Being Hangry: The neuroscience behind hunger and a sour mood

Where are our meals? The service at this restaurant is awful. We’ve been waiting for an hour and have yet to even see a glimpse of our appetizers! Those people ordered after us and they just got their food! I’m starving! Don’t tell me to relax; I’m starting to get hangry!

Eek! Sound like an all too familiar scenario? “Hanger”, the portmanteau or mash-up of the words hungry and anger describing a state of rage caused by lack of food, may actually be linked to levels of the neurotransmitter serotonin in the brain.

Be kind, consume some glucose

Photo credit: Carlos Santa Maria

Photo credit: Carlos Santa Maria

What happens to our mood when our body is running low on glucose a.k.a. sugar? Researchers at the University of Kentucky were interested in the link between low glucose levels and aggressive behavior, so they designed a devious study to investigate the sugar-mood association.

In the study, 62 college students were asked to drink lemonade containing either sugar or a sugar substitute. After drinking their randomized beverage, the students participated in a “game” where they were told that they were competing against an opponent to see who could press a button the fastest.

As it turns out, the whole thing was rigged. There was no opponent just a computer. The students were set-up from the beginning to lose about 50% of the time. The loser of each round would receive a blast of white noise in their headphones. Ouch! Additionally, before each new round, the student selected the level and duration of noise their “opponent” would receive following a loss on that round.

As students began receiving white-noise blasts after “losses”, they retaliated, as any frustrated person might do, and tried to return the favor to their opponent by matching the white-noise assault. Interestingly, researchers found that when students were provided with a sugar-substitute lemonade (no glucose) they were more aggressive, providing louder and longer noise blasts, than if they drank the lemonade with sugar. Feeling agitated? Have a glass with glucose and chill out!

How low blood sugar impacts the brain

Your brain needs fuel in order to function properly. Most often this fuel comes in the form of glucose. When you go several hours without eating, your blood sugar drops. Once it falls below a certain point, glucose-sensing neurons in your ventromedial hypothalamus, a brain region involved in feeding, are notified and activated resulting in level fluctuations of several different hormones. Ghrelin, a hormone that increases expression when blood sugar gets low and stimulates appetite through actions of the hypothalamus, has been shown to block the release of the neurotransmitter serotonin. The serotonin system is incredibly complex and contributes to a number of different central nervous system functions. One of the many hats this neurotransmitter wears is modulation of emotional state, including aggression.

Is your mood more difficult to control when serotonin is depleted?

Angry and neutral faces during the task. Brain regions impacted following serotonin depletion: vACC - ventral anterior cingulate cortex; VLPFC - ventrolateral prefronal cortex. (Passamonti et al. 2011)

Angry and neutral faces during the task. Brain regions impacted following serotonin depletion: vACC – ventral anterior cingulate cortex; VLPFC – ventrolateral prefronal cortex. (Passamonti et al. 2011)

Potentially yes, and here’s why. In an functional magnetic resonance imaging (fMRI) study, Passamonti et al. looked at how neuronal networks involved in processing aggression were altered in subjects with low serotonin levels. Nineteen healthy participants underwent brain scans on two separate days: once after consuming a tryptophan-depleting drink and again after drinking a placebo beverage containing tryptophan. Tryptophan is an essential amino acid, found in turkey among other protein sources, that is a building block for serotonin formation.  Your body does not make tryptophan on it’s own and you must get it through your diet. Don’t worry though, there’s plenty of it around! By reducing tryptophan levels, researchers were able to evaluate the effects of low serotonin levels on brain connectivity in individuals viewing angry faces.

After serotonin depletion, participants were scanned to assess brain responses to images of angry, sad, and neutral faces that were presented to them.  Participants were also asked to complete a personality questionnaire to evaluate their individual propensity for aggression.

What did they find? By reducing serotonin through tryptophan depletion, the connectivity between the amygdala and two prefrontal cortex regions, the ventral anterior cingulate cortex and the ventrolateral prefrontal cortex, was altered when processing angry faces but not sad or neutral faces.

Additionally, when looking at individuals that were more prone to aggression based on their personality questionnaires, their brain scans revealed weaker connections between the amygdala and the prefrontal cortex.  Meaning if you have a predisposition to aggression, low serotonin levels circulating in your brain may lead to altered communications between brain regions that wrangle aggressive behavior.

Angry at a restaurant? Stuck in traffic? Late for dinner and feeling a Dr. Jekyll and Mr. Hyde scenario about to unfold? It may be due to serotonin messing with your brain. Grab your emergency turkey sandwich and relax. Life is going to be okay.

