Metabolism and the Brain

Evidence for the role of insulin in mediating normal and abnormal brain function may lead to new treatments for neurological and psychiatric disorders.

By Oksana Kaidanovich-Beilin, Danielle S. Cha, and Roger S. McIntyre | December 1, 2012


Historically, insulin-shock therapy, also known as insulin coma therapy (ICT), was a form of psychiatric treatment in which patients were injected daily for several weeks or even months with a large dose of insulin in order to induce a coma. After about an hour in the coma, the treatment was ended by the administration of glucose. Originally introduced in 1933 by Austrian-American psychiatrist Manfred Sakel, the method was soon adopted by other psychiatrists in the United States and Europe. ICT was used extensively in the 1940s and ’50s to mitigate psychotic and affective symptoms, primarily in patients with schizophrenia. But the induced hypoglycemia, or pathologically low blood-glucose level, that resulted from ICT made patients extremely restless, sweaty, and, after long courses of treatment, even grossly obese. ICT was also associated with death and brain damage, and there was no scientific explanation for ICT’s often successful mechanism of therapeutic action. As a result, its use was abandoned in the U.S. by 1970. But the experience provides a valuable lesson: an intimate link exists between the brain and the metabolism of sugar—one that has too long been overlooked by the fields of neuroscience and psychiatry.

Neuropsychiatric disorders are debilitating conditions associated with inexplicable mood shifts, delusions and dementia, and even premature mortality. Disease modeling of these disorders implicates the role of abnormal cellular structure and function, resulting in disturbances in synaptic signaling and in entire neural circuits. Research underscores the role of genetic, epigenetic, and environmental pathogenic influences. However, the specific mechanisms underlying most neurological and psychiatric disorders have yet to be elucidated.

An intimate link exists between the brain and the metabolism of sugar—one that has too long been overlooked by the fields of neuroscience and psychiatry.

One idea that is gaining steam is a role for metabolism. Neuropsychiatric disorders often co-occur with metabolic disturbances, such as insulin resistance, diabetes, and obesity.1 And as ICT records illustrate, manipulating patients’ metabolism via injections of insulin can have striking effects on their mental state. Furthermore, researchers have documented roles for insulin, a pleiotropic peptide traditionally discussed in terms of metabolic disorders like diabetes and obesity, in neuron growth, neuroplasticity, and neuromodulation. Moreover, insulin appears to be important in the development of several neuropsychiatric disorders, including neurodegenerative diseases such as Alzheimer’s. (See Table below.) Stress and neuroinflammation are two physiological conditions affected by insulin-mediated signaling that have both metabolic and neurologic consequences, possibly explaining the co-occurrence of the two types of disorders. Taking into account such metabolic disturbances when refining disease models for neuropsychiatric disorders is an essential step in the development of preventive treatments, and targeting insulin-related pathways in the brain could lead to new approaches for treating neurological and psychiatric disorders.


The metabolic link

The association between disruptions in glucose metabolism and psychiatric disorders was first documented more than 3 centuries ago by the English doctor Thomas Willis. He noted that persons who had experienced stressful life events, depression, or “long sorrow,” often suffered from diabetes. Years later, in 1897, British psychiatrist Henry Maudsley observed that diabetes and insanity are often co-expressed in families, and in 1935, American psychiatrist William Claire Menninger postulated the existence of psychogenic diabetes and described a “diabetic personality.” More recently, researchers suggested that enhancing glucose metabolism and related insulin-signaling pathways in the brain improved functional activity of patients with schizophrenia.

The connection between metabolic disturbances and neuropsychiatric disorders has been strengthened by recent and ongoing human clinical studies, which document numerous and complex interactions between metabolism and the brain. For example, individuals with depression have an approximately 60 percent higher risk of developing type 2 diabetes. Conversely, individuals with diabetes are at an elevated risk of developing depression. Metabolic disturbances are also reported to be two to four times higher in people with schizophrenia, and patients prescribed psychotropic medications, such as antipsychotics and antidepressants, often experience disturbances in metabolic parameters, including high blood sugar, impaired glucose tolerance, and type 2 diabetes.

