Data on associations between inflammation and depressive symptoms largely originate from high income population settings, despite the greatest disease burden in major depressive disorder being attributed to populations in lower-middle income countries (LMICs).

We assessed the prevalence of low-grade inflammation in adults with treatment-resistant depression (TRD) in Pakistan, an LMIC, and investigated associations between peripheral C-reactive protein (CRP) levels and depressive symptoms.

This is a secondary analysis of two randomised controlled trials investigating adjunctive immunomodulatory agents (minocycline and simvastatin) for Pakistani adults with TRD (n = 191). Logistic regression models were built to assess the relationship between pre-treatment CRP (≥ or <3 mg/L) and individual depressive symptoms measured using the Hamilton Depression Rating Scale. Descriptive statistics and regression were used to assess treatment response for inflammation-associated symptoms.

High plasma CRP (≥3 mg/L) was detected in 87% (n = 146) of participants. Early night insomnia (odds ratio 2.33, 95% CI 1.16–5.25), early morning waking (odds ratio 2.65, 95% CI 1.29–6.38) and psychic anxiety (odds ratio 3.79, 95% CI 1.39–21.7) were positively associated, while gastrointestinal (odds ratio 0.38, 95% CI 0.14–0.86) and general somatic symptoms (odds ratio 0.34, 95% CI 0.14–0.74) were negatively associated with inflammation. Minocycline, but not simvastatin, improved symptoms positively associated with inflammation.

The prevalence of inflammation in this LMIC sample with TRD was higher than that reported in high income countries. Insomnia and anxiety symptoms may represent possible targets for personalised treatment with immunomodulatory agents in people with elevated CRP. These findings require replication in independent clinical samples.

Bipolar disorder (BD) leads to marked disability, morbidity, and premature death. Although pharmacological agents are an essential part of BD treatment, psychosocial interventions have played an important role in enhancing treatment adherence, functioning and quality of life in patients with BD. Building on a successful pilot randomised controlled trial (RCT) of a Culturally adapted PsychoEducation (CaPE) intervention for BD, CaPE is currently being evaluated in a large multicenter RCT for its clinical and cost-effectiveness across Pakistan. However, innovations are urgently needed due to limited human resources and disproportionately high clinical needs to bring effective interventions to scale. This study aims to develop and test a mHealth iteration of CaPE, digital CaPE (dCaPE), to be delivered via a mobile app.

The study will utilise a two-phased approach to i) develop a user-centred dCaPE mobile application and ii) assess the feasibility and preliminary efficacy of dCaPE for people with BD in a randomised controlled trial in Pakistan. For application development, we have conducted discussion groups with stakeholders i.e., mental health professionals (psychiatrists, psychologists, nurses) (n = 8) and patients and carers (n = 10) to gauge their valuable insights for app design, visual elements, cultural sensitivity, motivational and mood-monitoring features, and app functionality to improve user experience.

The findings from discussion groups informed the importance of visual elements, specifically font size and style. Participants recommended the use of soft and soothing colours like white, grey, and soft shades of pink to prevent overstimulation. Additionally, participants highlighted the need for culturally and linguistically inclusive features, including emojis and audio messages for effective engagement and to address the challenge of low literacy. The mHealth approach was deemed highly valuable, especially given the prevalence of mental health challenges and associated stigma. Endorsed by participants, the dCaPE application will offer customized psychoeducation messages along with daily 5-item (mood, energy, sleep, medication, and irritability) screening, a weekly comprehensive test for manic and depressive episodes based on DSM–5 criteria; weekly reminders to regulate sleep and eating habits, and visual representations of weekly mood monitoring reports with the incentive of badges or rewards for goal achievers.

This research has the potential to enhance clinical outcomes, social and occupational functioning, and the overall quality of life for BD patients while addressing substantial mental health treatment gaps with impact and implications extending to various low-resource settings.

Suicide and substance use all contribute significantly to the global burden of mortality and morbidity. While existing evidence establishes the association between substance use and suicidal behaviour in Lower- and Middle-Income Countries (LMICs), only a few studies illustrate how substance use affected deceased people's lifestyles and suicide attempts. The study addresses this gap by exploring the role of substance use (particularly, alcohol and drug use) in overall lifestyles and suicides of deceased with substance use in Pakistan – an underexplored and under-researched country regarding suicide and substance use.

