Abstract
Background
Social isolation and loneliness, objective and subjective features of dysfunctional social relationships, are more prevalent in patients with schizophrenia (SCZ) than in the general population. This study aimed to explore sex differences in loneliness and social isolation among Chinese chronic SCZ patients, and to investigate their relationships with psychiatric symptoms and cognitive functioning.
Methods
A total of 323 SCZ patients, comprising 136 males and 187 females, were recruited. Psychopathology, cognitive functioning, loneliness, social isolation were assessed using the Positive and Negative Syndrome Scale (PANSS), the Repeated Battery for Assessment of Neuropsychological Status (RBANS), the UCLA (University of California, Los Angeles) Loneliness Scale (Version 3) and the Social Isolation Index (ISI). Multiple linear regression models were conducted to test the independent, relative, and synergistic efects of loneliness and social isolation on psychiatric symptoms and cognitive performance for male and female patients separately.
Results
Male patients exhibited higher UCLA loneliness scale scores and social isolation scores compared to female patients (ps < 0.05). In male patients, both loneliness and social isolation significantly predicted PANSS total scores (ps< 0.01), negative subscale scores (ps < 0.05) and general psychopathology subscale scores (ps < 0.05). For female patients, loneliness (not social isolation) significantly predicted immediate memory (p < 0.001), language (p = 0.013), delayed memory (p = 0.017), and RBANS total scores (p = 0.002). Further examination of loneliness components in female patients revealed that personal feelings of isolation were negatively associated with language (r = -0.21, p = 0.001) and a negative correlation exists between lack of collective connectedness and delayed memory (r = -0.19, p = 0.048).
Conclusion
Loneliness and social isolation are more pronounced in male SCZ patients than in female patients. Both loneliness and social isolation are positively related to psychiatric symptoms in male patients, while loneliness is negatively associated with cognitive functioning in female patients.
Keywords: Schizophrenia, Loneliness, Social isolation, Psychiatric symptom, Cognitive functioning
Highlights
Loneliness and social isolation exhibit higher prevalence in male patients with schizophrenia (SCZ) compared to females.
Positive relationships are observed between loneliness, social isolation and psychiatric symptoms in male patients.
Loneliness demonstrates a negative relationship with cognitive functioning in female patients.
Introduction
Schizophrenia (SCZ) stands as a profound psychiatric disorder, with a global lifetime prevalence of 0.48% and a notable 0.83% prevalence in China [1, 2]. Characterized by positive symptoms such as hallucinations and delusions, negative symptoms like social withdrawal and lack of motivation, as well as cognitive impairments, SCZ patients often found themselves unable to engage in normal interpersonal interactions, leading to prolonged social disconnection and an increased susceptibility to feelings of isolation [3]. In addition, the stigma and discrimination faced by SCZ patients exacerbate challenges, resulting in compromised interpersonal relationships, diminished social networks, and further impeding the overall social functions of SCZ individuals [4, 5]. These multifaceted factors contribute to the pervasive experiences of social isolation, loneliness, and despair among SCZ patients, impacting their treatment outcomes and prognosis [6].
Loneliness, a psychological condition marked by the subjective suffering arising from disparities between desired and actual relationships [7], contrasts with social isolation, an objectively quantifiable variable encompassing aspects such as living alone and limited social ties [8]. These objective and subjective components represent dysfunctional social connections. Previous studies have reported markedly elevated self-reported annual loneliness rates (76-80%) among SCZ patients compared to the general population (35%) [9]. However, the majority of existing research has predominantly focused on the subjective experience of loneliness in SCZ patients, and less concern has been paid to the social isolation of chronic SCZ patients. Meta-analysis suggested a pivotal role of loneliness in the onset and persistence of psychotic symptoms [10] and is associated with the severity of hallucinations and paranoid thinking in SCZ [11, 12], suggesting that loneliness may be associated with the chronicity of the disease. Additionally, while studies in the general population underscore the strong relationship of both loneliness and social isolation with cognitive impairment across various domains [13], comparable research in the context of SCZ is notably scarce.
Sex differences emerge as a focal point of concern, considering that women often exhibit higher levels of social support and a greater inclination to engage in social activities. However, women may also be more sensitive to interpersonal relationships, with poor social connections having a potentially greater negative impact on women’s mental health compared to men’s [14]. Consequently, variations in loneliness and social isolation may occur based on sex, further compounded by significant sex differences in the incidence, age of onset, risk factors, symptoms and course of the SCZ. Notably, the incidence of SCZ is higher in males [15], while female patients tend to manifest more positive symptoms [16]. Sex differences in cognitive abilities in the context of SCZ remain inconclusive [17]. Some studies suggest that prior to the onset of SCZ, males may exhibit greater social isolation, withdrawal, lower educational attainment, reduced ability to maintain friendships and sexual relationships, and a lower likelihood of being married at the time of the first hospitalization compared to females [17]. However, the underlying mechanism of these sex differences remain unknown.
Given the absence of comprehensive studies simultaneously exploring sex differences in loneliness and social isolation within the SCZ population, the study aims to explore loneliness and social isolation in a Chinese chronic SCZ population. The primary objective is to scrutinize (a) the impact of sex on loneliness and social isolation among SCZ patients and (b) the relationship between loneliness and social isolation and psychiatric symptoms and cognitive functioning.
