Inflammatory profiles of severe treatment-resistant depression

Rebecca Strawbridge; John Hodsoll; Timothy R. Powell; Matthew Hotopf; Stephani L. Hatch; Gerome Breen; Anthony J. Cleare

doi:10.1016/j.jad.2018.12.037

Inflammatory profiles of severe treatment-resistant depression

Rebecca Strawbridge, John Hodsoll, Timothy R. Powell, Matthew Hotopf, Stephani L. Hatch, Gerome Breen, Anthony J. Cleare

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Abstract

Background Treatment-resistant depression (TRD) contributes substantially to the burden of mood disorders and is undoubtedly an important subpopulation in whom there are clear unmet treatment needs. Despite a paucity of research focusing specifically on TRD, recent studies indicate that inflammatory activity may be particularly elevated in these patients. Methods 36 patients with TRD were investigated longitudinally before and after undertaking a specialist inpatient treatment program. 27 inflammatory proteins were compared between patients and a matched sample of non-depressed controls, as well as between treatment responders and non-responders. Treatment outcomes were calculated from depression severity scores before and after admission, and at a long-term follow-up 3-12 months after discharge. Results TRD patients had higher levels of numerous inflammatory proteins than controls, and elevated interleukins 6 and 8, tumour necrosis factor, c-reactive protein and macrophage inflammatory protein-1 were associated with poorer treatment outcomes. A separate set of proteins (either anti-inflammatory in nature or attenuated at baseline) showed increases during treatment, regardless of clinical response. Participants with the greatest elevations in inflammation tended to be older, more cognitively impaired and more treatment-resistant at baseline. Limitations The small sample and large number of comparisons examined in this study must be taken into account when interpreting these results. Conclusions However, this study provides empirical support for theories that more severe, chronic or treatment-resistant depressive disorders are associated with dysregulated inflammatory activity. If a predictor or predictors of response in TRD are established, improved and targeted care might be more reliably provided to this vulnerable population.

Original language	English
Journal	Journal of Affective Disorders
Early online date	17 Dec 2018
DOIs	https://doi.org/10.1016/j.jad.2018.12.037
Publication status	E-pub ahead of print - 17 Dec 2018

Keywords

Inflammation
Treatment-resistant depression
Cytokines
Treatment response

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Inflammatory profiles of severe_STRAWBRIDGE_Firstonline17December2018_GREEN AAM (CC BY-NC-ND)Accepted author manuscript, 1.65 MBLicence: CC BY-NC-ND

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@article{dbb28ef777924359a29601e50ec79631,

title = "Inflammatory profiles of severe treatment-resistant depression",

abstract = "Background Treatment-resistant depression (TRD) contributes substantially to the burden of mood disorders and is undoubtedly an important subpopulation in whom there are clear unmet treatment needs. Despite a paucity of research focusing specifically on TRD, recent studies indicate that inflammatory activity may be particularly elevated in these patients. Methods 36 patients with TRD were investigated longitudinally before and after undertaking a specialist inpatient treatment program. 27 inflammatory proteins were compared between patients and a matched sample of non-depressed controls, as well as between treatment responders and non-responders. Treatment outcomes were calculated from depression severity scores before and after admission, and at a long-term follow-up 3-12 months after discharge. Results TRD patients had higher levels of numerous inflammatory proteins than controls, and elevated interleukins 6 and 8, tumour necrosis factor, c-reactive protein and macrophage inflammatory protein-1 were associated with poorer treatment outcomes. A separate set of proteins (either anti-inflammatory in nature or attenuated at baseline) showed increases during treatment, regardless of clinical response. Participants with the greatest elevations in inflammation tended to be older, more cognitively impaired and more treatment-resistant at baseline. Limitations The small sample and large number of comparisons examined in this study must be taken into account when interpreting these results. Conclusions However, this study provides empirical support for theories that more severe, chronic or treatment-resistant depressive disorders are associated with dysregulated inflammatory activity. If a predictor or predictors of response in TRD are established, improved and targeted care might be more reliably provided to this vulnerable population.",

keywords = "Inflammation, Treatment-resistant depression, Cytokines, Treatment response",

author = "Rebecca Strawbridge and John Hodsoll and Powell, {Timothy R.} and Matthew Hotopf and Hatch, {Stephani L.} and Gerome Breen and Cleare, {Anthony J.}",

year = "2018",

month = dec,

day = "17",

doi = "10.1016/j.jad.2018.12.037",

language = "English",

journal = "Journal of Affective Disorders",

issn = "0165-0327",

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T1 - Inflammatory profiles of severe treatment-resistant depression

