Factors influencing the age of first hospitalization in patients with chronic schizophrenia: Role of clinical features and blood parameters

doi:10.21203/rs.3.rs-4909934/v1

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Factors influencing the age of first hospitalization in patients with chronic schizophrenia: Role of clinical features and blood parameters

https://doi.org/10.21203/rs.3.rs-4909934/v1

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Background

This study aims to identify the factors influencing the age of first hospitalization in patients with chronic schizophrenia, focusing on clinical features and blood parameters.

Methods

A total of 1271 patients diagnosed with chronic schizophrenia were recruited from 17 psychiatric hospitals across China. Demographic and clinical data, including age of first hospitalization, were collected. The study also included assessments of psychiatric symptoms, duration of untreated psychosis (DUP), and various blood parameters. Statistical analyses were conducted to examine the relationships between these factors and the age of first hospitalization.

Results

The average age of first hospitalization was 28.07 ± 9.993 years. Single patients and those with a family history of mental illness were hospitalized at a younger age. Patients with suicidal ideation or behavior also had an earlier hospitalization age compared to those without such history. Regression analysis revealed that marital status (single), family history of mental illness, and suicide ideation or behavior were significant risk factors for earlier hospitalization age. Conversely, DUP, total protein (TP), and low-density lipoprotein (LDL) levels were positively correlated with the age of first hospitalization, while antipsychotic medication dosage and albumin (ALB) levels were negatively correlated.

Conclusions

The study identifies significant demographic, clinical, and biochemical factors associated with the age of first hospitalization in chronic schizophrenia patients in China. These findings underscore the importance of early intervention and targeted support for high-risk groups to improve treatment outcomes.

Chronic Schizophrenia

Age of First Hospitalization

Clinical Features

Blood Parameters

Duration of Untreated Psychosis

Schizophrenia is a chronic and debilitating mental disorder characterized by a range of symptoms including delusions, hallucinations, disorganized thinking, and cognitive impairment [1]. It significantly impacts patients' social, occupational, and personal functioning [2, 3]. Early intervention in schizophrenia is crucial for improving long-term outcomes[4], yet many patients experience substantial delays in receiving treatment [5]. This delay, often referred to as the duration of untreated psychosis (DUP), has been associated with worse prognoses and increased severity of symptoms at the time of first hospitalization [6].

Understanding the factors that influence the age of first hospitalization for patients with chronic schizophrenia is essential for developing strategies to reduce treatment delays and improve patient outcomes [7]. Previous research has identified several demographic and clinical variables associated with earlier or later hospitalization in schizophrenia patients [8]. These include gender, marital status, family history of mental illness, substance use, and suicidal behavior [9, 10]. However, the complex interplay of these factors and their relative contributions to the timing of first hospitalization remain poorly understood [11].

In China, the cultural, societal, and healthcare contexts may further complicate the pathways to treatment for individuals with schizophrenia [12–15]. The stigma associated with mental illness, differences in healthcare access, and varying levels of social support can all influence the timing and nature of psychiatric care [14, 16]. Despite the importance of these factors, large-scale studies specifically examining the age of first hospitalization for chronic schizophrenia patients in China are scarce [17].

Moreover, emerging evidence suggests that biological markers, such as blood parameters, may also play a role in the clinical course of schizophrenia and the timing of treatment interventions [18, 19]. Nutritional status, metabolic profiles, and other biochemical indices could potentially influence or reflect the underlying pathophysiology of schizophrenia and its progression [19, 20]. However, research exploring the relationship between these biological markers and the age of first hospitalization is limited.

This study aims to fill these gaps by investigating the factors influencing the age of first hospitalization in a large sample of Chinese patients with chronic schizophrenia. Our hypothesis is that the age of first hospitalization in chronic schizophrenia patients is potentially related to suicide risk, clinical severity, cognitive function, antipsychotic medication dosage, and biological markers. Thus, we explored the roles of clinical features, suicidal behavior, clinical symptoms and cognitive function, as well as blood parameters. By elucidating these relationships, we hope to contribute to a better understanding of the factors that delay or expedite hospitalization and to inform strategies for earlier intervention and improved management of schizophrenia in China.

