Metabolism

What is metabolism

Metabolism refers to all the physical and chemical processes in the body that convert or use energy.MedlinePlus Medical Encyclopedia (2024) Metabolism. Bethesda, MD: U.S. National Library of Medicine. Available at: https://medlineplus.gov/ency/article/002257.htm [Accessed 21 September 2026]. It underpins basic functions such as breathing and blood circulation, regulating body temperature, contracting muscles, processing nutrients, eliminating waste and powering the brain and nervous system.MedlinePlus Medical Encyclopedia (2024) Metabolism. Bethesda, MD: U.S. National Library of Medicine. Available at: https://medlineplus.gov/ency/article/002257.htm [Accessed 21 September 2026]. Every cell in the body relies on metabolism to turn the food we eat into usable energy, and to build and repair the structures that keep us alive.

The brain is an especially energy-hungry organ, using a disproportionate share of the body’s energy relative to its size, and its function depends heavily on a good supply and use of energy. Disturbances in how the brain and body produce and use energy are increasingly recognised as a feature of several mental health conditions.Andreazza, A.C., Barros, L.F., Behnke, A. et al. (2025) ‘Brain and body energy metabolism and potential for treatment of psychiatric disorders’,Nature Mental Health, 3(7), pp. 763–771. When the systems that handle sugars, fats, proteins and vitamins do not work well, the effects can reach the mind as well as the body, sometimes in ways that are easy to overlook because they masquerade as purely psychological symptoms.

Metabolic problems are extremely common. The World Health Organization estimates that around 2.5 billion adults worldwide are overweight, of whom 890 million are living with obesity, and that the proportion of adults who are overweight has risen sharply in recent decades..World Health Organization (2025) Obesity and overweight. Geneva: World Health Organization. Available at: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight[Accessed 21 September 2026]. Metabolic syndrome, a cluster of related problems including central weight gain, high blood pressure, unhealthy blood fats and raised blood sugar, is also widespread, and often develops gradually and silently over years before it is diagnosed.

This page looks at how disrupted whole-body metabolism, including weight regulation, blood fats, liver health, vitamin-dependent chemistry and amino-acid pathways, can affect mental health. Two closely related topics have their own pages: insulin and blood sugar and mitochondrial dysfunction, which look in more detail at how the body regulates blood sugar and produces cellular energy.

Metabolism and mental health

Metabolism and mental health are closely intertwined, and the relationship appears to run in both directions. People with metabolic syndrome have a higher risk of developing depression,Kim, H.-B., Wolf, B.J. and Kim, J.-H. (2023) ‘Association of metabolic syndrome and its components with the risk of depressive symptoms: a systematic review and meta-analysis of cohort studies’, Journal of Affective Disorders, 323, pp. 46–54. and a genetic predisposition to depression is itself linked to a higher risk of developing metabolic syndrome.Zhang, M., Chen, J., Yin, Z., Wang, L. and Peng, L. (2021) ‘The association between depression and metabolic syndrome and its components: a bidirectional two-sample Mendelian randomization study’, Translational Psychiatry, 11, article 633. In other words, poor metabolic health can contribute to poor mental health, and poor mental health can contribute to poor metabolic health, creating a cycle that can be difficult to break without addressing both sides at once. Recognising this connection matters because it means that supporting metabolic health, through diet, movement, sleep and, where needed, medical treatment, can be a genuine part of supporting mental health, and vice versa.

Possible mental health symptoms

Metabolic dysfunction has been linked to the following mental health symptoms:

