Abstract
Background
Insomnia, social dysfunction, suicidality, and depressive symptoms commonly co-occur in schizophrenia. Their joint cross-sectional associations and potential sex differences among rural adults with schizophrenia remain unclear.
Methods
This multicenter cross-sectional study included 931 rural adults with schizophrenia in Chaohu, China. Depressive symptoms, insomnia severity, social dysfunction, and suicidality were assessed using the Patient Health Questionnaire-9, Insomnia Severity Index, Social Disability Screening Schedule, and a composite suicidality score, respectively. Sex-stratified logistic regression and exploratory indirect-association analyses with 5,000 bootstrap resamples were conducted. A sensitivity analysis used a non-overlapping Patient Health Questionnaire-7 score excluding the sleep and suicidality items.
Results
Of 931 participants, 457 were male and 474 were female. Female participants had higher depressive-symptom, insomnia, suicidality, and social-dysfunction scores than male participants (all P≤0.005). In both sex-stratified models, higher insomnia, suicidality, and social-dysfunction scores were associated with greater odds of at least mild depressive symptoms. In the exploratory model, insomnia severity was directly associated with depressive-symptom score (b=0.388, 95% bootstrap confidence interval [CI], 0.345–0.431). Indirect associations via social dysfunction (0.042, 95% CI, 0.028–0.057) and suicidality (0.038, 95% CI, 0.021–0.058) were supported, whereas the serial indirect association was not (0.002, 95% CI, −0.0001 to 0.005). Sex did not moderate the indirect associations.
Conclusion
Women reported higher symptom and social-dysfunction scores than men, but sex did not moderate the estimated indirect associations. Insomnia, social dysfunction, suicidality, and depressive symptoms formed a clinically relevant cross-sectional pattern; however, temporal ordering and causality cannot be inferred. Longitudinal studies with non-overlapping measures and broader clinical covariates are needed.
Keywords: schizophrenia, depressive symptoms, insomnia, social functioning, suicidality, rural China
Introduction
Schizophrenia is a severe and persistent psychiatric disorder characterized by disturbances in cognition, emotion, and social functioning and is associated with substantial excess mortality.1 Although antipsychotic treatment is the cornerstone of care, many individuals continue to experience residual symptoms and impaired functioning after stabilization, with consequent reductions in quality of life.2 Recent meta-analytic evidence indicates that poor sleep quality is common in schizophrenia. The pooled prevalence was 63.4%, and patients with schizophrenia had higher odds of poor sleep quality than healthy controls.3 Rural residents with schizophrenia in China may face additional barriers to sustained treatment and rehabilitation. Rural residence, lower income, lack of health insurance, and illiteracy were associated with lower use of pharmacological treatment and psychotherapy in a nationwide longitudinal study.4 The rural setting is also clinically relevant to suicide prevention. In a 21-year follow-up study from rural China, suicide accounted for 13.8% of observed deaths among people with schizophrenia, although the magnitude and determinants of risk may differ across regions and care settings.5
Sex differences may also be relevant to the clinical presentation and course of schizophrenia. Compared with females, males tend to have an earlier illness onset, poorer premorbid functioning, more prominent negative symptoms, and lower levels of affective symptoms; however, findings for cognition, social functioning, and long-term functional outcomes are heterogeneous.6 Clinical studies further suggest that sex-related differences in schizophrenia may vary according to depressive-symptom status, cognition, and the outcome assessed, rather than following a uniform pattern across all domains.7,8 Whether the pattern and clinical correlates of depressive symptoms differ between male and female rural individuals with clinically stable schizophrenia therefore remain insufficiently understood.
Depressive symptoms are common in schizophrenia and are associated with adverse functional and suicide-related outcomes.9 In related cross-sectional studies, insomnia severity was associated with aggression, depressed mood was associated with aggression, stigma and perceived social isolation were associated with suicidality, and stigma and social functional impairment were associated with quality of life.10–13 These studies identified relevant pairwise associations but did not examine whether multiple symptom and functional domains were statistically interrelated with depressive symptoms in one model.
Sleep disturbance, social dysfunction, and suicidality may be clinically relevant to depressive symptoms in schizophrenia-spectrum disorders. In a rural Chinese sample of clinically stable inpatients with schizophrenia, sleep disturbance was cross-sectionally associated with depressive symptoms and quality of life. This finding supports the clinical relevance of sleep assessment in rural schizophrenia care, while not establishing directionality between sleep and affective symptoms.14 Sleep disturbance and sleep-related impairment have been associated with poorer perceived social relationships, community functioning, social networks, and social competence in psychosis, and poorer sleep quality has been associated with poorer social functioning in schizophrenia.15,16 Social dysfunction should also be considered a broad clinical domain rather than the consequence of a single symptom cluster. A systematic review and meta-analysis found that poorer social functioning in schizophrenia was associated with depressive symptoms, negative symptoms, positive symptoms, disorganization, and general psychopathology.17 Poorer social role functioning, negative social appraisals, and loneliness have also been associated with suicidal ideation or suicide risk in schizophrenia-spectrum samples.18–20 Suicidal ideation is common in schizophrenia. A worldwide systematic review and meta-analysis estimated lifetime and point prevalences of suicidal ideation of 34.5% and 29.9%, respectively, underscoring the importance of evaluating suicidality as a clinically meaningful correlate rather than a peripheral outcome.21 Depressive symptoms are consistently associated with suicidality in this population.22,23 These observations support examining the domains together, but do not establish a single temporal order.
