Bipolar disorder currently is believed to arise from interactions between the two forces that drive most of our biology: the genetic risk factors we inherited from our parents and the consequences of our environment. It is now clear that unpleasant events during childhood that lead to chronic stress or mental and physical trauma also contribute to the appearance of symptoms later in life. Studies using both MRI scans and postmortem investigations indicate that if adverse experiences occur during critical developmental periods, actual structural and functional changes develop in the brain. These changes may have long-lasting effects on adult brain function. Furthermore, developmental errors in brain wiring can be aggravated or unmasked later in life by exposure to stressful events. Clearly, exposure to significant stressors is a key risk factor in the appearance of bipolar symptoms.

  The cause of bipolar disorder is unknown, although it has a clear genetic component given that it tends to run in families. Most patients are diagnosed in their early twenties; however, for women the initial symptoms of the disorder may not appear until later in life around the onset of menopause. Overall, lifestyle factors likely interact with a complex blend of hormonal changes and genetic mutations. Imaging and genetic studies have identified interesting similarities between bipolar disorder and schizophrenia that might shed additional light on this complex disorder of mood.

  What is schizophrenia?

  The onset of numerous mental disorders peaks between the time of late adolescence and young adulthood, including attention deficit hyperactivity disorder, anxiety and mood disorders, schizophrenia, and substance abuse. What is the brain doing during this phase of life that coincides with the onset of so many disorders of higher mental function? One possible contributor is the completion of myelination of the frontal lobes that occurs during our mid-twenties. Myelination is analogous to the insulation on the wiring in your house; if it is not present, the wiring does not work correctly, or at all. Once a brain region finishes its myelination process, imaging studies have shown that the region becomes more active. Apparently, the complex interplay of neurons in your brain works best when their connections, that is, their axons, are fully insulated with myelin. The frontal lobes are the last region of the brain to finish this process of myelination; women finish by age 25 while men finish this process by age 30. You can see what this implies: on average, women have functioning frontal lobes at least five years sooner than men do. In general, men are diagnosed with schizophrenia earlier than women; however, the incidence of schizophrenia is higher in women after age 30. Scientists speculate that the problems in brain function become apparent, and thus more likely to be diagnosed, as the affected parts of the brain become fully active with development and maturation.

  The latest studies of susceptibility genes suggest that attention deficit disorders, anxiety, depression, bipolar illness, and schizophrenia share some key genetic components related to neural development. By age 18, about 20% of adolescents will show symptoms of a mental illness that will persist into adulthood. For example, oppositional defiant disorder, which tends to occur in families with a history of attention deficit or mood disorders, usually appears during early childhood; approximately 90% of these children will develop schizophrenia as adults. Human genome studies indicate that schizophrenia has a strong genetic component that may involve the function of hundreds of unique genes related to development and neuroplasticity. Many different environmental influences also have been identified as risk factors. Recent theories of schizophrenia invoke a dysregulation of dopamine and glutamate neural systems, particularly within the frontal lobes. This dysregulation leads to a failure of the frontal cortex to control limbic function and may underlie the characteristic cognitive symptoms of schizophrenia. Noninvasive techniques have allowed scientists to look for changes in glutamate function within vulnerable brain regions and then make fairly accurate predictions regarding which patients will undergo significant remission of symptoms, as well as which are not likely to show significant remission. This information allows psychiatrists to make informed judgments regarding patient therapy.

  Why do schizophrenics hear voices?

  Here is part of a long e-mail message from a schizophrenic patient who displays many common aspects of the disorder, in particular hearing voices.

  Dr. Wenk – I’m not sure if you’d have any clue about this, but if you do, please contact me. I believe I was injected with some sedating drug while sleeping in my bedroom, having a vague memory of partially waking up to the event. A few months later I began hearing soft voices that could communicate with me, and I figured that someone had implanted a remote radio brain probe in my head. In July I began to be extensively harassed, violated, and at times tortured via this device.

  Why do schizophrenics hear voices? Why do antipsychotic medications that block dopamine receptors usually alleviate this symptom? A recent study offered some potential answers to both questions. The study identified a significant disruption of neural circuitry within the auditory (sound processing) cortex in an animal model of schizophrenia. These neurons of the auditory cortex become inappropriately active when schizophrenic patients are hallucinating voices talking to them.

  Schizophrenics may hear either hostile voices goading them to jump off a bridge or a mother’s soothing words of advice; which type they hear depends on the cultures in which they live. In the United States, schizophrenics report hallucinations of disembodied voices that hurl insults and make violent commands. In India and Ghana, however, schizophrenics report quite positive relationships with hallucinated voices that they recognize as those of family members or God. Interestingly, schizophrenia tends to be more severe and long lasting in the United States than in India.