2.1 Participants

This study was conducted in accordance with the principles outlined in the Declaration of Helsinki and received approval from the Institutional Review Board of the Institute of Psychology, Chinese Academy of Sciences (approval number: H18031). Informed written consent was obtained from all participants after they received a detailed explanation of the research objectives and procedures.

A total of 1271 patients diagnosed with chronic schizophrenia were recruited from 17 psychiatric hospitals across China between October 2018 and September 2021. The inclusion criteria were: (1) age between 18–70 years and Han nationality; (2) a confirmed diagnosis of schizophrenia by two experienced psychiatrists using the Structured Clinical Interview for DSM-IV (SCID); (3) stable dose of antipsychotic medication for at least six months prior to enrollment; (4) ability to actively participate in psychopathological assessments and provide written informed consent.

Exclusion criteria were: (1) severe comorbid physical or neurological conditions, or mental retardation; (2) pregnancy or breastfeeding; (3) significant fluctuations in psychotic symptoms in the two weeks prior to the study. A flowchart detailing the study process is provided in Fig. 1.

In alignment with the typical male-to-female ratio in Chinese psychiatric hospitals for schizophrenia patients, our study maintained a male-to-female ratio of approximately 2:1, reflecting the demographic distribution of chronic schizophrenia inpatients in China.

2.2 Duration of untreated duration

The duration of untreated psychosis (DUP) was defined as the interval (in years) between the patient’s first noticeable symptoms and the initiation of the first pharmacological treatment [21, 22]. Initial symptoms such as unusual fears, hallucinations, delusions, and social withdrawal were identified through interviews with the patient and their primary caregiver. The patient’s medical history was also reviewed, including records from the initial consultation [23].

2.3 Clinical measurements

Demographic and clinical data were collected using self-administered questionnaires and included gender, age, age of first onset, education level, and medical history (e.g., diabetes, hypertension, cardiovascular diseases). Marital status was categorized as single (including divorced and widowed) or non-single (including married and remarried). Impulsive behaviors over the past year, as well as smoking and alcohol consumption habits, were documented in detail. Height and weight were measured by nursing staff, and Body Mass Index (BMI) was calculated as weight (kg) divided by height (m²) [24]. In addition, we recorded in detail the type and dose of antipsychotic medication. We then calculated the chlorpromazine equivalent dose of the antipsychotics [25].

Suicidal ideation and suicide risk were assessed using the Beck Scale for Suicide Ideation (SSI) [26], and suicidal events were categorized with the Colombian Classification Algorithm for Suicide Assessment (C-CASA) [27]. Suicide was defined according to C-CASA as a genuine intention to commit suicidal behavior without success [28]. Details about the date, method, and frequency of suicide attempts were recorded, with previous suicide status classified as none, suicide ideation, or suicide behavior.

Subjective insomnia severity over the past week was evaluated using the Insomnia Severity Index (ISI) [29], which includes seven items scored from 0 to 4, with higher scores indicating more severe insomnia [30]. Schizophrenia symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS) [31], with all personnel undergoing PANSS training and achieving an inter-rater reliability coefficient (ICC) exceeding 0.8 [32].

Cognitive functioning was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Form A) [33], which includes twelve subtests to derive five index scores and a total RBANS score. The Chinese-translated and validated version of RBANS was exclusively used [34]. The Modified Overt Aggression Scale (MOAS) was used to assess the aggressive symptoms of patients [35]. The MOAS includes verbal attack, property attack, self- attack, and physical attack. Additionally, the Hamilton Depression Rating Scale (HAMD) was employed to evaluate the depressive symptoms of patients [36]. The HAMD encompasses anxiety/somatization, weight loss, cognitive disturbances, diurnal variation, psychomotor, insomnia, and hopelessness. Researchers received training in administering these scales before the study commenced.

Fasting blood samples were collected by nursing staff between 6 and 8 a.m. and analyzed before 11 a.m. on the same day. Plasma samples were examined for various biochemical markers, including glycated hemoglobin (GHb), blood glucose (GLU), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), prolactin (PRL), red blood cells (RBC), white blood cells (WBC), hemoglobin (HGB), C-reactive protein (CRP), total protein (TP), albumin (ALB), globulin (Glo), cholesterol (CHO), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and homocysteine (Cys).

