Abstract

Background
Progress has been achieved in many fields in understanding the biological mechanisms of depression, including genome-wide association analysis, neurotransmitter system function, brain regions and neural networks, inflammatory response, neuroplasticity, neuroimaging, and neuro electrophysiology. These progresses provide a reliable basis for developing the medical and physical therapies for depression. However, the current treatments developed from biological mechanisms can only address less than 60% of depressive symptoms and have limited efficacy in improving social functioning and reducing recurrence. Studies have explored the non-biological mechanisms of depression in mental fields. These progresses are helpful to develop more interventions that could alleviate depressive symptoms, improve functional impairments, and reduce recurrence, thereby promoting a more comprehensive recovery in depressed patients. However, there is not a systematic and deep review to highlight the non-biological mechanisms of depression.

Methods
This study summarizes the recent progress in the non-biological fields of depression by searching publications on human studies in PubMed, PMC, and Google Schooler with exclusion of animal studies.

Results
This study reviews the intergenerational transmission characteristics, the relationship between depression and emotional trauma, cognitive deficit, relationship impairment, self-function, sense of the meaning of life, motivation deficit, and psycho-rationality of depression.

Conclusions
This study was clarified the non-biological mechanisms and characteristics of depression and provided a theoretical basis for the development of non-drug interventions.

Introduction

To date, studies on the pathogenesis of depression are mainly focus on its biological mechanisms (Miao & Chang, 2021), including studies on epigenetic alterations, genome-wide association, neurotransmitter system, brain regions and neural networks, inflammatory responses, neuroplasticity, neuroimaging, and neuro electrophysiological changes (Li et al., 2021). The outstanding contributions of these studies provide a theoretical basis for pharmacotherapy and physical therapy of depression (Li et al., 2019). However, the current treatments developed from biological mechanisms can only relieve 58% of depressive symptoms (Ormel et al., 2019). Moreover, these current pharmacotherapy and physical therapy have limited efficacy in improving prognosis and social function, as well as reducing relapse rates (Cieślik et al., 2020). The cognitive behavioral therapy has been shown to be highly effective in treating depression but has limited impact on generational deficits and trauma-related emotional responses in the symptomatic components of depressive symptoms (Johnsen, T. J., & Friborg, O. 2015). The eye movement desensitization and reprocessing therapy has shown some positive outcomes in helping individuals to reprocess traumatic memories of some emotional traumas, but it is not appropriate for traumatized populations of all backgrounds and can exacerbate symptoms in some populations. Therefore, its limitations and side effects need to be considered (Shapiro, F. 2014). Thus, exploration of new mechanisms and subsequent development of new treatments is an urgent need for patients with depression.

Results

۳٫۱٫ Non-biological transgenerational transmission of depression
Intergenerational transmission of pathological psychology refers to the phenomenon that psychological disorders or problems presented in the previous generation can reappear in the next generation, or that the behavior or psychological trauma of the previous generation causes mental and psychological problems in the next generation. These problems may span generations and manifest in different ways and degrees (Cooke et al., 2019). In recent years, evidence on the intergenerational transmission of depression has been accumulated. In the biomedical field, family and twin studies have repeatedly validated that the intergenerational transmission of depression is often a result of gene-mediated genetic disorders or epigenetic inheritance (Goodman, 2020, Park et al., 2019). However, the non-biological transgenerational mechanisms of depression have also attracted attention recently (Gotlib et al., 2020).

More and more non-biological transmissions have been observed, while the intergenerational phenomenon of depression and its transmission ways have different explanations (Hentges et al., 2021). For example, parental depression may be transmitted to the next generation through multiple pathways: intergenerational transmission of trauma (Hankerson et al., 2022); intergenerational damage to emotions, self-esteem, and cognition; family culture; parenting style; and behavioral consequences etc. (Kang et al., 2021, Risi et al., 2021, Kujawa et al., 2020, Johnco et al., 2021). These transgenerational mechanisms may indirectly influence the biological changes that evolve into the symptoms of depression (Allison et al., 2023). In the intergenerational transmission of depression, offspring may not inherit the symptoms of depression, but instead display a variety of psychological dysfunctions a variety of psychological dysfunctions, including a tendency to react negatively to emotions (Israel & Gibb, 2024), a state of self-esteem hypersensitivity, cognitive biases, and excessive self-focus (Woody et al., 2022). In addition, offspring may also display relationships with alienation, control, and unclear boundaries (Wei et al., 2023), and even the characteristics of illness that appear in early adulthood or suicidal tendencies (Gijzen et al., 2021).