The present cross-sectional study had two aims. First, we examined sex differences in depressive symptoms and related demographic and clinical characteristics among rural adults with schizophrenia. Second, we examined the cross-sectional associations among insomnia severity, social dysfunction, suicidality, and depressive symptoms using an exploratory indirect-association model, and explored whether the estimated indirect associations differed by sex. We hypothesized that insomnia severity would be associated with depressive symptoms and that the observed association would be statistically consistent with indirect associations involving social dysfunction and suicidality. All findings were interpreted as associations rather than evidence of temporal ordering or causality.
Materials and Methods
Participants
This multicenter cross-sectional survey was conducted from September to October 2022 in rural communities in the Chaohu region of Hefei, Anhui Province, China. The sampling frame was the Severe Mental Disorder Management Database System of Chaohu City, which contained more than 3,000 registered service users. Participants were selected using stratified sampling by township and village to improve geographic representativeness and were recruited from six suburban districts and 12 townships.
Paper questionnaires were administered at participants’ residences using standardized verbal instructions. Assessments were conducted by psychiatrists and graduate students who received unified training. The mean completion time was approximately 60 minutes. Standardized assistance was available for participants with limited formal education, either from the attending physician or an accompanying family member. Participants could discontinue the assessment at any time. If marked distress or impulsive behavior occurred, the assessment was stopped and supportive stabilization was provided.
A total of 1,205 questionnaires were distributed. Questionnaires with incomplete data for key variables (n = 135), questionnaires from individuals who declined to complete the assessment (n = 78), and questionnaires from individuals unable to complete the assessment because of cognitive impairment or severe psychiatric symptoms (n = 61) were excluded. The final analytic sample included 931 participants, giving a valid-response rate of 77.3%. Participant flow is shown in Figure 1.
Figure 1.
Participant Flow.
Eligible participants were aged 18–75 years, lived in rural Chaohu, had schizophrenia diagnosed according to the International Classification of Diseases, Tenth Revision (ICD-10),24 and were able to complete the assessment. Diagnoses were verified by psychiatrists through review of hospital medical records and management-database records. Clinical stability was defined as a change of <5% in the dosage of the primary psychotropic medication during the preceding 3 months. Participants were excluded if they had neurological disorders or substance abuse, severe physical illness, pregnancy or breastfeeding, or acute alcohol/substance-related risk symptoms.
Demographic and Clinical Characteristics
Demographic and clinical information was collected using a study-specific questionnaire. Variables included age, sex, body mass index (BMI), marital status, educational level, smoking status, alcohol-use status, age at onset, illness duration, number of hospitalizations, physical illness, family history of psychiatric disorders, and exercise frequency. Smoking status, alcohol-use status, and exercise frequency were assessed by self-report. Smoking and alcohol use were classified as non-use, current use (any use in the past 30 days), or former use (a history of use but no use in the past 30 days). Exercise frequency was classified as 0, 1–2, 3–5, or >5 days per week on the basis of moderate- or vigorous-intensity activity lasting at least 30 minutes per session during the preceding week.
Depressive Symptoms
Depressive symptoms during the preceding 2 weeks were assessed using the 9-item Patient Health Questionnaire (PHQ-9).25 Items are scored from 0 (not at all) to 3 (nearly every day), yielding a total score of 0–27; higher scores indicate more severe depressive symptoms. The Chinese PHQ-9 has acceptable reliability and validity.26 For descriptive analyses and sex-stratified logistic regression, scores ≤4 indicated no/minimal depressive symptoms and scores ≥5 indicated at least mild depressive symptoms. This operational classification was not used to diagnose depressive disorder. The continuous PHQ-9 score was used as the outcome in the exploratory indirect-association analyses.
Because PHQ-9 item 3 assesses sleep disturbance and item 9 assesses thoughts of death or self-harm, the primary indirect-association analysis was repeated using a non-overlapping PHQ-7 score that excluded these two items. The PHQ-7 score ranged from 0 to 21.
