Suicide, the act of intentionally injuring oneself with the intent of dying, including attempt, preparation, ideation, and planning, is a challenging and complex public health problem that affects all countries (1). According to the WHO website data, close to 703,000 people died by suicide worldwide in 2019 (2). The latest data from the United States referenced 47,511 people dying of suicide in 2019 (3). Meanwhile, that number in China was approximately 126,000 people and ranked 13 in all-cause mortality in 2017 (4). Suicide can occur at any time of life, but in young people aged 15–29, it ranks fourth among causes of death in a report from 2019 (2). There are many reasons people commit suicide, such as physical diseases, mental disorders, life stressors, or events. Studies on factors leading to suicide have been undertaken for decades. The dimensions include but are not limited to genes, neuroanatomy, biochemistry, the environment, nutrition, physical and mental diseases, mainly depression, and alcohol abuse (2, 5–9), but suicide prevention remains an area of uncertainty and needs further research (10).

According to a cross-sectional epidemiological nationwide study conducted during 2013–2015 in China, the lifetime prevalence of mood disorders was 7.4% (4). People with mood disorders’ lifetime prevalence of suicidal ideation, planning, and attempts were 53.1, 17.5, and 23.7%, respectively (11), which were much higher than those in the Chinese general population (3.1, 0.9, and 1.0%, respectively) (12). Those study results make mood disorder an unignorable factor for suicide prevention.

Temperament describes individual differences in behavior based on biology (13). It derives from the original theory of Hippocrates and Galen about chemical imbalance and modern studies of neurochemistry and psychiatry (13). Temperament traits are diverse among different populations, and there have been some independent studies on depressive patients and the general population (14–16), but there is still a lack of comparative studies between the two kinds of populations.

In China, the majority of patients with first-episode depression will present to primary care, with problems other than mood disorder (17). As there is a low recognition rate, many patients with depression commit suicide before they seek treatment at psychiatric clinics, which still lack data but provide a lot of news. For suicide prevention, we need to find a relationship between suicide and temperament. There were many scales that could be chosen for our research purpose, for example, the Functional Ensemble of Temperament (FET) including emotional, physical, verbal, and mental aspects traits of behavior (18, 19). Since mood is the main clinical symptom of depressed patients, we mainly choose a scale measuring temperament only. Two studies evaluating participants from the general population and patients with depressive disorder assessed by the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) showed that cyclothymic, irritable, and especially dysthymic temperaments might be important factors in self-harm in adolescents (20). In patients with depression, cyclothymic and dysthymic temperaments were associated with suicide acts in bipolar disorder compared with major depressive disorder (MDD) (21). These studies are the basis of our further research on temperament traits in first-onset MDD. We know that temperament cannot solely predict suicide risk in neither the general population nor depressive disorders, but we hope to sketch features associated with suicide act and find some common characteristics as either a theoretical foundation or practical guidance for clinicians.

Biopsychosocial factors converge in suicide is allostasis, as an adaptive physiological response occurs when an organism is challenged. There were some hypothesizes on the converge relations. Previous studies indicate that cyclothymic and anxious temperament traits (assessed with the TEMPS-A) are associated with higher stress (29). Stress alters neuroplasticity in humans assessed with transcranial magnetic stimulation, and altered neuroplasticity has been associated with worsening of depression (30, 31). Indeed, indicators of stress (increased allostatic load) have been associated with suicide (32). The convergent relations include all the pathological mechanism and social and psychological factors.

To the best of our knowledge, this is the first study exploring the associations of temperament, depressive symptoms, and suicidal risk among patients with first-episode of MDD. In these first-onset MDD subjects, we obtained the following: (1) suicide rate; (2) temperament trait differences from HCs; (3) demographic characteristics and temperament differences between the suicidal and non-suicidal groups; and (4) cyclothymic and dysthymic temperament, as well as sex, age, and severe depression, were independent suicidal risk factors.

Many studies have shown that depressive episode frequency is closely related to suicidal risk (8, 33, 34). A higher episode frequency means a higher suicide rate. In this study, we found that the suicide rate of first-episode of MDD was as high as 47.62%, close to previous studies of MDD from 47 to 69% (35–37), meaning that nearly half of the patients with depression had suicidal ideation or attempted suicide during their first major depressive episode, so we should pay attention to the suicide risk from the very first episode of MDD.

Approximately 20% of the general population has a certain type of emotional temperament (13). In this study, the mean rank direction of temperaments in HCs was hyperthymic > irritable > anxious > cyclothymic > dysthymic, and in MDD was dysthymic > cyclothymic > anxious > irritable > hyperthymic. These directions showed the different temperament tendencies in different population. The two exactly opposite directions in two populations is interesting and needs further research. This study tried to identify suicide risk factors in patients with first-episode depression. Compared with HCs, patients with first-episode MDD scored significantly different on dysthymic and cyclothymic temperaments. Generally, women are prone to have dysthymic, cyclothymic, and anxious temperament, while men are prone to have hyperthymic and irritable temperament (15). In our study, the mean rank direction of temperament in MDD also showed that the dysthymic outnumbered hyperthymic temperament, which also proved to be the truth that women were more prone to being depressed than men.