We conducted in-depth qualitative interviews (N = 11) with close relatives and friends of those who died by suicide and have a history of substance use. The topic guide was comprised of a narrative part exploring the circumstances that surrounded the suicidal death of the deceased and a problem-focused part collecting comprehensive details about the deceased's personal, family, psychological, and social context and the role of substance use in the lifestyles and the suicide of the deceased.

The content analysis of interviews revealed five key themes: 1) Reasons for suicide, 2) Personality traits, 3) Psychological distress, 4) Initiation of substance use, and 5) Suicidal tendencies. Most of the participants reported the reason for their loved one's suicide was either an overdose of drugs or alcohol, family dynamics, or societal attitudes such as difficulty in building trust and finding acceptance within the family or society. Deceased individuals were perceived as impulsive with low control over their emotional states. Participants highlighted the underlying psychological distress in the deceased, emphasising the complexity of mental health and substance use problems. Participants reported that the deceased initiated drugs at an early age; had suicidal ideations; and overdosed themselves as a means of suicide.

This study provides valuable insights into the role of substance use in suicide. The findings highlight the need for a holistic approach to understanding the multifaceted factors that may influence suicidal behaviours in individuals with substance use. Understanding these factors can help develop targeted suicide prevention and intervention strategies, particularly in low-resource settings such as Pakistan.

The burden of mental health difficulties is a global problem and preventing them from childhood is paramount. Children living in challenged and underserved settings can suffer various harmful lifelong consequences including alcohol and substance abuse, low self-esteem, health issues, poor school performance, self-harm and suicide. This study aims to assess the feasibility, acceptability and efficacy of the culturally adapted Strong Families program in improving child behaviour and family functioning in families living in a challenged setting i.e. Gilgit-Baltistan (GB), Pakistan.

This is a two-arm, multisite feasibility randomised controlled trial with 90 families (n = 45 in intervention, and n = 45 in waitlist group) including a female primary caregiver (mostly mother) and at least one of their children between the age of 8–15 years in three districts of GB. There will be three raters’ blind assessments: at baseline, week 2, and 6 weeks after Strong Families Program sessions.

Strong Families Program is a brief evidence-based prevention programme designed to improve parenting skills, child well-being and family mental health. The primary outcome measures include the feasibility of Strong Families, as determined by families' recruitment, attendance rates, and program completeness (mean number of sessions attended, attrition rates). Additionally, purposefully selected participants, including up to 5 caregivers from each study site, researchers, and facilitators delivering the intervention, will be interviewed. Descriptive statistics will be used to analyse primary and secondary outcomes. The process evaluation will be conducted in terms of program context, reach, fidelity, dose delivered and received, implementation, and recruitment.

The findings from this feasibility trial hold the potential to carry out the large multicentre trial of clinical and cost-effectiveness and scale-up across Pakistan and other similar settings to meaningfully impact child behaviour and family dynamics in culturally diverse contexts.

Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups.

To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire.

Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas.

A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased.

Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence.

Suicide is one of the leading causes of mortality worldwide, and the majority of suicide deaths occur in low- and middle-income countries.

To evaluate the demographic and clinical characteristics of individuals who have presented to health services following self-harm in Pakistan.

This study is a cross-sectional baseline analysis of participants from a large multicentre randomised controlled trial of self-harm prevention in Pakistan. A total of 901 participants with a history of self-harm were recruited from primary care clinics, emergency departments and general hospitals in five major cities in Pakistan. The Beck Scale for Suicide Ideation (BSI), Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS) and Suicide Attempt Self Injury Interview assessment scales were completed.

Most participants recruited were females (n = 544, 60.4%) in their 20s. Compared with males, females had lower educational attainment and higher unemployment rates and reported higher severity scores on BSI, BDI and BHS. Interpersonal conflict was the most frequently cited antecedent to self-harm, followed by financial difficulties in both community and hospital settings. Suicide was the most frequently reported motive of self-harm (N = 776, 86.1%). Suicidal intent was proportionally higher in community-presenting patients (community: N = 318, 96.9% v. hospital: N = 458, 79.9%; P < 0.001). The most frequently reported methods of self-harm were ingestion of pesticides and toxic chemicals.

