Psychiatric Diagnoses and Medications in Wolfram Syndrome

Abstract

Background: Wolfram Syndrome is a rare genetic disorder usually resulting from pathogenic variation in the WFS1 gene, which leads to an exaggerated endoplasmic reticulum (ER) stress response. The disorder is typically characterized by diabetes insipidus, diabetes mellitus, optic nerve atrophy, hearing loss, and neurodegenerative features. Existing literature suggests it may also have psychiatric manifestations.

Objective: To examine lifetime psychiatric diagnoses and medication history in Wolfram Syndrome.

Method: Child, adolescent, and young adult Wolfram Syndrome participants (n=39) were assessed by a child & adolescent psychiatrist to determine best estimate DSM-5 lifetime psychiatric diagnoses as well as psychoactive medication history. In addition, the Child & Adolescent Symptom Inventory-5 (CASI-5) Parent Checklist was used to determine likely psychiatric diagnoses based on symptom counts in Wolfram Syndrome patients (n=33), type 1 diabetes (n=15), and healthy comparison (n=18) groups.

Results: Study participants with Wolfram Syndrome had high lifetime rates of anxiety disorders (77%). Also, 31% had an obsessive-compulsive spectrum disorder, 33% had a mood disorder, 31% had a neurodevelopmental or disruptive behavior disorder, and 31% had a sleep-wake disorder. More than half of Wolfram Syndrome participants had taken at least one psychoactive medication, and one third had taken at least one selective serotonin reuptake inhibitor (SSRI). Some individuals reported poor response to sertraline but better response after switching to another SSRI (fluoxetine or citalopram). In general, people with Wolfram Syndrome often reported benefit from psychotherapy and/or commonly used psychoactive medications appropriate for their psychiatric diagnoses.

Conclusions: Wolfram Syndrome may be associated with elevated risk for anxiety and obsessive-compulsive spectrum disorders, which seem generally responsive to usual treatments for these disorders.

Keywords: Anxiety; ER stress; Obsessive Compulsive Disorder; Psychiatry; Wolfram Syndrome; medication.

Figure 1

Lifetime Psychiatric Severity Score Distribution. Score Interpretation: 0 = Few or no symptoms; 1 = Mild symptoms, little or no impairment; 2= Mild symptoms, some impairment; 3= Moderate symptoms, clear impairment; 4= Severe symptoms, clear impairment (see methods for more detailed description). Numbers above each bar are the percentage of Wolfram Syndrome participants with the indicated lifetime severity level as of the most recent clinic visit.