  The gene that underlies the presence of auditory hallucinations may be responsible for the production of a specific dopamine receptor. Schizophrenics appear to have too many of these dopamine receptors; therefore, it is not surprising that medications that selectively block dopamine receptors can reduce the frequency of these auditory hallucinations effectively. This is just a single example of how systematic studies of brain chemistry and physiology are slowly advancing scientists’ understanding of the complex interactions of the genetic, neurochemical, and anatomical changes that underlie this disorder. Hopefully, the results of these investigations will lead to better treatments for schizophrenic patients.

  Are dolphins schizophrenic?

  Scientists have wondered whether the occurrence of schizophrenia and autism in humans is due to the rapid evolution of our brains. Are psychiatric diseases the cost of the higher brain function in humans? A study of the molecular evolution of the genes associated with schizophrenia, autism, and other neuropsychiatric diseases compared across mammalian species and among disease classes, with a focus on primate (chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, baboon, marmoset, and squirrel monkey) and human lineages. This study concluded that genes associated with schizophrenia and autism are not evolving uniquely or more frequently in humans. Interestingly, one species stood out in the analysis as possessing a much higher number of both schizophrenia and autism genes: the bottlenose dolphin. Can a dolphin experience paranoia? No one knows. It is worth considering, however, that the surprisingly intelligent behaviors of these mammals are due to the presence of some unexpected genes.

  How is schizophrenia treated?

  Whatever the causes of schizophrenia might be, almost universally, the treatment is to block dopamine receptors. Does this mean that schizophrenia is due to a problem with dopamine? No, not at all. In fact, an alteration in dopamine function probably does not cause schizophrenia; rather, the symptoms are most likely just a secondary consequence of alterations of some other neural system, such as glutamate, in the brain. This may explain why the blockade of some dopamine receptors within the brain reduces the severity of a few bothersome symptoms, but not others. The antagonism of dopamine receptors simply may compensate for the presence of an error of chemistry that exists somewhere in
the brain. All neuroscientists know for certain is that whatever the reason may be for their efficacy, antipsychotics that block dopamine receptors provide significant benefits for some, but not all, schizophrenic patients. Unfortunately, these drugs—especially the antipsychotics introduced in the 1950s—have side effects that make these patients move as though they have Parkinson’s disease. Given the very unpleasant side effects of these drugs, it is easy to appreciate why so many schizophrenics hate taking their medications. The side effects of dopamine receptor blockade occur rather quickly, but the clinical benefits require two to three weeks, or longer, to develop fully. The time it takes for these drugs to produce a noticeable benefit implies that compensatory changes in brain function are required for these drugs to produce clinical benefits in schizophrenic patients. The nature of these compensatory changes is not understood.

  3

  HOW DO FOOD AND DRUGS INFLUENCE MY BRAIN?

  The brain is the organ of your mind; therefore, food and drugs can have a profound influence on how you think, act, and feel. These effects can be profound, subtle, or barely noticeable. Why do some chemicals in your diet affect your brain and how you feel, while others do not? Many drugs or nutrients that potentially might influence brain function are never able to enter the brain because of the presence of a series of barriers; the most important of these is the blood–brain barrier.

  This barrier allows the easy entry of drugs and nutrients that are lipid-soluble (i.e., fat-soluble) and restricts the entry of drugs and nutrients that are water-soluble. Extremely lipid-soluble drugs enter the brain rapidly; they also tend to exit rather rapidly, which reduces the duration of their action. Some familiar examples of lipid-soluble nutrients are the vitamins A, D, E, and K. Nicotine and caffeine are also quite lipid-soluble and enter the brain easily; if they did not, then it is highly unlikely that anyone would bother consuming them so often. Take a moment to appreciate how this fact has been an incredible boon to the evolutionary success of tobacco and coffee plants: their discovery by our species, coupled with the fortuitous nature of our brain chemistry, led to their widespread cultivation and protection as two of the most important plants on earth. Human behavior has impacted these plants as much as they have impacted human history; for example, the introduction of coffee and tea fueled the Enlightenment and the Industrial Revolution.

  This chapter will discuss the foods and drugs that affect your brain and, thereby, your behavior. The distinction between what is considered a drug (i.e., something that your body wants or needs to function optimally) and food (i.e., something that your body wants or needs to function optimally) is becoming increasingly difficult to define. Indeed, the routine use of some substances, such as stimulants and depressants, is so universal that most of us do not even consider them to be drugs but, rather, actual food. Are coffee, tea, tobacco, alcohol, cocoa, or marijuana nutrients or drugs? For many people, the distinction has become rather meaningless because their body craves many of these substances at all times. Obviously, anything you take into your body should be considered a drug whether it is nutritious or not. For the remainder of this chapter, I will make no distinction between drugs and food: they are essentially just chemicals that have unique effects on the body.

  The foods we eat and many of our most popular psychoactive drugs often come from plants. Many plants contain chemicals that are very similar to the chemicals in our brains. The similar nature of these chemicals underlies why the contents of our diets can influence brain function.

