Negative symptoms, characterized by deficits in motivation, communication, emotion, and social functioning (1), are considered a core feature of schizophrenia—a chronic and debilitating mental disorder (2). These symptoms significantly deteriorate the functioning and quality of life of patients with schizophrenia (2–5), imposing a substantial burden on patients, their families, and the healthcare system (6). Negative symptoms primarily denote the decrease or absence of typical behaviors (such as indulgence, anhedonia, and social engagement) or expressions (such as emotional dullness, apathy) associated with motivation and interest (7, 8). The current consensus classifies negative symptoms into five domains: Blunted affect, characterized by a reduction in emotional expression, demonstrated by decreased facial and vocal expressions, and physical movements; Alogia, referring to a decrease in the quantity of speech and spontaneous elaboration; Asociality, indicating a diminished drive to engage in interpersonal relationships, leading to reduced social interactions; Anhedonia, describing a decreased capacity to derive pleasure from current activities or anticipate enjoyment from future engagements; Avolition, representing a diminished ability to initiate and maintain goal-oriented activities due to a lack of motivation (9).

Negative symptoms have been differentiated into either primary symptom intrinsic to schizophrenia, or secondary symptom resultant from other underlying factors (6). Primary negative symptoms, considered inherent aspects of schizophrenia’s core pathology, are thus direct manifestations of the disorder (10). Secondary negative symptoms, however, are thought to arise from exogenous factors, they are typically transient and more prevalent than primary negative symptoms (11). Given their clear causative factors, secondary negative symptoms are generally more responsive to treatment compared to primary negative symptoms (11, 12). Secondary negative symptoms in schizophrenia can stem from a variety of sources, including positive symptoms, depressive symptoms, side effects of antipsychotic medication (such as extrapyramidal symptoms), or prolonged social isolation due to extended hospitalization (2, 13–15). According to the European Psychiatric Association (EPA) guidance on assessment of negative symptoms in schizophrenia, there are three key factors that might serve as “secondary factors” which include depressive symptoms, positive symptoms, and extrapyramidal symptoms (7). For instance, extrapyramidal symptoms can lead to a blunted affect and alogia, both of which form part of the negative symptoms (2). However, it remains unclear whether these secondary factors impede social functioning by exacerbating negative symptoms.

Social functioning, defined as the capacity to comprehend and partake in social activities, thus facilitating effective and regular involvement in social life (16), constitutes a crucial facet of the rehabilitation journey for individuals diagnosed with schizophrenia (17). It is important to highlight that impaired social functioning is a typical characteristic of those with schizophrenia, with negative symptoms serving as a major contributor to such deficits (18). Notably, the co-occurrence of depressive symptoms is another influential factor, as it has been found to result in markedly detrimental consequences on social functioning in patients with schizophrenia (19). It is also noteworthy that positive symptoms have been identified as influencing social functioning in patients with this disorder. Furthermore, existing literature has established that patients presenting more severe motor impairments, such as extrapyramidal symptoms, often correspondingly display worsened social functioning (20). Motor abnormalities, such as extrapyramidal symptoms, are believed to result from a combination of brain dysfunction and the side effects of antipsychotic medication (20, 21). Despite these observations, the interrelationships among these secondary factors (which contribute to secondary negative symptoms), negative symptoms themselves, and social functioning call for further exploration.

The main objective of this study is 2-fold. Firstly, we aimed to investigate several potential “secondary factors” that might lead to negative symptoms in chronic schizophrenia. Secondly, by employing mediation analysis, the relationship among (1) negative symptoms, (2) secondary factors (including positive symptoms, depressive symptoms, and extrapyramidal symptoms), and (3) social functioning were explored. For this study, our hypothesis suggests that the “secondary factors” has an impact on social functioning by a mediator of the severity of negative symptoms.