Metabolic disturbances have also been implicated in neurodegenerative disorders, including Alzheimer’s, Huntington’s, and Parkinson’s diseases. Multiple clinical observations have demonstrated that dementia in general, and Alzheimer’s disease in particular, are associated with type 2 diabetes and obesity. Moreover, type 2 diabetes is considered an independent risk factor for dementia, with the prevalence of dementia in diabetic populations double that of healthy patient populations. Other clinical observations have shown that prevalence rates for type 2 diabetes and insulin abnormalities are approximately 7-fold higher in patients with Huntington’s disease when compared to healthy controls, and impaired glucose tolerance affects up to 80 percent of Parkinson’s patients.

Taken together, clinical studies have provided ample evidence supporting an overlap between metabolic disturbances and neuropsychiatric disorders. The question now is: What links the two? The data suggest that an imbalance in brain function and metabolic status share underlying pathophysiological mechanisms and common intracellular signaling molecules. If true, targeting these underlying pathways could serve as novel therapies for both types of disorders.


Insulin in the brain

A notable signaling pathway that affects both neuropsychiatric and metabolic processes is one mediated by insulin, the main hormone traditionally discussed in the context of  blood-glucose regulation. Dysregulation of insulin’s intracellular effects has been implicated in the pathogenesis of both metabolic and neuropsychiatric disorders. (See illustration below.)
The brain is a particularly energy-intensive organ; approximately 25 percent of total body glucose utilization is required for proper brain function. But despite this high need for glucose, the brain has traditionally been viewed as functioning independently of insulin. This view, however, has recently been challenged.

INSULIN’S ROLE IN BODY AND BRAIN: Insulin, long recognized as a primary regulator of blood glucose, is now also understood to play key roles in neuroplasticity, neuromodulation, and neurotrophism, the process of neuronal growth, stimulated by neuronal differentiation and survival. View full size JPG | PDFPRECISION GRAPHICS; HEAD © 3D4MEDICAL.COM/CORBISInsulin’s ability to cross the blood-brain barrier was evinced approximately 40 years ago following the observation that spikes in circulating insulin levels increase the peptide’s concentration in the brain. Researchers subsequently identified insulin receptors, insulin downstream signaling molecules, and insulin-sensitive glucose transporters in the mammalian central nervous system (CNS), on both neurons and astrocytes (support cells) throughout the brain and spinal cord,2 suggesting that insulin is required for normal brain function. This idea has since been supported by numerous studies in transgenic animal models, and insulin has come to be known as a neuropeptide critical for neuroplasticity, neuromodulation, and neurotrophism, the process of neuronal growth, stimulated by neuronal differentiation and survival.

One role for insulin in the brain is in regulating feeding behavior. Studies in rodents have shown that direct administration of insulin into the brain inhibits food intake and reduces body weight, while mice lacking insulin receptors in the brain become obese.3 Similarly, the deletion of insulin receptors from midbrain dopamine neurons in mice results in increased appetite and body weight,4 and brain-specific insulin receptor substrate-2 (IRS2) knockout mice are also overweight, hyperinsulinemic, and glucose intolerant.5 These results suggest that insulin-related weight gain is regulated specifically by insulin signaling in the brain. Indeed, the ablation of insulin receptors from adipose tissue produces the opposite effect—weight loss.

In addition, insulin plays an important role in dopamine-mediated reward circuits, which are involved in the motivating, rewarding, and reinforcing properties of food. Studies in human subjects have identified an imbalance in several neuronal circuits of obese patients, affecting aspects of reward saliency, motivation, and learning. A novel hypothesis postulates that obesity is a consequence of addictive food behaviors.6 Indeed, obesity is characterized by deficits in the striatal dopamine 2 receptor (D2R). And new evidence suggests that insulin-mediated signaling components may play a key part in regulating that addiction.

