میزان سطوح سرمی کاهش یافته اسید غیر اشباع چرب و فولات، غیر از عامل نوروتروفیک مشتق از مغز، در دوران کودکی و دختران نوجوان مبتلا به افسردگی

Evidence from observational studies suggests that there is an association among depression and brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs), and folate; however, this association has yet to be examined in childhood and adolescent depression. The objective was to determine whether the BDNF, PUFAs, and folate in serum differ between first-episode childhood and adolescent depressed patients and healthy controls. We measured the serum levels of BDNF, PUFAs, and folate of cases admitted to the hospital for depression (n=24) and compared it to that of controls (n=26). Subjects and their parents were informed about the nature and the purpose of this study, and a consent form was signed by parents. The ethics committee of Hirosaki University Graduate School of Medicine approved the study protocol. There were significant differences in the docosahexanoic acid (DHA), arachidonic acid (AA), and folate levels between cases and controls. Serum levels of DHA, AA, and folate levels in the patients group were statistically lower than those in the control group, while serum levels of BDNF were not different between cases and controls. These results are in line with findings of previous studies involving adult and elderly subjects, demonstrating lower levels of PUFAs and folate in patients with depression than healthy controls. However, further studies using larger sample size are warranted.

Childhood and adolescent depression is a chronic and serious illness that can result in marked functional impairment of the human biological system. It has also been shown that depression in adults has its roots in childhood and adolescence (Birmaher et al., 1996, Weissman et al., 1999 and Danese et al., 2008). Recently, there have been reported many studies on understanding the role of different laboratory parameters such as inflammatory markers, brain derived neurotrophic factor (BDNF), and nutritional factors, to elucidate the underlying pathophysiology of depression in adults (Lang and Borgwardt, 2013). However, similar studies in childhood and adolescent depression are a few. Accumulating evidence suggests that BDNF plays an important role in the pathophysiology of depression, as well as in the mechanisms underlying the therapeutic actions of antidepressants (Duman et al., 1997, Altar, 1999, Nestler et al., 2002, Hashimoto et al., 2004, Martinowich et al., 2007 and Hashimoto, 2010). Several studies including meta-analyses reported that the serum BDNF levels in adult patients with depression were significantly lower serum levels of BDNF than healthy control, and increased after antidepressant treatment (Shimizu et al., 2003, Sen et al., 2008, Brunoni et al., 2008, Bocchio-Chiavetto et al., 2010, Molendijk et al., 2011 and Yoshida et al., 2012). Therefore, it is likely that the serum BDNF levels would be a potential biomarker for depression. In the studies intended for adolescent or pediatrics depressed patients, there are a few studies examining the serum BDNF levels. Pallavi et al. (2013) reported that adolescent patients with depression had significantly lower levels of BDNF. Sasaki et al. (2011) also reported that serum levels of BDNF in male pediatric patients with depression were significantly lower than those in the male control group. However, there is still not enough information about the serum BDNF in adolescent depression. Polyunsaturated fatty acids (PUFAs) are essential fatty acids, and classified mainly into omega-3 and omega-6 groups. In animals, dietary omega-3 PUFAs deficiency alters brain chemistry, development and neurotransmission (Das, 2003 and De la Presa Owens and Innis, 1999). In clinical, some studies including meta-analyze reported that low blood levels of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), and omega-6 fatty acids arachidonic acid (AA) are associated with depression in adults (Edwards et al., 1998, Maes et al., 1999, Mamalakis et al., 2002, De Vriese et al., 2003, Su et al., 2003, Freeman et al., 2006 and Dinan et al., 2009). In addition, the blood omega-6 to omega-3 PUFA ratio has been found to be higher in depressed patients compared to controls (Maes et al., 1996 and Riemer et al., 2010). However, not all studies have shown decreased omega-3 PUFA in depressed patients as opposed to healthy subjects (Ellis and Sanders, 1977 and Fehily et al., 1981). Mamalakis et al. (2004) reported that the Beck Depression Scale (BDI) was negatively associated with EPA, while the Center for Epidemiologic Studies Depression Scale (CES-D) was positively associated with dihomo-gamma linolenic acid (DGLA) in adipose tissue of adolescent depression. In addition, Pottala et al. (2012) reported that the red blood cell of DHA was inversely associated with depression in adolescent, but this is not a consistent finding (Crowe et al., 2007). Folate is involved in the metabolism of monoamines like serotonin in the brain (Bottiglieri, 2005) and thus may be related to mood disorder. Several (Morris et al., 2003, Lerner et al., 2006, Kim et al., 2008, Beydoun et al., 2010 and Nanri et al., 2012) but not all (Penninx et al., 2000; Tiemeier et al., 2002) observational studies have reported an inverse association between blood folate concentrations and depressive symptoms in middle age or elderly. Furthermore, Murakami et al. (2010) reported that higher intake of dietary folate and vitamin B-6 is independently associated with lower prevalence of depressive symptoms in healthy early adolescent, whereas Fulkerson et al. (2004) found no association between depressed symptoms and folate. Almost all previous studies have been conducted in adults or elderly, particularly depressive symptoms and serum BDNF and folate levels, therefore, we examined a case-control study comparing serum PUFAs, folate, and BDNF levels in 28 childhood and adolescent patients with depression and 24 healthy controls.

Demographic and clinical characteristics of the patients and healthy control group are complied in Table 1. The distribution of age and body mass index (BMI) was similar amongst patients and the controls. Either in patients or control groups, PUFAs, folate and BDNF levels were not correlated with age, BMI, respectively. There was no correlation among PUFAs, folate, and BDNF levels and the BDI-II or DSRSC scores in patient groups. The DHA, AA, and folate levels in the patients group were statistically lower than those in the control group (p<0.001, p=0.001, and p=0.01, respectively). Serum BDNF was not different in patients and control groups. Table 1. Demographic characteristics and serum BDNF, unsaturated fatty acid, and folic acid in adolescent depression patients vs. healthy controls. Variables Depression patients (n=24) Healthy control (n=26) t-Value p-Value Age (year) 16.0±2.2 17.2±2.4 1.8 0.075 BMI (kg/m2) 20.8±3.4 20.0±2.8 −0.9 0.386 BDI-II score 29.7±13.1 – – – DSRSC score 23.3±6.0 – – – BDNF 20,642±4916 18,885±4076 1.4 0.174 DGLA 27.5±10.5 31.2±9.6 −1.3 0.190 AA (C20:4n−6) 133.5±27.8 166.9±31.7 −3.9 <0.001 EPA (C22:5n−3) 24.1±12.7 27.3±15.3 −0.8 0.435 EPA/AA ratio 0.18±0.09 0.17±0.10 0.5 0.629 DHA 63.1±14.5 79.0±17.4 −3.5 0.001 Folate 3.0±1.6 4.4±2.0 −2.7 0.010 n=Number of subjects. Values are expressed as Mean±S.D. BMI: body mass index. BDI-II: Beck Depression Inventory-II. DSRSC: Depression Self Rating Scale for Children. BDNF: brain-derived neurotrophic factor. DGLA: dihomo-gamma linolenic acid. AA: arachidonic acid. EPA: eicosapentaenoic acid. DHA: docosahexanoic acid.