Possible Physical Signs

Metabolic dysfunction often shows up physically before or alongside mental health symptoms, which makes it worth paying attention to the body as well as the mind. Common signs include a larger waist circumference (central obesity), raised triglycerides, low HDL (“good”) cholesterol, raised blood pressure and raised blood glucose — together known as metabolic syndrome.ZKim, H.-B., Wolf, B.J. and Kim, J.-H. (2023) ‘Association of metabolic syndrome and its components with the risk of depressive symptoms: a systematic review and meta-analysis of cohort studies’, Journal of Affective Disorders, 323, pp. 46–54. Zhang, M., Chen, J., Yin, Z., Wang, L. and Peng, L. (2021) ‘The association between depression and metabolic syndrome and its components: a bidirectional two-sample Mendelian randomization study’,Translational Psychiatry, 11, article 633.Weight gain and insulin resistance linked to some psychiatric medicationsStogios, N., Humber, B., Agarwal, S.M. and Hahn, M. (2023) ‘Antipsychotic-induced weight gain in severe mental illness: risk factors and special considerations’, Current Psychiatry Reports, 25(11), pp. 707–721., fat accumulation in the liver,Åström, H., Shang, Y., Hagström, H. and Wester, A. (2024) ‘Persons with metabolic dysfunction-associated steatotic liver disease are at increased risk of severe depression’, Liver International, 44(10), pp. 2551–2563. and persistent tiredness or sluggishness are other physical signs worth being aware of, and worth mentioning to a doctor alongside any mood or cognitive symptoms.

The brain's energy supply

Energy metabolism in both brain and body is altered across a range of mental health conditions. Deficits in the mitochondrial system that generates cellular energy, and impaired glucose handling in the brain, have been documented in schizophrenia and depression, and insulin resistance is linked to a weaker response to antidepressant treatment.Andreazza, A.C., Barros, L.F., Behnke, A. et al. (2025) ‘Brain and body energy metabolism and potential for treatment of psychiatric disorders’,Nature Mental Health, 3(7), pp. 763–771. Genetic research also implicates the mitochondrial system that produces cellular energy in bipolar disorder and schizophrenia, with genes involved in the mitochondrial respiratory chain and in sugar metabolism emerging as shared signals across several conditions.Zou, S., Mendes-Silva, A.P., Dos Santos, F.C., Ebrahimi, M., Kennedy, J.L. and Gonçalves, V.F. (2025) ‘Multi-omics analysis of energy metabolism pathways across major psychiatric disorders’,Molecular Neurobiology, 62(10), pp. 13272–13285. This helps explain why some people with mental illness also experience physical symptoms of low energy, and why energy metabolism is now seen as a genuine biological contributor to psychiatric illness, rather than simply a consequence of it.

This growing field is sometimes referred to as “metabolic psychiatry”, and includes approaches such as ketogenic diets, the diabetes drug metformin, aerobic exercise, time-restricted eating and NAD+ supplementation, which are discussed further below.Andreazza, A.C., Barros, L.F., Behnke, A. et al. (2025) ‘Brain and body energy metabolism and potential for treatment of psychiatric disorders’,Nature Mental Health, 3(7), pp. 763–771. Insulin resistance and cellular energy production are each covered in more depth on our pages on Insulin hormone imbalances and Mitochondrial dysfunction.

Metabolic syndrome and depression

Metabolic syndrome describes several metabolic problems that occur together: central obesity, raised blood pressure, raised triglycerides, low HDL cholesterol and raised blood glucose.Kim, H.-B., Wolf, B.J. and Kim, J.-H. (2023) ‘Association of metabolic syndrome and its components with the risk of depressive symptoms: a systematic review and meta-analysis of cohort studies’, Journal of Affective Disorders, 323, pp. 46–54.People with metabolic syndrome have a higher risk of developing depressive symptoms, with central obesity, low HDL cholesterol and raised triglycerides most strongly linked to depression.Kim, H.-B., Wolf, B.J. and Kim, J.-H. (2023) ‘Association of metabolic syndrome and its components with the risk of depressive symptoms: a systematic review and meta-analysis of cohort studies’, Journal of Affective Disorders, 323, pp. 46–54.

Genetic research suggests that depression itself may raise the risk of developing metabolic syndrome, including a larger waist circumference, raised blood pressure, higher triglycerides and lower HDL cholesterol. The reverse relationship — metabolic syndrome causing depression — is less well supported by genetic evidence, suggesting that depression may be a more direct contributor to metabolic problems than the other way around, although shared underlying factors, such as chronic stress, poor sleep and inflammation, are also likely to play a part in both.Zhang, M., Chen, J., Yin, Z., Wang, L. and Peng, L. (2021) ‘The association between depression and metabolic syndrome and its components: a bidirectional two-sample Mendelian randomization study’, Translational Psychiatry, 11, article 633. For someone experiencing both low mood and metabolic symptoms, this is a reminder that treating the two together, rather than treating one and hoping the other resolves on its own, may give the best chance of improvement.

