Sleeping, Eating, Socializing, and Exercising

Sleep is critical for neurotransmitter balance, hormonal regulation, and neuroplasticity. You can improve your sleep with good sleep hygiene. High quality sleep is a function of the following components: schedule, substances (alcohol, caffeine, nicotine), avoiding naps, suitable bedtime activities, light exposure, diet, and exercise.

Diet and nutrition influences inflammation, neurotransmission, and neurotrophic factors. Eating a Mediterranean diet can improve mental health by reducing inflammation, supporting the gut-brain axis, and providing neuroprotective effects that lower the risk and severity of depression, anxiety, and cognitive decline.

Dysbiosis (disruption to your normal gut microbiome) promotes inflammation and can contribute to anxiety/depression. Support your microbiome with fermented foods and prebiotic/probiotics.

Social connectivity directly influences mood-regulating neurochemistry (oxytocin, dopamine, endorphins). Be kind to other people. Join group activities and volunteer with organizations. Review these CDC tips for ways to increase your social connectivity.

Exercise improves mental health by releasing endorphins, dopeamine, and BDNF—reducing stress, enhancing mood, improving sleep, and boosting self-esteem. Regular physical activity is associated with lower levels of anxiety and depression, and it can be an effective part of treatment for various mental health conditions.

Stress Management

Chronic stress impairs neurotransmitter function, BDNF, and HPA axis regulation.

Emerging Lifestyle Domains

The WHO-5 Wellbeing Index was adapted into the HERO Wellness Scale, which assesses holistic mental wellness from a positive psychology perspective. HERO covers four aspects of mental health that matter in our daily wellbeing.

Cutivate positive mind-states in order to improve your mental wellbeing.

Ok, now one more time let’s just run through this stuff; it’s important and worth repeating:

These are complicated, but I’ve created a table that discusses (in broad strokes) their function and ways they can be tweaked to optimize function.

β-endorphin, enkephalins, and dynorphins are the most important endorphins, acting via opioid receptors to mediate analgesia, mood, and stress responses. Their function can be optimized through regular physical activity and positive social interactions. Certain pharmacologic agents such as antidepressants and NSAIDs, which may enhance endogenous opioid activity.

β-endorphin is the most prominent and well-studied endorphin. It is produced primarily in the pituitary gland and hypothalamus and acts as a potent agonist at the μ-opioid receptor, leading to analgesia (pain relief), euphoria, and modulation of the stress response. Enkephalins and dynorphins are also important, with enkephalins primarily targeting δ-opioid receptors and dynorphins acting on κ-opioid receptors.

Mechanisms of Action

• β-endorphin binds to opioid receptors (primarily μ-opioid) in the CNS and PNS, inhibiting the release of neurotransmitters involved in pain transmission and stress, and modulating the hypothalamic-pituitary-adrenal (HPA) axis.
• It exerts analgesic effects at the spinal, supraspinal, and peripheral levels.
• β-endorphin also influences the secretion of pituitary hormones (e.g., ACTH, prolactin, growth hormone) and reduces catecholamine levels in the brain, particularly dopamine, which is involved in reward and mood regulation.

Role in Mental Health

• Mood and Euphoria: β-endorphin is associated with feelings of well-being and euphoria, and is implicated in the reward and reinforcement pathways of the brain.
• Stress and Anxiety: Endorphins modulate the stress response and may buffer against anxiety and depressive symptoms by regulating the HPA axis and neurotransmitter release.
• Addiction and Reward: β-endorphin contributes to the reinforcing effects of certain drugs and behaviors, playing a role in addiction and substance use disorders.

Lifestyle Interventions to Optimize Endorphins:

• Physical Exercise: Aerobic and endurance exercise (e.g., running, cycling) robustly increases endorphin release, contributing to the “runner’s high” and improved mood.
• Social Interaction and Laughter: Positive social engagement and laughter stimulate endorphin release.
• Meditation and Mindfulness: Practices such as yoga and meditation can enhance endogenous opioid activity.
• Music and Art: Enjoyable sensory experiences, including music and creative activities, may also boost endorphin levels.