This study aimed to examine the presence of negative symptoms in patients with chronic schizophrenia and to identify factors associated with secondary negative symptoms. Our findings revealed that negative symptoms were significantly associated with positive symptoms and depressive symptoms.

Depressive symptoms are highly prevalent in patients with schizophrenia, occurring in approximately 25% of cases (31), and can manifest at any stage of the disease (11). Moreover, more than 60% of patients with schizophrenia experience depressive symptoms (32), whereas secondary comorbidities of depression are common in chronic schizophrenia (33). Our study confirmed previous findings, which suggest a significant positive correlation between depressive symptoms and negative symptoms in patients with chronic schizophrenia (34). For example, the degree and duration of depressive symptoms in psychiatric patients were correlated with negative symptoms (35).

Furthermore, an overlap between depressive symptoms and negative symptoms in patients with schizophrenia has been noted (11). Anhedonia and avolition are common symptoms of both schizophrenia and depression (36). The key feature of this overlap is anhedonia, which is a core symptom of depression and an important feature of schizophrenia (37, 38). Depressive symptoms are one of the most common factors associated with secondary negative symptoms of schizophrenia (15). Depression can lead to secondary negative symptoms, such as lack of energy, amotivation, and decreased interest (11). Our study also showed that both depressive symptoms and negative symptoms were significantly negatively correlated with GAF scores. A previous study has found that the more prominent the negative and depressive symptoms of schizophrenic patients were, the more severe their impairment of social function (39). In our study, we conducted a mediating analysis and found that negative symptoms completely mediated the relationship between depressive symptoms and social functioning. That is, depressive symptoms had no significant direct effect on social functioning, but mainly influenced it through secondary negative symptoms. Therefore, in the rehabilitation of social functioning in chronic schizophrenia, it is important to pay attention to patients with depressive symptoms, and to intervene possible secondary negative symptoms associated with these depressive symptoms.

Another important factor contributing to negative symptoms being the positive symptoms. Our study found a significant negative correlation between positive and negative symptoms in patients with chronic schizophrenia. However, previous studies have suggested a positive correlation, with improvement of positive symptoms leading to remission of negative symptoms (40). For instance, delusions of victimhood or hallucinations can cause social withdrawal, hindering the patient’s ability to engage in communication or enjoy group activities (34). By treating positive symptoms, such as hallucinations and delusions, negative symptoms secondary to positive symptoms may be alleviated (40). Concerning the discrepancy between our findings and the previous ones, we suspect the characteristics of participants might played a role. All participants in our study were long-term hospitalized patients with chronic schizophrenia, whose negative symptoms were more prominent and positive symptoms relatively mild. When a patient’s condition fluctuates, psychiatrists may increase the dose of antipsychotics, potentially worsening negative symptoms (41). At the same time, decreased positive symptoms may lead to alleviated secondary negative symptoms, which can be relieved by antipsychotics. These results suggest a complex relationship between positive symptoms and secondary negative symptoms that may require further investigation.

Our study results indicate a correlation between extrapyramidal symptoms and negative symptoms. However, these extrapyramidal symptoms do not seem to influence social functioning through negative symptoms. Currently, the relationship between extrapyramidal symptoms and negative symptoms remains unclear. In the two-factor model of negative symptoms, the deficit in the expressive dimension could be affected by extrapyramidal symptoms (2). Therefore, it is plausible that extrapyramidal symptoms could exacerbate the deficit in the expressive dimension of negative symptoms. However, these relationships need further exploration, it is indeed very challenging to differentiate between the Expressive Deficit domain of negative symptoms, which includes blunted affect and alogia (7). Another critical point is the use of antipsychotic medications. The dosage of antipsychotic medications may be a significant factor (7). Future research could focus on exploring the relationship between the dosage of antipsychotic medications, extrapyramidal symptoms, and the deficit in the expressive dimension of negative symptoms.

