• Interferon treatment
• HCV+ patients
• Depression
• Subthreshold mania

Background: Depression is considered the most frequent interferon (IFN)-a-induced psychiatric disorder. However, other neuropsychiatric side effects of IFN treatment, such as irritability, anxiety, and manic episodes, are reported as well. We analyzed the impact of lifetime manic–hypomanic symptoms and anxiety on the development of depression in hepatitis-C-virus-infected subjects treated with two different types of IFN-α.
Methods: Psychiatric diagnostic assessment was conducted at baseline using the Structured Clinical Interview for DSMIV for Axis I DSM-IV Disorders, patient edition (SCID-I/P), to confirm the absence of any current or lifetime psychiatric disorders. During treatment, subjects were administered interviewer-based instruments, such as the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impressions Scale (CGI), the Bech-Rafaelsen Mania-Melancholia Scale (BRMMS) and a set of self-report instruments such as the Mood Spectrum Self-Report Version (MOODS-SR), the State-Trait Anxiety Inventory (STAI), and the Medical Outcomes Study short-form 36 (SF-36).
Results: Six (12%) of 49 individuals with a negative history of psychiatric disorders developed major depression during treatment with IFN. The onset of depression was significantly associated with the presence of lifetime subthreshold manic–hypomanic symptoms. Subjects exceeding manic threshold were more likely to develop depression than those below threshold (33.3% vs. 7.5%, P=.033). Of these six patients, two dropped out because severity of depression was not compatible with prosecution of IFN treatment The remaining four patients were treated with citalopram and achieved remission by the fifth month of treatment and completed the study.
Conclusions: Our data suggest that individuals treated with IFN with no past history of mental disorders are more likely to develop depression if they experienced subthreshold manic–hypomanic symptoms in their lifetime. These findings derive from an exploratory study and may have important implications for the prevention of IFN-induced depression if replicated in larger studies and remark the usefulness of the MOODS-SR instrument to identify phenotypes at risk of depression.