Pharmacologic Interventions:

• Antidepressants: Certain antidepressants like SSRIs & SNRIs may indirectly modulate endorphin pathways improving mood and pain, though this is not their primary mechanism. Activation of serotonin 5-HT1A receptors by these agents has been shown to increase β-endorphin release. This effect may contribute to their mood-elevating and anxiolytic properties.
• NSAIDs (e.g., ibuprofen, naproxen): Some evidence suggests NSAIDs may enhance analgesia (pain relief) by increasing β-endorphin activity, though the exact mechanisms remain under investigation.
• Opioid Agonists: Exogenous opioids (e.g., morphine, oxycodone) mimic endorphin action but carry significant risk for dependence and are not used to optimize endogenous function—in fact, opioid drugs can actually distort and hypersensitize the endogenous nociceptive system, making chronic pain worse. Chronic opioid use also causes dysphoria/depression and suppresses sex hormones leading to impotence in men, menstrual irregularities in women, and feelings of fatigue.

There are too many hormones to list tem all here, but the most important hormones for mental and metabolic health include cortisol, insulin, thyroid hormones, sex steroids (estrogen, testosterone), melatonin, and leptin. Below is a table summarizing their normal serum levels, physiologic pathways, and lifestyle interventions to optimize their function.

Key physiologic pathways:

• Cortisol: Hypothalamic-pituitary-adrenal (HPA) axis; chronic elevation impairs mood and metabolism.
• Insulin: Pancreatic secretion in response to blood glucose; resistance leads to metabolic syndrome.
• Thyroid hormones: Hypothalamic-pituitary-thyroid axis; essential for neurodevelopment and metabolic rate.
• Estrogen/Oxytocin/Testosterone: Hypothalamic-pituitary-gonadal axis; influence mood, cognition, and metabolic health.
• Leptin: Adipose tissue to hypothalamus signaling; regulates satiety and energy expenditure
• Melatonin is produced in the pineal gland from the amino acid tryptophan, with synthesis and release tightly regulated by the light-dark cycle. 

While melatonin is primarily produced in the pineal gland, it’s also made by our skin cells in response to sunlight, and it plays a hugely important role in skin health and metabolic regulation throughout the body. Melatonin acts on MT1 and MT2 receptors, which are widely distributed in the central nervous system. MT1 and MT2 receptors are also found in peripheral organs (e.g., blood vessels, GI tract, reproductive organs, immune system), where melatonin regulates physiological processes such as vascular tone, immune responses, and reproductive function.

Melatonin Pathways

Melatonin exerts its effects through MT1 and MT2 receptors (modulating cAMP, calcium, and kinase pathways), intracellular protein interactions, and nuclear receptor binding, resulting in regulation of circadian rhythms, antioxidant activity, immune modulation, and neuroprotection.

Lifestyle interventions such as regular physical activity, stress reduction, adequate sleep, and balanced nutrition are central to optimizing the function of these hormones and supporting both mental and metabolic health.

There are two other pathways that are worth mentioning in a discussion of metabolic psychiatry.

• AMPK acts as a cellular energy sensor (“the master nutrient sensor”) and is a negative regulator of synaptic plasticity and memory formation in the hippocampus. High AMPK activity impairs memory and fear formation, likely through inhibition of mTORC1 and downstream effects on BDNF and synaptic proteins.
• BDNF is crucial for neuronal health, synaptic plasticity, and memory. Its expression is influenced by AMPK and mTORC1 signaling, and it is upregulated by interventions that promote neuroplasticity. BDNF can be upregulated by increasing your consumption of healthy foods containing Omega-3 fatty acids (flaxseeds, chia seeds, walnuts, fish oil), polyphenols (berries, grapes, vegetables, nuts), prebiotic fiber (bananas, oats, onions), and reducing your sugar and processed food intake. Getting 7-9 hours of sleep will increase BDNF. Photobiomodulation increases BDNF.
• Pharmacologic interventions that activate AMPK (e.g., metformin) are used for metabolic health, while antidepressants and experimental BDNF agonists may enhance BDNF signaling.
• Lifestyle interventions such as exercise, caloric restriction, and cognitive engagement optimize both AMPK and BDNF function, supporting both mental and metabolic health.
• Timing is important for AMPK activation: while AMPK directly acts to protect metabolic and mitochondrial health, Interventions that increase AMPK can blunt the positive effects of exercise like post-exercise muscle hypertrophy and post-exercise mitochrondrial adaptation, so hormetic interventions like intermittent fasting and metformin should be timed to avoid coinciding with post-exercise recovery. After you exercise, get some protein, and avoid metformin in recovery (metformin’s peak concentration is 3hrs after ingestion, half life 6hrs).