Insomnia
Insomnia severity during the preceding 2 weeks was assessed using the 7-item Insomnia Severity Index (ISI).27 Items are scored from 0 to 4, producing a total score of 0–28; higher scores indicate more severe insomnia. A score ≥8 indicated clinically significant insomnia. The Chinese ISI has shown acceptable psychometric properties.28
Suicidality
Suicidality during the preceding year was assessed with three questions addressing suicidal ideation, suicide planning, and suicide attempt. The item responses were summed to create a composite suicidality score; higher scores indicate a greater number of endorsed suicidality components.29
Social Functioning
Social functioning was assessed with the Social Disability Screening Schedule (SDSS), a Chinese simplified version of the World Health Organization Disability Assessment Schedule.30 The SDSS comprises 10 items rated from 0 (no or minimal impairment) to 2 (severe impairment); higher total scores indicate greater social dysfunction. Scores coded as 9 (not applicable) were not included in the total-score calculation. A total score ≥2 indicated social disability.
Statistical Analysis
Analyses were conducted using IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA), GraphPad Prism version 10.1.2 (GraphPad Software, Boston, MA, USA), and the PROCESS macro version 5.0. Categorical variables are reported as frequencies and percentages. Continuous variables are reported as mean ± standard deviation. Between-group comparisons were performed using Pearson chi-square tests for categorical variables and Mann–Whitney U-tests for continuous variables. All tests were two-sided, and P < 0.05 was considered statistically significant.
Sex-stratified binary logistic regression models were used to examine factors associated with at least mild depressive symptoms, defined as PHQ-9 score ≥5 versus ≤4. Separate models were fitted for female and male participants. Variables that differed by depressive-symptom status within each sex were entered into the corresponding sex-specific model, together with ISI score, suicidality score, and SDSS score. In the female model, the entered variables were physical illness, family history of psychiatric disorders, age, exercise frequency, illness duration, ISI score, suicidality score, and SDSS score. In the male model, the entered variables were physical illness, exercise frequency, BMI, ISI score, suicidality score, and SDSS score. Odds ratios (ORs) and 95% confidence intervals (CIs) are reported.
Exploratory cross-sectional indirect-association analyses were conducted using PROCESS.31 In Model 6, ISI score was specified as X, SDSS score as the first mediator (M1), suicidality score as the second mediator (M2), and continuous PHQ-9 score as Y. In Model 83, sex was specified as a moderator of the ISI-to-SDSS path. Indirect associations were estimated from 5,000 bootstrap resamples with percentile 95% CIs; an indirect association was considered statistically supported when its CI did not include zero. These analyses were interpreted as theory-informed exploratory associations, not as evidence of temporal ordering or causality.
Sensitivity Analyses
To assess possible measurement overlap, the serial indirect-association analysis was repeated using the non-overlapping PHQ-7 score as the outcome. The analytic sample, predictor, mediators, and unadjusted model specification were unchanged. We used 5,000 nonparametric bootstrap resamples to derive percentile 95% CIs for the direct and indirect associations.
Results
Participant Characteristics by Sex
Of the 931 participants, 457 (49.1%) were male and 474 (50.9%) were female. Demographic characteristics differed by sex for religion (P=0.007), educational level (P<0.001), marital status (P<0.001), smoking status (P<0.001), alcohol-use status (P<0.001), and exercise frequency (P=0.005; Table 1).
Table 1.
Demographic Characteristics of Rural Adults with Clinically Stable Schizophrenia by Sex
| Variable | Male (n=457) | Female (n=474) | χ2 | P |
|---|---|---|---|---|
| Religion: | 7.291 | 0.007 | ||
| Yes | 54 (11.8%) | 86 (18.1%) | ||
| No | 403 (88.2%) | 388 (81.9%) | ||
| Physical illness: | 3.776 | 0.052 | ||
| Yes | 156 (34.1%) | 191 (40.3%) | ||
| No | 301 (65.9%) | 283 (59.7%) | ||
| Family history of psychiatric disorders: | 1.690 | 0.214 | ||
| Yes | 81 (17.7%) | 100 (21.1%) | ||
| No | 376 (82.3%) | 374 (78.9%) | ||
| Education level: | 14.655 | <0.001 | ||
| ≤Middle school | 363 (79.4%) | 420 (88.6%) | ||
| High school | 73 (16.0%) | 42 (8.9%) | ||
| >High school | 21 (4.6%) | 12 (2.5%) | ||
| Marital status: | 275.860 | <0.001 | ||
| Never married | 264 (57.8%) | 48 (10.1%) | ||
| Married | 134 (29.3%) | 361 (76.2%) | ||
| Divorced | 53 (11.6%) | 33 (7.0%) | ||
| Widowed | 6 (1.3%) | 32 (6.8%) | ||
| Smoking status: | 197.805 | <0.001 | ||
| No | 278 (60.8%) | 464 (97.9%) | ||
| Current | 155 (33.9%) | 10 (2.1%) | ||
| Former | 24 (5.3%) | 0 (0.0%) | ||
| Alcohol-use status: | 41.626 | <0.001 | ||
| No | 389 (85.1%) | 460 (97.0%) | ||
| Current | 17 (3.7%) | 2 (0.4%) | ||
| Former | 51 (11.2%) | 12 (2.5%) | ||
| Exercise frequency, days/week: | 12.941 | 0.005 | ||
| 0 | 288 (63.0%) | 309 (65.2%) | ||
| 1–2 | 57 (12.5%) | 80 (16.9%) | ||
| 3–5 | 28 (6.1%) | 34 (7.2%) | ||
| >5 | 84 (18.4%) | 51 (10.8%) |
Notes: Values are n (% within sex). Pearson chi-square tests were used. Definitions of smoking, alcohol use, and exercise frequency are provided in Methods.