Diabetes, insulin resistance and depression

Diabetes is a metabolic condition in its own right, and depression is very common alongside it, affecting more than a third of people with diabetes.Yang, K., Fang, Y., He, J. and Li, J. (2025) ‘Prevalence and risk factors of depression in patients with diabetes mellitus: a systematic review and meta-analysis’,Frontiers in Endocrinology, 16, article 1660478. Insulin resistance, a state in which the body’s cells respond poorly to insulin and blood sugar control becomes harder to maintain, is also linked to a higher likelihood of depression, and can be measured using a simple blood test.Wan, W. and Yu, Y. (2024) ‘Association between the triglyceride glucose index and depression: a meta-analysis’,Frontiers in Psychiatry, 15, article 1390631.

Genetic evidence points to a two-way relationship between depression and type 2 diabetes: a genetic predisposition to depression raises the risk of developing type 2 diabetes, and a genetic predisposition to type 2 diabetes modestly raises the risk of depression, an effect that seems to be driven largely by obesity and insulin resistance.Bala, R., Handley, D., Gillett, A.C., Green, H., Bowden, J., Wood, A.R., Barroso, I., Lewis, C.M. and Tyrrell, J. (2025) ‘Evidence of bidirectional relationship between type 2 diabetes and depression; a Mendelian randomization study’, Molecular Psychiatry, 30(11), pp. 5013–5023. For more on insulin and blood sugar, see our page on Insulin hormone imbalances.

Obesity, fat tissue and leptin

Fat tissue is not simply a store of energy — it is biologically active, releasing hormones and inflammatory messengers that signal to the brain and influence mood, appetite and metabolism. Leptin, a hormone released by fat cells that normally helps regulate appetite and signal fullness, has attracted particular interest. Leptin resistance, in which the brain stops responding properly to leptin, is a feature of obesity, and raised leptin appears to promote inflammation in a self-reinforcing loop that helps to perpetuate obesity.Hontecilla-Prieto, L., García-Domínguez, D.J., Berlanga-Gil, C. et al. (2025) ‘Leptin a potential link between obesity and depression’, Cellular and Molecular Life Sciences, 82(1), article 365. Leptin levels tend to rise in step with the severity of depression.Hontecilla-Prieto, L., García-Domínguez, D.J., Berlanga-Gil, C. et al. (2025) ‘Leptin a potential link between obesity and depression’, Cellular and Molecular Life Sciences, 82(1), article 365.

Obesity and depression appear to have a bidirectional relationship, in which each condition can increase the risk of the other. Raised inflammatory markers are a likely pathway between the two, and the association appears to be stronger in women.Hontecilla-Prieto, L., García-Domínguez, D.J., Berlanga-Gil, C. et al. (2025) ‘Leptin a potential link between obesity and depression’, Cellular and Molecular Life Sciences, 82(1), article 365. This does not mean weight alone determines mood, but it is another reason why addressing weight and metabolic health can be a meaningful part of supporting mental health. See also our page on Inflammation.

Blood fats (lipids)

The picture for cholesterol and other blood fats is more complicated than “high is bad”. Higher triglycerides are linked to a greater risk of developing depression, and HDL cholesterol levels are also linked with the onset of depression, while LDL and total cholesterol show a less consistent picture.Jin, X., Kang, C., Lu, Y., Yang, Y., Zhou, F., Gao, T., Liu, X. and Yan, Y. (2025) ‘Exploring the bidirectional relationship between depressive disorder and dyslipidemia: a systematic review and meta-analysis’, Frontiers in Psychiatry, 16, article 1498773. Genetic research paints a more nuanced picture still, in which triglycerides, HDL, LDL and other blood fats relate differently to depression, anxiety, ADHD and schizophrenia — a reminder that blood fats relate to different mental health conditions in different ways, and that a simple “good fat, bad fat” story does not fully capture what is going on.Hu, W., Wu, Y. and Li, P. (2026) ‘Causal association between lipid profile and mental disorders: evidence from a bidirectional Mendelian randomization study’, European Archives of Psychiatry and Clinical Neuroscience, 276(4), pp. 1825–1836.