Injection of insulin into the brains of rodents, for example, increases the amount and activity of dopamine transporters in the substantia nigra, a midbrain structure involved in reward, addiction, and movement.7 Furthermore, obese and diabetic leptin-deficient mice have low levels of tyrosine hydroxylase, an enzyme involved in dopamine synthesis, in their midbrain dopamine neurons. These mice also release less dopamine into the nucleus accumbens; harbor decreased stores of dopamine in the ventral tegmental area, which is implicated in drug and natural reward circuitry; and show diminished sensitivity to the dopamine-dependent motivational and psychomotor stimulant effects of cocaine and amphetamines. These symptoms can be reversed by treatment of leptin-deficient mice with dopamine receptor agonists, which reduces excessive hunger and obesity and improves insulin sensitivity.

Insulin has come to be known as a neuropeptide critical for neuron growth, neuroplasticity, and neuromodulation.

Insulin and insulin-mediated signaling pathways also play an important role in the regulation of normal emotional and cognitive brain functions. Several studies have shown that insulin may contribute to learning and memory. For example, training for memory tasks in animals causes an upregulation of insulin receptors in the hippocampus. Historically, cognitive impairment has been associated with insulin resistance and type 2 diabetes and was classified as diabetic encephalopathy. To take a more extreme case, obesity has been identified as a risk factor for dementia. Individuals with Alzheimer’s disease have a lower concentration of insulin in their cerebrospinal fluid and a higher concentration in their blood than controls, both of which indicate impaired insulin metabolism in the brain.

Given this intimate link between insulin signaling and brain function, it should be no surprise that insulin treatment in individuals with Alzheimer’s disease has produced beneficial effects on memory performance. The systemic infusion of insulin also improves patients’ verbal memory and selective attention. Intranasal administration of insulin has proven to be another way to facilitate memory, and rodents receiving injections of insulin directly into the brain performed better on memory tasks. However, it is still unclear whether insulin has a direct effect on brain function or whether these changes are a consequence of disturbances in peripheral glucose metabolism.

Insulin-mediated signaling pathways could also influence Alzheimer’s patient outcome by clearing β-amyloid from the brain. Competitively blocking an insulin-degradation enzyme in Alzheimer’s patients also reduced β-amyloid levels. Moreover, insulin treatment lowers the plasma concentrations of the amyloid precursor protein, which has been implicated in the development of Alzheimer’s disease.

Work in mouse models also supports a role for insulin signaling in Alzheimer’s pathogenesis. In a mouse model with a double mutation of this amyloid precursor protein, insulin-like growth factor (IGF-1) has a protective effect against the development of amyloid deposits, but plaque formation increased when mice consumed a high-fat diet and developed insulin resistance. Mouse models with brain-specific deletions of insulin signaling molecules also display increased levels of phosphorylated tau, another protein implicated in Alzheimer’s disease.

Collectively, these data support the notion that Alzheimer’s disease could be conceptualized as a metabolic disease, with progressive impairment of the brain’s capacity to utilize glucose and respond to insulin and IGF-1. Furthermore, the findings suggest that insulin signaling may play a key role in the development of the disease, and that these pathways may serve as viable drug targets to prevent and treat Alzheimer’s-related dementia.

INFLAMMATION: Chronic neuroinflammation—as measured by high levels of circulating inflammatory cytokines and activated astrocytes and microglia in the brain—can affect the synthesis, release, and reuptake of neurotransmitters, partially contributing to the pathogenesis of neuropsychiatric disturbances. Neuroinflammation is also associated with obesity.PRECISION GRAPHICSINFLAMMATION

One common physiological process that may be influenced by insulin-mediated signaling and involved in the pathogenesis of both neuropsychiatric and metabolic disorders is inflammation. Abnormal levels of immunomodulating agents, such as cytokines, are associated with inflammatory processes in the brain and peripheral organs, and studies in humans and rodents have demonstrated that chronic inflammation may be a key factor in the pathogenesis of both types of disorders.