Compared with male participants, female participants were older (mean ± SD, 50.89 ± 12.43 vs 46.46 ± 11.94 years; P<0.001), had a higher BMI (25.29 ± 4.58 vs 24.41 ± 3.85 kg/m2; P=0.003), and had a later age at onset (26.76 ± 13.35 vs 24.37 ± 12.14 years; P=0.038). Female participants also had higher PHQ-9 scores (7.88 ± 6.30 vs 6.64 ± 5.93; P=0.002), ISI scores (6.27 ± 7.99 vs 5.12 ± 7.57; P=0.004), suicidality scores (0.38 ± 0.84 vs 0.26 ± 0.65; P=0.005), and SDSS scores (11.41 ± 5.37 vs 9.77 ± 4.99; P<0.001). Illness duration and number of hospitalizations did not differ by sex (both P>0.05; Table 2).
Table 2.
Clinical Characteristics of Rural Adults with Clinically Stable Schizophrenia by Sex
| Variable | Male (n=457) | Female (n=474) | Z | P |
|---|---|---|---|---|
| Age, years | 46.46 ± 11.94 | 50.89 ± 12.43 | −5.679 | <0.001 |
| BMI, kg/m2 | 24.41 ± 3.85 | 25.29 ± 4.58 | −2.941 | 0.003 |
| Age at onset, years | 24.37 ± 12.14 | 26.76 ± 13.35 | −2.070 | 0.038 |
| Illness duration, years | 22.27 ± 12.50 | 23.98 ± 13.25 | −1.843 | 0.065 |
| Hospitalizations, n | 2.89 ± 3.98 | 3.21 ± 4.59 | −0.939 | 0.348 |
| PHQ-9 score | 6.64 ± 5.93 | 7.88 ± 6.30 | −3.033 | 0.002 |
| ISI score | 5.12 ± 7.57 | 6.27 ± 7.99 | −2.851 | 0.004 |
| Suicidality score | 0.26 ± 0.65 | 0.38 ± 0.84 | −2.809 | 0.005 |
| SDSS score | 9.77 ± 4.99 | 11.41 ± 5.37 | −4.745 | <0.001 |
Note: Values are mean ± SD. Z values are from Mann–Whitney U-tests. SDSS responses coded as 9 (not applicable) were not included in the total-score calculation.
Abbreviations: BMI, body mass index; PHQ-9, Patient Health Questionnaire-9; ISI, Insomnia Severity Index; SDSS, Social Disability Screening Schedule.
Depressive-Symptom Status Within Each Sex
Among female participants, 181 (38.2%) had no/minimal depressive symptoms (PHQ-9 ≤4) and 293 (61.8%) had at least mild depressive symptoms (PHQ-9 ≥5). The groups differed in physical illness (P<0.001), family history of psychiatric disorders (P=0.023), exercise frequency (P=0.015), age (P<0.001), and illness duration (P=0.049). ISI, suicidality, and SDSS scores were higher among participants with at least mild depressive symptoms (all P<0.001; Table 3).
Table 3.