Methods
Participants
A total of 323 SCZ patients (136 males and 187 females) participated in our cross-sectional study conducted at Tianjin Anding Hospital, China, from September 2022 to November 2023. These patients came from both outpatient and inpatient settings. Inclusion criteria were as follows (1) a diagnose of SCZ according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria; (2) Han Chinese ethnicity; (3) a history of SCZ for a minimum of 2 years; and (4) maintenance on a stabilized dose of antipsychotic medication for at least 3 months before enrollment. Exclusion criteria included: (1) presence of organic brain disease or brain injury; (2) severe physical, infectious, neurological, or immune system disease; (3) pregnancy or lactation; and (4) a history of alcohol or drug abuse or dependence, with the exception of previous nicotine use. Antipsychotic medication dosages were converted to chlorpromazine (CPZ) equivalents [18]. Clinical trial numbers do not applicable to this article. The study protocol received approval from the Institutional Review Board of Tianjin Anding Hospital (ID: 2022-09), and all participants provided written informed consent.
Measures
Demographic factors and general variables were obtained through self-designed questionnaires. Demographic factors included age (years), education level (below high school or high school and above), and duration of condition (years). Smoke and being the only child were dichotomously defined as yes or no. Body mass index (BMI) was calculated using body weight and height (kg/m2). The medical history of hypertension and diabetes mellitus was collected through patients’ self-reporting, review of medical records, and other reliable sources of data. Four experienced researchers underwent comprehensive training in the assessment of the scales before the study, including the Positive and Negative Syndrome Scale (PANSS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). To ensure the reliability of their evaluations, these researches underwent monthly reassessments, and their correlation coefficients were monitored to be consistently above 0.8. This rigorous process aimed to maintain high consistency and reliability, ensuring strong agreement among raters throughout the study. Minimal missing data in this study were addressed by using complete-case analysis, relying on comprehensive medical records and meticulous data collection practices.
Clinical assessment
The Positive and Negative Syndrome Scale (PANSS), widely used for psychiatric symptoms assessment [19]. The PANSS consists of 30 items, each with a specific definition and a 7- point rating scale. The first 7 items form the positive subscale (P subscale), the subsequent 7 items make up the negative subscale (N subscale), and the remaining 16 items contribute to the general psychopathology subscale (G subscale). The total PANSS score is the sum of all 30 items scores, with a higher score indicating greater symptom severity.
Cognitive measures
Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [20], demonstrating good validity and reliability in the Chinese population. Comprising 12 subtests, RBANS measures five cognitive domains: immediate memory (vocabulary learning, story retelling), visuospatial/structural (graphic copying, line positioning), language (pictorial naming and semantic fluency), attention (digital breadth, coding test), and delayed memory (vocabulary reacquaintance, vocabulary recall, story recall, graphic recall). Raw scores for neuropsychological variables were corrected for age and standardized to T-scores using the best available criteria from the appropriate manuals. Based on the mean T-scores of the five cognitive domains, the final total score defined the overall T-score for cognitive functioning.
Loneliness
The UCLA (University of California, Los Angeles) Loneliness Scale (Version 3), developed by Russell et al. in 1996, stands as the preeminent instrument for quantifying loneliness [21]. Comprising 11 items framed in a negative/lonely context and 9 items framed positive/non-lonely direction. This 20-item scale encompasses three components: personal feelings of isolation (11 items, including feelings of aloneness, rejection, and withdrawal), lack of relational connectedness (5 items, reflecting a sense of unfamiliarity, closeness, and support absence), and lack of collective connectedness (4 items, indicating a deficiency in group identification and cohesion) [22]. Participants express their agreement levels with these statements on a 4-point Likert scale, ranging from 1 (never) to 4 (often). Total scores range from 20 to 80 points, with higher scores denoting a heightened degree of loneliness.
Social isolation
We utilized Social Isolation Index (ISI) by assigning one point if the subject was unmarried, had less than monthly contact (including face-to-face, telephone, or written/e-mail contact) with each of their children, other family members, and friends, and did not engage in any social activities over the past year (e.g. interaction with friends, playing chess or cards, community club participation, attendance at sports, social, or other clubs, involvement in voluntary or charity work). Scores ranged from 0 to 5, with increased scores indicate higher levels of social isolation [23].
Statistical analyses
All statistical analyses were conducted using SPSS 25.0. The figures were made using Origin 2021. Sociodemographic and clinical variables between male and female patients were compared using the following methods: The Kolmogorov-Smirnov test was used to determine the distribution of the data. The chi-square test for categorical variables, analysis of variance (ANOVA) for continuous variables with normal distribution, and Mann-Whitney nonparametric test for continuous variables with non-normal distribution. The association between loneliness, social isolation, PANSS scores and RBANS scores was examined using Spearman’s correlation.