Benefits correlated with higher BDNF levels

• Improved memory and learning: Elevated BDNF is associated with better memory retention and learning capacity.
• Mood regulation and well-being: Higher BDNF levels are linked to improved mood and emotional regulation, potentially reducing the risk of mood disorders.
• Cognitive preservation in aging: Increased BDNF helps maintain cognitive function and may protect against age-related cognitive decline and neurodegenerative diseases.
• Enhanced neuroplasticity: Higher BDNF supports the brain’s ability to adapt and reorganize in response to new experiences, injury, or disease.

Sleep quality and duration have a significant and scientifically validated effect on BDNF levels, with chronic sleep loss and insomnia lowering BDNF, and acute sleep deprivation sometimes causing a transient increase. Evidence suggests a role for specific nutrients like Omega-3s and polyphenols and dietary patterns like the Mediterranean diet in increasing BDNF levels. This jives with what we already know, that the Mediterranean diet offers significant benefits for cognitive function and brain morphology.

Emerging research demonstrates that red and near-infrared light therapies are powerful tools in increasing BDNF expression.

Mitochondria and Oxidative Stress

The term “antidepressants” refers broadly to medications that improve symptoms of depression, anxiety, and related mood disorders. Their effects extend far beyond symptom relief, and even though they are called “antidepressants,” they’re even better at treating anxiety. Modern neuroscience shows that these medications don’t just alter brain chemistry — they help the brain heal, adapt, and rewire itself.

Antidepressants restore neurotransmitter balance, enhance neuroplasticity, and recalibrate brain circuits.

• SSRIs: Increase synaptic serotonin.
• SNRIs: Increase serotonin and norepinephrine.
• NDRIs: Increase dopamine and norepinephrine.
• MAOIs/TCAs: Rarely used but effective for treatment-resistant or atypical depression.
• Rapid-acting agents: Ketamine/esketamine modulate glutamate and BDNF pathways for fast symptom relief.

Neuroplasticity Effects:

• Receptor down/upregulation restores equilibrium.
• BDNF and synaptogenesis are upregulated, enhancing connectivity in prefrontal cortex, hippocampus, and amygdala.
• Adaptive changes can persist after medication discontinuation, provided adequate dose and duration.

By increasing the availability of these neurotransmitters, antidepressants help restore balance in brain circuits that have become dysregulated in depression and anxiety.

Neuroplasticity: Helping the Brain Rebuild Itself

One of the most profound effects of antidepressants is their ability to enhance neuroplasticity — the brain’s capacity to form new neural connections and reorganize itself.
This process underlies learning, memory, and emotional regulation.

When neurotransmitter levels are modulated by antidepressants, a cascade of downstream effects occurs:

• Receptor sensitivity adjusts: Certain receptor subtypes become less reactive (downregulated) to prevent overstimulation, while others are upregulated to restore equilibrium.
• Gene expression changes: Antidepressants influence genes that control the production of growth factors like BDNF (Brain-Derived Neurotrophic Factor), which supports neuron survival and synaptic growth.
• Circuit remodeling: Over time, these molecular changes enhance synaptic connectivity in key mood-regulating areas of the brain such as the prefrontal cortex, amygdala, and hippocampus.

The end result is greater emotional resilience and more stable mood regulation. Interestingly, these adaptive brain changes can persist long after the medication is discontinued — but only if the medication is taken at an adequate dose and for a sufficient duration to allow neuroplastic remodeling to occur.

