Despite the significant prevalence of Major Depressive Disorder in the pediatric population, the pathophysiology of this condition remains unclear, and the treatment outcomes poor. Investigating tools that might aid in diagnosing and treating early-onset depression seems essential in improving the prognosis of the future disease course. Recent studies have focused on searching for biomarkers that constitute biochemical indicators of MDD susceptibility, diagnosis, or treatment outcome. In comparison to increasing evidence of possible biomarkers in adult depression, the studies investigating this subject in the youth population are lacking. This narrative review aims to summarize research on molecular and biochemical biomarkers in child and adolescent depression in order to advocate future directions in the research on this subject. More studies on depression involving the youth population seem vital to comprehend the natural course of the disease and identify features that may underlie commonly observed differences in treatment outcomes between adults and children.

Alterations in brain-derived neurotrophic factor (BDNF) expression have been suggested to mediate the influence of environmental factors on the emergence of depression through epigenetic modifications. However, research on this subject in the developmental population is lacking and the pathophysiology of adolescent depression remains unclear. We aimed to investigate the alterations in BDNF expression and global DNA methylation in depression among adolescent girls. Thirty female inpatients with the initial diagnosis of depression were assessed before and after the period of antidepressant treatment and compared with thirty age-matched healthy controls. The assessment involved BDNF and proBDNF serum levels, the BDNF gene exon IV promoter methylation, and global DNA methylation. The methylation level in the BDNF gene exon IV promoter was significantly lower in the studied group compared with the control and correlated negatively with the severity of depression. The test distinguished the studied group from the controls with a sensitivity of 37% and specificity of 90%. The differences were no longer present after the period of antidepressant treatment. No differences in the global DNA methylation, BDNF, and proBDNF levels were found. We concluded that decreased methylation in the BDNF exon IV promoter could be considered as a biomarker of a depression state among adolescent girls.

Depression is a chronic psychiatric disorder with a heavy socioeconomic burden. Studies on biomarkers are needed to comprehend the pathophysiology of depression and to improve treatment outcomes. Research points to the importance of imbalance between mature brain-derived neurotrophic factor (BDNF) and its precursor, pro–brain–derived neurotrophic factor (proBDNF), in the pathophysiology of mood disorders and the potential neurodegenerative role of calcium-binding protein B (S100B). Our objective was to compare BDNF, proBDNF, and S100B serum levels before and after the treatment of acute depressive episodes and to assess their correlation with the severity of symptoms and history of stress. We also aimed to investigate the differences in BDNF, proBDNF, and S100B levels between depression in the course of bipolar disorder (BD) and major depressive disorder (MDD). We recruited 31 female patients diagnosed with BD or MDD who were hospitalized due to current depressive episodes. The patients had their serum BDNF, proBDNF, and S100B levels evaluated using the ELISA method upon admission and after the symptoms improved, at discharge. We found that proBDNF levels decreased significantly with the treatment (p = 0.0478), while BDNF and S100B levels were not altered significantly. No differences in biochemical parameters between MDD and BD subjects were observed. Consequently, we concluded that a decrease in serum proBDNF levels could be considered a biomarker of recovery from depressive episodes.

Anorexia nervosa (AN) is an eating disorder characterized by restrictive eating and significant weight loss. In the course of AN, changes are observed in appetite regulation, including orexigenic ghrelin and potentially anorexigenic obestatin. The study aimed to determine if any changes in serum ghrelin and obestatin levels during treatment of AN are observed, while investigating the correlations between these peptides and the severity of disturbed eating attitudes, depression, and anxiety. Thirty adolescent inpatients with AN (examined twice: before hospitalization treatment AN-BT and after treatment AN-AT) and thirty healthy age- and height-matched girls (CG) participated in the study. Anthropometric, serum ghrelin and obestatin concentrations and psychometric evaluations (Eating Attitudes Test 26 Item-EAT-26, Beck Depression Inventory-BDI, Hamilton Depression Rating Scale-HDRS, and Yale Brown Obsessive-Compulsive Scale-Y-BOCS) were performed. The study revealed significantly higher ghrelin and obestatin levels in AN-BT than in AN-AT. A trend toward lower levels during treatment provided partial normalizations. Analyzing correlations in the AN-BT vs. CG group, correlations of peptides with EAT-26, BDI, and HDRS scores were detected. These results suggest a potential role for ghrelin and obestatin in the context of defense mechanisms regulating appetite and body weight in the course of AN and in terms of psychopathological changes co-occurring with this eating disorder.

Background/Objectives: Adolescents admitted for emergency psychiatric hospitalization frequently present with severe and heterogeneous psychopathology. In clinical practice, some adolescent inpatients appear to present a broader symptom pattern suggestive of emotional dysregulation. However, it remains unclear whether they can truly be distinguished in this population and whether they differ meaningfully from adolescents with predominantly depressive presentations. Methods: We conducted a retrospective cross-sectional chart review with subgroup analysis based on the medical records of patients aged 11–17 years hospitalized on an emergency basis at the Department of Child and Adolescent Psychiatry in Poznań, Poland, between January and December 2024. Patients were assigned either to an emotional dysregulation group, defined by affective dysregulation and behavioral dyscontrol, or to a depressive presentations group, comprising adolescents with depressive presentations who did not meet criteria for the emotional dysregulation profile. Broader clinical characteristics, adverse childhood experiences, and prior treatment history were compared between groups. Results: A total of 139 adolescents were included (85 in the emotional dysregulation group and 54 in the depressive presentations group). The median age was 13 years [Q1–Q3: 13–14] in the emotional dysregulation group and 14 years [Q1–Q3: 12.25–14] in the depressive presentations group; girls comprised 77.6% and 83.3% of the groups, respectively. The emotional dysregulation group more often presented with conflict-ridden relationships, a more frequent history of suicide attempts (72.9% vs. 50.0%, p = 0.006), and a higher number of suicide attempts (median 1 [Q1–Q3: 0–2] vs. 0.5 [Q1–Q3: 0–1], p = 0.012), as well as more frequent exposure to adversity-related experiences. Furthermore, this group had a higher number of previous psychiatric hospitalizations (median 1 [Q1–Q3: 1–2] vs. 1 [Q1–Q3: 1–1], p = 0.001) and a longer history of psychiatric treatment. In contrast, social withdrawal was more characteristic of the depressive presentations group. Conclusions: Routinely collected clinical records may capture a clinically meaningful subgroup of adolescents with a symptom profile suggestive of emotional dysregulation. Compared with the depressive presentations group, these adolescents showed greater interpersonal difficulties, more recurrent suicide attempts, greater adversity burden, and a longer history of psychiatric treatment. Further prospective studies using standardized measures are needed.