The link between inflammation and diseases of the brain is no surprise. Higher-than-normal levels of circulating inflammatory cytokines, together with activated astrocytes and microglia in the brain, are found in patients with Parkinson’s, Alzheimer’s, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and mood disorders. Cytokines have the capacity to influence the synthesis, release, and reuptake of neurotransmitters, such as dopamine and serotonin. Likely for this reason, antidepressants that target these systems are less effective in individuals with an active inflammatory state, and antidepressant efficiency may be enhanced when combined with anti-inflammatory agents, such as aspirin (acetylsalicylic acid). Furthermore, the injection of a bacterial endotoxin, which activates pro- as well as anti-inflammatory cytokines, into healthy volunteers induces depressive symptoms and verbal and nonverbal memory deficits. Similarly, the systemic administration of pro-inflammatory cytokines in rodents induces “sickness behavior,” including anorexia, sleep disturbance, neurocognitive impairment, fatigue, and reduced self-care behaviors.

Evidence supporting inflammation as a possible link between brain and metabolic disorders comes from fat tissue–derived cytokines called adipokines. One such adipokine, leptin, has been found to be elevated in patients with depression, and postmortem studies of depressed patients who committed suicide revealed a downregulation of leptin receptors in the frontal cortex. On the metabolism side of the coin, obesity is classified as a state of chronic low-grade inflammation1 and is associated with abnormal levels of adipokines.2 (See “Fat's Immune Sentinels”) For example, mice with a mutation in the leptin or leptin receptor gene have demonstrated deficits in cell-mediated immunity, and are obese and diabetic. In addition, animal studies have demonstrated that Toll-like receptor (TLR) signaling, which is a fundamental component in the innate immune system response, is implicated in mediating insulin and leptin resistance in the brain.

1. G.S. Hotamisligil, “Inflammation and metabolic disorders,” Nature, 444:860-67, 2006.

2. J.P. Thaler et al., “Hypothalamic inflammation and energy homeostasis: resolving the paradox,” Front Neuroendocrinol, 31:79-84, 2010.


STRESS: Chronic stress conditions can disrupt signaling of the hypothalamic-pituitary-adrenal (HPA) axis, which is involved in the production of stress hormones known as glucocorticoids. Such signaling disruption can result in cognitive impairments, mood changes, and metabolic complications.© DORLING KINDERSLEY/GETTY IMAGESSTRESS

Stress is another condition that is influenced by insulin-mediated signaling and may be an additional link between metabolic and neurological disturbances. Whether it be hunger, childhood adversity, or challenging life events, stress has been implicated in the development of obesity as well as addiction and other psychiatric disorders.1

Hunger, for example, can trigger intense bouts of feeding in rodents, monkeys, and humans, and rats undergoing cyclical periods of caloric restriction and refeeding demonstrate compulsive-like consumption of palatable foods. Also, mice overexpressing corticotropin-releasing hormone, a peptide hormone and neurotransmitter involved in the stress response, eat more, gain weight, and exhibit insulin resistance, increased anxiety, impaired learning, and altered adaptations to stress. Collectively, these data suggest that stress impacts both an organism’s metabolism and its neurological processes, and thus may serve as a common pathology to explain the observed association between metabolic and neurological disorders.

The underlying physiology of stress yields clues about its broad reach. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in the overproduction of stress hormones known as glucocorticoids. There are a number of lines of evidence linking glucocorticoids to both metabolic and psychiatric disorders. For one, glucocorticoid resistance—the inability to respond to the physiological concentrations of the hormones—has been found in more than 50 percent of mood disorder cases, which are known to be triggered by various types of stress. Second, exogenous administration of glucocorticoids is associated with excess levels of circulating insulin and insulin resistance. And third, obese patients have increased levels of an enzyme that converts cortisone into the active stress hormone cortisol following activation of glucocorticoid receptors; this enzyme has been reported to be a candidate biomarker for depression.2

1. M.F. Dallman et al., “Chronic stress and obesity: a new view of ‘comfort food,’ ” PNAS, 100:11696-701, 2003.

2. R. Desbriere et al., “11b-hydroxy-steroid dehydrogenase type 1 mRNA is increased in both visceral and subcutaneous adipose tissue of obese patients,” Obesity, 14:794-98, 2006.



