The principal finding of the present study was the correlation between psychiatric symptoms, especially suicidal ideation, and low serum lipid levels (TC, TG, LDL). Also, a statistically significant difference was observed between the baseline and 3rd month BDI and BAI scores. Furthermore, although increased were observed in BSS and BPRS scores after the treatment, these increases were not statistically significant.
Several studies have investigated the factors that could increase the suicide risk in patients under ITT treatment [8,9,13,14,33]. Certain studies reported that several factors such as female gender, previous psychiatric treatment, psychiatric treatment history in the family, absence of supportive factors, and ethnicity increased the risk of suicide. There was no clear consensus on the impact of any factor, and controversial results were reported in the literature. Singer et al.  reported in a retrospective study based on FDA reports that depressive side effects accounted for 42.3% of the psychiatric adverse effects associated with ITT treatment. Monthly mental check-up of psychiatric side effects, which are mostly observed in the 10-19 age group (52.5%), was recommended by the authors. Certain studies demonstrated that depression and suicidal ideation induced by ITT could be related to BDNF (Brain-derived neurotrophic factor) and folic acid treatment and dose reduction could be beneficial .
The determination of the correlation between ITT and psychiatric symptoms is problematic due to several factors such as exclusion of patients with a psychiatric disease anamnesis in the studies, similar to the present study, the fact that research has been conducted by both psychiatrists and dermatologists, lack of double-blind studies due to the skin dryness adverse effect of ITT, and preference of ITT in severe acne cases with psychiatric symptoms. . Thus, several controversial findings have been reported on the psychiatric side effects of ITT [8,9,13].
Although Brenner et al.  reported that there was a strong correlation between ITT use, and psychiatric side effects based on the psychiatric literature, several dermatological studies could not evidence this correlation, and reported that ITT had a therapeutic effect on psychiatric symptoms [9,35]. Although increases were observed in depression and anxiety scores after treatment in the current study, the increases were not significant in suicidal ideation and BPRS scores. This could suggest that factors other than depression could also affect suicidal ideation. Thus, serum lipid levels, which were associated with impulsivity and suicidal ideation, could be considered.
Retrospective studies on ITT treatment reported a possible correlation between ITT and depression, while prospective studies emphasized that there was no evidence on development of depression [8,9,13]. In the current study, an increase was observed in the depression scale scores on the 3rd month after the treatment when compared to baseline. However, it should be noted that this increase was lower than the anxiety scores.
One of the most frequently detected laboratory abnormalities during ITT treatment is hyperlipidemia [6, 36]. This rate is reversed when treatment is terminated. Certain studies reported that 50% of the patients had elevated TG and 30% had elevated cholesterol levels. . Due to the correlation between serum lipid levels and psychiatric disorders and suicide, it could be suggested that the changes in lipid levels observed during ITT treatment could be associated with psychiatric symptoms.
Certain studies emphasized the association between serum lipid levels and impulsivity, depression, or suicide attempts. In previous studies conducted by our group, it was determined that low serum leptin, ghrelin, and cholesterol levels could be associated with impulsive and suicidal behavior, and even violent suicide attempts in individuals with schizophrenia  and those who committed suicide [25,26,38]. Two meta-analyses on the correlations between serum lipid levels and suicide markers [39,40] were published recently. Wu et al.  emphasized that individuals with suicidal tendencies and psychiatric patients exhibited lower total serum cholesterol and TG levels. However, Bartoli et al  reported that the correlation was controversial and could be significant in patients with a history of psychiatric disease. Although the focus has been on suicidal behavior and low serum cholesterol levels, other publications emphasized that this correlation was controversial . Perhaps, routine lipid screening could not be justified in the evaluation of suicide risk; however, it could be beneficial to consider the lipid profile in routine controls in acne patients treated with ITT with a significant suicide risk.
The correlation between suicide, a global public health problem, and anxiety and susceptibility to anxiety is well known . In a previous meta-analysis, susceptibility to anxiety and its subscales were associated with suicide risk and ideation . Furthermore, depression symptoms are not the sole predictors of suicide attempts. However, focusing only on depression symptoms as a predictor of suicide in patients under ITT treatment could lead to the neglection of suicide risk. The current study findings demonstrated that anxiety symptoms increased more than depressive symptoms in patients treated with ITT, and this increase was associated with suicidal ideation. Thus, anxiety symptoms should be considered and followed-up as well as depression when monitoring the psychological symptoms and suicidal risk in patients under ITT treatment.
The correlation between psychiatric symptoms and ITT is clear. However, a successful ITT treatment in severe acne could also improve psychiatric symptoms. The analysis of depressive symptoms and suicidal ideation, which are significant concerns for dermatologists in ITT treatment could with a multidisciplinary approach that would include a psychiatrist in the early period, and consideration of routine blood lipid level follow-up could resolve this issue.
Suicidal behavior is quite complex and multidimensional. The contradicting findings were reported by studies on the correlation between ITT and suicidal behavior could be induced by this complexity. To date, it has been suggested that the best way for clinicians to evaluate suicide risk is to screen for suicide histories in the anamnesis of the patients and their families . It could be suggested that this method is still valid for patients under ITT treatment. The relative protective effect of hyperlipidemia and the potential benefits of optimizing lipid levels could be beneficial for clinicians in monitoring psychiatric symptoms during ITT treatment. Thus, there is still a need for further parameters that could be employed as biomarkers.
The other view about the development of psychiatric symptoms, namely vulnerability, is an interesting approach since individual cases differ about the development psychiatric symptoms, complicating the situation. These have been explained with genetic traits and a history of psychiatric treatment in the patient and the family. However, no previous study investigated the correlations between individual differences, biomarker data or serum lipid levels.
The correlation between psychiatric symptoms and ITT is still debated. Serum lipid levels are affected during ITT treatment. The correlation between the onset and exacerbation of psychiatric diseases and serum lipid levels has been studied in several studies. The current is the first in the literature where the correlation between the significant psychiatric adverse effects of ITT treatment and serum lipid levels in acne patients.
First, suicide attempt could be measured; however, recognition of suicidal ideation is only possible with scales, which may not always lead to accurate results. Second, we could exclude major psychiatric pathologies that could complicate the correlation between lipid profile and suicidal ideation that we could identify in the anamnesis. Third, although we only included metabolically healthy individuals in the study, it was not possible to completely exclude the effects of other biological factors that affected lipid serum levels. Finally, lipid subclasses could play different roles in suicide risk; however, we routinely checked lipid parameters in the current study. Thus, it should be accepted that we could not exclude all clinical and complex psychosocial models that could affect the correlation between serum lipid levels and suicide attempt.