A Molecular Theory of Mental Disease

In 1876, Robert Koch proposed four postulates that needed to be met to establish that a specific microorganism was the cause of a disease (1) the organism had to be present in all patients with the disease (2) the organism had to be isolated from the patient (3) when the organism is injected into a susceptible host, it must cause the same disease as that in the original host and (4) the organism must be isolated a second time from the infected host 

The time has come to create a molecular theory of mental disease. Instead of putting patients into diagnostic pigeon holes, such as depression, Parkinson s disease, or schizophrenia, that are poorly defined, heterogeneous, and nonspecific, we can use molecular imaging to relate a patient s problems to regional brain chemistry. 

Molecular imaging as the foundation of diagnosis is not new. Half a century ago, imaging the rate of accumulation of radioactive sodium iodide by the thyroid was the first example of molecular imaging, although it was called radioisotope scanning. 

Whenever a molecular process is measured in some part of the human body, in theory, two diseases are possible—one disease in which the process is abnormally fast, and the other disease in which it is abnormally slow. In the thyroid, the diseases are called hyper and hypo-thyroidism. 

The regional chemistry of molecules, such as epinephrine, dopamine (DA), or serotonin (5-hydroxytryptoamine, 5-HT), can now be examined in the brain of patients with mental illness. One day, a patient s diagnosis will be his name, characterized by a personal database containing all the patient s manifestations of health or disease. 

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Two diseases that were defined half a century ago can illustrate a molecular theory of mental disease. The rate of accumulation of radioactive iodine by the thyroid could be measured by radiation detectors pointed at the neck. Patients, who had a disease subsequently called hyperthyroidism were found to have an increased accumulation of radioactive iodine, whereas radioiodine uptake was low in patients with hypothyroidism. Patients with hyperthyroidism were nervousness and anxious, and suffered from weight loss, whereas hypothyroid patients were lethargic and had impaired mental functions. These two diseases illustrate the fundamental principle that if one can measure a chemical process in some part of the body, there will be patients in which the chemical process is abnormally slow, and others in which it is abnormally fast (Fig. 19.1). 

The basic premise of this book is that we can create a molecular theory of mental illness, analogous to the germ theory of disease. Molecular imaging makes it possible to search for patterns in the chemical processes in the brain that are related to violence and other forms of mental illness, involving hormones, neurotransmitters, neuroreceptors, reuptake sites, ions, peptides, and proteins. 

Most theories about the origin of mood disorders refer to the subcellular or molecular level, mainly emphasizing an imbalance between different transmitter systems [17] as a possible cause for unipolar depression as well as bipolar disorders. No concrete concepts exist to explain how and in which way such molecular disturbances modify the neural dynamics and lead to an increased mental vulnerability with progressive occurrence of disease episodes. 

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