2.4 Statistical analysis

All statistical analyses were performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used to summarize demographic and clinical characteristics, presented as mean ± standard deviation (SD) for continuous variables and frequencies and percentages for categorical variables. Comparisons between groups were conducted using independent samples t-tests or one-way analysis of variance (ANOVA) for continuous variables, and chi-square tests for categorical variables. Post-hoc analyses were performed using the Bonferroni correction method for pairwise comparisons.

Pearson correlation analysis was employed to examine the relationships between continuous variables. When the correlation coefficient between two variables is greater than 0.7, it is generally considered an indication of high collinearity [37]. Multivariate linear regression models were constructed to explore the factors associated with the age of first hospitalization, with adjustments made for potential confounding variables such as gender, age, marital status, family history of mental illness, alcohol consumption, suicidal ideation, DUP, and dosage of antipsychotics.

To assess collinearity among independent variables, variance inflation factors (VIFs) were calculated, with values exceeding 10 indicatives of multicollinearity. The significance level for all statistical tests was set at P < 0.05. Furthermore, correlation matrices and scatterplots were generated using GraphPad Prism 9.0 to visualize the relationships between age of first hospitalization and age at first onset, as well as DUP, respectively.

3.1 Demographic and clinical characteristics

The demographic and clinical characteristics of chronic schizophrenia patients are shown in Table 1. Among these patients, 808 were male (63.57%) and 463 were female (36.43%). The age of first hospitalization for chronic schizophrenia patients was 28.07 ± 9.993 years. The average duration of untreated psychosis (DUP) was 3.14 ± 6.076 years, with a range of 0–39 years. Additionally, 11.80% of the patients had a DUP of ≥ 10 years.

Table 1

Demographic and clinical characteristics of patients with chronic schizophrenia
Variables	Frequency	%
Gender
Male	808	63.57
Female	463	36.43
Marriage status
Single	978	76.95
Non-single	293	23.05
Living style
Living alone	1088	85.60
Living with others	183	14.40
Impulsive behavior
No	1206	94.89
Yes	65	5.11
Family history
No	1051	82.69
Yes	220	17.31
Alcohol consumption
No	981	77.18
Yes	290	22.82
Smoking history
No	848	66.72
Yes	423	33.28
Suicide status
None	964	75.85
Suicide ideation	159	12.51
Suicide behavior	148	11.64
Variables	Mean	SD
Age of first hospitalization	28.07	9.933
Educational years	9.15	3.124
Age of first onset	25.04	8.112
DUP	3.14	6.076
Antipsychotic dose (chlorpromazine equivalent)	379.96	467.221
BMI	24.46	4.795
SSI score	34.28	30.406
ISI score	3.21	4.161
PANSS total score	80.02	19.557
PANSP score	17.27	6.363
PANSN score	22.87	7.229
PANSG score	39.90	10.067
RBANS total score	65.05	18.249
Immediate Memory	57.33	14.165
Visuospatial	75.89	15.586
Language	78.80	13.262
Attention	79.18	15.267
Delayed Memory	64.45	16.943
MOAS total score	1.63	2.675
Verbal Attack	0.37	0.506
Property Attack	0.38	0.832
Self-Attack	0.31	0.986
Physical Attack	0.58	1.479
HAMD total score	8.03	4.490
Anxiety/Somatization	2.21	1.314
Weight loss	0.15	0.270
Cognitive disturbances	1.52	1.236
Diurnal Variation	0.25	0.369
Psychomotor	2.04	1.417
Insomnia	0.88	0.921
Hopelessness	0.98	0.977
Note: DUP, duration of untreated psychosis. BMI, Body Mass Index. SSI, Scale for Suicide Ideation. ISI, Insomnia Severity Index. PANSS, Positive and Negative Syndrome Scale. PANSP, Positive and Negative Syndrome Scale of Positive. PANSN, Positive and Negative Syndrome Scale of Negative. PANSG, Positive and Negative Syndrome Scale of General Pathology. RBANS, Repeatable Battery for the Assessment of Neuropsychological Status. MOAS, Modified Overt Aggression Scale. HAMD, Hamilton Depression Rating Scale.