AU - Strawbridge, Rebecca

AU - Hodsoll, John

AU - Powell, Timothy R.

AU - Hotopf, Matthew

AU - Hatch, Stephani L.

AU - Breen, Gerome

AU - Cleare, Anthony J.

PY - 2018/12/17

Y1 - 2018/12/17

N2 - Background Treatment-resistant depression (TRD) contributes substantially to the burden of mood disorders and is undoubtedly an important subpopulation in whom there are clear unmet treatment needs. Despite a paucity of research focusing specifically on TRD, recent studies indicate that inflammatory activity may be particularly elevated in these patients. Methods 36 patients with TRD were investigated longitudinally before and after undertaking a specialist inpatient treatment program. 27 inflammatory proteins were compared between patients and a matched sample of non-depressed controls, as well as between treatment responders and non-responders. Treatment outcomes were calculated from depression severity scores before and after admission, and at a long-term follow-up 3-12 months after discharge. Results TRD patients had higher levels of numerous inflammatory proteins than controls, and elevated interleukins 6 and 8, tumour necrosis factor, c-reactive protein and macrophage inflammatory protein-1 were associated with poorer treatment outcomes. A separate set of proteins (either anti-inflammatory in nature or attenuated at baseline) showed increases during treatment, regardless of clinical response. Participants with the greatest elevations in inflammation tended to be older, more cognitively impaired and more treatment-resistant at baseline. Limitations The small sample and large number of comparisons examined in this study must be taken into account when interpreting these results. Conclusions However, this study provides empirical support for theories that more severe, chronic or treatment-resistant depressive disorders are associated with dysregulated inflammatory activity. If a predictor or predictors of response in TRD are established, improved and targeted care might be more reliably provided to this vulnerable population.

AB - Background Treatment-resistant depression (TRD) contributes substantially to the burden of mood disorders and is undoubtedly an important subpopulation in whom there are clear unmet treatment needs. Despite a paucity of research focusing specifically on TRD, recent studies indicate that inflammatory activity may be particularly elevated in these patients. Methods 36 patients with TRD were investigated longitudinally before and after undertaking a specialist inpatient treatment program. 27 inflammatory proteins were compared between patients and a matched sample of non-depressed controls, as well as between treatment responders and non-responders. Treatment outcomes were calculated from depression severity scores before and after admission, and at a long-term follow-up 3-12 months after discharge. Results TRD patients had higher levels of numerous inflammatory proteins than controls, and elevated interleukins 6 and 8, tumour necrosis factor, c-reactive protein and macrophage inflammatory protein-1 were associated with poorer treatment outcomes. A separate set of proteins (either anti-inflammatory in nature or attenuated at baseline) showed increases during treatment, regardless of clinical response. Participants with the greatest elevations in inflammation tended to be older, more cognitively impaired and more treatment-resistant at baseline. Limitations The small sample and large number of comparisons examined in this study must be taken into account when interpreting these results. Conclusions However, this study provides empirical support for theories that more severe, chronic or treatment-resistant depressive disorders are associated with dysregulated inflammatory activity. If a predictor or predictors of response in TRD are established, improved and targeted care might be more reliably provided to this vulnerable population.

KW - Inflammation

KW - Treatment-resistant depression

KW - Cytokines

KW - Treatment response

U2 - 10.1016/j.jad.2018.12.037

DO - 10.1016/j.jad.2018.12.037

M3 - Article

SN - 0165-0327

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

ER -

Inflammatory profiles of severe treatment-resistant depression

Abstract

Keywords

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