The way forward

Normal and pathological conditions have an immediate impact on brain functions. Moreover, neurons and glial cells exist in a tight, mutual structure-function relationship that is highly dependent on the peripheral supply of glucose—the cells’ major energy source. Converging evidence indicates that insulin serves several critical roles in the CNS under both normal and abnormal conditions. Insulin receptors are expressed in the brain, affecting a wide range of normal brain functions, such as reward, motivation, cognition, attention, and memory formation, and dysregulation of insulin signaling leads to characteristic signs of neurodegenerative and psychiatric diseases. Thus, pharmacological targeting of insulin-mediated signaling pathways may be beneficial in treating brain disorders.

Furthermore, the totality of evidence suggests that metabolic and neuropsychiatric disorders may share a common pathophysiological nexus. Critical effectors of this association include alterations in whole-body energy metabolism, oxidative stress, inflammation, insulin resistance, and corticosteroid signaling, as well as imbalances in cytokines and adipokines. Investigations that aim to refine the relative contributions of these effector systems, with a particular focus on convergent molecular pathways, may provide the basis for disease-related biomarker discovery, as well as novel treatment approaches for both metabolic and neuropsychiatric conditions. 

Oksana Kaidanovich-Beilin is a postdoctoral fellow in Jim Woodgett’s laboratory at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto, Ontario, and an editor of special research topics for Frontiers in Molecular Neuroscience. Danielle S. Cha is an undergraduate student at the University of Toronto in the lab of Roger S. McIntyre. McIntyre is a professor of psychiatry and pharmacology at the University of Toronto and head of the Mood Disorders Psychopharmacology Unit at Toronto Western Hospital, University Health Network.



1.    R.S. McIntyre et al., “Mechanisms of antipsychotic-induced weight gain,” J Clin Psychiatry,
62 Suppl:23-29, 2001.

2.    J. Havrankova et al., “Insulin receptors are widely distributed in the central nervous system of the rat,” Nature, 272:827-29, 1978.

3.    J.C. Brüning et al., “Role of brain insulin receptor in control of body weight and reproduction,” Science, 289:2122-25, 2000.

4.    A.C. Könner et al., “Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis,” Cell Metab, 13:720-28, 2011.

5.    A. Taguchi et al., “Brain IRS2 signaling coordinates life span and nutrient homeostasis,” Science, 317:369-72, 2007.

6.    N.D. Volkow, R.A. Wise, “How can drug addiction help us understand obesity?” Nat Neurosci, 8:555-60, 2005.

7.    D.P. Figlewicz et al., “Intraventricular insulin increases dopamine transporter mRNA in rat VTA/substantia nigra,” Brain Res, 644:331–34, 1994.

This article is adapted from a review in F1000 Biology Reports, DOI:10.3410/B4-14 (open access at

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Avatar of: nrose


Posts: 1

December 6, 2012

Hi there!  I found this article fascinating because I have had panic disorder and generalized anxiety disorder since childhood and I have also suffered from frequent bouts of hypoglycemia since childhood.  I have always been a very thin person and I am currently 27 years old, active and a healthy weight.  I have long-observed that my anxiety often triggers my hypoglycemic episodes (rather than the other way around).  As you expressed. "exogenous administration of glucocorticoids is associated with excess levels of circulating insulin and insulin resistance."  I hypothesize that perhaps my lack of obesity protects me from developing insulin resistance (at least for now) and therefore I may have always been more affected by the excees insulin resulting from the anxiety-provoked glucocorticoid release.  I know I am just one person but I wonder if other healthy-weight or thin people with mood disorders also suffer from hypoglycemic episodes following stress and panic?  I guess my point is: a lot of the research on metabolism and psychiatric disorders seems to focus on obese subjects.  I would like to see more research on metabolism and psychiatric disorders in non-obese subjects as well. Do stress reactions occur differently in the more insulin-resistant obese than in those of a "healthier" weight and how would that effect metabolism-centered therapies? I guess we are a bit far from knowing but I just wanted to put that out there.  Thanks!