3.2 Differences in age of first hospitalization among different populations

Differences in the age of first hospitalization among different demographic groups are shown in Table 2. Single patients were hospitalized at a significantly younger age than non-single patients (P < 0.001). Furthermore, patients with a family history of mental illness were hospitalized at a significantly younger age than those without such a history (P = 0.002). Patients who consumed alcohol had a later age of first hospitalization compared to non-drinkers. Bonferroni post-hoc analysis indicated that patients with suicidal ideation or behavior were hospitalized at a younger age than those without a history of suicide (P < 0.05). However, there was no significant difference in the age of first hospitalization between patients with suicidal ideation and those with suicidal behavior (P > 0.05).

Table 2

Comparison of age of first hospitalization for different demographic variables in the chronic schizophrenia
Variable	n (%)	Age of first hospitalization, Mean ± SD	t/F	P
Gender			-0.301	0.767
Male	808 (63.57)	24.99 ± 7.83
Female	463 (36.43)	25.13 ± 8.59
Marriage status			-7.822	< 0.001
Single	978 (76.95)	23.98 ± 7.42
No-single	293 (23.05)	28.59 ± 9.24
Living style			0.101	0.923
Living alone	1088 (85.60)	25.05 ± 7.99
Living with others	183 (14.40)	24.99 ± 8.81
Impulsive behavior			-0.491	0.624
No	1206 (94.89)	25.02 ± 8.04
Yes	65 (5.11)	25.52 ± 9.33
Family history			3.082	0.002
No	1051 (82.69)	25.36 ± 8.24
Yes	220 (17.31)	23.52 ± 7.29
Alcohol consumption			-2.332	0.020
No	981 (77.18)	24.75 ± 8.08
Yes	290 (22.82)	26.02 ± 8.15
Smoking history			0.102	0.924
No	848 (66.72)	25.06 ± 8.04
Yes	423 (33.28)	25.01 ± 8.26
Suicide status			4.581	0.010
No	964 (75.85)	25.37 ± 8.05
Suicide ideation	159 (12.51)	24.70 ± 8.90
Suicide behavior	148 (11.64)	23.25 ± 7.38
Note: SD: standard deviation.

3.3 Analysis of factors related to age of first hospitalization

As shown in Table 3, age of first onset and DUP were positively correlated with the age of first hospitalization (P < 0.001). Additionally, antipsychotic medication dosage, SSI, anxiety/somatization, and diurnal variation were negatively correlated with the age of first hospitalization (P < 0.05). Supplementary Fig. 1 shows that PRL, TP, and LDL were positively correlated with the age of first hospitalization (P < 0.05), whereas ALB was negatively correlated with the age of first hospitalization (P < 0.05). Figure 2A demonstrates a significant positive correlation between the age at onset and the age of first hospitalization (R = 0.773, P < 0.001), indicating a notable collinearity. Figure 2B shows that DUP was positively correlated with the age of first hospitalization (R = 0.584, P < 0.001).

Table 3

Linear correlation analysis of age of first hospitalization in the chronic schizophrenia
Variables	Age of first hospitalization
Variables	R	P
Educational years	-0.052	0.063
Age of first onset	0.773	≤ 0.001
DUP	0.584	≤ 0.001
Antipsychotic dose	-0.055	0.049
BMI	-0.019	0.504
SSI	-0.102	≤ 0.001
ISI	0.017	0.547
PANSS total score	-0.001	0.958
PANSP score	-0.038	0.175
PANSN score	0.013	0.645
PANSG score	0.014	0.626
RBANS total score	-0.009	0.748
Immediate memory	-0.028	0.323
Visuospatial	0.035	0.208
Language	0.016	0.558
Attention	0.027	0.339
Delayed Memory	0.043	0.127
MOAS total score	-0.040	0.150
Verbal Attack	-0.040	0.154
Property Attack	-0.050	0.077
Self-Attack	-0.024	0.391
Physical Attack	-0.015	0.588
HAMD total score	-0.055	0.052
Anxiety/Somatization	-0.056	0.047
Weight loss	0.046	0.098
Cognitive disturbances	-0.027	0.345
Diurnal Variation	-0.061	0.029
Psychomotor	-0.040	0.152
Insomnia	-0.001	0.962
Hopelessness	-0.048	0.086
Note: DUP, duration of untreated psychosis. BMI, Body Mass Index. SSI, Scale for Suicide Ideation. ISI Insomnia Severity Index. PANSS, Positive and Negative Syndrome Scale. PANSP, Positive and Negative Syndrome Scale of Positive. PANSN, Positive and Negative Syndrome Scale of Negative. PANSG, Positive and Negative Syndrome Scale of General Pathology. RBANS, Repeatable Battery for the Assessment of Neuropsychological Status. MOAS, Modified Overt Aggression Scale. HAMD, Hamilton Depression Rating Scale.