Characteristics of Female Participants by Depressive-Symptom Status
| Variable | No/Minimal (n=181) |
At Least Mild (n=293) |
χ2/Z | P |
|---|---|---|---|---|
| Religion: | 0.042 | 0.837 | ||
| Yes | 32 (17.7%) | 54 (18.4%) | ||
| No | 149 (82.3%) | 239 (81.6%) | ||
| Physical illness: | 10.654 | <0.001 | ||
| Yes | 56 (30.9%) | 135 (46.1%) | ||
| No | 125 (69.1%) | 158 (53.9%) | ||
| Family history of psychiatric disorders: | 5.172 | 0.023 | ||
| Yes | 48 (26.5%) | 52 (17.7%) | ||
| No | 133 (73.5%) | 241 (82.3%) | ||
| Education level: | 5.097 | 0.078 | ||
| ≤Middle school | 153 (84.5%) | 267 (91.1%) | ||
| High school | 21 (11.6%) | 21 (7.2%) | ||
| >High school | 7 (3.9%) | 5 (1.7%) | ||
| Marital status: | 3.229 | 0.358 | ||
| Never married | 22 (12.2%) | 26 (8.9%) | ||
| Married | 131 (72.4%) | 230 (78.5%) | ||
| Divorced | 16 (8.8%) | 17 (5.8%) | ||
| Widowed | 12 (6.6%) | 20 (6.8%) | ||
| Exercise frequency: | 10.483 | 0.015 | ||
| 0 | 105 (58.0%) | 204 (69.6%) | ||
| 1–2 | 34 (18.8%) | 46 (15.7%) | ||
| 3–5 | 13 (7.2%) | 21 (7.2%) | ||
| >5 | 29 (16.0%) | 22 (7.5%) | ||
| Age, years | 47.99 ± 11.91 | 52.69 ± 12.43 | −4.326 | <0.001 |
| BMI, kg/m2 | 25.61 ± 4.47 | 25.10 ± 4.64 | −1.270 | 0.204 |
| Age at onset, years | 25.21 ± 11.50 | 27.71 ± 14.31 | −1.324 | 0.186 |
| Illness duration, years | 22.49 ± 12.54 | 24.90 ± 13.60 | −1.966 | 0.049 |
| Hospitalizations, n | 3.18 ± 5.00 | 3.23 ± 4.32 | −0.067 | 0.946 |
| ISI score | 1.69 ± 3.46 | 9.11 ± 8.65 | −8.906 | <0.001 |
| Suicidality score | 0.09 ± 0.38 | 0.56 ± 0.99 | −7.164 | <0.001 |
| SDSS score | 9.43 ± 5.71 | 12.62 ± 4.76 | −5.972 | <0.001 |
Notes: Values are n (% within depressive-symptom group) or mean ± SD. The PHQ-9 grouping is an operational indicator of depressive-symptom severity, not a clinical diagnosis. Pearson chi-square tests and Mann–Whitney U-tests were used as appropriate.
Among male participants, 202 (44.2%) had no/minimal depressive symptoms and 255 (55.8%) had at least mild depressive symptoms. The groups differed in physical illness (P=0.030), exercise frequency (P<0.001), and BMI (P=0.048). ISI, suicidality, and SDSS scores were higher among men with at least mild depressive symptoms (all P<0.001; Table 4).
Table 4.
Characteristics of Male Participants by Depressive-Symptom Status
| Variable | No/Minimal (n=202) |
At Least Mild (n=255) |
χ2/Z | P |
|---|---|---|---|---|
| Religion: | 0.109 | 0.741 | ||
| Yes | 25 (12.4%) | 29 (11.4%) | ||
| No | 177 (87.6%) | 226 (88.6%) | ||
| Physical illness: | 4.735 | 0.030 | ||
| Yes | 58 (28.7%) | 98 (38.4%) | ||
| No | 144 (71.3%) | 157 (61.6%) | ||
| Family history of psychiatric disorders: | 0.880 | 0.348 | ||
| Yes | 32 (15.8%) | 49 (19.2%) | ||
| No | 170 (84.2%) | 206 (80.8%) | ||
| Education level: | 3.548 | 0.170 | ||
| ≤Middle school | 154 (76.2%) | 209 (82.0%) | ||
| High school | 35 (17.3%) | 38 (14.9%) | ||
| >High school | 13 (6.4%) | 8 (3.1%) | ||
| Marital status: | 5.562 | 0.135 | ||
| Never married | 129 (63.9%) | 135 (52.9%) | ||
| Married | 51 (25.2%) | 83 (32.5%) | ||
| Divorced | 20 (9.9%) | 33 (12.9%) | ||
| Widowed | 2 (1.0%) | 4 (1.6%) | ||
| Exercise frequency: | 26.799 | <0.001 | ||
| 0 | 103 (51.0%) | 185 (72.5%) | ||
| 1–2 | 38 (18.8%) | 19 (7.5%) | ||
| 3–5 | 12 (5.9%) | 16 (6.3%) | ||
| >5 | 49 (24.3%) | 35 (13.7%) | ||
| Age, years | 46.38 ± 11.52 | 46.53 ± 12.28 | −0.290 | 0.772 |
| BMI, kg/m2 | 24.78 ± 3.79 | 24.12 ± 3.88 | −1.976 | 0.048 |
| Age at onset, years | 24.65 ± 11.52 | 24.15 ± 12.61 | −0.651 | 0.515 |
| Illness duration, years | 22.18 ± 13.01 | 22.33 ± 12.10 | −0.571 | 0.568 |
| Hospitalizations, n | 2.92 ± 3.19 | 2.86 ± 4.52 | −1.755 | 0.079 |
| ISI score | 1.64 ± 3.48 | 7.87 ± 8.72 | −7.744 | <0.001 |
| Suicidality score | 0.10 ± 0.43 | 0.38 ± 0.77 | −4.906 | <0.001 |
| SDSS score | 7.65 ± 4.80 | 11.44 ± 4.49 | −7.961 | <0.001 |
Notes: Values are n (% within depressive-symptom group) or mean ± SD. The PHQ-9 grouping is an operational indicator of depressive-symptom severity, not a clinical diagnosis. Pearson chi-square tests and Mann–Whitney U-tests were used as appropriate.