For brain health in later life, the picture is clearer: the Lancet Commission on dementia identifies higher LDL cholesterol in midlife as one of the modifiable risk factors for dementia, alongside obesity, diabetes and physical inactivity.Livingston, G., Huntley, J., Liu, K.Y., Costafreda, S.G., Selbæk, G., Alladi, S. et al. (2024) ‘Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission’, The Lancet, 404(10452), pp. 572–628. Keeping blood fats within a healthy range in midlife is therefore worth attending to for long-term brain health, quite apart from its well-known benefits for the heart.

The liver

The liver plays a central role in metabolism, processing nutrients, filtering toxins and regulating blood sugar and fats. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition in which excess fat builds up in the liver in the context of metabolic dysfunction, and it is becoming increasingly common alongside rising rates of obesity. People with MASLD have a higher risk of developing severe depression.Åström, H., Shang, Y., Hagström, H. and Wester, A. (2024) ‘Persons with metabolic dysfunction-associated steatotic liver disease are at increased risk of severe depression’, Liver International, 44(10), pp. 2551–2563. Because early liver disease often causes no obvious symptoms, it can be worth discussing liver health with a doctor if other metabolic risk factors, such as weight gain or raised blood sugar, are also present.

Vitamin-dependent chemistry: homocysteine and one-carbon metabolism

Homocysteine is an amino acid produced during normal metabolism. It can be recycled back into methionine, a step that needs folate and vitamin B12, or converted into cysteine and glutathione, which needs vitamin B6. When these B vitamins are lacking, homocysteine can build up, and raised homocysteine is also seen in conditions such as an underactive thyroid.McCaddon, A. and Miller, J.W. (2023) ‘Homocysteine—a retrospective and prospective appraisal’, Frontiers in Nutrition, 10, article 1179807.

Raised homocysteine may contribute to cognitive decline and Alzheimer’s disease through several mechanisms, including effects on brain chemistry and increased oxidative stress.McCaddon, A. and Miller, J.W. (2023) ‘Homocysteine—a retrospective and prospective appraisal’, Frontiers in Nutrition, 10, article 1179807. The benefit of B vitamin supplementation depends on a person’s starting homocysteine level and B vitamin status, so testing before treatment is worthwhile rather than supplementing blindly. See our pages on Nutritional imbalances and Thyroid hormone imbalances.

Amino-acid metabolism: the kynurenine pathway

Tryptophan is an amino acid best known as a building block for serotonin, but the body can also break it down along a different route. Inflammatory messengers switch on an enzyme that diverts tryptophan away from serotonin production and into the kynurenine pathway instead.O’Regan, G., Plummer, Z., Christie, B.R., Shultz, S.R. and Allen, J. (2026) ‘Kynurenine pathway dysregulation in major depressive disorder: the convergence of excitotoxicity, neuroinflammation, and oxidative stress’, Journal of Neuroinflammation, 23(1), article 179. One product of this pathway, quinolinic acid, overstimulates receptors in the brain and can damage nerve cells, while another, kynurenic acid, is generally protective. Both also add to oxidative stress in the brain.O’Regan, G., Plummer, Z., Christie, B.R., Shultz, S.R. and Allen, J. (2026) ‘Kynurenine pathway dysregulation in major depressive disorder: the convergence of excitotoxicity, neuroinflammation, and oxidative stress’, Journal of Neuroinflammation, 23(1), article 179.

People with major depressive disorder tend to show lower kynurenic acid and higher quinolinic acid, and this imbalance has been linked to greater symptom severity, anhedonia and suicidality.O’Regan, G., Plummer, Z., Christie, B.R., Shultz, S.R. and Allen, J. (2026) ‘Kynurenine pathway dysregulation in major depressive disorder: the convergence of excitotoxicity, neuroinflammation, and oxidative stress’, Journal of Neuroinflammation, 23(1), article 179. The kynurenine pathway is a meeting point between metabolism, inflammation and mood, and helps explain why inflammatory conditions so often come with changes in mental state. It is discussed further on our Inflammation page.