Additionally, our study found a strong association between apathy, one of the subscales of SANS (24), and social functioning. Apathy is a prevalent negative symptom (42) that significantly affects the social functioning of patients with chronic schizophrenia (43). Our results hinted that reducing apathy should be a priority in the rehabilitation of patients with schizophrenia. Moreover, we proposed that factors leading to secondary negative symptoms might indirectly affect social functioning through negative symptoms. However, our findings indicated that positive symptoms had a direct negative effect on social functioning, consistent with a previous study (44), which reported a significant negative association between positive symptom clusters and social functioning. However, we also found that positive symptoms can positively moderate social functioning by moderating negative symptoms. The relationship between positive symptoms, negative symptoms, and social functioning is complex, and it is affected by drug treatment, side effects, and other factors.

Our study has several clinical implications. First, patients with chronic schizophrenia require special attention and treatment of negative symptoms during social functioning recovery. Among factors contributing to negative symptoms, depressive symptoms and positive symptoms should be the focus of intervention. The intervention of extrapyramidal symptoms should also be considered comprehensively. The treatment process would benefit from controlling depressive symptoms and positive symptoms while minimizing adverse drug reactions, which may aggravate negative symptoms.

Certain limitations in our study merit attention. First, our assessment of negative symptoms solely relied on the SANS and PANSS scales. Future research might benefit from incorporating more recent second-generation negative symptom scales, such as the Brief Negative Symptom Scale (BNSS) and Clinical Assessment Interview for Negative Symptoms (CAINS). These updated scales resonate more with current conceptualizations of negative symptoms and enable a clear distinction between primary and secondary negative symptoms. Secondly, our study lacked data pertaining to the temporal relationship between the onset of negative symptoms and the commencement and augmentation of antipsychotic treatment. As such, we were unable to verify whether all extrapyramidal symptoms we noted were indeed secondary to antipsychotic treatment. Thirdly, considering that not all aspects of function might be impacted by negative symptoms, future research could potentially adopt rating scales that offer a clear separation of functional aspects. This could provide a more nuanced assessment of patients’ social functioning. Fourthly, the relatively small sample size in our study may limit the extrapolation of our findings. To validate our results, larger-scale studies are recommended. Finally, to further unravel the temporal dynamics of negative symptoms and their contributory factors, it would be beneficial for future research to include longitudinal data.

This study indicates that factors depressive symptoms and positive symptoms may play significant roles in the evolution of secondary negative symptoms in schizophrenia. Our findings propose that negative symptoms act as pivotal mediators in the correlation between “secondary factors” (including the depressive symptoms and positive symptoms) and social functioning. Therefore, in managing chronic schizophrenia, the targeted treatment of depressive symptoms, as well as the positive symptoms could represent a crucial strategy for enhancing social functioning by addressing secondary negative symptoms.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.

The study protocol was approved by the Ethics Committee of one Mental Health Center in Beijing (protocol number: 109). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

The concept for this article was proposed by YL, and NH, WL, HD, JS, HY, JC, WH, HW, XZ, PZ, SH, YC, and TF collaborated to develop the protocol, establish the search strategy, and define the inclusion and exclusion criteria. Data collection was conducted by NH, WL, HD, JS, HY, JC, WH, HW, PZ, SH, XZ, and YC, while YL performed the statistical analyses, interpreted the data, and created the figures and tables. NH and TF drafted the initial version of the report with critical feedback from YL and YC. NH, WL, HD, JS, HY, JC, WH, HW, XZ, PZ, SH, YC, TF, and YL participated in the interpretation of the findings, and revision of the report, and gave their final approval of the manuscript. All authors contributed to the article and approved the submitted version.

This work was supported by the National Natural Science Foundation of China under Grant Nos. 81901345, 82001445, and 82171538, the Natural Science Foundation of Beijing Municipality under Grant Nos. 7212035, and the Beijing Municipal Administration of Hospitals’ Youth Program under Grant No. QML20232006, QML20232003, and QML20211203.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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