Pleiotropic (System-Wide) Effects

Antidepressants have some pleiotropic effects, meaning they influence multiple biological systems beyond the brain:

• Cardiovascular benefits: SSRIs have been shown to improve outcomes in patients with heart disease, possibly by reducing platelet aggregation and inflammatory activation.
• Pain modulation: SNRIs can reduce chronic pain syndromes such as neuropathic pain and fibromyalgia by enhancing descending inhibitory pain pathways.
• Neurohormonal and immune modulation: Antidepressants can normalize stress hormone signaling (HPA axis) and temper pro-inflammatory cytokine activity.
• Cognitive and motivational enhancement: Bupropion’s dopaminergic activity may improve attention, focus, and motivation. Bupropion can also improve sexual dysfunction, and overweight or obese people on bupropion can experience 5-10% weight loss. 
• Metabolic benefits: Bupropion is associated with modest weight loss (typically 5–10% in overweight patients) and may counteract SSRI-related weight gain.
• Vasomotor stability: SNRIs such as venlafaxine can reduce the frequency and intensity of hot flashes in peri- and postmenopausal individuals.

Antidepressants do not simply “boost serotonin.” They initiate a complex process of neural recalibration — restoring balance across multiple neurotransmitter systems, enhancing neuroplasticity, and improving overall physiological resilience. When taken correctly and consistently, they can help the brain regain its natural capacity for flexibility, stability, and well-being.

Mitochondria, the “powerhouses” of your cells, produce ATP—the energy your body and brain need for thinking, moving, repairing tissues, and regulating metabolism. They also help control inflammation, support cell survival, and influence how neurons communicate, making them vital for brain function, mood, and stress resilience.

• Exercise: High-intensity and resistance training stimulate mitochondrial growth in muscles and brain.
• Nutrition & Supplements: Omega-3s, CoQ10, alpha-lipoic acid, and creatine protect mitochondria, reduce oxidative stress, and support energy production.
• Pharmacologic/Nutraceutical Support: medications like telmisartan act on PPARγ to increase mitochondrial biogenesis and function.
• Red/Near-Infrared Light (Photobiomodulation): These therapies stimulate cytochrome c oxidase in mitochondria, increasing ATP production, reducing oxidative stress, promoting new mitochondria, and supporting cellular repair and neurotrophic signaling.
• By combining these strategies, you can optimize cellular energy, protect neurons, and improve overall resilience and health.

Chronic stress, poor diet, sleep loss, and toxins can impair mitochondrial function, leading to lower energy, increased free radicals, reduced neurotransmission, fatigue, brain fog, and mood disturbances.

Mitochondria are critical for brain signaling because neurons require large amounts of energy to communicate. When mitochondrial function is impaired, neurotransmitter production and synaptic activity can decline, contributing to anxiety, depression, and cognitive fog. Supporting mitochondria with exercise, omega-3s, CoQ10, and even red/NIR light therapy has been shown to improve both energy and mental well-being.

PBM (specifically red light & near infrared light therapy) is a safe and effective way to improve brain metabolism, inflammation, anxiety, and depression, improve cognitive performance and reduce PTSD symptoms following traumatic brain injury, treat neurodegenerative diseases including multiple sclerosis. PBM reduces neuroinflammatory cytokines (TNF-α, IL-1β, and others), and it increases the expression of neurotrophic factors important for neuroplasticity. You can maximize the benefits of red & NIR light with a special device, but you can also get it by walking outside and getting some sunlight on your skin.

Alex Fergus measured the NIR/red light output from the sun (in Dubai and New Zealand) and gathered the following data:

Using today’s LED panels, you can maximize the benefits of near infrared & red light.

If you can catch the sun every morning, you can enjoy some of the benefits of NIR/red light therapy, but keep in mind that the irradiance of a dedicated NIR/red light panel or bulb will be much more powerful (typically 30-60 mW/cm²).

If you’re interested in learning more about PBM, read the HHNY PBM page.