While previous PKU intervention research has largely focused on pharmacological treatment of elevated Phe levels, the adaptation of evidence-based psychosocial therapy holds promise for addressing cognitive and psychological symptoms and significantly improving quality of life. Study goals include: (1) to demonstrate the efficacy and feasibility of a short-term skills-based intervention (Show Me FIRST) for anxiety and depression in adolescents with PKU, and (2) to further establish the psychometric validity of novel assessment measures recently developed by the Investigators that utilize ecological momentary assessment (EMA) to capture "in the moment" neurocognitive and psychological function. The Investigators propose to conduct a randomized controlled trial wherein 30 adolescents with PKU will be randomized to either an immediate intervention group or wait-list/delayed intervention group.

A sample of 30 adolescents (age 10-17) with PKU and a history of elevated anxiety and/or depression symptomatology will be recruited to participate in a randomized control trial. Following screening and informed consent, participants will be randomized to an immediate intervention group (n=15) or wait-list/delayed intervention group (n=15). Participants will receive the 10-week Show Me First program for treatment of anxiety and depression. Participants will complete extensive psychological and neurocognitive evaluations at three timepoints: Weeks 0, 11, and 22. The assessments and intervention will all be administered remotely via secure videoconference and cell-phone based applications.

Inclusion Criteria:

• Youth 10-17 years old and at least one parent/guardian
• Formal diagnosis of PKU (as confirmed/reported by caregiver): identified by newborn screening with PKU as evidenced by a blood Phe level ≥ 360μmol/L; received treatment within the first 30 days of life.
• Interest in receiving a brief, psychotherapeutic skills program to prevent and treat symptoms of anxiety and/or depression, according to parent- and youth-report
• Located in Missouri, Kansas, or Illinois.

Exclusion Criteria:

• Have significant intellectual disability (IQ<70) or significant expressive or receptive language that would interfere with psychotherapy, according to parent- or youth-report
• Plans to receive non-study psychotherapy during the course of study participation, according to parent- or youth-report
• Plans to change current psychoactive or PKU-related medication during the course of study participation, according to parent- or youth-report
• Have active suicidal ideation that would necessitate immediate treatment or require higher level of care than brief psychotherapy, according to parent- or youth-report