Inherited metabolic conditions

Inborn errors of metabolism are rare inherited conditions in which a specific step of metabolism does not work properly. Research shows that these conditions can present with depression, anxiety, psychosis, bipolar disorder, autism spectrum disorder, ADHD and obsessive-compulsive disorder.van de Burgt, N., van Doesum, W., Grevink, M., van Niele, S., de Koning, T., Leibold, N., Martínez-Martínez, P., van Amelsvoort, T. and Cath, D.C. (2023) ‘Psychiatric manifestations of inborn errors of metabolism: a systematic review’, Neuroscience & Biobehavioral Reviews, 144, article 104970. Mitochondrial disorders carry the highest psychiatric burden, mostly depression and anxiety, often alongside chronic fatigue and muscle weakness. Some disorders, such as Niemann-Pick type C, frequently present with psychosis and behavioural disturbance and are often mistaken for primary psychiatric illness.van de Burgt, N., van Doesum, W., Grevink, M., van Niele, S., de Koning, T., Leibold, N., Martínez-Martínez, P., van Amelsvoort, T. and Cath, D.C. (2023) ‘Psychiatric manifestations of inborn errors of metabolism: a systematic review’, Neuroscience & Biobehavioral Reviews, 144, article 104970.

The psychiatric presentation is often atypical and can appear before any physical symptoms, contributing to long delays in diagnosis.van de Burgt, N., van Doesum, W., Grevink, M., van Niele, S., de Koning, T., Leibold, N., Martínez-Martínez, P., van Amelsvoort, T. and Cath, D.C. (2023) ‘Psychiatric manifestations of inborn errors of metabolism: a systematic review’, Neuroscience & Biobehavioral Reviews, 144, article 104970. These conditions are uncommon, but a persistent, unusual or treatment-resistant psychiatric picture, particularly alongside physical symptoms such as unexplained fatigue, muscle weakness or developmental changes, may sometimes have a metabolic explanation worth investigating with a doctor.

Medication and metabolic side effects

Some medicines used to treat mental illness can themselves disturb metabolism, which can create a difficult cycle if metabolic symptoms are then mistaken for a worsening of the underlying mental health condition. Antipsychotics, including first-generation drugs, are associated with weight gain, with some carrying a higher risk than others. Weight gain is often greatest in the early stages of treatment, which is a useful window for monitoring and early intervention.Stogios, N., Humber, B., Agarwal, S.M. and Hahn, M. (2023) ‘Antipsychotic-induced weight gain in severe mental illness: risk factors and special considerations’, Current Psychiatry Reports, 25(11), pp. 707–721.

The proposed mechanisms include blockade of dopamine signalling that affects appetite regulation, changes in hormones such as leptin and ghrelin, insulin resistance that can occur independently of weight gain, and possible changes in the gut microbiome.Stogios, N., Humber, B., Agarwal, S.M. and Hahn, M. (2023) ‘Antipsychotic-induced weight gain in severe mental illness: risk factors and special considerations’, Current Psychiatry Reports, 25(11), pp. 707–721. Anyone concerned about weight or blood-sugar changes on a prescribed medicine should discuss this with their prescriber rather than stopping it suddenly, since alternatives or additional monitoring may be available.

Cognitive decline and dementia

The Lancet Commission on dementia names several metabolic factors among its modifiable risk factors for dementia: obesity, diabetes, physical inactivity and higher LDL cholesterol in midlife. It estimates that nearly half of dementia cases could be prevented or delayed by addressing all modifiable risk factors together.Livingston, G., Huntley, J., Liu, K.Y., Costafreda, S.G., Selbæk, G., Alladi, S. et al. (2024) ‘Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission’, The Lancet, 404(10452), pp. 572–628. Metabolic health in midlife is therefore relevant not only to mood but to long-term brain health, and the earlier these risk factors are addressed, the more time there is for them to make a difference.