Sex-Stratified Correlates of Depressive-Symptom Status
In the female model, higher ISI score (OR per point, 1.203; 95% CI, 1.142–1.267; P<0.001), higher suicidality score (OR per point, 3.425; 95% CI, 2.019–5.812; P<0.001), and higher SDSS score (OR per point, 1.112; 95% CI, 1.061–1.165; P<0.001) were associated with greater odds of at least mild depressive symptoms. A family history of psychiatric disorders was associated with lower odds of at least mild depressive symptoms (OR, 0.548; 95% CI, 0.308–0.976; P=0.041; Table 5).
Table 5.
Multivariable Logistic Regression Associated with at Least Mild Depressive Symptoms in Female Participants
| Variable | P | OR | 95% CI |
|---|---|---|---|
| Physical illness, yes vs no | 0.093 | 1.538 | 0.930–2.542 |
| Family history of psychiatric disorders, yes vs no | 0.041 | 0.548 | 0.308–0.976 |
| Age, per year | 0.556 | 1.007 | 0.984–1.031 |
| Exercise frequency: | |||
| 1–2 vs 0 | 0.727 | 1.117 | 0.599–2.085 |
| 3–5 vs 0 | 0.720 | 0.846 | 0.338–2.115 |
| >5 vs 0 | 0.288 | 0.639 | 0.280–1.460 |
| Illness duration, per year | 0.994 | 1.000 | 0.979–1.021 |
| ISI score, per point | <0.001 | 1.203 | 1.142–1.267 |
| Suicidality score, per point | <0.001 | 3.425 | 2.019–5.812 |
| SDSS score, per point | <0.001 | 1.112 | 1.061–1.165 |
Notes: Outcome: at least mild depressive symptoms (PHQ-9 ≥5) versus no/minimal symptoms (PHQ-9 ≤4). The model includes the variables displayed.
Abbreviations: OR, odds ratio; CI, confidence interval; ISI, Insomnia Severity Index; SDSS, Social Disability Screening Schedule.
In the male model, higher ISI score (OR per point, 1.173; 95% CI, 1.117–1.232; P<0.001), higher suicidality score (OR per point, 2.318; 95% CI, 1.373–3.911; P=0.002), and higher SDSS score (OR per point, 1.159; 95% CI, 1.102–1.218; P<0.001) were associated with greater odds of at least mild depressive symptoms. Exercise 1–2 days per week, compared with no exercise, was associated with lower odds of at least mild depressive symptoms (OR, 0.341; 95% CI, 0.169–0.691; P=0.003; Table 6).
Table 6.
Multivariable Logistic Regression Associated with at Least Mild Depressive Symptoms in Male Participants
| Variable | P | OR | 95% CI |
|---|---|---|---|
| Physical illness, yes vs no | 0.264 | 1.321 | 0.811–2.151 |
| Exercise frequency: | |||
| 1–2 vs 0 | 0.003 | 0.341 | 0.169–0.691 |
| 3–5 vs 0 | 0.969 | 0.980 | 0.358–2.689 |
| >5 vs 0 | 0.376 | 0.756 | 0.407–1.404 |
| BMI, per kg/m2 | 0.521 | 0.981 | 0.925–1.040 |
| ISI score, per point | <0.001 | 1.173 | 1.117–1.232 |
| Suicidality score, per point | 0.002 | 2.318 | 1.373–3.911 |
| SDSS score, per point | <0.001 | 1.159 | 1.102–1.218 |
Notes: Outcome: at least mild depressive symptoms (PHQ-9 ≥5) versus no/minimal symptoms (PHQ-9 ≤4). The model includes the variables displayed.
Abbreviations: OR, odds ratio; CI, confidence interval; BMI, body mass index; ISI, Insomnia Severity Index; SDSS, Social Disability Screening Schedule.
Exploratory Cross-Sectional Indirect-Association Analyses
In the primary Model 6 analysis, the direct association between ISI score and PHQ-9 score was b=0.388 (95% bootstrap CI, 0.345–0.431). The total indirect association through SDSS and suicidality scores was 0.082 (95% CI, 0.059–0.108). The estimated indirect associations via SDSS alone and suicidality alone were 0.042 (95% CI, 0.028–0.057) and 0.038 (95% CI, 0.021–0.058), respectively. The estimated serial indirect association through both SDSS and suicidality was 0.002 (95% CI, −0.0001 to 0.005); because its CI included zero, this serial association was not statistically supported (Table 7 and Figure 2).