Avatar of: mlerman


Posts: 71

December 7, 2012


This is a very interesting, informative, wellwritten paper. I remember studying psychiatry in medical school in Moscow (USSR) was a very painful experience. I remember diagnosis was always quite accurate but treatment almost nonexisting. The doctor who invented the insulin coma treatment probably had a vision and expected positive results. The enormous complexity of the brain cortex and its function(s) precluded at that time and even today a rational approach based on knowledge of neuron connectivity and functions.   Micnael Lerman, M.D., Ph.D.  


Avatar of: Christopher R. Lee

Christopher R. Lee

Posts: 17

December 8, 2012

I used to have an interest in an aspect of this that ought perhaps to be revisited. It concerns the small molecule metabolites / degradation products of carbohydrates.

In the early 1970s, under the direction of F A Jenner and R J Pollitt at Sheffield UK, I was involved in what is now called a metabolomic study of patients with rapid-cycling periodic disorders. We had a metabolic clinic that maintained a constant daily diet for cooperative patients, the best we could do despite the fluctuating physical activity. We were looking for correlations between the metabolic profile and the mood swings, without interference from inter-individual variations. The study of bipolar patients didn't really get started at Sheffield (see below). A similar clinic at Edinburgh ((L G Murray) provided complete urine collections from one patient with a less certain diagnosis.

We found changes in urinary S-3,4-dihydroxybutyrate (DHB) coinciding with the mood swings. DHB of unestablished stereochemistry was already known as a degradation product of carbohydrates. That put us into unknown territory, but we  were able to establish the stereochemistry and show that it is a metabolite of 4-hydroxybutyric acid. There was a brief publication in a volume of mass spectrometry conference proceedings, but it was decided not to submit the full paper as the study had never really got started as we had intended.

Subsequently, a Japanese group found that DHB and some other compounds had a role in satiety and hunger modulation. The papers I have are: Bull ChemSoc Jpn 1988, 61, 2025_2029 and J Exp Biol Med 2003, 228, 1146_1155. This is the work that should, at least, be re-read.

Our own clinical project was considered a failure as, for ethical reasons, our bipolar patients had to be given a trial of lithium soon after joining the clinic. Rapid cycling is generally associated with severity of illness. Nevertheless, everyone who accepted the treatment got better and went home, sometimes after decades of hospitalisation. The clinicians didn't seem surprised, and they attributed their success to the particularly friendly and supportive conditions.





Avatar of: HealthNow


Posts: 1

Replied to a comment from nrose made on December 6, 2012

December 8, 2012

Hi nrose,

Most everyone today with any kind of a health challenge is missing one or more of the Eight Necessary Plant Sacchrides our bodies need for the cells to comminicate properly. I don't know how to attach the files here for you to read but it has been proven in tests. I'm told we have between 65 to 100 trillion cells so its kind of important for all of them to be communicating correctly. We are only getting two of the eight saccharides in our modern diets.These supplements are plant based so the body recognizes them totally. It would be nice if you could contact me directly, I would be happy to help you. Take care.

Avatar of: j.zeit


Posts: 1

December 13, 2012

Hi HealthNow


I tried to contact you for info on the Eight Necessary Plant Sacchrides. Could not get contact info. Would you please send info to joe [at]


Thank you.