Young females are the dominant demographic group in this population and are more likely to attend community settings to seek help. Suicidal intent as the motivator of self-harm and use of potentially lethal methods may suggest that this population is at high risk of suicide.

Suicidal ideation and attempts are growing public health concerns globally. Evidence from high-income countries suggests that individuals with psychosis and bipolar disorder are at increased risk of suicidal ideation and attempts, but there is a scarcity of evidence from South Asia.

To estimate the prevalence of suicidal ideation and attempts in individuals with psychosis and bipolar disorder in South Asia.

In this systematic review and meta-analysis, four databases (PsycINFO, Web of Science, EMBASE and Medline) were searched until December 2022. Pooled prevalence was estimated with random-effects models. Heterogeneity was quantified with the I2-statistic.

The pooled sample size across the 21 studies was 3745 participants, 1941 (51.8%) of which were male. The pooled prevalence of suicide attempts in South Asian people with either psychosis or bipolar disorder was 22% (95% CI 17–27; n = 15). The pooled prevalence of suicidal ideation with psychosis or bipolar disorder combined was 38% (95% CI 27–51; n = 10). Meta-regression, subgroup and sensitivity analysis showed that the pooled prevalence estimates for both suicide attempt and ideation remained unaffected by variations in critical appraisal ratings and study designs. Only one study reported data on suicide-related deaths.

One in four individuals diagnosed with psychosis or bipolar disorder have reported suicide attempts, whereas up to one in three have experienced suicidal ideation. These findings underscore the urgent need for clinicians to regularly assess and monitor suicidal ideation and attempts among individuals with these disorders in South Asia.

There has been increased interest in repurposing anti-inflammatories for the treatment of bipolar depression. Evidence from high-income countries suggests that these agents may work best for specific depressive symptoms in a subset of patients with biochemical evidence of inflammation but data from lower-middle income countries (LMICs) is scarce. This secondary analysis explored the relationship between pretreatment inflammatory markers and specific depressive symptoms, clinical measures, and demographic variables in participants with bipolar depression in Pakistan.

The current study is a cross-sectional secondary analysis of a randomized controlled trial of two anti-inflammatory medications (minocycline and celecoxib) for bipolar depression (n = 266). A series of logistic and linear regression models were completed to assess the relationship between C-reactive protein (CRP) (CRP > or < 3 mg/L and log10CRP) and clinical and demographic features of interest and symptoms of depression. Baseline clinical trial data was used to extract clinical and demographic features and symptoms of depression were assessed using the 24-item Hamilton Depression Rating Scale.

The prevalence of low-grade inflammation (CRP > 3 mg/L) in the sample was 70.9%. After adjusting for baseline body mass index, socioeconomic status, age, gender, symptoms related to anhedonia, fatigue, and motor retardation were most associated with low-grade inflammation.

Bipolar disorder (BD) patients from LMICs may experience higher rates of peripheral inflammation than have been reported in Western populations with BD. Future trials of repurposed anti-inflammatory agents that enrich for participants with these symptom profiles may inform the development of personalized treatment for bipolar depression in LMICs.

Bipolar disorder is a source of marked disability, morbidity and premature death. There is a paucity of research on personalised psychosocial interventions for bipolar disorder, especially in low-resource settings. A pilot randomised controlled trial (RCT) of a culturally adapted psychoeducation intervention for bipolar disorder (CaPE) in Pakistan reported higher patient satisfaction, enhanced medication adherence, knowledge and attitudes regarding bipolar disorder, and improvement in mood symptom scores and health-related quality of life measures compared with treatment as usual (TAU).

The current protocol describes a larger multicentre RCT to confirm the clinical and cost-effectiveness of CaPE in Pakistan. Trial registration: NCT05223959.

A multicentre individual, parallel-arm RCT of CaPE in 300 Pakistani adults with bipolar disorder. Participants over the age of 18, with a diagnosis of bipolar I or II disorder who are currently euthymic, will be recruited from seven sites: Karachi, Lahore, Multan, Rawalpindi, Peshawar, Hyderabad and Quetta. Time to recurrence will be the primary outcome assessed using the Longitudinal Interval Follow-up Evaluation (LIFE). Secondary measures will include mood symptoms, quality of life and functioning, adherence to psychotropic medications, and knowledge and attitudes regarding bipolar disorder.