To explore the independent, relative, and synergistic impacts of loneliness and social isolation on psychiatric symptoms and cognitive performance for male and female patients separately, we employed multiple linear regression. Four models were fitted. First, psychiatric symptoms and cognitive performance scores were repressed separately on loneliness (Model 1) or social isolation (Model 2). Second, both loneliness and social isolation were simultaneously entered into the model (Model 3). Finally, an interaction effect between loneliness and social isolation was tested (Model 4). All regression analyses were adjusted for age, education, duration of condition, BMI, only child, smoking status, hypertension and diabetes. Results were presented using both unstandardized regression coefficients (B) and standardized regression coefficients (β). The significance level was set at 0.05.
Results
Sex differences in sociodemographic, clinical variables and cognitive functioning
Table 1 displays the comparison of sociodemographic, clinical variables and cognitive functions between male (n = 136) and female (n = 187) SCZ patients. In comparison to female patients, male patients exhibited a higher likelihood of being an only child (p = 0.009) and engaging in smoking behavior (p < 0.001). No significant differences were observed between males and females with SCZ in terms of age, education, total disease duration, BMI, prevalence of hypertension and diabetes (ps > 0.05).
Table 1.
Sociodemographic, clinical variables and cognitive functions between male and female patients
| Variables | Male (mean, SD) (n = 136) |
Female (mean, SD) (n = 187) |
F, Z or χ2 | p |
|---|---|---|---|---|
| Age (years) | 57.51 (14.06) | 59.89 (13.80) | 2.305 | 0.130 |
|
Education (<high school, %) (school,%) |
48.5 | 38.0 | 3.596 | 0.058 |
| Duration of condition (years) | 21.03 (13.94) | 22.16 (14.50) | -0.294 | 0.769 |
| BMI | 25.55 (4.39) | 24.98 (4.93) | -1.430 | 0.153 |
| Only child (yes, %) | 36.8 | 22.2 | 9.383 | 0.009 |
| Smokers (yes, %) | 49.3 | 3.7 | 92.381 | < 0.001 |
| Hypertension (yes, %) | 12.5 | 11.8 | 0.040 | 0.841 |
| Diabetes (yes, %) | 14.0 | 14.4 | 0.014 | 0.905 |
| PANSS | ||||
| Total score | 63.93 (16.28) | 67.93 (15.18) | 5.133 | 0.024 |
| P subscore | 14.17 (5.80) | 16.60 (6.20) | -3.636 | < 0.001 |
| N subscore | 19.50 (8.32) | 19.67 (7.91) | -0.346 | 0.730 |
| G subscore | 30.15 (6.74) | 31.66 (6.76) | -2.179 | 0.029 |
| RBANS | ||||
| Total score | 70.33 (13.85) | 70.82 (16.08) | -0.004 | 0.997 |
| Immediate memory | 61.74 (16.69) | 63.23 (20.34) | -0.184 | 0.854 |
| Visuospatial/constructional | 79.73 (19.24) | 77.26 (19.21) | -1.076 | 0.282 |
| Language | 84.83 (14.91) | 80.44 (17.88) | 5.22 | 0.023 |
| Attention | 88.79 (15.37) | 89.06 (15.97) | 0.022 | 0.882 |
| Delayed memory | 66.81 (20.54) | 67.76 (20.59) | 0.435 | 0.663 |
Note: BMI, body mass index; PANSS, the Positive and Negative Syndrome Scale; P subscore, PANSS positive symptom subscore; N subscore, PANSS negative symptom subscore; G subscore, PANSS general subscore; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status. Bolding represents p < 0.05
Female patients demonstrated higher PANSS total score (p = 0.024), PANSS P subscale scores (p < 0.001), and PANSS G subscale scores (p = 0.029) compared to male patients. Regarding cognitive functioning, male patients exhibited superior verbal functioning than their female counterparts (males = 84.83 ± 14.91, females = 80.44 ± 17.88, p = 0.023), with no discernible differences in other domains of cognitive performance.
Sex differences in loneliness and social isolation in SCZ patients
Among chronic SCZ patients, sex disparities in loneliness and social isolation were evident. As shown in Table 2, male patients exhibited higher UCLA total scores (p = 0.041) and the domain of lack of relational connectedness (p = 0.015) compared to their female counterparts. Conversely, female patients demonstrated lower social isolation scores (p = 0.008) than male patients, specifically in the domains of unmarried (p = 0.002) and less than monthly contact with children (p = 0.014).
Table 2.
