Depression in Childhood and Early Adolescence: Parental Expressed Emotion and Family Functioning.

Across development depression is associated with impairments in interpersonal and family functioning. In turn, these impairments may predict a more negative depression course and outcome. This study examined family functioning and parental Expressed Emotion (EE) among depressed youth during middle childhood and early adolescence and their relationship to demographic and clinical factors. Data were drawn from pretreatment evaluations of 132 depressed youth ages 7-14 and their families enrolled in a randomized clinical trial comparing family to individual treatment for youth depressive disorders. Families completed semi-structured diagnostic interviews, self-report measures of family functioning, and the Five Minute Speech Sample EE measure. High parental EE was more common in one-parent, as opposed to two-parent families, and early adolescent youth were more likely than pre-adolescent youth to have high critical EE parents. Severity and chronicity of child depression, child comorbidity, functional impairment, and maternal depressive symptoms were not associated with parental EE. Parental high EE overall and critical EE in particular were associated with reports of higher conflict and lower cohesion by both parents and children when compared to low parental EE. Similar patterns of associations were evident for youth across pre-adolescent and early adolescent developmental periods. Single parent status may be an indicator of greater family stress; and higher levels of critical EE may reflect the higher levels of parent-child conflict characteristic of the transition from late childhood to early adolescence. Among youth with depression parental EE appears to reflect potentially important impairments in family functioning.

N-linked carbohydrates in tyrosinase are required for its recognition by human MHC class II-restricted CD4(+) T cells.

Glycosylation of mammalian proteins is known to influence their intracellular trafficking, half life, and susceptibility to enzymatic degradation. Rare instances of natural T cell epitopes dependent upon glycosylation for recognition have been described. We report here on human CD4(+) T lymphocyte cultures and clones from two melanoma patients that recognize the melanoma-associated Ag tyrosinase in the context of HLA-DR4 and -DR8. These T cells recognize tyrosinase, normally a heavily glycosylated molecule, when expressed constitutively in melanoma cells or in COS-7 transfectants pulsed as lysates onto autologous APC. However, these T cells fail to recognize tyrosinase expressed in bacteria, nor do they react with overlapping peptides covering full-length tyrosinase, suggesting a critical role for glycosylation in the processing and / or composition of the stimulatory epitopes. The requirement for glycosylation was demonstrated by the failure of tyrosinase-specific CD4(+) T cells to recognize tyrosinase synthesized in the presence of glycosylation inhibitors, or deglycosylated enzymatically. Site-directed mutagenesis of each of seven potential N-glycosylation sites showed that four sites were required to generate forms of tyrosinase that could be recognized by individual T cell clones. These data indicate that certain carbohydrate moieties are required for processing the tyrosinase peptides recognized by CD4(+) T cells. Post-translational modifications of human tumor-associated proteins such as tyrosinase could be a critical factor for the development of antitumor immune responses.