Major Depressive Disorder (MDD) is a complex mental health condition characterized by a wide spectrum of symptoms. According to the Diagnostic Statistical Manual 5 (DSM-5) criteria, patients can present with up to 1,497 different symptom combinations, yet all receive the same MDD diagnosis. This diversity in symptom presentation poses a significant challenge to understanding the disorder in the wider population. Subtyping offers a way to unpick this phenotypic diversity and enable improved characterization of the disorder. According to reviews, MDD subtyping work to date has lacked consistency in results due to inadequate statistics, non-transparent reporting, or inappropriate sample choice. By addressing these limitations, the current study aims to extend past phenotypic subtyping studies in MDD.

(1) To investigate phenotypic subtypes at baseline in a sample of people with MDD;

(2) To determine if subtypes are consistent between baseline 6- and 12-month follow-ups; and

(3) To examine how participants move between subtypes over time.

This was a secondary analysis of a one-year longitudinal observational cohort study. We collected data from individuals with a history of recurrent MDD in the United Kingdom, the Netherlands and Spain (N=619). The presence or absence of symptoms was tracked at three-month intervals through the Inventory of Depressive Symptomatology: Self-Report (IDS-SR) assessment. We used latent class and three-step latent transition analysis to identify subtypes at baseline, determined their consistency at 6- and 12-month follow-ups, and examined participants’ transitions over time.

We identified a 4-class solution based on model fit and interpretability, including (Class 1) severe with appetite increase, (Class 2), severe with appetite decrease, (Class 3) moderate, and (Class 4) low severity. The classes mainly differed in terms of severity (the varying likelihood of symptom endorsement) and, for the two more severe classes, the type of neurovegetative symptoms reported (Figure 1). The four classes were stable over time (measurement invariant) and participants tended to remain in the same class over baseline and follow-up (Figure 2).

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We identified four stable subtypes of depression, with individuals most likely to remain in their same class over 1-year follow-up. This suggests a chronic nature of depression, with (for example) individuals in severe classes more likely to remain in the same class throughout follow-up. Despite the vast heterogeneous symptom combinations possible in MDD, our results emphasize differences across severity rather than symptom type. This raises questions about the meaningfulness of these subtypes beyond established measures of depression severity. Implications of these findings and recommendations for future research are made.

C. Oetzmann Grant / Research support from: C.O. is supported by the UK Medical Research Council (MR/N013700/1) and King’s College London member of the MRC Doctoral Training Partnership in Biomedical Sciences., N. Cummins: None Declared, F. Lamers: None Declared, F. Matcham: None Declared, K. White: None Declared, J. Haro: None Declared, S. Siddi: None Declared, S. Vairavan Employee of: S.V is an employee of Janssen Research & Development, LLC and hold company stocks/stock options., B. Penninx : None Declared, V. Narayan: None Declared, M. Hotopf Grant / Research support from: M.H. is the principal investigator of the RADAR-CNS programme, a precompetitive public–private partnership funded by the Innovative Medicines Initiative and the European Federation of Pharmaceutical Industries and Associations. The programme received support from Janssen, Biogen, MSD, UCB and Lundbeck., E. Carr: None Declared

The goal of the Patient-Centered Outcomes Research Partnership was to prepare health care professionals and researchers to conduct patient-centered outcomes and comparative effectiveness research (CER). Substantial evidence gaps, heterogeneous health care systems, and decision-making challenges in the USA underscore the need for evidence-based strategies.

We engaged five community-based health care organizations that serve diverse and underrepresented patient populations from Hawai’i to Minnesota. Each partner nominated two in-house scholars to participate in the 2-year program. The program focused on seven competencies pertinent to patient-centered outcomes and CER. It combined in-person and experiential learning with asynchronous, online education, and created adaptive, pragmatic learning opportunities and a Summer Institute. Metrics included the Clinical Research Appraisal Inventory (CRAI), a tool designed to assess research self-efficacy and clinical research skills across 10 domains.

We trained 31 scholars in 3 cohorts. Mean scores in nine domains of the CRAI improved; greater improvement was observed from the beginning to the midpoint than from the midpoint to conclusion of the program. Across all three cohorts, mean scores on 52 items (100%) increased (p ≤ 0.01), and 91% of scholars reported the program improved their skills moderately/significantly. Satisfaction with the program was high (91%).

Investigators that conduct patient-centered outcomes and CER must know how to collaborate with regional health care systems to identify priorities; pose questions; design, conduct, and disseminate observational and experimental research; and transform knowledge into practical clinical applications. Training programs such as ours can facilitate such collaborations.