Avatar of: jeenious


Posts: 45

December 13, 2012

In reading the four preceding comments, several issues are raised for me. In the first a commenter speaks of one thing triggering another. In researching symptoms, the chronological order in which symptoms occur, or in which a patient becomes aware of them, does not always indicate that the former triggers the latter. The commenter indicates the more research is needed in reference to symptom relationships. That is a reasonable observation. However, let us wonder how many researchers already have worked, and are now working, in accordance with how many different hypotheses surrounding these symptoms, already. In the second of the four comments, reference is made to how many diagnoses of mental illness was quite accurate. As time has gone on, diagnoses of mental illnesses have become increasingly controversial. While certain constellations of symptoms tend to occur, there are what might be termed "symptom noise" and "symptoms in common" among them, such that -- as one young family member of one patient so aptly put it -- "We took Momma to six different psychiatrists and got six different names to call what's wrong with her, and it seems like three different prescriptions for each name, and when she's not in a medicated stupor, she's still the same -- crazy."

Out of the mouths of babes.

This is not take away from what mentally ill patients, or those in psychiatric research, and psycho-pharmacological research, and patients and the families of patients are up against. Neither is this meant to detract from the need for medical attention and care-taking and medical research. I only wish, here, to point out that it is a stretch to say that any large group of psychological diagnosticians is accurate in pinning "the correct" name on the actions and words of patients who are mentally (or emotionally) ill.

The third comment I do not take exception to, except to pose this question: Of all the thousands of studies that have been done, is there any central repository of rulings in and rulings out of hypotheses concerning metabolomics what percentage, let us wonder, are productively redundant (that is, ascertain that the same experiment, set up and conducted by multiple researchers will produce the same, or a reasonably ballpark statistical result?).

Many kinds of research projects provide results that are statistical, and redundant trials of many different sample groups, depending upon size of sample, and degree of assurance that unknown parameters may be measured unwittingly, so even outcomes that are drastically different may, when added together, and analyzed with utmost objectivity, help to reveal what some of those other parameters are, and why they must be factored in. Some varieties of experimental or observational approaches and some varities in how constellations of symtoms are categorized (and named) may, themselves, seem to present different results.

The article is well-conceived and well-written. Its value is not ine being "the answer" to all the questions surrounding the subject. But few studies, standing alone, provide the "right" answers or "all" the answers.

As to the fourth comment, it sniffs of snake oil. That is not to say that it is snake oil, but it just makes something that is not clear and obvious and simple, seem to be clear and obvious and simple, and the commenter seems to posit that he has it all figured out and, if contacted directly, in private, will set everything straight.

Are all the studies just naive and confusing and done by clutzes. And are the issues just cut and dried and "known" to the writer of the fourth commenter?

(Hopefully these comments will remain in chronological order as submitted, so that what is first, second, third and fourth remain so.)

Avatar of: feng


Posts: 1

December 13, 2012

Very interesting article. To understand the neuroscience could basically guide you have a much better life. In my opinion, all diseases are bascally divided neuro-dependent dieases, cancers, and organs faiture related diseases and neuro-disseases decides the rest of diseases. Because life style determines your  current and future life qualities(whether you will have diseases), it will be wise to know what kind of life style is proper. It is the brain guides you to make a right decision to pick up life style, therefore, we need a well functional brain. To know the right neurosciences in the brain function is priority in science.  Goverment should know about this and make the right direction of research.


Avatar of: Marcos Hardy

Marcos Hardy

Posts: 9

December 13, 2012

The mantra in Medicine has always been that there are no insulin receptors in the brain. Not because they were looked for and not found. The idea stemmed simply from the "fact" that they "make no sense" in the brain, as sugar diffuses by gradients into neurons "because" it is needed "fast," as in "metabolic emergencies." I remember when some years ago (in 2000?) the first report of the finding of the insulin receptors in the brain was published in Science. I was happily impressed because, among other things, the finding might be the first step towards an explanation of why practically all antipsychotic medications many times produce an increase in body weight and a type 2 diabetes. I reported it in a meeting of psychiatrists and of nutritionists in my hospital, a major city hospital affiliated with a major Medical School and where all attendees were academicians. For example, do these brain insulin receptors are blocked by neuroleptics? If so, can we find a way of reversing the binding to the insulin receptors? The audience was thoroughly unimpressed because "there's nothing we can do with this new knowledge." Translation: does not change our practice and is not reimbursable; so, why should we care?  Most psychiatrists prefer to operate in ignorane and darkness, with the actions of their medications seemingly affecting the unkown contents of a black box, where "stuff (and, sometimes, a 'miracle') happens." Articles like the present one can go a long way in mobilizing psychiatrists to at least question what they do and to attempt strides away from a "machen" psychpharmacology and towards the development of a "denken" or "thoughtful" psychpoharmacology, as the notions expounded in the article fly in the face of the long-standing notion that insulin is involved solely in the storage of glucose and its conversion to fat and with resulting weight gain.

