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Exploring interleukin-6, lipopolysaccharide-binding protein and brain-derived neurotrophic factor following 12 weeks of adjunctive minocycline treatment for depression
- Kyoko Hasebe, Mohammadreza Mohebbi, Laura Gray, Adam J. Walker, Chiara C. Bortolasci, Alyna Turner, Michael Berk, Ken Walder, Michael Maes, Buranee Kanchanatawan, Melanie M. Ashton, Lesley Berk, Chee H. Ng, Gin S. Malhi, Ajeet B. Singh, Olivia M. Dean
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- Journal:
- Acta Neuropsychiatrica / Volume 34 / Issue 4 / August 2022
- Published online by Cambridge University Press:
- 23 December 2021, pp. 220-227
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This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.
Equivalency of the diagnostic accuracy of the PHQ-8 and PHQ-9: a systematic review and individual participant data meta-analysis – ERRATUM
- Yin Wu, Brooke Levis, Kira E. Riehm, Nazanin Saadat, Alexander W. Levis, Marleine Azar, Danielle B. Rice, Jill Boruff, Pim Cuijpers, Simon Gilbody, John P.A. Ioannidis, Lorie A. Kloda, Dean McMillan, Scott B. Patten, Ian Shrier, Roy C. Ziegelstein, Dickens H. Akena, Bruce Arroll, Liat Ayalon, Hamid R. Baradaran, Murray Baron, Charles H. Bombardier, Peter Butterworth, Gregory Carter, Marcos H. Chagas, Juliana C. N. Chan, Rushina Cholera, Yeates Conwell, Janneke M. de Manvan Ginkel, Jesse R. Fann, Felix H. Fischer, Daniel Fung, Bizu Gelaye, Felicity Goodyear-Smith, Catherine G. Greeno, Brian J. Hall, Patricia A. Harrison, Martin Härter, Ulrich Hegerl, Leanne Hides, Stevan E. Hobfoll, Marie Hudson, Thomas Hyphantis, Masatoshi Inagaki, Nathalie Jetté, Mohammad E. Khamseh, Kim M. Kiely, Yunxin Kwan, Femke Lamers, Shen-Ing Liu, Manote Lotrakul, Sonia R. Loureiro, Bernd Löwe, Anthony McGuire, Sherina Mohd-Sidik, Tiago N. Munhoz, Kumiko Muramatsu, Flávia L. Osório, Vikram Patel, Brian W. Pence, Philippe Persoons, Angelo Picardi, Katrin Reuter, Alasdair G. Rooney, Iná S. Santos, Juwita Shaaban, Abbey Sidebottom, Adam Simning, Lesley Stafford, Sharon Sung, Pei Lin Lynnette Tan, Alyna Turner, Henk C. van Weert, Jennifer White, Mary A. Whooley, Kirsty Winkley, Mitsuhiko Yamada, Andrea Benedetti, Brett D. Thombs
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- Journal:
- Psychological Medicine / Volume 50 / Issue 16 / December 2020
- Published online by Cambridge University Press:
- 19 August 2019, p. 2816
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Equivalency of the diagnostic accuracy of the PHQ-8 and PHQ-9: a systematic review and individual participant data meta-analysis
- Yin Wu, Brooke Levis, Kira E. Riehm, Nazanin Saadat, Alexander W. Levis, Marleine Azar, Danielle B. Rice, Jill Boruff, Pim Cuijpers, Simon Gilbody, John P.A. Ioannidis, Lorie A. Kloda, Dean McMillan, Scott B. Patten, Ian Shrier, Roy C. Ziegelstein, Dickens H. Akena, Bruce Arroll, Liat Ayalon, Hamid R. Baradaran, Murray Baron, Charles H. Bombardier, Peter Butterworth, Gregory Carter, Marcos H. Chagas, Juliana C. N. Chan, Rushina Cholera, Yeates Conwell, Janneke M. de Man-van Ginkel, Jesse R. Fann, Felix H. Fischer, Daniel Fung, Bizu Gelaye, Felicity Goodyear-Smith, Catherine G. Greeno, Brian J. Hall, Patricia A. Harrison, Martin Härter, Ulrich Hegerl, Leanne Hides, Stevan E. Hobfoll, Marie Hudson, Thomas Hyphantis, Masatoshi Inagaki, Nathalie Jetté, Mohammad E. Khamseh, Kim M. Kiely, Yunxin Kwan, Femke Lamers, Shen-Ing Liu, Manote Lotrakul, Sonia R. Loureiro, Bernd Löwe, Anthony McGuire, Sherina Mohd-Sidik, Tiago N. Munhoz, Kumiko Muramatsu, Flávia L. Osório, Vikram Patel, Brian W. Pence, Philippe Persoons, Angelo Picardi, Katrin Reuter, Alasdair G. Rooney, Iná S. Santos, Juwita Shaaban, Abbey Sidebottom, Adam Simning, Lesley Stafford, Sharon Sung, Pei Lin Lynnette Tan, Alyna Turner, Henk C. van Weert, Jennifer White, Mary A. Whooley, Kirsty Winkley, Mitsuhiko Yamada, Andrea Benedetti, Brett D. Thombs
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- Journal:
- Psychological Medicine / Volume 50 / Issue 8 / June 2020
- Published online by Cambridge University Press:
- 12 July 2019, pp. 1368-1380
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Background
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
MethodsWe conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
ConclusionsPHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Telephone-delivered psychosocial interventions targeting key health priorities in adults with a psychotic disorder: systematic review
- Amanda L. Baker, Alyna Turner, Alison Beck, Katherine Berry, Gillian Haddock, Peter J. Kelly, Sandra Bucci
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- Journal:
- Psychological Medicine / Volume 48 / Issue 16 / December 2018
- Published online by Cambridge University Press:
- 25 May 2018, pp. 2637-2657
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Background
The mental and physical health of individuals with a psychotic illness are typically poor. Access to psychosocial interventions is important but currently limited. Telephone-delivered interventions may assist. In the current systematic review, we aim to summarise and critically analyse evidence for telephone-delivered psychosocial interventions targeting key health priorities in adults with a psychotic disorder, including (i) relapse, (ii) adherence to psychiatric medication and/or (iii) modifiable cardiovascular disease risk behaviours.