Sex differences in loneliness and social isolation
| Variables | Male (mean, SD) (n = 136) |
Female (mean, SD) (n = 187) |
F, Z or χ2 | p |
|---|---|---|---|---|
| UCLA total score | 43.77 (10.56) | 41.33 (11.63) | -2.042 | 0.041 |
| Personal feelings of isolation | 24.25 (7.25) | 22.74 (7.36) | -1.818 | 0.069 |
| Lack of relational connectedness | 11.28 (3.35) | 10.58 (4.87) | -2.441 | 0.015 |
| Lack of collective connectedness | 8.24 (2.86) | 8.01 (3.06) | -0.097 | 0.329 |
| Social isolation | 3.23 (1.38) | 2.84 (1.26) | -2.642 | 0.008 |
| Not married (yes, %) | 0.82 (0.39) | 0.66 (0.48) | -3.141 | 0.002 |
| Less than monthly contact with children (yes, %)(yes, %) | 0.82 (0.39) | 0.70 (0.46) | -2.463 | 0.014 |
| Less than monthly contact with family members (yes, %) | 0.54 (0.50) | 0.45 (0.50) | -1.587 | 0.112 |
| Less than monthly contact with friends (yes, %) | 0.71 (0.46) | 0.79 (0.41) | -1.764 | 0.078 |
| nonparticipation in any social activities (yes, %) | 0.35 (0.48) | 0.25 (0.43) | -1.949 | 0.051 |
Note: UCLA, UCLA Loneliness Scale, University of California at Los Angels. Bolding represents p < 0.05
Relationships of loneliness and social isolation to psychiatric symptoms and cognitive performance in male and female SCZ patients
To discern sex-specific influence of loneliness and social isolation on psychiatric symptoms and cognitive performance, separate analyses were conducted for males and females. The results of Spearman’s correlation analysis are presented in a heat map, with the results for male patients shown in Fig. 1a and the results for female patients shown in Fig. 1b.
Fig. 1.
(a) Correlation of loneliness and social isolation with psychopathological symptoms and cognitive performance in male patients. (b) Correlation of loneliness and social isolation with psychopathological symptoms and cognitive performance in female patients. (c) Correlation of personal feelings of isolation with language in female patients. (d) Correlation of lack of collective connectedness with delayed memory in female patients. Note: PANSS, the Positive and Negative Syndrome Scale; P subscore, PANSS positive symptom subscore; N subscore, PANSS negative symptom subscore; G subscore, PANSS general subscore; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status. The solid line and the red area indicate the estimates and their corresponding 95% confidence intervals, respectively. ***p < 0.001, **p < 0.01, *p < 0.05
In male patients, loneliness exhibited positive correlations with PANSS total score and subscale scores (ps ≤ 0.001), and negative correlations with verbal functioning and attention (p = 0.010, 0.036). Social isolation was positively correlated with PANSS total score (p < 0.001), N subscale scores (p < 0.001), and G subscale scores (p = 0.004), while also showing negative correlations with immediate memory and delayed memory (p = 0.038, 0.042). In female patients, loneliness lacked significant correlations with clinical symptoms severity but was negatively correlated with immediate memory, verbal functioning, delayed memory, and RBANS total scores (ps < 0.001, p = 0.010, 0.021, 0.003). Social isolation showed a positive correlation with N subscale scores (p = 0.002) but not with cognitive functioning. Importantly, loneliness had a significant correlation with social isolation in both male and female patients (p = 0.046, 0.006).
Multiple linear regression was employed to explore the independent, relative, and synergistic effects of loneliness and social isolation on psychiatric symptoms and cognitive performance in male and female patients. For male patients (Table 3), both loneliness and social isolation predicted PANSS total scores (β = 0.288, p < 0.01; β = 0.247, p < 0.01), N subscale scores (β = 0.176, p < 0.05; β = 0.300, p < 0.01) and G subscale scores (β = 0.291, p < 0.01; β = 0.125, p < 0.05). After Bonferroni correction we found that loneliness and social isolation still significantly predicted PANSS total scores, social isolation remained a significant predictor of N subscale scores, and loneliness significantly predicted G subscale scores (ps < 0.05/4 = 0.0125). When both loneliness and social isolation were included in the regression model (Model 3), the coefficients for both decreased to varying degrees, and both remained significant only in the PANSS total scores (β = 0.252, p < 0.01; β = 0.190, p < 0.05). In contrast, for female patients (Table 4), loneliness significantly predicted immediate memory (β = -0.281, p < 0.001), language (β = -0.186, p < 0.05), delayed memory (β = -0.181, p < 0.05), and RBANS total scores (β = -0.231, p < 0.01), whereas social isolation did not significantly correlate with cognitive performance in female patients. After Bonferroni correction, loneliness was still found to be a significant predictor of immediate memory and RBANS total scores (ps < 0.05/6 = 0.0083). When both loneliness and social isolation were included in the regression model (Model 3), the coefficient on loneliness was reduced but still significant (ps < 0.05). No significant interaction (Model 4) between loneliness and social isolation were observed in either male or female patients (Tables 3 and 4).
Table 3.