We compared the temperament differences between suicidal and non-suicidal risk in patients with depression. As expected, cyclothymic and dysthymic temperaments were associated with a greater risk of suicide. The five factors significantly and independently differentiated patients with vs. without suicidal risk based on multivariable logistic regression modeling are as follows: female sex, current age, dysthymic temperament, cyclothymic temperament, and higher HAMD score. The five factors set a model of high suicide risk. The final factors/features of suicide-risk patients were the same as the clinical impressions. People with cyclothymic temperament traits show instability in mood, thoughts, and behaviors, while mood instability usually leads to suicidal behavior, and quickly changing mood stations enhance suicidal ideation and attempts (15). Depressive patients with cyclothymic temperament traits are probably developing bipolar disorder (38), as well as high rates of suicide and hospitalization (21, 39). All the bad outcomes make the early recognition of MDD and suicide risk necessary.

Many previous studies have examined the demographic characteristics of suicide risk factors in patients with depressive disorder. As expected, the onset age was strongly associated with suicide, which was also supported by other studies (40). Early onset age (especially <18 years) of depression is associated with an increasing rate of conversion to bipolar disorder (41), which is also a highly risk factor for suicide (21, 42). Subjects of this study were people with a current age over 18 years, and the mean illness duration was 6–6.5 months; we did not obtain the suicide rate of younger adolescents, which still needs further research. Other demographic suicide risk factors in MDD included female sex (71.25%) and unmarried status (76.25%), which were in accordance with previous observations (21, 43). We found that a greater suicide risk was more associated with female sex, which was also confirmed in other studies (16, 44). However, men may have more violent suicide attempts than women, and lethal action makes their suicide death rate higher than in women (42), which also needs further study. Our study showed that unmarried and unemployed people are easily prone to depression, and unmarried people have significantly higher instances of thoughts or actions related to suicide.

In our study, first-episode depression was detected by HAMD. We found that HAMD had removed the third (suicide) item score, which could still predict suicidal risk in MDDs. This means, in addition to the third (suicide) item, all the other HAMD-17 items’ total score is closely linked to suicide risk (45, 46). Particularly of note, the standardized HAMD scale predicting suicide may result in approximately 30% false positives (47), so it is risky to take HAMD score as a sole predict factor of suicide risk. The best chance to recognize suicide risk would be to confirm predictors as much as we can.

After confirming the predictors of suicidal risk, especially the temperament factor, could suicide be intervened? Serotonin is a neurotransmitter involved in many brain and body functions. Impaired serotonergic function is involved in the development of suicide behavior and was proven decades ago (48). Some studies on genes showed that depression and suicide were at the same gene locus (6, 49–51), other than a causal relationship. They found that the S allele in the serotonin transporter-linked polymorphic region (5-HTTLPR) may be associated with affective temperament, especially cyclothymic temperament (52). Sarmiento-Hernández’s study showed that the S-allele and the SS genotypes of 5-HTTLPR were associated with suicide attempts (53). They provide a theoretical basis for the relationship between cyclothymic temperament and suicide. If the suicide risk and temperament are genetic phenotypes and share the same locus, is intervention difficult? Other studies have shown that affective temperaments may change to some degree, and people could exhibit one type of character trait during puberty and deviate when they grow up (54). They provide the basis that temperament is changeable throughout a person’s life (55). Japanese researcher Inoue studied the influence of ambient temperature on temperament (56), which makes us believe that the final outcome could be intervened.

Several important limitations should be considered. First, our study had a cross-sectional design, and the factors associated with suicide should not be considered direct risk factors or “causes.” Second, the self-report scale may cause recall bias. Third, the single site of observation may cause selection bias, and some high suicide risk patients did not ask doctors for help. Fourth, due to cultural background differences, the results may not be suitable for other populations or ethnicities. Finally, there were few analyzable factors in our study. More factors would make the results more convincing.

The findings of the study support the notion that there are temperament differences between the general population and patients with depression. People with cyclothymic or dysthymic temperament traits have a higher suicide risk than those with other temperament traits in patients with first-onset MDD. Young women with cyclothymic or dysthymic temperaments may be the highest suicidal risk population.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Ethics Committee of Beijing HuiLongGuan Hospital. The patients/participants provided their written informed consent to participate in this study.

LY: conceptualization, data curation, formal analysis, and writing the original draft. T-HS: conceptualization, methodology, validation, investigation, and writing the original draft. Y-YW and L-GZ: funding acquisition, conceptualization, supervision, and validation. S-JZ: investigation, methodology, supervision, and validation. J-JY and L-YZ: investigation, methodology, and supervision. H-JL: investigation and methodology. J-XC: study design. All authors contributed to the article and approved the submitted version.

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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