This trial will assess the effectiveness of the CaPE intervention compared with TAU in reducing the time to recurrence for people with bipolar disorder currently in remission in Pakistan and determine the effect on clinical outcomes, quality of life and functioning.

A successful trial might lead to rapid implementation of CaPE in clinical practice, not only in Pakistan, but also in other low-resource settings, including those in high-income countries, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority group patients with bipolar disorder.

Prevalence of post-traumatic stress disorder (PTSD) is high in Pakistan both due to natural disasters and ongoing conflicts. Offspring of trauma survivors are at increased risk for mental and physical illnesses. Parental PTSD has been linked to troubled parent–child relationships, behaviour problems, trauma symptoms, and depression in children. This study aims to explore the acceptability, feasibility and indications of the effectiveness of group learning through play plus trauma-focused cognitive behaviour therapy (LTP Plus TF-CBT) for parents experiencing PTSD.

This is a two-arm pilot cluster randomised controlled trial (RCT). We aim to recruit 300 parents with a diagnosis of PTSD. The screening will be done using the Impact of Event Scale-Revised. Diagnosis of PTSD will be confirmed using the Clinician-Administered PTSD Scale-5 (CAPS-5). Union Councils from Peshawar and Karachi will be randomised into either group LTP Plus TF CBT arm or treatment as usual (TAU). The intervention includes 12 sessions of LTP Plus TF-CBT delivered weekly in the first 2 months and then fortnightly in a group setting by trained psychologists. The groups will be co-facilitated by the community health workers (CHWs). Parents will be assessed at baseline and 4th month (end of the intervention), using the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder (GAD-7) Scale, Client Service Receipt Inventory (CSRI), and Ages and Stages Questionnaire (ASQ-3)

This trial would help build an understanding of the acceptability, feasibility and indications of the effectiveness of a low-cost parenting intervention.

Among low- and middle-income countries (LMICs), bipolar disorder is recognized as one of the leading causes of disease burden for adults and is associated with marked suicide risk. There are limited data on suicidal ideation in bipolar disorder from LMICs. This study presents cross-sectional data on the prevalence of suicidality and associated patient characteristics among patients with bipolar depression in Pakistan, a lower-middle income country and the fifth most populous country in the world.

Participants were recruited through outpatient psychiatric clinics in between 2016–2019 in Karachi, Lahore, Hyderabad and Rawalpindi between 2016–2019. Participants were aged 18 to 65 years with a known diagnosis of bipolar disorder and currently in a depressive episode. Suicidality was assessed using the suicide item of the 17-item Hamilton Depression Rating Scale (HAM-D) and levels of severity were categorized as absent, mild/moderate, or severe. Biometric data and biomarkers were obtained. Descriptive statistics were used to describe prevalence and proportional odds regression models were applied to establish correlates to suicidal ideation.

Among the 266 participants, 67% indicated suicidality of any level and 16% endorsed severe suicidality. Lower body mass index (BMI) (OR = 0.93, 95% CI = 0.88–0.98), higher HAM-D score (OR = 1.29, 95% CI = 1.16–1.43), lower C-reactive protein (CRP) level (OR = 0.53, 95% CI = 0.40–0.70), and increased number of inpatient hospitalizations (OR = 1.16, 95% CI = 1.03–1.31) were identified as significant predictors of suicidality in the fully adjusted regression model. No patient demographic data, including age, gender, marital status, socioeconomic status, and years of education were associated with severity of suicidality.

There exists a high prevalence of suicidal ideation among patients with bipolar depression in Pakistan. Our findings add to the limited literature on suicidality in bipolar disorder in the LMIC context and suggest roles of biological variables such as BMI and CRP level in predicting suicidal ideation and potentially suicidal behaviours in bipolar depression. More studies are needed to see whether such findings can be replicated in other similar LMIC settings, and to explore potential physiological pathways linking BMI, inflammatory biomarkers and suicidality in bipolar disorder.

The evidence base for stigma in mental health largely originates from high-income countries.

This study from Pakistan aimed to address the gap in literature on stigma from low- and middle-income countries.