Metabolic approaches being studied

Because metabolic dysfunction appears alongside so many mental health conditions, researchers are exploring whether treating it can also help the mind. These approaches are promising but still being studied, and should be discussed with a clinician, particularly for anyone taking psychiatric or diabetes medication, since some carry interactions or risks that need medical supervision.

Early trials of ketogenic diets in people with bipolar disorder and schizophrenia have shown improvements in weight, insulin resistance and triglycerides, alongside improvements in psychiatric symptoms.Sethi, S., Wakeham, D., Ketter, T., Hooshmand, F., Bjornstad, J., Richards, B., Westman, E.C., Krauss, R.M. and Saslow, L.R. (2024) ‘Ketogenic diet intervention on metabolic and psychiatric health in bipolar and schizophrenia: a pilot trial’, Psychiatry Research, 335, article 115866. Diabetes and weight-loss drugs known as GLP-1 receptor agonists (such as semaglutide) are also being studied for possible cognitive and mental health benefits, with some early research suggesting they may reduce the risk of dementia.De Giorgi, R., Ghenciulescu, A., Dziwisz, O., Taquet, M., Adler, A.I., Koychev, I., Upthegrove, R., Solmi, M., McCutcheon, R., Pillinger, T., Cowen, P.J. and Harmer, C.J. (2025) ‘An analysis on the role of glucagon-like peptide-1 receptor agonists in cognitive and mental health disorders’, Nature Mental Health, 3(3), pp. 354–373. Metabolic psychiatry more broadly is exploring metformin, pioglitazone, intermittent fasting, ketogenic therapy and exercise as ways of targeting metabolic dysregulation in mental illness, and calls for routine metabolic screening in people with mental health conditions are growing, reflecting a shift towards seeing mental and metabolic health as two sides of the same coin.Sethi, S., Berk, M., Andreazza, A.C., Mujica-Parodi, L.R., Campbell, I., Campbell, H. et al. (2026) ‘Metabolic psychiatry targeting metabolic dysregulation in mental health’, Nature Mental Health, 4(4), pp. 508–520. Laurent, N., Bellamy, E.L., Hristova, D. and Houston, A. (2024) ‘Ketogenic diets in clinical psychology: examining the evidence and implications for practice’, Frontiers in Psychology, 15, article 1468894.

Causes of metabolic dysfunction

Metabolic dysfunction rarely has a single cause. The research described above points to several overlapping contributors.

Diet and nutrient status

The food we eat supplies both the fuel and the raw materials for metabolism. Diets high in refined sugar and processed food, and low in fibre, healthy fats and micronutrients, are a well-established contributor to metabolic dysfunction. Vitamin B12, folate and vitamin B6 are essential for homocysteine metabolism, and shortfalls impair it.McCaddon, A. and Miller, J.W. (2023) ‘Homocysteine—a retrospective and prospective appraisal’, Frontiers in Nutrition, 10, article 1179807. Dietary change can also shift metabolic markers for the better, as seen with ketogenic diets.Sethi, S., Wakeham, D., Ketter, T., Hooshmand, F., Bjornstad, J., Richards, B., Westman, E.C., Krauss, R.M. and Saslow, L.R. (2024) ‘Ketogenic diet intervention on metabolic and psychiatric health in bipolar and schizophrenia: a pilot trial’, Psychiatry Research, 335, article 115866. See our page on Nutritional imbalances.

Inflammation

Raised inflammatory messengers accompany obesity and leptin resistance,Hontecilla-Prieto, L., García-Domínguez, D.J., Berlanga-Gil, C. et al. (2025) ‘Leptin a potential link between obesity and depression’, Cellular and Molecular Life Sciences, 82(1), article 365. and they also redirect tryptophan metabolism towards the kynurenine pathway.O’Regan, G., Plummer, Z., Christie, B.R., Shultz, S.R. and Allen, J. (2026) ‘Kynurenine pathway dysregulation in major depressive disorder: the convergence of excitotoxicity, neuroinflammation, and oxidative stress’, Journal of Neuroinflammation, 23(1), article 179. Metabolism and inflammation influence each other, so that inflammation from any source, whether diet, infection, stress or toxin exposure, can worsen metabolic health. See Inflammation.