Table 7.
Exploratory Cross-Sectional Indirect-Association Estimates Linking Insomnia Severity with Depressive-Symptom Score
| Pathway | Estimate | Bootstrap 95% CI |
|---|---|---|
| Direct association: ISI → PHQ-9 | 0.388 | 0.345 to 0.431 |
| Total indirect association | 0.082 | 0.059 to 0.108 |
| Indirect via SDSS | 0.042 | 0.028 to 0.057 |
| Indirect via suicidality | 0.038 | 0.021 to 0.058 |
| Serial indirect via SDSS and suicidality | 0.002 | −0.0001 to 0.005 |
Notes: Unstandardized estimates from the exploratory Model 6 analysis with 5,000 percentile bootstrap resamples (n=931). The serial indirect-association CI includes zero and is not statistically supported.
Abbreviations: ISI, Insomnia Severity Index; SDSS, Social Disability Screening Schedule; PHQ-9, Patient Health Questionnaire-9.
Figure 2.
Exploratory cross-sectional indirect-association model linking insomnia severity with depressive-symptom score.
Notes: Unstandardized path coefficients. Blue arrows indicate statistically significant paths (all P<0.001); the gray arrow indicates the non-significant path from SDSS to suicidality (d21 = 0.009, P=0.065). Indirect associations use 5,000 percentile bootstrap resamples (n=931). Indirect association via SDSS = 0.042 (95% CI, 0.028 to 0.057); Indirect association via suicidality = 0.038 (95% CI, 0.021 to 0.058); Serial indirect association = 0.002 (95% CI, −0.0001 to 0.005), not supported; Total indirect association = 0.082 (95% CI, 0.059 to 0.108).
Abbreviations: ISI, Insomnia Severity Index; SDSS, Social Disability Screening Schedule; PHQ-9, Patient Health Questionnaire-9.
In the Model 83 analysis, the index of moderated mediation for the indirect association via SDSS was 0.021 (95% bootstrap CI, −0.008 to 0.050), and the index for the serial indirect association was 0.003 (95% CI, −0.001 to 0.009). Neither CI excluded zero (Table 8).
Table 8.
Conditional Indirect-Association Estimates by Sex
| Pathway | Sex | Estimate | Bootstrap 95% CI |
|---|---|---|---|
| Indirect via SDSS | Female | 0.031 | 0.016 to 0.050 |
| Indirect via SDSS | Male | 0.052 | 0.030 to 0.077 |
| Index of moderated mediation (via SDSS) | — | 0.021 | −0.008 to 0.050 |
| Serial indirect via SDSS and suicidality | Female | 0.001 | −0.003 to 0.004 |
| Serial indirect via SDSS and suicidality | Male | 0.004 | 0.001 to 0.008 |
| Index of moderated mediation (serial) | — | 0.003 | −0.001 to 0.009 |
Notes: Unstandardized estimates from exploratory Model 83 with 5,000 percentile bootstrap resamples (n=931). Both indices of moderated mediation include zero; therefore, the present analysis does not provide evidence that sex moderates these indirect associations.
Abbreviations: ISI, Insomnia Severity Index; SDSS, Social Disability Screening Schedule; PHQ-9, Patient Health Questionnaire-9.
Sensitivity Analysis Excluding Overlapping PHQ-9 Items
When PHQ-9 item 3 (sleep disturbance) and item 9 (suicidality) were removed, the direct association between ISI score and the non-overlapping PHQ-7 score remained (b=0.254; 95% percentile bootstrap CI, 0.215–0.293). The total indirect association also remained (0.071; 95% CI, 0.051–0.094), as did the indirect associations via SDSS (0.039; 95% CI, 0.027–0.053) and suicidality (0.030; 95% CI, 0.016–0.047). The serial indirect association was not statistically supported (0.002; 95% CI, −0.0001 to 0.004; Supplementary Table S1).
Discussion
Women reported higher depressive-symptom, insomnia, suicidality, and social-dysfunction scores than men. In both sex-stratified models, higher insomnia, suicidality, and social-dysfunction scores were associated with greater odds of at least mild depressive symptoms. The primary exploratory analysis supported direct and two single-mediator indirect associations between insomnia severity and PHQ-9 depressive-symptom score. It did not support the hypothesized serial association through both social dysfunction and suicidality, and sex did not moderate the estimated indirect associations. The same pattern was observed when overlapping PHQ-9 sleep and suicidality items were removed.
