Optimizing Long-Term Outcomes for Winter Depression With CBT-SAD and Light Therapy

Winter seasonal affective disorder (SAD) is a subtype of recurrent depression involving major
depressive episodes during the fall and/or winter months that remit each spring. The central
public health challenge in the management of SAD is prevention of winter depression
recurrences. This application focuses on two SAD treatments that each work for some patients:
light therapy (LT) and a SAD-tailored group cognitive-behavioral therapy (CBT-SAD). LT is the
acute SAD treatment with the most substantial evidence to support its efficacy. Correction of
circadian phase is LT's established target and mechanism. In our recently completed R01-level
efficacy trial, post-treatment outcomes for CBT-SAD and LT were very similar, but CBT-SAD was
associated with fewer depression recurrences over 2-year followup than LT (27.3% in CBT-SAD
vs. 45.6% in LT). CBT-SAD engaged and altered a specific mechanism of action, seasonal
beliefs, which improved at twice the rate during CBT-SAD compared to LT, and this improvement
was associated with lower risk for recurrence following CBT-SAD. This confirmatory efficacy
R01 will apply the experimental therapeutics approach to determine how each treatment works
when it is effective and to identify the best candidates for each. We will ascertain whether
theoretically-derived candidate biomarkers of each treatment's target and effect are
prescriptive of better outcomes in that treatment vs. the other. Biomarkers of LT's target
and effect include circadian phase angle difference (PAD) and the post-illumination pupil
response (PIPR). Biomarkers of CBT-SAD's target and effect include pupil dilation and
sustained gamma band EEG responses to seasonal words, which are hypothesized to reflect less
engagement with seasonal stimuli following CBT-SAD and corroborate with the established
target of seasonal beliefs. In addition to determining change mechanisms, we will test the
efficacy of a "switch" decision rule upon recurrence to inform clinical decision-making in
practice. We will randomize 160 adults with SAD to 6-weeks of CBT-SAD or LT in Winter 1;
follow subjects in Winter 2; and, if a depression recurrence occurs, cross them over into the
alternate treatment (i.e., switch from LT to CBT-SAD or CBT-SAD to LT). All subjects will be
followed in Winter 3. Biomarker assessments will occur at pre-, mid-, and post-treatment in
Winter 1, at Winter 2 followup (and again at mid-/post-treatment for those crossed-over), and
at Winter 3 followup. Consistent with NIMH's priorities for demonstrating target engagement
at the level of RDoC-relevant biomarkers, this work aims to confirm the targets and
mechanisms of LT and CBT-SAD to maximize the impact of future dissemination efforts.

Inclusion Criteria:

- Principle DSM-5 diagnosis of Major Depression, Recurrent, with Seasonal Pattern. -Meet
Structured Interview Guide for the Hamilton Rating Scale for Depression—Seasonal
Affective Disorder Version (SIGH-SAD) criteria for a current SAD episode (see below).

- No use or stable use of antidepressants (i.e., a consistent dose of the same
medication maintained for > 4 weeks with no plans to change).

Exclusion Criteria:

- Current or past light therapy or CBT for SAD.

- Presence of a comorbid Axis I disorder that requires immediate treatment (i.e.,
bipolar disorder, psychotic disorders, substance use disorder).

- Acute and serious suicidal intent.

- Planned absences of >1 week from the area through March.

- History of conditions that are known contra-indications to LT, including conditions
associated with toxicity of bright light to the retina (i.e., macular degeneration or
any retinopathy).