3.4 Factors influencing the age of first hospitalization

Table 4 presents the regression analysis results for the age of first hospitalization in chronic schizophrenia patients. We found that marital status (single), family history (yes), alcohol consumption (no), and suicidal status (suicidal ideation and behavior) were risk factors for an earlier age of first hospitalization. DUP, TP, and LDL were positively correlated with the age of first hospitalization (P < 0.05). Additionally, antipsychotic medication dosage and ALB were negatively correlated with the age of first hospitalization (P < 0.05).

Table 4

Regression analysis of factors influencing age of first hospitalisation.
Model		Unstandardized coefficient		Standardized coefficient	t	P	95% confidence interval for B		VIF
Model		B	Standard Error	Beta	t	P	Lower	Upper	VIF
Age of first hospitalisation	Constant	19.953	1.562		12.770	< 0.001	16.888	23.018
	Marriage status	4.404	0.514	0.187	8.565	< 0.001	3.395	5.412	1.014
	Family history	-1.633	0.574	-0.062	-2.844	0.005	-2.759	-0.506	1.020
	Alcohol consumption	1.254	0.517	0.053	2.427	0.015	0.240	2.268	1.017
	Suicide status	-0.815	0.383	-0.056	-2.130	0.033	-1.566	-0.064	1.465
	DUP	0.934	0.036	0.571	26.225	< 0.001	0.864	1.004	1.011
	Antipsychotic dose	-0.001	0.000	-0.052	-2.404	0.016	-0.002	0.000	1.011
	SSI score	-0.007	0.009	-0.020	-0.770	0.441	-0.023	0.010	1.476
	Anxiety/Somatization	-0.256	0.185	-0.034	-1.386	0.166	-0.618	0.106	1.271
	Diurnal Variation	-0.547	0.655	-0.020	-0.835	0.404	-1.833	0.738	1.263
	PRL	0.000	0.000	0.027	1.233	0.218	0.000	0.001	1.022
	TP	0.036	0.011	0.070	3.204	0.001	0.014	0.058	1.007
	ALB	-0.046	0.019	-0.054	-2.504	0.012	-0.083	-0.010	1.005
	LDL	0.079	0.025	0.068	3.110	0.002	0.029	0.128	1.011
Note: DUP, duration of untreated psychosis. SSI, Scale for Suicide Ideation. PRL, prolactin. TP, total protein. ALB, albumin. LDL, low-density lipoprotein. R² = 0.0.410, ΔR² = 0.404, F = 67.290, P < 0.001.

To our knowledge, this is the first large-sample study exploring the age of first hospitalization among chronic schizophrenia patients in China. Our primary findings are as follows: 1. Age of first hospitalization in Chinese chronic schizophrenia patients is related to marital status, family history of mental illness, alcohol consumption, and suicidal status. 2. Age of first hospitalization is negatively correlated with antipsychotic medication dosage and ALB levels. 3. Additionally, age of first hospitalization is positively correlated with DUP, TP, and LDL levels.

We found a significant difference in the age of first hospitalization based on marital status, with single patients being hospitalized at a younger age than non-single patients. The impact of marriage on mental illness has been extensively studied [38, 39]. Previous research has found that married schizophrenia patients have a shorter DUP, indicating that they receive treatment sooner after the onset of illness [40]. Moreover, married schizophrenia patients tend to have a later onset age [41]. Some researchers suggest that marriage may have a protective effect against mental illness [40] and a better prognosis [42], although the specific mechanisms remain unclear. We hypothesize that married patients may receive more social support, which in turn results in a later age at hospitalization [40] compared to single patients.