The higher symptom and social-dysfunction scores among women occurred alongside older age and later illness onset. This pattern is broadly compatible with literature indicating that sex-related differences in schizophrenia may involve illness onset, affective symptoms, and functional outcomes, although findings are heterogeneous.6 The current results do not show that female sex causes greater symptom burden or that the estimated associations operate differently by sex. The absence of moderated mediation and the observed age difference both warrant caution.
The concurrent associations in this study are consistent with the wider literature. Sleep disturbance has been associated with poorer social relationships and functioning in psychosis and schizophrenia.15,16 Poor social role functioning, negative social appraisals, and loneliness have been associated with suicidality,18–20 while depressive symptoms are consistently associated with suicidality in schizophrenia-spectrum populations.22,23 The present study extends prior work from our group, which evaluated insomnia, depressed mood, stigma, social functioning, aggression, suicidality, and quality of life in separate cross-sectional analyses.10–13 It does not establish a causal mechanism or a temporal sequence among these domains. Long-term evidence also indicates that social functioning follows heterogeneous but often persistent trajectories across psychotic disorders. Such evidence supports the clinical importance of social functioning but does not specify a single temporal pathway linking sleep disturbance, social dysfunction, suicidality, and depressive symptoms.32
The sensitivity analysis reduces concern that the observed direct and single-mediator indirect associations were solely attributable to overlapping PHQ-9 content. However, it does not remove shared-method bias. The lack of support for the serial association in both the primary and sensitivity analyses means that the ordering from insomnia to social dysfunction to suicidality to depressive symptoms should not be presented as an established chain. Alternative or reciprocal associations are plausible, and medication exposure, illness severity, negative symptoms, physical comorbidity, stigma, and socioeconomic disadvantage may have contributed to the observed pattern. In particular, depressive and negative symptoms can overlap phenomenologically. Low mood, suicidal ideation, and pessimism may be relatively more specific to depression, whereas alogia and blunted affect may be relatively more specific to negative symptoms; anhedonia, anergia, and avolition may occur in both domains. Future studies should therefore include detailed negative-symptom and illness-severity assessments.33
Limitations
Firstly, the cross-sectional design precludes temporal and causal inference. More specifically, cross-sectional mediation-type analyses can yield estimates that differ substantially from longitudinal indirect effects. The present indirect-association findings should therefore be regarded as theory-informed descriptions of covariation, pending longitudinal studies that compare competing temporal models.34 Secondly, medication exposure, illness severity, negative symptoms, physical comorbidities, stigma, socioeconomic conditions, and other potential confounders were not comprehensively measured or adjusted for. Thirdly, self-reported measures, including past-year suicidality, may be affected by recall, reporting, and social-desirability bias. Finally, the sample comprised clinically stable, registered rural residents of the Chaohu region who could complete the assessment, which limits generalizability to other settings and acutely unwell populations.
Longitudinal studies with repeated assessments, non-overlapping measures of depressive symptoms, and more comprehensive clinical and social covariates are needed to compare competing temporal models. Replication in urban, inpatient, and acutely unwell populations would clarify generalizability.
Clinical Implications
Within these limits, the findings support assessing sleep complaints, social functioning, suicidality, and depressive symptoms together during routine follow-up of rural adults with clinically stable schizophrenia. This approach may help identify individuals with greater overall symptom burden and prompt individualized clinical review, including suicide-risk evaluation when indicated.
Conclusion
In this rural sample of adults with schizophrenia, women reported higher depressive-symptom, insomnia, suicidality, and social-dysfunction scores than men. Insomnia, social dysfunction, and suicidality were cross-sectionally associated with depressive symptoms in both sexes. The exploratory analysis supported direct and single-mediator indirect associations but not the serial association through both social dysfunction and suicidality.
Acknowledgments
The authors thank all participants for their time and contribution.
Funding Statement
This study was supported by the Key Project of Research Fund of Anhui Institute of Translational Medicine (2023zhyx-B18), the Hengrui innovative drug research project of Anhui Provincial Health Commission (AHWJ2023BAc10004), the Key Research Project on Enhancing Medical Service Capabilities of County Medical Institutions of National Health Commission Hospital Management Research Institute (PS202518), the Anhui Province Traditional Chinese Medicine Inheritance and Innovation Research Program (2025CCCX003), the Huainan Science and Technology Plan Project (2023A286), and the Research Fund of Anhui Medical University (2023xkj064). The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.
Data Sharing Statement
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
Ethics Approval and Informed Consent
The study was approved by the Ethics Committee of Chaohu Hospital of Anhui Medical University (KYXM-202212-013). Written informed consent was obtained from all participants or, where applicable, from their legal guardians. The study was conducted in accordance with the Declaration of Helsinki.
Author Contributions
All authors made a significant contribution to the work reported; participated in conception, study design, execution, data acquisition, analysis, interpretation, drafting, revision, or critical review; approved the final version; agreed on the journal to which the article was submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare no conflicts of interest in this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.