Sex Differences in Pediatric Major Depressive Episodes: a crosssectional study on psychiatric symptoms in early onset mood disorders

Massimo Apicella^1,2*Elisa Andracchio¹Giorgia Della Santa¹Caterina Lanza¹Clotilde Guidetti^1,3Monia Trasolini¹Maria Elena Iannoni¹Gino Maglio¹Stefano Vicari^1,4Giulia Serra^1*

• ¹Bambino Gesù Children's Hospital (IRCCS), Rome, Italy
• ²Department of Neurosciences; università Cattolica del Sacro Cuore, Rome, Italy
• ³Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
• ⁴Catholic University of the Sacred Heart, Rome, Rome, Sicily, Italy

Background: Sex differences in psychiatric symptoms among children and adolescents with Major Depressive Episode (MDE) are less studied than among adults. Previous non recent studies reported a greater severity in adolescent girls and small differences between sexes in specific symptoms. We aim to explore differences between males and females in diagnoses, comorbidities, and psychiatric symptoms in a large cohort of pediatric patients referred to a tertiary center for child and adolescent psychiatry.Methods: We collected cross-sectional data on 382 consecutively referred patients (age6-18; 73.8%females) with current MDEs (unipolar or bipolar) thoroughly evaluated with clinician (Children's Depression Rating Scale-Revised; K-SADS Mania Rating Scale; Columbia Suicide Severity Rating Scale), self and parent report (Children's Depression Inventory-2, Multidimensional Anxiety Scale for Children-2, Child Behavior CheckList) standardized measures. Bivariate analyses were followed by a logistic regression model to assess significant predictors of MDE phenotype of female (versus male) patients.Results: Females were more likely to show severe MDEs (41.5%vs.26.0%,p=0.006), suicidal ideation (63.9%vs47.0%;p<0.001) and behaviors (29.4%vs13.0%,p=0.001) and non-suicidal selfinjury (58.5%vs27.0%;p<0.001). Males were more frequently diagnosed with bipolar disorder (21%vs.11%,p=0.012) and/or comorbid ADHD/behavior disorders (20%vs.8.9%, p=0.003). Males had also more frequently significant mixed hypo/manic symptoms (17%vs.7.7%, p=0.01), were younger at the onset of first psychiatric symptom (6.32vs7.75 years;p=0.003), onset of the mood disorder (11.3vs12.5 years;p=0.005) and evaluation (14.0vs15.2 years;p=0.001).Several symptoms were significantly and independently associated with females diagnosed with a current MDE, including: a) excessive weeping (OR 1.53; p<0.001); b) mood lability (OR 1.50; p=0.014); c) excessive fatigue (OR 1.38; p=0.002); d) appetite disturbance (OR 1.28; p=0.041); and e) attention problems (OR 1.07; p=0.001). Distractibility (OR 0.55; p=0.009) and conduct problems (OR 0.93; p=0.001) were in turn correlated with MDE among males.Discussion: The study confirms that females with MDEs exhibit more severe affective symptoms, while males present with more externalizing behaviors and comorbidities. We further report more mixed symptoms and bipolar disorder diagnoses in males, which also have an earlier onset of psychiatric symptoms. These findings are discussed also considering implications for the diagnosis of pediatric bipolar disorder. A high clinical sensitivity is needed for highlighting subtle mixed and/or atypical features in severe MDEs among girls.