Dr. Grossi's Blog

The final three months of the study was designated the re-feeding period.  The men received from 1,877 to 4,158 calories.  During the first six weeks moodiness, irritability, poor morale, depression and loss of interest in earlier humanitarian concerns for starving people were prominent findings.  They were quarrelsome and more aggressive but less introverted and interested in their surroundings. Hunger during the first 12 weeks of re-feeding was immense with many eating to the feeling of bursting with food. Their preoccupation with food continued and their table manners deteriorated. During week 13, all food restrictions were lifted and the men ate an average of 5,218 calories. They ate and slept continuously. By week 15 social behavior at meals was returning to normal.  By week 20 all subjects felt normal and were less preoccupied with food.  Slowly humor, sociability and interest returned to the subjects who began planning for the future. 

Re-feeding had noticeable effects on their bodies. The men gained fat quickly and lean tissue more slowly.  Physical discomforts did not disappear quickly. Apathy, lethargy, and dizziness disappeared relatively quickly but it took longer to recover from tiredness, weakness, and reduced libido. Thirst increased and edema continued to be an issue.

(Read about personality and social changes, as well as food preoccupation, in the starvation stage of this study.)

Hoarding has become a disorder in the spotlight, a subject of intense interest by the general public. From a psychiatrist's point of view it was entirely off the radar until the mid 1990s when a number of articles studying the phenomena began to appear. Literary references have been present for many hundreds of years with one of the earliest in Dante Alighieri's Divine Comedy written in the 14th century. Other literary references include Krook in Charles Dickens Bleak House and Sherlock Holmes, the detective created by Sir Arthur Conan Doyle. Intermittently there are articles in the newspapers about specific examples of hoarding as there were in New York papers about the Collyer brothers who died amid their junk about eighty years ago or a man who lived and died in San Francisco and who was described and pictured in the San Francisco Chronicle in the early 1970s. His apartment was piled from floor to ceiling with papers and one needed to move about in the apartment in what appeared to be tunnels between the stacks. The popular television series has greatly expanded interest in this topic.

Buttressing this attention is the new knowledge that hoarding is a significant public health problem. Timpano and colleagues have conducted epidemiological investigations and found a current population estimate of 5.8%, which is startling in that it exceeds the prevalence of autism, schizophrenia, OCD, and panic disorder. Other epidemiological studies have produces estimates of 5.3% and 4.6%, which still exceed the prevalence of the above-mentioned disorders. It is more common in men and increases with age. It does tend to run in families with between 12% to 25% of first degree relatives being hoarders or pack rats. Hoarders are also more likely to have impaired family and work domains as well as increased rates of chronic medical disease and increased usage of psychiatric services.

Frost and Gross published the first systematic definition of hoarding. They defined hoarding as "the acquisition of, and failure to discard, possessions which appear to be of useless or of limited value". Hoarding was associated with perfectionism and indecisiveness in their study. This study also confirmed the large number of first degree relatives with the disorder and disconfirmed the notion that the problem arose out of material deprivation earlier in life. It has been thought in the past that hoarding is a symptom dimension of obsessive compulsive disorder (OCD); however, recently that thinking has changed for many reasons and the DSM-V which is in preparation will likely list hoarding as a separate disorder.

In summary, hoarding represents the connection of three problems. First collecting too many things. Second, having great difficulty disposing of the items which seems to be driven by fear of losing important information or emotional attachment or just behaving wastefully. Third, hoarders manifest tremendous disorganization and attention problems.  These people tend to shop too much, collect free things, keep packing materials or even shoplift ot steal things.  The hallmark feature is the inability to dispose of things, especially clothes, newspapers, and books.  Finally, there is a manifest inability to organize their possessions which probably stems from an information processing problem and problems with attention, categorization, and decision making.  Often valuable items are mixed with worthless ones and often these individuals move possessions from one place to another without any effective result.

Discussions about sleep occupy a prominent place in many discussions in the office. It is surprising that many people do not practice good sleep hygiene especially in light of the fact that the elements of good sleep hygiene are well known.  I am setting them out for easy reference.

Good sleep hygiene starts with a quiet, somewhat cool room with a comfortable bed which can be made dark.  It should be used only for sleep and sex. The bed should not be used as a work area. It is desirable to go to sleep at the same time every day including weekends and to arise at about the same time every day including weekends. If an alarm is needed then it should be used and the time should be adjusted so that the person is not experiencing daytime sleepiness. It is best to avoid eating within two hours of bedtime and avoid heavy meals within four hours of bedtime.  Excessive fluids in the evening should be avoided as should energy drinks or caffeine. Avoid or change the schedule of any medications that interfere with sleep so that they are taken earlier in the day. Many over-the-counter medications interfere with sleep.