Linear regression for PANSS scores in male patients
| Age | Education | Duration of condition | BMI | Only child | Smokers | Hypertension | Diabetes | Loneliness | Social isolation | Loneliness×Social isolation | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total score | ||||||||||||
| MODEL 1 | B | 0.400* | -7.237* | -0.108 | 0.151 | 0.884 | 6.650* | -5.872 | -0.785 | 0.464** | ||
| β | 0.336 | -0.218 | -0.090 | 0.040 | 0.026 | 0.200 | -0.112 | -0.017 | 0.288 | |||
| MODEL 2 | B | 0.452* | -8.625** | -0.291 | 0.290 | 0.803 | 8.473** | -4.034 | -2.679 | - | 2.931** | |
| β | 0.380 | -0.260 | -0.243 | 0.076 | 0.023 | 0.255 | -0.077 | -0.057 | - | 0.247 | ||
| MODEL3 | B | 0.417* | -6.793* | -0.209 | 0.256 | 0.726 | 6.685* | -4.58 | -2.170 | 0.407** | 2.259* | |
| β | 0.350 | -0.205 | -0.174 | 0.067 | 0.021 | 0.202 | -0.088 | -0.046 | 0.252 | 0.190 | ||
| MODEL4 | B | 0.474** | -6.812* | -0.248 | 0.192 | 0.254 | 6.557* | -5.767 | -1.506 | 0.836** | 8.613* | -0.148 |
| β | 0.398 | -0.205 | -0.208 | 0.050 | 0.007 | 0.198 | -0.110 | -0.032 | 0.519 | 0.725 | -0.657 | |
| N subscore | ||||||||||||
| MODEL 1 | B | 0.178* | -3.084* | 0.048 | -0.047 | 1.335 | 1.817 | -3.577 | -0.323 | 0.142* | ||
| β | 0.299 | -0.186 | 0.081 | -0.025 | 0.077 | 0.109 | -0.137 | -0.014 | 0.176 | |||
| MODEL 2 | B | 0.199* | -3.220* | -0.045 | 0.037 | 1.241 | 2.286 | -2.513 | -1.444 | - | 1.789** | |
| β | 0.334 | -0.194 | -0.074 | 0.019 | 0.072 | 0.138 | -0.096 | -0.061 | - | 0.300 | ||
| MODEL3 | B | 0.191* | -2.766 | -0.024 | 0.029 | 1.222 | 1.842 | -2.649 | -1.317 | 0.101 | 1.622** | |
| β | 0.319 | -0.166 | -0.04 | 0.015 | 0.070 | 0.111 | -0.101 | -0.056 | 0.125 | 0.272 | ||
| MODEL4 | B | 0.211* | -2.772 | -0.038 | 0.006 | 1.052 | 1.796 | -3.076 | -1.078 | 0.255 | 3.908 | -0.053 |
| β | 0.354 | -0.167 | -0.064 | 0.003 | 0.061 | 0.108 | -0.118 | -0.046 | 0.316 | 0.656 | -0.471 | |
| G subscore | ||||||||||||
| MODEL 1 | B | 0.133 | -2.744* | -0.070 | 0.161 | -0.436 | 2.628* | -1.386 | 0.497 | 0.192** | ||
| β | 0.272 | -0.202 | -0.144 | 0.103 | -0.031 | 0.194 | -0.065 | -0.026 | 0.291 | |||
| MODEL 2 | B | 0.153* | -3.359** | -0.141 | 0.213 | -0.460 | 3.396** | -0.692 | -0.215 | - | 1.094* | |
| β | 0.313 | -0.247 | -0.289 | 0.137 | -0.032 | 0.250 | -0.032 | -0.011 | - | 0.225 | ||
| MODEL3 | B | 0.139 | -2.585* | -0.107 | 0.199 | -0.492 | 2.641* | -0.922 | 0.001 | 0.172** | 0.811 | |
| β | 0.285 | -0.190 | -0.218 | 0.127 | -0.035 | 0.194 | -0.043 | 0.001 | 0.260 | 0.167 | ||
| MODEL4 | B | 0.155* | -2.590* | -0.118 | 0.181 | -0.628 | 2.605* | -1.262 | 0.190 | 0.295* | 2.628 | -0.042 |
| β | 0.318 | -0.191 | -0.241 | 0.116 | -0.044 | 0.192 | -0.059 | 0.010 | 0.446 | 0.540 | -0.459 |
Note: PANSS, the Positive and Negative Syndrome Scale; BMI, body mass index; P subscore, PANSS positive symptom subscore; N subscore, PANSS negative symptom subscore; G subscore, PANSS general subscore; ***p < 0.001, **p < 0.01, *p < 0.05
Table 4.