MethodsTen peer-reviewed and four grey literature databases were searched for English-language studies examining psychosocial telephone-delivered interventions targeting relapse, medication adherence and/or health behaviours in adults with a psychotic disorder. Study heterogeneity precluded meta-analyses.
ResultsTwenty trials [13 randomised controlled trials (RCTs)] were included, involving 2473 participants (relapse prevention = 867; medication adherence = 1273; and health behaviour = 333). Five of eight RCTs targeting relapse prevention and one of three targeting medication adherence reported at least 50% of outcomes in favour of the telephone-delivered intervention. The two health-behaviour RCTs found comparable levels of improvement across treatment conditions.
ConclusionsAlthough most interventions combined telephone and face-to-face delivery, there was evidence to support the benefit of entirely telephone-delivered interventions. Telephone interventions represent a potentially feasible and effective option for improving key health priorities among people with psychotic disorders. Further methodologically rigorous evaluations are warranted.
Probability of major depression diagnostic classification using semi-structured versus fully structured diagnostic interviews
- Brooke Levis, Andrea Benedetti, Kira E. Riehm, Nazanin Saadat, Alexander W. Levis, Marleine Azar, Danielle B. Rice, Matthew J. Chiovitti, Tatiana A. Sanchez, Pim Cuijpers, Simon Gilbody, John P. A. Ioannidis, Lorie A. Kloda, Dean McMillan, Scott B. Patten, Ian Shrier, Russell J. Steele, Roy C. Ziegelstein, Dickens H. Akena, Bruce Arroll, Liat Ayalon, Hamid R. Baradaran, Murray Baron, Anna Beraldi, Charles H. Bombardier, Peter Butterworth, Gregory Carter, Marcos H. Chagas, Juliana C. N. Chan, Rushina Cholera, Neerja Chowdhary, Kerrie Clover, Yeates Conwell, Janneke M. de Man-van Ginkel, Jaime Delgadillo, Jesse R. Fann, Felix H. Fischer, Benjamin Fischler, Daniel Fung, Bizu Gelaye, Felicity Goodyear-Smith, Catherine G. Greeno, Brian J. Hall, John Hambridge, Patricia A. Harrison, Ulrich Hegerl, Leanne Hides, Stevan E. Hobfoll, Marie Hudson, Thomas Hyphantis, Masatoshi Inagaki, Khalida Ismail, Nathalie Jetté, Mohammad E. Khamseh, Kim M. Kiely, Femke Lamers, Shen-Ing Liu, Manote Lotrakul, Sonia R. Loureiro, Bernd Löwe, Laura Marsh, Anthony McGuire, Sherina Mohd Sidik, Tiago N. Munhoz, Kumiko Muramatsu, Flávia L. Osório, Vikram Patel, Brian W. Pence, Philippe Persoons, Angelo Picardi, Alasdair G. Rooney, Iná S. Santos, Juwita Shaaban, Abbey Sidebottom, Adam Simning, Lesley Stafford, Sharon Sung, Pei Lin Lynnette Tan, Alyna Turner, Christina M. van der Feltz-Cornelis, Henk C. van Weert, Paul A. Vöhringer, Jennifer White, Mary A. Whooley, Kirsty Winkley, Mitsuhiko Yamada, Yuying Zhang, Brett D. Thombs
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- Journal:
- The British Journal of Psychiatry / Volume 212 / Issue 6 / June 2018
- Published online by Cambridge University Press:
- 02 May 2018, pp. 377-385
- Print publication:
- June 2018
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Background
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
AimsTo evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
MethodData collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
ResultsA total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
ConclusionsThe MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interestDrs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.