Avatar of: Marcos Hardy

Marcos Hardy

Posts: 9

Replied to a comment from mlerman made on December 7, 2012

December 13, 2012

During the induction of the insulin coma the hypoglycemia triggers seizure-like convulsions. The same was obtained with camphor and with the application of electricity through head electrodes. Actually, Meduna introduced the induction of seizures in the treatment of mental disorders because he believed that epilepsy and schizophrenia are "antagonistic" disorders. Meduna was wrong in his assumptions but he clearly obtained positive results. Thus, in principle, the common thread is that it is the resulting convulsion (neither the insulin or coma or hypoglycemia, nor the electricity per se) that has salutatory effects on mental illness. Electricity (Electro-Convulsive Therapy or ECT) won the day not because it was more effective than the other two but because it was technically easier to administer and regulate. The men that developed it, the italian neuropsychiatrists Cerletti and Bini, were shortlisted for the Nobel, but didn't get it. Still today we have no firm grasp on the knowledge of why seizures can help the mentally ill. Today ECT is mostly restricted to the treatment of medication-resistant melancholia, bipolar disorder and catatonia. And it works great! Now, it is possible that there are other factors that contribute to the final outcomes of induced-convulsions in psychiatric treatments. Further research is obviously needed, and this article is "a call to arms"... I mean... to the laboratory to try to understand and open new horizons.

Avatar of: Kenny


Posts: 1

December 13, 2012

Makes one wonder, if schizophrenia is found in a patient, could insulin be administered gradually to reduce symptomatic issues? If anyone is willing to conduct more research I am onboard.

Avatar of: IvanD


Posts: 1

December 14, 2012

In endurance sports like ultra-marathon or marathon these process is going on unintentionally. Lowering blood sugar during movement till the next aid station. And then enormous eating of sugar rich ingredients.

Avatar of: Dr Ichha Purak

Dr Ichha Purak

Posts: 18

December 15, 2012

Insulin acts as a primary regulator of blood glucose  and so plays a key role  in neuroplasticity. Insulin a neuropeptide ,which is directly related with neuron growth,neuromodultion because their exists  a link between metabolism of sugar  and brain activities. The article explain these interrelations in a very elaborative way


Avatar of: Blayne


Posts: 1

January 6, 2013

"but plaque formation increased when mice consumed a high-fat diet and developed insulin resistance"


How exactly does a high-fat diet contribute to insulin resistance? Typically insulin resistance develops with chronic, high carbohydrate feedings.

Avatar of: Dug


Posts: 1

April 2, 2014

A very interesting and informative article. I am, however, troubled by the following statement. "but plaque formation increased when mice consumed a high-fat diet and developed insulin resistance" Please could you share your source for this as, to the best of my knowledge, a high fat diet would have precisely the opposite effect. Perhaps the mice were fed only omega 6 or trans fats?
Avatar of: arlene


Posts: 1

June 15, 2016

I wonder if anyone has tried eliminating all refined sugar products, substituting complex carbs served with fish, meat, poultry, vegetables and fruit in smaller meals, more frequently through out the day, just to see what effect this has on neuropsychiatric disorders?

Isn't it possible, all of it, including Alzheimers, is directly caused by refined sugar? I'd like to see it eliminated as the culprit, before wasting any more money on disease and research.

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