Linear regression for RBANS scores in female patients
| Age | Education | Duration of condition | BMI | Only child | Smokers | Hypertension | Diabetes | Loneliness | Social isolation | Loneliness×Social isolation | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Immediate memory | ||||||||||||
| MODEL 1 | B | -0.229 | 8.348** | -0.131 | 0.308 | 0.703 | 0.883 | 8.886 | 0.364 | -0.498*** | ||
| β | -0.153 | 0.198 | -0.092 | 0.075 | 0.016 | 0.008 | 0.138 | 0.006 | -0.281 | |||
| MODEL 2 | B | -0.147 | 8.685** | -0.217 | 0.243 | -0.817 | 4.728 | 8.761 | 1.156 | - | 0.435 | |
| β | -0.098 | 0.206 | -0.152 | 0.059 | -0.019 | 0.045 | 0.136 | 0.020 | - | 0.027 | ||
| MODEL3 | B | -0.203 | 8.361** | -0.186 | 0.302 | 0.684 | 1.226 | 9.047 | 0.068 | -0.514*** | 1.122 | |
| β | -0.136 | 0.199 | -0.130 | 0.073 | 0.016 | 0.012 | 0.141 | 0.001 | -0.290 | 0.070 | ||
| MODEL4 | B | -0.208 | 8.147** | -0.190 | 0.337 | 0.969 | 1.413 | 8.799 | -0.084 | -0.715* | -1.470 | 0.067 |
| β | -0.139 | 0.194 | -0.133 | 0.082 | 0.022 | 0.014 | 0.137 | -0.001 | -0.403 | -0.091 | 0.217 | |
| Language | ||||||||||||
| MODEL 1 | B | -0.258 | 7.401* | 0.017 | 0.436 | 3.761 | -6.986 | 6.473 | 0.352 | -0.191* | ||
| β | -0.195 | 0.199 | 0.013 | 0.120 | 0.097 | -0.076 | 0.114 | 0.007 | -0.186 | |||
| MODEL 2 | B | -0.218 | 7.591** | -0.017 | 0.400 | 2.892 | -4.869 | 6.356 | 0.891 | - | -0.065 | |
| β | -0.165 | 0.204 | -0.013 | 0.110 | 0.074 | -0.053 | 0.112 | 0.017 | - | -0.005 | ||
| MODEL3 | B | -0.251 | 7.405* | 0.001 | 0.434 | 3.756 | -6.884 | 6.521 | 0.265 | -0.296* | 0.331 | |
| β | -0.190 | 0.199 | 0.001 | 0.120 | 0.096 | -0.075 | 0.115 | 0.005 | -0.189 | 0.023 | ||
| MODEL4 | B | -0.257 | 7.128* | -0.004 | 0.480 | 4.125 | -6.642 | 6.199 | 0.068 | -0.557 | -3.029 | 0.087 |
| β | -0.194 | 0.192 | -0.004 | 0.133 | 0.106 | -0.072 | 0.109 | 0.001 | -0.355 | -0.213 | 0.319 | |
| Delayed memory | ||||||||||||
| MODEL 1 | B | 0.037 | 10.121** | -0.031 | 0.391 | -1.035 | 0.356 | 6.895 | -4.150 | -0.325* | ||
| β | 0.024 | 0.237 | -0.022 | 0.094 | -0.023 | 0.003 | 0.106 | -0.070 | -0.181 | |||
| MODEL 2 | B | 0.079 | 10.330** | -0.063 | 0.352 | -2.000 | 2.672 | 6.749 | -3.520 | - | -0.189 | |
| β | 0.052 | 0.242 | -0.044 | 0.085 | -0.045 | 0.025 | 0.104 | -0.059 | - | -0.012 | ||
| MODEL3 | B | 0.043 | 10.124** | -0.044 | 0.390 | -1.039 | 0.432 | 6.931 | -4.216 | -0.329* | 0.251 | |
| β | 0.028 | 0.237 | -0.030 | 0.094 | -0.023 | 0.004 | 0.106 | -0.071 | -0.183 | 0.015 | ||
| MODEL4 | B | 0.039 | 9.944** | -0.047 | 0.420 | -0.801 | 0.589 | 6.724 | -4.343 | -0.497 | -1.921 | 0.056 |
| β | 0.026 | 0.233 | -0.032 | 0.101 | -0.018 | 0.006 | 0.103 | -0.073 | -0.276 | -0.118 | 0.179 | |
| RBANS total score | ||||||||||||
| MODEL 1 | B | -0.056 | 8.191** | -0.025 | 0.361 | -3.202 | 1.078 | 3.667 | -2.639 | -0.325** | ||
| β | -0.047 | 0.245 | -0.022 | 0.111 | -0.092 | 0.013 | 0.072 | -0.057 | -0.231 | |||
| MODEL 2 | B | -0.022 | 8.395** | -0.042 | 0.324 | -4.150 | 3.281 | 3.481 | -1.942 | - | -0.472 | |
| β | -0.018 | 0.251 | -0.037 | 0.100 | -0.119 | 0.040 | 0.068 | -0.042 | - | -0.037 | ||
| MODEL3 | B | -0.057 | 8.190** | -0.023 | 0.361 | -3.201 | 1.067 | 3.661 | -2.629 | -0.325** | -0.037 | |
| β | -0.048 | 0.245 | -0.020 | 0.111 | -0.092 | 0.013 | 0.072 | -0.057 | -0.231 | -0.003 | ||
| MODEL4 | B | -0.062 | 7.956** | -0.027 | 0.400 | -2.889 | 1.272 | 3.390 | -2.796 | -0.545* | -2.874 | 0.073 |
| β | -0.052 | 0.238 | -0.024 | 0.123 | -0.083 | 0.015 | 0.067 | -0.060 | -0.387 | -0.225 | 0.300 |
Note: RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; BMI, body mass index; ***p < 0.001, **p < 0.01, *p < 0.05
Further exploration of the components of loneliness, along with the correlation between patients’ clinical symptoms and cognitive functioning, revealed that in female patients, personal feelings of isolation was negatively related to verbal functioning (r = -0.21, p < 0.01) (Fig. 1c), and a negative correlation existed between lack of collective connectedness and delayed memory (r = -0.19, p < 0.05) (Fig. 1d).