Our study found that patients with a family history of mental illness were hospitalized at an earlier age. This result aligns with our hypothesis that patients with a family history of mental illness are at a higher risk of developing the disorder [43], leading to an earlier age of first hospitalization. Mental illness is a polygenic hereditary disorder influenced by both genetic and environmental factors [43, 44]. Previous research has identified patients with a family history of schizophrenia as a high-risk group for developing mental disorders [45]. Previous studies have also shown a genetic predisposition to mental illness [45, 46]. Therefore, the mental health of individuals with a family history of mental illness should receive more attention [47].

The relationship between alcohol consumption and mental illness is well-established [48]. Alcohol can lead to various mental and behavioral disorders, including alcohol dependence, delirium, sleep disorders, and dementia [49, 50]. However, previous research has not explored the relationship between alcohol consumption and hospitalization. Interestingly, we found that schizophrenia patients who consumed alcohol were hospitalized at a later age than non-drinkers. This result may be due to the complex effects of alcohol on schizophrenia patients [51, 52]. Previous studies have found that schizophrenia patients who consume alcohol have more severe psychiatric symptoms [53]. We hypothesize that alcohol, as an ancient psychoactive substance, may suppress certain symptoms of schizophrenia, such as intrinsic motivation[54]; alternatively, alcohol drinking may be a defensive strategy used by schizophrenia patients to cope with hallucinations and delusions. However, alcohol use is associated with violence and self-harm in schizophrenia [55, 56]. Hence, the relationship between alcohol and treatment-seeking behavior in schizophrenia patients requires further exploration.

The relationship between suicide and schizophrenia has been widely studied [57, 58]. We found that schizophrenia patients with a history of suicidal behavior were hospitalized at an earlier age, which is consistent with our hypothesis. The incidence of suicide in schizophrenia is high, with a lifetime prevalence of 34.5% for suicidal ideation and 44.3% for suicide planning. Suicide increases the risk of disability and death, leading to urgent medical intervention [59]. In China, mental health laws allow for the compulsory hospitalization of schizophrenia patients with suicidal behavior [60, 61]. Despite the long-standing and widespread stigma associated with seeking treatment and hospitalization for mental illness in China, the issue of suicide is receiving increasing attention [62]. As a result, caregivers and the community are likely to promptly hospitalize patients exhibiting suicidal behavior [63].

Another important finding of our study is the negative correlation between age of first hospitalization and antipsychotic medication dosage. This result indicates that higher doses of antipsychotic medication are associated with longer periods of community living and, consequently, later ages at first hospitalization. Higher doses of antipsychotic medication may also correlate with more severe illness [25, 64]. Surprisingly, we found no correlation between age of first hospitalization and PANSS scores, which contradicts our initial hypothesis. Possible reasons for this result include: first, chronic schizophrenia is primarily characterized by negative symptoms [65]. Previous studies have found that disease duration is associated with negative symptoms in schizophrenia [66]. Negative symptoms, such as emotional blunting and behavioral withdrawal, may lead to delayed or urgent medical treatment [67]. Second, the PANSS total score in chronic schizophrenia patients is not high (average score of 80.02). Therefore, these patients may live in the community rather than being hospitalized. Finally, there may be differences in the recognition of psychiatric symptoms between psychiatrists and primary caregivers [68]. For example, professionals can accurately assess hallucinations and emotional blunting in chronic schizophrenia, which may be difficult for caregivers to identify. Thus, while PANSS scores represent clinical severity, they do not correlate with age of hospitalization as the decision to admission is primarily made by the caregivers or guardians.

Another major finding of our study is the positive correlation between DUP and age of first hospitalization. Research on DUP has gained increasing attention over the past 20 years [69, 70]. Longer DUP is associated with poorer prognosis in patients [71]. We found that longer DUP is positively correlated with later age of first hospitalization, implying that delayed intervention in schizophrenia leads to a later age of first hospitalization. Our previous studies have identified long DUP phenomenon in both chronic schizophrenia [17] and first-episode drug-naïve schizophrenia [9]. The current study confirms the delay in treatment-seeking behavior for schizophrenia in China, whether considering DUP or age of first hospitalization. Therefore, future research should continue to explore treatment-seeking behavior in Chinese schizophrenia patients, and proactive intervention measures are urgently needed in public management of schizophrenia.