Cognitive symptoms are common during and following episodes of depression. Little is known about the persistence of self-reported and performance-based cognition with depression and functional outcomes.

This is a secondary analysis of a prospective naturalistic observational clinical cohort study of individuals with recurrent major depressive disorder (MDD; N = 623). Participants completed app-based self-reported and performance-based cognitive function assessments alongside validated measures of depression, functional disability, and self-esteem every 3 months. Participants were followed-up for a maximum of 2-years. Multilevel hierarchically nested modelling was employed to explore between- and within-participant variation over time to identify whether persistent cognitive difficulties are related to levels of depression and functional impairment during follow-up.

508 individuals (81.5%) provided data (mean age: 46.6, s.d.: 15.6; 76.2% female). Increasing persistence of self-reported cognitive difficulty was associated with higher levels of depression and functional impairment throughout the follow-up. In comparison to low persistence of objective cognitive difficulty (<25% of timepoints), those with high persistence (>75% of timepoints) reported significantly higher levels of depression (B = 5.17, s.e. = 2.21, p = 0.019) and functional impairment (B = 4.82, s.e. = 1.79, p = 0.002) over time. Examination of the individual cognitive modules shows that persistently impaired executive function is associated with worse functioning, and poor processing speed is particularly important for worsened depressive symptoms.

We replicated previous findings of greater persistence of cognitive difficulty with increasing severity of depression and further demonstrate that these cognitive difficulties are associated with pervasive functional disability. Difficulties with cognition may be an indicator and target for further treatment input.

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.

We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.

16 742 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).

PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

Exposure to armed conflict and forced displacement constitute significant risks for mental health. Existing evidence-based psychological interventions have limitations for scaling-up in low-resource humanitarian settings. The WHO has developed a guided self-help intervention, Self Help Plus (SH+), which is brief, implemented by non-specialists, and designed to be delivered to people with and without specific mental disorders. This paper outlines the study protocol for an evaluation of the SH+ intervention in northern Uganda, with South Sudanese refugee women.

A two-arm, single-blind cluster-randomised controlled trial will be conducted in 14 villages in Rhino Camp refugee settlement, with at least 588 women experiencing psychological distress. Villages will be randomly assigned to receive either SH+ with enhanced usual care (EUC), or EUC alone. SH+ is a five-session guided self-help intervention delivered in workshops with audio-recorded materials and accompanying pictorial guide. The primary outcome is reduction in overall psychological distress over time, with 3 months post-treatment as the primary end-point. Secondary outcomes are self-defined psychosocial concerns, depression and post-traumatic stress disorder symptoms, hazardous alcohol use, feelings of anger, interethnic relations, psychological flexibility, functional impairment and subjective wellbeing. Psychological flexibility is a hypothesised mediator, and past trauma history and intervention attendance will be explored as potential moderators.

This trial will provide important information on the effectiveness of a scalable, guided self-help intervention for improving psychological health and wellbeing among people affected by adversity.

ISRCTN50148022; registered 13/03/2017.

In this period of unprecedented levels of displacement, scalable interventions are needed to address mental health concerns of forced migrants in low-resource settings. This paper describes the adaptation and piloting of a guided, multi-media, self-help intervention, Self-Help Plus (SH+), which was developed to reduce psychological distress in large groups of people affected by adversity.

Using a phased approach that included community consultations, cognitive interviewing, facilitator training, pilot implementation, and a qualitative process evaluation, we adapted SH+ for use among South Sudanese refugees in a refugee settlement in northern Uganda.

The SH+ materials, including audio-recorded sessions and an accompanying illustrated manual, were translated into Juba Arabic. Cognitive interviewing primarily resulted in adaptations to language with some minor adaptations to content. Facilitator training and supervision led to further suggested changes to delivery methods. An uncontrolled pilot study (n = 65) identified changes in the expected direction on measures of psychological distress, functional impairment, depression, wellbeing, and psychological flexibility. The process evaluation resulted in further adaptations to intervention materials and the decision to focus future effectiveness evaluations of the intervention in its current form on South Sudanese female refugees.

We found that this potentially scalable, guided self-help intervention could be adapted for and feasibly implemented among female South Sudanese refugees in northern Uganda. These findings lay the groundwork for a future rigorous evaluation of SH+ in this context.

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.

To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.

Data 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.

A 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).

The 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.

Drs 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.