Sleep and Circadian Rhythm

Sleep and body clock also play an important role in metabolic health. Short sleep, under about six hours a night, is consistently linked to metabolic syndrome, and irregular sleep timing raises the risk further. “Social jetlag” — a mismatch between weekday and weekend sleep timing of two hours or more — is linked to roughly double the risk of metabolic syndrome.Bewket, B. and Pimenta, A.M. (2026) ‘The association between sleep duration, insomnia and sleep patterns with metabolic syndrome: an integrative review’, Frontiers in Clinical Diabetes and Healthcare, 7, article 1794920.

Proposed mechanisms include changes in the appetite hormones leptin and ghrelin, higher sympathetic nervous system activity, inflammation and impaired function of the blood-vessel lining.Bewket, B. and Pimenta, A.M. (2026) ‘The association between sleep duration, insomnia and sleep patterns with metabolic syndrome: an integrative review’, Frontiers in Clinical Diabetes and Healthcare, 7, article 1794920. Keeping a consistent sleep schedule, not just getting enough sleep, may therefore be an underappreciated part of metabolic health.

Physical inactivity and other lifestyle factors

Physical inactivity, obesity and diabetes are among the modifiable risk factors for dementia identified by the Lancet Commission,Livingston, G., Huntley, J., Liu, K.Y., Costafreda, S.G., Selbæk, G., Alladi, S. et al. (2024) ‘Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission’, The Lancet, 404(10452), pp. 572–628. and aerobic exercise is among the approaches being explored within metabolic psychiatry.Andreazza, A.C., Barros, L.F., Behnke, A. et al. (2025) ‘Brain and body energy metabolism and potential for treatment of psychiatric disorders’, Nature Mental Health, 3(7), pp. 763–771. Regular movement supports insulin sensitivity, healthy blood fats and a healthy weight, all of which feed back into mental as well as physical health.

Medication

Antipsychotic medicines are an established cause of weight gain and insulin resistance in some people.Stogios, N., Humber, B., Agarwal, S.M. and Hahn, M. (2023) ‘Antipsychotic-induced weight gain in severe mental illness: risk factors and special considerations’, Current Psychiatry Reports, 25(11), pp. 707–721.

Genetics and inherited conditions

Rare inherited enzyme and mitochondrial disorders can disrupt metabolism from birth or emerge in adulthood.van de Burgt, N., van Doesum, W., Grevink, M., van Niele, S., de Koning, T., Leibold, N., Martínez-Martínez, P., van Amelsvoort, T. and Cath, D.C. (2023) ‘Psychiatric manifestations of inborn errors of metabolism: a systematic review’, Neuroscience & Biobehavioral Reviews, 144, article 104970. Genetic predisposition to depression itself may also raise the risk of metabolic syndrome. See Genetic factors.

Hormones

Hormones such as leptin and thyroid hormone are closely tied to metabolism. Leptin resistance is a feature of obesity,Hontecilla-Prieto, L., García-Domínguez, D.J., Berlanga-Gil, C. et al. (2025) ‘Leptin a potential link between obesity and depression’, Cellular and Molecular Life Sciences, 82(1), article 365. and an underactive thyroid can raise homocysteine.McCaddon, A. and Miller, J.W. (2023) ‘Homocysteine—a retrospective and prospective appraisal’, Frontiers in Nutrition, 10, article 1179807.See Hormone imbalances.

Liver health

Fat accumulation in the liver is linked to a higher risk of severe depression, so liver health is part of the metabolic picture, and is worth supporting through diet, alcohol moderation and regular activity.

What this means for you

If you recognise several of the physical signs or symptoms on this page alongside ongoing mood, energy or cognitive difficulties, it may be worth asking your doctor for basic metabolic blood tests, such as fasting glucose, HbA1c, a lipid panel and liver function tests, alongside a review of your weight, waist circumference and blood pressure. These are simple, widely available tests that can highlight metabolic problems early, often well before they would otherwise cause noticeable physical symptoms. Addressing metabolic health, through diet, movement, sleep, stress management and, where appropriate, medical treatment, is not a replacement for mental health care, but can be a valuable part of it.