In general anything that produces stimulation should be avoided near bedtime.  This would include exciting television programs, video games, arguments, fights, disagreements, and strenuous exercise. It is best to exercise in the morning or afternoon. If possible, the bedroom should not have a television, game console, or computer. Generally naps should be avoided and exposure to a lot of natural light all during the day should be encouraged. Most people find it helpful to have a brief routing leading up to going to bed.  This could include a warm shower or bath, reading, a small snack, etc.

Following the above simple principles will help to produce sleep reliably.

(Read the related post about circadian rhythms.) 

Where are we going in terms of understanding the causes and treatment of depression? It may be instructive to start by looking at where we have been.  Literary references abound.  The Iliad written almost 3000 years ago describes Achilles grief reaction to the death of Patroceles which, had it continued, would have been a depression.  Shakespeare's portrayal of Hamlet, the depressed Dane, in words such "How weary, stale, flat, and unprofitable seem to me all the uses of this world" is a good example. (Shakespeare had words for everything, often the best words.) In the mid 1980s William Styron produced a beautiful description of depression in the short book, Darkness Visible.

Emil Kraepelin, the father of modern psychiatry, divided psychotic disorders into those whose core disturbance was either one of cognition or one of mood.  In modern terminology those disturbances of cognition are the schizophrenias and those of mood are bipolar disorders or recurrent major depressive disorders. The schizophrenias are found in about 1% of all populations around the world and the mood disorders have a prevalence of about 5%.  These are both causes of major disability in the age group 15 to 45 years of age.

In 1928 Mary Hare (later Mary Bernheim), a young biochemistry graduate student at Cambridge, discovered an enzyme in liver cells which she named tyramine hydroxylase. About ten years later Ernst Zeller renamed the enzyme monoamine oxidase after demonstrating its activity on other monoamines. In 1952 two drugs, isoniazid and iproniazid, made their way to the United States to be used in treatment trials for tuberculosis. During those trials the investigators noticed that the patients became "energized", "inappropriately happy", and even "discipline problems". After several years of investigation, it was discovered that these drugs worked by inhibiting monoamine oxidase.

These findings led to the monoamine hypothesis of depresssion as described in a 1965 paper by Joseph Schildkraut. He contended that low levels of neurotransmitters were associated with depression. This also led to more investigations of the serotonin and norepinephrine pathways in the brain. They were found to arise in the brain stem and branch out or arborize up to the cortex,  the most developed part of the brain. The focus was mostly on the modulating influence of these neurotransmitters and the focus was largely on the synapse. This theory and the following research underpinned the research by pharmaceutical companies that eventuated in the development and marketing of SSRIs, SNRIs, and NDRI antidepressants in the late 1980s and early 1990s.

In the early 1990s a new tool emerged to study neural activity. This was the fMRI, which measures and locates brain activity by changes in blood flow. Investigations of depressed people using this tool revealed that dysfunction in depression was not localized in one brain area but many areas dysfunctionally working, some overactive, others under-active. In turn this led to the idea that depression is a disorder of circuits. Helen Mayberg and her group discovered that a small area deep in the frontal lobe called the subcallosal cingulate (or area 25) was the negative mood regulator. This area was tightly connected to the amygdala, an almond-shaped brain structure which is involved in the processing of emotional, stressful, or novel stimuli.  Also in this circuit is the hypothalmus, hippocampus, insula, and the prefrontal cortex. The hypothalmus  regulates drives such as libido, appetite, and sleep; the hippocampus, which houses memory, provides a context for the area 25 presentation.  The insula makes us internally aware, and finally the prefrontal cortex systhesizes and plans what action to take, if any. The point is that there is a complex set of interactions between all these areas and that depression influences those interactions by influencing many parts of the circuit.

Some recent work built on the above findings was done by Jeffrey Meyer and colleagues using a different technique.  They used harmine labeled with carbon 11 selective for MAO-A and a PET scan was used to measure the MAO-A specific distribution volume which is an indication of MAO-A density in different brain regions. In their 2006 paper they found that depressed individuals had higher MAO-A density in the prefrontal cortex, temoral cortex, anterior cingulate cortex, posterior cingulate cortex, thalmus, caudate, hippocampus and midbrain.  This led to the conclusion that elevated MAO-A density is the primary monoamine lowering process during major depression. in their 2009 paper they wanted to determine whether MAO-A levels in the brain are elevated in patients who have recovered and go on to have a recurrence. They found that subjects with major depressive disorder in recovery but with subsequent recurrence had significantly higher regional MAO-A density in all brain regions than healthy participants.

The most important point to be made is that the circuits of mood disorders are being revealed and many clues are present to unravel this problem in some reasonable time frame.  The same cannot be said for the primarily cognitive disorders such as schizophrenia. Dealing with that problem will be a very long slog indeed.