepressant pharmacotherapy is associated with restoration of the underlying physiology.Clinicians are advised to intervene with MDD using an early, comprehensive treatment approach that has remission as the goal.

View Article: PubMed Central - PubMed

Affiliation: School of Medicine, University of South Carolina, Greer, SC 29650, USA. vmaletic@bellsouth.net

ABSTRACT

Aims: The objectives of the present review were to summarise the key findings from the clinical literature regarding the neurobiology of major depressive disorder (MDD) and their implications for maximising treatment outcomes. Several neuroanatomical structures in the prefrontal and limbic areas of the brain are involved in affective regulation. In patients with MDD, alterations in the dynamic patterns of activity among these structures have profound implications for the pathogenesis of this illness.

Discussion: The present work reviews the evidence for the progressive nature of MDD along with associated changes in neuroanatomical structure and function, especially for the hippocampus. The role of glucocorticoids, inflammatory cytokines and brain-derived growth factors are discussed as mediators of these pathological alterations. From this integrated model, the role of antidepressant therapy in restoring normative processes is examined along with additional treatment guidelines.

Conclusion: Major depressive disorder is an illness with significant neurobiological consequences involving structural, functional and molecular alterations in several areas of the brain. Antidepressant pharmacotherapy is associated with restoration of the underlying physiology. Clinicians are advised to intervene with MDD using an early, comprehensive treatment approach that has remission as the goal.

Show MeSH
Related in: MedlinePlus