This cross-sectional study surveyed 1470 adults from Karachi, Pakistan. Participants from three groups (healthcare professionals, healthcare students and the general public) completed the adapted Bogardus Social Distance Scale (SDS) as a measure of stigma.

All three groups reported higher scores of stigma toward mental disorders compared with physical disorders. SDS scores for mental illness in the general public were significantly higher than in healthcare students (mean difference (MD) 6.93, 95% CI 5.45–8.45, P < 0.001) and healthcare professionals (MD 6.93, 95% CI 5.48–8.38, P < 0.001). However, SDS scores between healthcare students and healthcare professionals were not significantly different (MD 0.003, 95% CI −1.14–1.14, P > 0.99). Being female was associated with lower stigma scores and being over the age of 30 years was associated with higher stigma scores.

Stigma campaigns in Pakistan need to target the general population. However, evidence of negative attitudes toward mental illness in healthcare students and healthcare professionals supports the need for stronger emphasis on psychiatric education within undergraduate and postgraduate training in Pakistan.

A third of patients diagnosed with major depressive disorder (MDD) experience treatment-resistant depression (TRD). Relatively few pharmacological agents have established efficacy for TRD. Therefore, the evaluation of novel treatments for TRD is a pressing priority. Statins are pleiotropic agents and preclinical studies as well as preliminary clinical trials have suggested that these drugs may have antidepressant properties.

To report on a protocol for a 12-week, randomised, double-blind, placebo-controlled trial of add-on treatment with simvastatin for patients meeting DSM-5 criteria for MDD who have failed to respond to at least two adequate trials with approved antidepressants. The trial has been registered with Clinicaltrials.gov in (ClinicalTrials.gov identifier: NCT03435744).

After screening and randomisation to the two parallel arms of the trial, 75 patients will receive simvastatin and 75 patients will receive placebo as adjuncts to treatment as usual. The primary outcome is change in Montgomery–Åsberg Depression Rating Scale scores from baseline to week 12 and secondary outcomes include changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. Assessments will take place at screening, baseline, and weeks 2, 4, 8 and 12. Checklists for adverse effects will be undertaken at each visit. Simvastatin (20 mg) will be given once daily. Other secondary outcomes include C-reactive protein and plasma lipids measured at baseline and week 12.

This trial will assess simvastatin's efficacy and tolerability as an add-on treatment option for patients with TRD and provide insights into its putative mechanisms of action.

As the first trial investigating the use of simvastatin as an augmentation strategy in patients with TRD, if the results indicate that adjuvant simvastatin is efficacious in reducing depressive symptoms, it will deliver immediate clinical benefit.

I.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. R.R. and M.M.H. have received educational grants and support for academic meetings from Pfizer, Roche, Novartis and Nabiqasim. A.H.Y. has been commissioned to provide lectures and advice to all major pharmaceutical companies with drugs used in affective and related disorders. A.H.Y. has undertaken investigator-initiated studies from Astra Zeneca, Eli Lilly, Lundbeck and Wyeth. None of the companies have a financial interest in this research.

Self-harm is a major risk factor for completed suicide.

To determine the efficacy of a brief psychological intervention – culturally adapted manual-assisted problem-solving training (C-MAP) – delivered following an episode of self-harm compared with treatment as usual (TAU).

The study was a randomised controlled assessor-masked clinical trial (trial registration: ClinicalTrials.gov NCT01308151). All patients admitted after an episode of self-harm during the previous 7 days to the participating medical units of three university hospitals in Karachi, Pakistan, were included in the study. A total of 250 patients were screened and 221 were randomly allocated to C-MAP plus treatment as usual (TAU) or to TAU alone. All patients were assessed at baseline, at 3 months (end of intervention) and at 6 months after baseline. The primary outcome measure was reduction in suicidal ideation at 3 months. The secondary outcome measures included hopelessness, depression, coping resources and healthcare utilisation.

A total of 108 patients were randomised to the C-MAP group and 113 to the TAU group. Patients in the C-MAP group showed statistically significant improvement on the Beck Scale for Suicide Ideation and Beck Hopelessness Inventory, which was sustained at 3 months after the completion of C-MAP. There was also a significant reduction in symptoms of depression compared with patients receiving TAU.

The positive outcomes of this brief psychological intervention in patients attempting self-harm are promising and suggest that C-MAP may have a role in suicide prevention.