Discussion
Our study first explored sex-specific intricacies in how loneliness and social isolation influence clinical symptoms and cognitive functioning in SCZ patients. The findings offer valuable insights into the complex interplay of sex, loneliness, and social isolation in shaping psychiatric symptoms and cognitive functioning in SCZ individuals. Major findings include: 1) Male SCZ patients exhibited heightened feelings of loneliness, a lack of relational connectedness, and increased higher social isolation, with a higher likelihood of being unmarried and experiencing infrequent contact with their children compared to females. (2) Robust correlations were found between elevated loneliness and social isolation levels and increased the severity of psychiatric symptoms, including negative symptoms and general psychopathology in male patients. (3) Among female patients, loneliness, but not social isolation, demonstrated a negative relationship with cognition functioning, specifically immediate memory, verbal functioning and delayed memory. Further analysis of loneliness components revealed that personal feelings of isolation were negatively related to language, while a lack of collective connectedness was negatively associated with delayed memory. (4) No synergistic interaction between loneliness and social isolation was observed for clinical symptoms and cognitive functioning in either sex.
Our study revealed a notable sex disparity, with male SCZ patients experiencing a heightened sense of loneliness and social isolation compared to female patients, aligning with findings from previous studies [24, 25]. In our sample, which consisted mostly of long-term hospitalized chronic SCZ patients, a larger proportion of men were unmarried and lacked children for care, contributing to diminished relational ties and social support from their spouses, potentially amplifying stress levels compared to female patients [26]. In addition to this, Research has consistently demonstrated that females tend to have more extensive social networks, engage more in social activities, and derive greater enjoyment from interpersonal interactions [14, 27]. Therefore, male patients may encounter heightened levels of social isolation and loneliness.
We also found that psychiatric symptoms in SCZ patients may be related to loneliness and social isolation. Following the exclusion of confounding factors, our analysis unveiled that among male patients, elevated loneliness and increased social isolation related to increased PANSS total scores, N subscale scores, and G subscale scores, consistent with existing research. A meta-analysis showed a mid-significant relationship between loneliness and psychiatric symptoms in psychotic patients [10]. Badcock et al. reported that loneliness in patients with mental disorders was specifically associated with impaired thinking and reduced pleasure [28]. The precise mechanisms behind this correlation remain elusive, yet from the cognitive model of psychosis proposed by Garety et al., it can be postulated that loneliness may exacerbate psychiatric symptoms by reinforcing their negative perceptions and lowering their self-esteem [29]. In addition to this, loneliness may contribute to more severe psychiatric symptoms by intensifying anxiety and depression [30]. Whereas, social isolation, acting as a stressor, induces endocrine changes and alters neurotransmitters levels, potentially precipitating neurological and psychiatric disorders [31]. Ewelina Bator et al. concluded that social isolation in adolescents induces SCZ-like behaviors [32]. After Bonferroni correction we found that loneliness and social isolation still significantly predicted PANSS total scores, social isolation remained a significant predictor of N subscale scores, and loneliness significantly predicted G subscale scores. However, our study did not find an interaction between loneliness and social isolation on psychiatric symptoms, suggesting that the effects of loneliness and social isolation on psychiatric symptoms may be independent and relative in SCZ patients.
In this study, the relation of loneliness and social isolation to cognitive functioning in SCZ patients was also a key concern. Numerous studies in the general population have established loneliness and social isolation as risk factors for cognitive impairments [33, 34], although our findings present a nuanced perspective. Upon excluding confounding factors, our study found that elevated loneliness, but not social isolation, may be associated with reduced immediate memory, verbal functioning, delayed memory, and overall RBANS scores in female patients. After Bonferroni correction, loneliness was still found to be a significant predictor of immediate memory and RBANS total scores. Consistent with past cross-sectional research, loneliness has been shown to adversely impact various cognitive domains in older populations, particularly memory [35]. Lisa Boss et al. found that a negative correlation between loneliness intelligence quotient, processing speed, immediate memory, and delayed memory, yet the correlation became nonsignificant after controlling for various risk factors. Longitudinal studies further indicate that loneliness is significantly correlated with impaired language over the years compared to baseline [36, 37]. Despite the observed impact of loneliness on cognitive function in many studies, the mechanisms underlying this connection remain unclear. One theory proposes that loneliness induces dysfunction in circadian cortisol release from the hypothalamic-pituitary-adrenal (HPA) axis, leading to cognitive decline [38, 39]. However, conflicting findings, including a lack of association between loneliness and cognition, has also been reported [40, 41]. Our findings also found no synergistic effect of loneliness and social isolation on cognitive functioning in SCZ patients, which is inconsistent with past findings. Synergistic effects of loneliness and social isolation on cognitive functioning were found by some researchers. A longitudinal study with English older adults indicated that both social isolation and loneliness were significantly associated with poorer cognitive function. Further research is needed in the future regarding both the relative and synergistic influences of social isolation and loneliness on cognitive functioning.
