Heat and Mental Health - PART 2

BACKGROUND AND RATIONALE Rising ambient temperatures are associated with worsening mood outcomes, and young adults with depressive disorders may be particularly susceptible. The mechanisms underlying this association remain poorly characterized. Three candidate pathways are measurable and potentially modifiable: sleep-wake disturbance, impaired cognitive performance, and reduced physical activity. Establishing whether these pathways carry the effect of heat on mood would identify targets for intervention that do not require modifying the thermal environment itself, which is often less modifiable.

A central and under-examined question is whether the timing of heat exposure matters. Nocturnal heat is hypothesized to act principally through sleep disruption, whereas daytime heat may act through effects on activity, cognition, and direct thermal discomfort. Distinguishing these requires an experimental contrast in exposure timing rather than a comparison between heat and its absence. Alongside affective outcomes, the study examines anger, aggression, and prosocial versus antisocial behavior, domains with an established association with ambient heat but limited experimental characterization in clinical populations.

RELATIONSHIP TO COMPANION OBSERVATIONAL STUDY This trial is conducted alongside a companion observational study within the same research program, Heat Effects on Mental Health in Young Adults (HEAT-MIND Lab PART 1), in which young adults are monitored while in their home environments across the summer months without assignment of any exposure. The observational study characterizes naturally occurring heat exposure and its association with sleep, mood, cognition, and activity in real-world conditions; while the present trial establishes directionality under controlled exposure. The two studies share a subset of monitoring instrumentation and measurement definitions, supporting comparison between experimentally controlled and naturalistic findings. PART 1 involves no assignment of interventions by the investigators and is reported separately.

STUDY DESIGN AND EXPOSURE This is a randomized, counterbalanced crossover study in which each participant serves as their own control across two laboratory weekends separated by two weeks. The two conditions are matched for total heat exposure and differ only in its timing.

In the daytime-heat condition, ambient temperature is maintained at 32°C from 08:00 to 20:00 and at 22°C overnight. In the nighttime-heat condition, this schedule is reversed. Absolute humidity is held constant at approximately 13 g/m³ across both conditions and both temperatures. Temperature and humidity are monitored continuously throughout both laboratory weekends.

Because both conditions contain heat, this design does not include a thermoneutral control arm. The contrast of interest is the differential effect of heat timing, and the exposure-matched structure removes total thermal load as a competing explanation for observed differences between weekends.

CONTINUOUS MONITORING PERIOD Individual participation spans 28 days. Ecological momentary assessment and wearable monitoring run continuously across this entire period, including during both laboratory weekends, using the HEAT-MIND mobile application (Avicenna Research) in combination with wearable sensors. Continuous monitoring captures repeated assessment of mood, anxiety, anger and aggression, cognitive performance, daily sleep diaries, wrist actigraphy, heart rate, ambient light exposure, and ambient temperature and humidity in the participant's own environment. This design permits each laboratory weekend to be interpreted against the participant's own preceding and following real-world baseline rather than against a single pre-study assessment.

Pre-laboratory sleep schedules and dietary intake are not controlled. This is a deliberate design choice grounded in the translational aims of the study: the research question concerns how real-world heat exposure affects young adults with depression against the background of their usual routines. Pre- and post-laboratory home-monitoring data (e.g., sleep duration, timing, physical activity, and environmental exposures) will be incorporated as model covariates and in sensitivity analyses of within-participant differences between the two laboratory weekends.

LABORATORY PROCEDURES AND MEASUREMENT Laboratory weekends are conducted at the Yale Biobehavioral Sleep Laboratory at the Yale School of Nursing, with participants resident from Friday afternoon through Monday midday, spanning three nights.

Overnight sleep is assessed by 18-channel attended polysomnography, including electroencephalography, electrooculography, electromyography, electrocardiography, respiratory inductance plethysmography, and airflow and thermistor channels, with concurrent wrist actigraphy.

Separately, waking neurophysiology is assessed by high-density electroencephalography using a 128-lead saline cap, administered at multiple timepoints across each weekend. This approximately 30-minute protocol comprises resting-state recording as well as auditory and visual oddball paradigms, supporting assessment of hypofrontality and functional connectivity in the Default Mode and Salience networks under each thermal condition.

On the final night of each laboratory weekend, participants are awakened at 02:00 for a scheduled nocturnal assessment comprising an additional ecological momentary assessment battery while being monitored through polysomnographic electroencephalography. This procedure allows mood, cognitive performance, and hypofrontality to be characterized during nocturnal wakefulness under each thermal condition. Because it occurs on the final night of both weekends, the procedure is symmetric across conditions and does not differentially perturb one exposure relative to the other.

Personal peripheral and core temperature measurement is continuous. Core body temperature is measured using an ingestible telemetric capsule (e-Celsius), peripheral temperature by iButton sensors (6 locations), and ambient temperature and humidity by fixed and portable environmental monitors (Kestrel Drop and SwitchBot IP65). Under-covers temperature and humidity are also measured with an iButton while participants are in bed, characterizing the sleep microenvironment, which may diverge from room-level conditions. Continuous heart rate is collected in parallel and additionally serves as a validated surrogate for core temperature, providing continuity in the event of capsule failure or early voiding and permitting internal cross-validation between measured and estimated core temperature within the sample.

Behavioral and affective assessment during laboratory weekends includes a semi-structured qualitative interview conducted by a research assistant on the final morning. The qualitative component provides participant-reported context on the experience of each exposure condition.

Cognitive tasks and measurements of mood and depression severity are administered via ecological momentary assessment.

STANDARDIZATION OF THE LABORATORY ENVIRONMENT While the pre-laboratory period is intentionally naturalistic, the laboratory environment is tightly standardized and held consistent across a participant's two weekends. Meals are provided on a fixed schedule, with calorie-counted meals and snacks, post-meal photography to estimate consumption, and documentation of additional intake. Bedding, sleepwear, and room furnishings are standardized. Lighting practices are held constant across weekends, including consistent overhead lighting, yellow-shifted emergency lighting overnight, and consistent management of the common-area window during evening and overnight periods; bedrooms have no windows. Ambient light exposure is additionally measured continuously by wearable photometric sensors (ActLumus), permitting light conditions to be characterized analytically rather than assumed constant.

Because participants are studied in the same physical environment under the same schedule across both weekends, stable features of the setting are not expected to bias one exposure condition relative to the other.

SAFETY MONITORING The study is overseen by an independent Data Safety Monitoring Board. Physician coverage during laboratory weekends is divided by call type, with heat-related clinical questions directed to a sleep medicine physician and psychiatric questions directed to a psychiatrist. Participants undergo alcohol and substance use screening at the outset of each laboratory weekend; and hydration is assessed via urine refractometry both at the weekend's outset and twice daily throughout the weekend, with a rehydration protocol in place if dehydration is noted (urine specific gravity >1.020).

STAKEHOLDER INVOLVEMENT Young adults with lived experience of mood disorders contributed to protocol development. A nationally recruited group of lived experience experts will participate in developing multimedia materials communicating findings to peers.