DeWall C.N., Deckman T., Gailliot M.T. & Bushman B.J. (2011). Sweetened blood cools hot tempers: physiological self-control and aggression, Aggressive Behavior, 37 (1) 73-80. DOI:

Passamonti L., Crockett M.J., Apergis-Schoute A.M., Clark L., Rowe J.B., Calder A.J. & Robbins T.W. (2011). Effects of acute tryptophan depletion on prefrontal-amygdala connectivity while viewing facial signals of aggression., Biological psychiatry, PMID:

Surprising brain scan of individual “living” with Walking Corpse Syndrome

“I am coming to prove that I am dead”

Photo credit: Joe King

Photo credit: Joe King

Graham spent his time at the graveyard. His visits would last so long that the local police would find him there, among the gravestones, and bring him back home. He had been suffering from severe depression and several months prior attempted suicide by bringing an electrical appliance into the bath. Graham believed that his brain was dead. He felt he had fried it in the bath. Now living a sort of half-life, stuck between being alive but having a dead brain, Graham’s trips to the cemetery served as the closest connection he could make with death.

Chilling accounts of individuals living with the adamant belief they are dead, like Graham’s, are common among sufferers of a rare and mysterious psychiatric disorder known as Cotard’s syndrome or the Walking Corpse Syndrome.

First described by French neurologist Jules Cotard in 1880, Cotard’s syndrome is a nihilistic delusion characterized by the conviction that one’s own organs, soul, or entire body have been spontaneously destroyed, died, or no longer exist. In denying the existence of the body parts, many patients with Cotard’s will conclude that they are dead and no longer need to eat, sleep, or bathe. Tragically, there have been accounts of people with Cotard’s dying of starvation as a consequence of these delusions.

Currently, Cotard’s syndrome is not recognized as a distinct disorder by the DSM-IV-TR, a manual published by the American Psychiatric Association that outlines the standard criteria for classifying mental disorders; however, the syndrome has been associated with a number of neurological conditions, most commonly appearing with severe depression and/or psychosis.

The prevalence of Cotard’s syndrome is unclear. To date only one study has looked at the question of prevalence. In Hong Kong, case reports of elderly psychiatric patients with diagnoses including major depression, dementia, schizophrenia, and generalized anxiety were retrospectively studied. Of the 349 patients, two individuals, both with major depression, had symptoms congruent with Cotard’s syndrome, suggesting a Cotard’s prevalence of 0.57%. Even without more extensive prevalence studies, it is generally agreed upon that Cotard’s syndrome is a relatively rare condition, making it difficult to study. The available literature on Cotard’s syndrome is largely comprised of single case studies.

A recent case study published in Cortex by Charland-Verville and colleagues is the first of its kind to investigate Cotard’s syndrome using positron emission tomography (PET) imaging.

PET imaging allowed researchers to capture 3D images of Graham’s brain and evaluate the relative levels of metabolism across his cerebral cortex. The results of his PET scans were surprising.

PETCotard

PET image of Cotard’s syndrome patient. Regions highlighted in blue indicate lower metabolism. (Charland-Verville et al., 2013)

Extensive low metabolism was observed across several brain regions in the fronal and parietal cortex responsible for conscious awareness and our ability to create a sense of self including the precuneus, adjacent posterior cingulate cortex and mesiofrontal regions. Graham’s brain metabolism was significantly lower and more widespread than what is normally observed in patients with major depression. In fact his brain’s metabolism was so low (a 22% reduction in overall gray matter metabolism compared to normal controls) that it was reminiscent of a brain under anaesthesia, asleep, or otherwise in a vegetative state.

At the time of the PET scan, medication Graham was taking may have factored into why levels of brain metabolism were severely low but it likely does not account for the full extent of the problem.  It should be noted that conclusions about Cotard’s syndrome (or any imaging study) should not be drawn from a single patient. With that being said, this data is in and of itself quite interesting. Is reduced metabolism in brain regions critical for consciousness causative of why Graham’s thoughts and perceptions about his brain were altered? Only future studies with additional patients will tell.

Read Graham’s full interview with NewScientist HERE.

Chiu H.F.K. (1995). Cotard’s syndrome in psychogeriatric patients in Hong Kong, General Hospital Psychiatry, 17 (1) 54-55. DOI:

Charland-Verville V, Bruno MA, Bahri MA, Demertzi A, Desseilles M, Chatelle C, Vanhaudenhuyse A, Hustinx R, Bernard C, Tshibanda L, Laureys S, & Zeman A (2013). Brain dead yet mind alive: A positron emission tomography case study of brain metabolism in Cotard’s syndrome. Cortex; a journal devoted to the study of the nervous system and behavior, 49 (7), 1997-9 PMID: 23664000