Chrononutrition interventions for mental health: addressing atypical depression, ultra-processed food use disorder, and circadian dysregulation

Atypical depression is characterized by mood reactivity (improvement in mood in response to positive events) combined with features such as hyperphagia, hypersomnia, leaden paralysis, and a longstanding sensitivity to interpersonal rejection (1). Metabolically, it tends to co-occur with weight gain, insulin resistance, dyslipidemia, and elevated inflammatory markers like C-reactive protein and pro-inflammatory cytokines (2, 3). Traditional treatments—psychopharmacology and psychotherapy—often fall short in fully remediating these underlying metabolic or immuno-inflammatory drivers (4).

Concurrently, ultra-processed food use disorder (UPFUD) has gained attention as a factor that may worsen both metabolic and psychiatric conditions (5). In this article, we use the working term UPFUD to describe a hypothesized condition in which ultra-processed foods—such as those defined by the NOVA classification—are consumed in a pattern that fulfills core "use disorder" criteria (loss of control, continued use despite harm, and craving), while acknowledging that formal nosological status and final terminology are still under discussion.

Ultra-processed foods, typically high in refined carbohydrates, added sugars, industrial fats, and artificial additives, can hyperactivate dopaminergic reward pathways, leading to craving, binge-eating, tolerance, and even withdrawal-like symptoms upon cessation (6, 7). This addictive-like eating pattern can further disrupt energy balance, insulin sensitivity, and inflammatory homeostasis (8). Such disruptions have been implicated in various mental health problems—including but not limited to atypical depression, anxiety, and impulsive–compulsive spectrum disorders (9).

While atypical depression offers a compelling model for understanding the metabolic–mood nexus, numerous other psychiatric conditions share overlapping mechanisms of circadian dysregulation and metabolic dysfunction (3, 10). Evidence suggests that anxiety, insomnia, agitation, impulsivity, compulsivity, and cognitive deficits (e.g., focus and attention problems) may also be exacerbated by circadian misalignment and poor dietary habits (11). Interventions that address the "when" of eating, not just the "what," therefore hold promise for a wide range of symptom domains.

Chronopsychiatry—the clinical and pathophysiological interface between circadian rhythms and mental illness—provides the scaffold for timing-based interventions in routine care. Recent position papers emphasize that sleep–circadian abnormalities are implicated across disorders and outcomes, arguing for pragmatic, transdiagnostic levers. We situate chrononutrition, particularly Time-Restricted Eating (TRE), as one such lever that may help realign peripheral clocks and stabilize symptom clusters relevant to anxiety, insomnia, compulsivity/impulsivity, and mood (30, 31). Complementing this clinical lens, mechanistic reviews underscore bidirectional interactions between circadian rhythms, gut microbiota, and neuroendocrine–inflammatory signaling, with feeding timing emerging as a promising chronotherapeutic input (31).

The circadian system, governed by the suprachiasmatic nucleus (SCN) in the hypothalamus, synchronizes physiological processes over ~24-hour cycles (10). While light–dark cycles are the best-known zeitgeber, meal timing is a potent regulator of peripheral clocks in organs such as the liver, pancreas, and adipose tissue (12). Disrupted feeding–fasting schedules can lead to chronodisruption, characterized by misaligned internal clocks that compromise hormonal secretion (e.g., melatonin, cortisol), metabolic processes (e.g., glucose regulation), and mood regulation (13).

Many mental health conditions, including atypical depression, obsessive–compulsive behaviors, and even certain anxiety disorders, feature elevated inflammatory markers (e.g., IL-1β, IL-6, TNF-α) (2, 9). Chronically heightened inflammation is believed to disrupt neuroplasticity (particularly via BDNF) and monoamine metabolism, contributing to persistent symptoms of agitation, insomnia, and emotional dysregulation (14, 16). Aligning meal timing and improving diet quality may help modulate these immune–inflammatory pathways.

Time-Restricted Eating involves restricting daily food intake to a consistent window—often between 8 and 12 hours—while fasting for the remaining 12–16 hours (17). This feeding–fasting rhythm is believed to restore peripheral clock gene patterns and improve metabolic variables such as insulin sensitivity, leptin signaling, and inflammation markers (18). TRE may also reduce late-night snacking behaviors, specifically those involving highly palatable, ultra-processed foods.

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