We also found correlations between age of first hospitalization and blood biomarkers. Previous research has not explored the relationship between blood biomarkers and age of first hospitalization. Our study found that age of first hospitalization is negatively correlated with ALB levels and positively correlated with TP and LDL levels. ALB and TP indicate patients' nutritional status [72], while LDL is a lipid indicator [73]. These results suggest a possible association between age of first hospitalization and patients' nutritional and lipid profiles. Schizophrenia can cause abnormal eating and metabolism [74], which may influence treatment-seeking behavior. However, the use of antipsychotic medication can also lead to metabolic syndrome, including disturbances in blood glucose and lipids [75]. Therefore, further research is needed to clarify the relationship between blood biomarkers and treatment-seeking behavior in schizophrenia patients.

Limitations

Our study has several limitations that should be acknowledged. First, the cross-sectional design of the study limits our ability to draw causal inferences about the relationships between the identified factors and the age of first hospitalization. Longitudinal studies are needed to better understand the temporal dynamics of these associations. Second, our sample was recruited from 17 psychiatric hospitals across China, which may not be fully representative of the entire population of patients with chronic schizophrenia in the country. Regional variations in healthcare access and practices could influence the generalizability of our findings. Third, self-reported data on alcohol consumption and other behaviors may be subject to recall bias or social desirability bias, potentially affecting the accuracy of these measures. Fourth, while we included a wide range of clinical and biochemical variables, other potentially relevant factors such as cognitive function and environmental stressors were not assessed. Additionally, although we have identified a relationship between blood markers and the age of hospitalization, this does not imply causation. For instance, it is possible that prolonged schizophrenia could lead to abnormal blood markers. Therefore, future studies should include controlled research to further elucidate the relationship between blood markers and the age of hospitalization. Finally, the study did not control for potential confounders such as socioeconomic status, which could influence both the timing of hospitalization and the observed clinical and biochemical variables.

In conclusion, our study provides important insights into the factors influencing the age of first hospitalization in patients with chronic schizophrenia in China. We found that marital status, family history of mental illness, alcohol consumption, and suicidal behavior are significant predictors of the age of first hospitalization. Additionally, we identified correlations between age of first hospitalization and several blood parameters, including ALB, TP, and LDL levels. These findings highlight the complex interplay of psychosocial, clinical, and biological factors in determining the timing of psychiatric care in chronic schizophrenia. Our results underscore the need for targeted interventions aimed at reducing delays in treatment. Future research should focus on longitudinal studies to confirm these associations and explore the underlying mechanisms.

Conflict of Interest Statement: The authors declare no conflicts of interest.

Funding: This work was supported by the National Natural Science Foundation of China [81973759]. This source had no further role in this study design, in the data collection and analysis, in the writing of the report, and in the decision to submit the paper for publication. The authors acknowledged the nurses and psychiatrists that provided professional support when conducting data collection.

Ethics approval and consent to participate: The protocol for the research project had been approved by the Institutional Review Board (IRB) of the Institute of Psychology, Chinese Academy of Sciences (approval number: H18031), and had therefore been performed following the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Patients' informed consent forms were obtained, and their anonymity was protected.

Data availability statement: The data supporting this study's findings are available on request from the corresponding author.

Acknowledgements: The authors would like to show their great gratitude to all the patients who participated in this study for their participation.

Author Contributors: GSL and XYZ were responsible for the study design and manuscript preparation. GSL, QLH, YY, and STY were involved in evolving the ideas and editing the manuscript. QLH, STY, YD, and CL were responsible for recruiting the patients, performing the clinical rating, and statistical analysis. GSL and YD collected the data, provided language help and writing assistance. All authors have contributed to and approved the final manuscript.

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Factors influencing the age of first hospitalization in patients with chronic schizophrenia: Role of clinical features and blood parameters

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Abstract

Background

Methods

Results

Conclusions

Figures

1. Introduction

2. Methods

2.1 Participants

2.2 Duration of untreated duration

2.3 Clinical measurements

2.4 Statistical analysis

3. Results

3.1 Demographic and clinical characteristics

3.2 Differences in age of first hospitalization among different populations

3.3 Analysis of factors related to age of first hospitalization

3.4 Factors influencing the age of first hospitalization

4. Discussion

Limitations

Conclusion

Declarations

References

Additional Declarations

Supplementary Files

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