Table 1 Objectives and hypotheses

1.

Using a 12-week RCT, assess whether SSM improves depressive symptoms in LLD compared to an active-control condition; HEP

(a) In participants with LLD, SSM participants, compared to HEP controls, will have a greater reduction in depressive symptoms from baseline to 12-week follow-up, as measured by the Hamilton Rating Scale for Depression (HRSD-17)

(b) Compared to HEP, a higher percentage of SSM LLD participants will meet the clinical criteria for remission, as defined by HRSD-17 scores < 8 at the 12-week follow-up

2.

To assess the effects of SSM on a specific executive function, i.e., organization ability in LLD

In participants with LLD, compared to HEP, SSM will be associated with better organization ability, at 12-week follow-up

3.

To assess the effects of SSM on other executive function domains in LLD

In participants with LLD, compared to HEP, SSM will be associated with better executive functions, at 12-week follow-up

4.

To assess the effects of SSM on global cognition in LLD

In participants with LLD, compared to HEP, SSM will be associated with better global cognition, at 12-week follow-up

5.

Using magnetic resonance spectroscopy (MRS), assess the effects of SSM on functional connectivity measured by rs-fMRI particularly within the area implicated on the default mode network, volume increase in the bilateral hippocampi and posterior cingulate cortices and levels of glutathione (GSH)

Compared to HEP, SSM will show an increase in functional connectivity especially within the area implicated on the default mode network and also a volume increase in the bilateral hippocampi and posterior cingulate cortices and an increase in levels of GSH in key mood-regulating brain areas (ventro-medial prefrontal cortex)

6.

To investigate whether SSM intervention is associated with sustained improvements in participants’ views of disability (WHODAS 2.0), sleep (Athens Insomnia Scale), quality of life (Euro-QOL), anxiety (Generalized Anxiety Disorder GAD-7, and overall psychological well-being (Ryff’s Scales of Psychological Well-Being; SPWB 9 items) at 12-week follow-up compared to HEP

SSM will be superior to HEP at 12 weeks on all self-rated measures of disability, sleep, quality of life, anxiety, and psychological well-being

7.

To investigate the effects of SSM and HEP on mood and cognition at 26-week follow-up

SSM will continue to be superior to HEP at 26-week follow-up with regard to HRSD-17 scores and executive functioning

8.

To identify and quantify the extent of gait impairment in participants with LLD and explore the effects of SSM intervention on gait impairments at 12 weeks

SSM will be superior to HEP in improving gait measures, including stride length, gait velocity and fear of falling and risk of falling as measured by the Falls Efficacy Scale – International (FES-I) at 12-week follow-up

9.

To explore whether blood inflammation markers, circadian rhythm, and sleep quality (Acti-watch), predict treatment response with SSM

Depression and anxiety symptoms will be associated with levels of inflammatory markers. Levels of inflammatory markers will be decreased, as well as circadian rhythm and sleep quality (Acti-watch) will be improved, in the SSM participants at 12-week follow-up compared to HEP, which in turn will be associated with greater reductions in depression/anxiety scores

10.

To assess participant experience after participating in the interventions (SSM or HEP)

Using the semi-structured McGill Illness Narrative Interview, elucidate what is the participant experience participating in either SSM or HEP?

11.

To assess the extent to which participanting in SSM or HEP is associated with any change in mindfulness scores using the Five Facet Mindfulness Questionnaire (FFMQ)

Compared to HEP, SSM is associated with greater increases in FFMQ mindfulness scores. This in turn is associated with greater improvements in HRSD-17 depression scores (see main outcome section)

12.

To explore whether there are any changes in level of consciousness, at week 12, participants will fill out the self-report Phenomenology of Consciousness Inventory (PCI) after their meditation session for the SSM group or analogous activities for the HEP group

Participants practicing SSM will be in an altered state of consciousness compared to participants engaged in HEP