Moreover, a crucial aspect of our study lies in revealing that the effects of loneliness and social isolation on psychiatric symptoms and cognitive functioning in SCZ patients may differ by gender. Individual responses to loneliness and social isolation vary, influenced by unique characteristics, such as genetics, personality traits, and diverse perceptions [42, 43]. Animal studies have indicated that isolated male rats exhibit reduced plasma corticosterone levels, whereas females tend to displayed higher levels compared to their group-housed counterparts. This may reflect differing vulnerability stress within the context of social pressures [44, 45]. The influence of social isolation and loneliness on mental health also manifests differently in women and men, with lonely men exhibiting increased susceptibility to mental health problems [46]. Additionally, women experience a more rapid decline in cognitive performance compared to men [47, 48], and according to the cognitive reserve hypothesis, loneliness may diminish an individual’s reserve capacity for cognitive performance [49], potentially contributing to sex differences in the relationship of loneliness and cognitive impairments. Various hypotheses, including gender dimorphism in hormone secretion, inflammatory responses, and biobehavioral mechanisms, have been s proposed as potential contributors to this observed sex difference [48]. Our findings suggest that early interventions, such as psychotherapy and the development of interests, may be beneficial in preventing or slowing down cognitive impairment among SCZ patients with high levels of loneliness, especially females.
The strengths of our study include the simultaneous assessment of both loneliness and social isolation in SCZ patients, as well as sex differences in their impact on patients’ clinical symptoms and cognitive functioning. Demographics, health factors, and disease duration were included as potential confounders in this study, and cognitive functioning was assessed by objective tests. We also were able to construct a comprehensive social isolation index that included contact with children, relatives, friends and participation in any social activities.
There are also limitations. First, being a cross-sectional study, it only describes correlations rather than causality and inherently lacks the capacity to account for the myriad complex psychosocial factors that may have impact psychiatric symptoms and cognition. Future research could employ longitudinal designs with larger sample sizes, set up a healthy control group and consider a broader range of covariates, including socioeconomic status and medication adherence. Specifically, examining whether baseline levels of loneliness and social isolation predict changes in cognitive functioning and psychiatric symptoms over time may offer valuable insights into the causal pathways of these relationships. Such studies could inform targeted interventions, helping to mitigate the adverse effects of loneliness and social isolation in SCZ patients through evidence-based strategies. Second, our study did not incorporate a detailed assessment of the personality of the study participants. Certain personality traits known to heighten vulnerability to loneliness were not explored. Third, the inclusion of predominantly long-term hospitalized chronic SCZ patients which were all from one single center in our sample may limit the generalizability of findings to the broader patient population. Finally, we recognize that the use of an unvalidated questionnaire is a limitation, and in future studies we will consider using validated instruments to further improve data accuracy and reliability.
Conclusion
In conclusion, our study highlights higher levels of loneliness and social isolation in male SCZ patients. Moreover, loneliness and social isolation exhibit positive association with psychiatric symptoms and cognitive functioning in male patients, while loneliness is negatively related to cognitive functioning in female patients. These findings underscore the potential impact of loneliness and social isolation on patients’ conditions, may affecting their quality of life and contributing to cognitive impairment. In addition, the present study has some methodological limitations, such as a cross-sectional design that only describes correlations rather than causality. Future research needs to expand the sample size to explore in depth the effects of loneliness and social isolation on cognition and psychiatric symptoms through high-quality longitudinal studies.
Acknowledgements
We thank all the participants in the study.
Author contributions
Shen Li and Lili Wang provided the evolution of overarching research goals, design of methodology, oversight and leadership responsibility for the research and acquisited of the financial support for the project leading to this publication. Jinghui Chi, Qiaona Jiang and Chenghao Lu complished the experiments. Yanzhe Li, Nannan Liu, Tian Tian and Xiaofei Zhang analyzed the study data. Xiaofei Zhang, Yanyan Ma, Jinghui Chi, Chenghao Lu and Qiaona Jiang conducted the research and investigation process. Jinghui Chi, Chenghao Lu and Qiaona Jiang scrubed data and maintained research data for initial use and later reuse. Jinghui Chi; Nannan Liu, Tian Tian and Shen Li writed original draft. Shen Li and Lili Wang reviewed and edited. Jinghui Chi, Nannan Liu, Tian Tian and Shen Li Prepared visualization and data presentation. Nannan Liu, Tian Tian, Yanyan Ma and Yanzhe Li Managed and coordinated responsibility for the research activity planning and execution.
Funding
This work was supported by National Natural Science Foundation of China (82371512), Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-033 A), Tianjin Municipal Education Commission Scientific Research Program Project (2022KJ265), Foundation of Tianjin Health Commission for Young Scholars (TJWJ2021QN064). All funding had no role in study design, data analysis, paper submission and publication.
Data availability
The data are not publicly available due to the containing information that could compromise the privacy of research participants. The data presented in this study are available on request from the corresponding author.
Declarations
Ethics approval and consent to participate
The study protocol received approval from the Institutional Review Board of Tianjin Anding Hospital (ID: 2022-09), and all participants provided written informed consent.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Jinghui Chi, Nannan Liu and Tian Tian contributed equally to this work.
Contributor Information
Lili Wang, Email: tjadyywll@163.com.
Shen Li, Email: lishen@tmu.edu.cn.
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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 data are not publicly available due to the containing information that could compromise the privacy of research participants. The data presented in this study are available on request from the corresponding author.