  Why do plants affect the human brain?

  Plants produce chemicals that are capable of affecting our brain because they share an evolutionary history with us on this planet. Even primitive one-celled organisms produce many of the same chemicals that are in your brain. Therefore, whether you choose to eat a bunch of broccoli or a large pile of amoeba, the chemicals they contain may alter how your neurons function and, therefore, how you feel or think.

  The fact that you share an evolutionary history with insects and reptiles also underlies the ability of venoms to produce the unpleasant affects you feel if you are stung by a bee or bitten by a snake. The bugs add serotonin to their venom in order to increase blood flow to the site of the bite or sting, thus increasing the chances that you will absorb most of the venom. Our shared history with plants and animals here on earth leads to some interesting predictions. For example, consider the following science fiction scenario: A spaceman is walking on an earth-like planet and is suddenly bitten by an unfriendly and grizzly looking creature. The spaceman can see that he is injured and that a liquid substance was injected under his skin by the beast. Does he die? No, he does not die, because his species and that of the creature on this foreign planet do not share an evolutionary past or a common ancestor. Their independent evolutionary paths make it highly improbable that they use similar neurotransmitter molecules within their respective brains and bodies.

  Back on earth, people in ancient cultures were certainly very aware of the unique properties of certain plants and of the consequences of consuming them; indeed, they often sought them out as remedies for a variety of physical illnesses. This ancient use of plant extracts as medicines was also likely the beginning of a long series of reforms in our concept of how the brain functions and what its role is as the organ of the mind. For example, the realization that it might be possible to treat mental illness in the same way that one treats physical illness—that is, by using drugs or diet—was slow to gain general approval in part because of the wide-ranging, and for some still quite frightening, implications about what this meant regarding the nature of the human mind. Our grandchildren will likely have a whole host of highly modified chemicals added to their diets strategically designed to enhance a broad range of mental functions. In fact, we already do have a vast pharmacopeia, legal and otherwise, that can affect the brain, and no end of debate about its value and effectiveness.

  Three basic principles apply to any substance you ingest that might affect your brain. First, these substances should not be viewed as being either “good” or “bad.” Drugs and nutrients in your diet are simply chemicals—no more, no less. They initiate actions within your brain that you either desire or would like to avoid. Second, everything you consume likely has multiple effects. Because your brain and body are so complex and because the chemicals you ingest are free to act in many different areas of your brain and body at the same time, they will often have many different effects—both direct and indirect—on your brain function and behavior. Third, the effect of a drug or nutrient on your brain always depends on the amount consumed. Varying the dose of any particular chemical changes the magnitude and the character of its effects. This principle is called the “dose–response effect”; that is, in general, greater doses lead to greater effects on your brain. Sometimes, however, greater doses produce completely opposite effects from those of lower doses. For example, aspirin reduces body temperature when taken at normal therapeutic doses but increases body temperature when taken at high doses.

  How do we become addicted to specific foods and drugs?

  Sometimes the effects of certain chemicals are present in the brain for so long that the brain slowly adjusts to their presence. Over time, the brain acts as though the drug or nutrient has become a necessary component of normal brain function. You experience your brain’s adjustment to the eventual absence of this substance as craving. Consider, for example, the very powerful drug, sugar. Your brain needs sugar (usually in the form of glucose) to function normally. The many billions of neurons in your brain require a constant supply of glucose to maintain their ability to produce energy and communicate with other neurons. The brain consumes the equivalent of about 12 donuts worth of glucose every day. Neurons can tolerate a deprivation of glucose for only a few minutes before they begin to die. Therefore, as blood levels of sugar decrease with the passage of time since your last meal, you begin to experience a craving for food, preferably something sweet. The presence of sugar in your brain is consi
dered normal, and its absence leads to the feeling of craving and the initiation of hunting or foraging behaviors, such as seeking out a vending machine for a chocolate bar. If you wish to experience the truly overwhelming and powerful nature of drug craving, just stop eating for a full day.

  Now you can easily recognize a parallel with the experience of a heroin addict. Within a few hours you will not be able to think of anything but food (heroin), you will do anything, sell anything, or steal from anyone to get food (heroin); as time passes, nothing is more important to you than the next meal (shot of heroin). The brain behaves as though it cannot tell the difference between a food and a drug; they are both just chemicals. The constant consumption of caffeine, nicotine, or almost any chemical can produce similar types of compensatory changes within your brain and lead to craving when they are absent from the brain. This response is exactly what your brain evolved to do for you: to be flexible and learn how to survive, to adapt to a changing environment, and to adapt to the variety of chemicals that you consume. When this situation of “normalcy” is lost because of the absence of something that your brain has become accustomed to having regularly available (e.g., sugar, amphetamine, heroin, or anything else that you are accustomed to consuming), your brain reacts by creating in you the urge to replenish its supply. You experience this feeling as a craving, regardless of the legality, safety, or cost of the substance being craved.