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2 Why Do I Feel This Way?locked

2 Why Do I Feel This Way?locked

  • Gary L. Wenk

“How do you feel?” You have asked, and been asked, this question many times. How does your brain answer this question? How you feel is determined by far more factors than your level of happiness or depression. Maybe you feel thirsty or hungry or cold; all of these would affect your answer to the question. Your answer to the question of how you feel is intimately connected with your survival.

The purpose of your emotions is to control evolutionarily conserved behaviors that are critical to your survival. If you are cold or hungry, you need to act upon this information in order to increase your likelihood of survival. For this reason, your brain has evolved a series of interwoven systems that work together with sensory inputs from inside your body to answer the question of how you feel; this brain network is called the limbic system. The limbic system controls many aspects of your survival, including the balance of energy and water, body temperature, hormones, sexual behavior, and your ability to experience pleasure. The limbic system also influences what you learn and remember. Your limbic system encourages the brain to remember those things, events, or people who pleased or frightened you in order to control future behaviors related to your survival. We rely upon our memory to make decisions about who we like, what foods made us sick, and what places or things frightened us.

p. 22A few cortical regions are considered to be part of the limbic system and play important roles in the expression of emotion; I will focus on just two. The first one is deep inside the brain and is called the cingulate gyrus. Imaging studies have discovered that this part of the brain determines the perceived level of pleasantness and unpleasantness of sensory stimuli, such as pain or the taste of chocolate. When you enjoy the smooth richness and flavor of a piece of chocolate, you can thank your cingulate gyrus. One Freudian psychologist summed up the function of the cingulate gyrus as where your superego and id compete to determine what you will do at any given moment. Another important role of the cingulate gyrus is the control of punishable behaviors; this region provides inhibitory control of behaviors that you have learned to avoid. For example, when you were young, you might have been punished for making loud sounds in public or jumping up and down on the sofa. Many years ago neurosurgeons discovered that if they destroyed small regions at the front end of the cingulate gyrus, patients were better able to control their symptoms of obsessive compulsive disorder, such as repeated handwashing.

The second cortical limbic region of interest is called the insula; this brain region interprets for us whether we like or dislike complex sensory inputs. The insula lies in a crevice, called the lateral fissure, deep on the side of the brain at about the level of the top of your ear. The insula is activated when we are listening to music that we like, when we hear the voice of someone we like, or when someone we like is stroking our arm. The insula also is activated by disgust, such as having a stranger on a bus begin stroking your arm or begin touching you, or by watching videos of unpleasant or repulsive images. I mentioned these two limbic cortical areas for another reason: the cingulate and insula are selectively activated when subjects report that their minds are wandering. Possibly, when our mind wanders, we activate these brain regions in order to p. 23judge the degree to which we like or dislike the contents of our daydream.

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What is fear?

Judging what you like or dislike allows you to enjoy life. In addition, knowing what you should fear, and quickly recognizing the biological changes in your body that indicate fear, could save your life. This critical task is largely handled by a small almond-shaped structure, the amygdala, which lies deep within the bottom of the brain, not far from your ears. The amygdala receives information from many brain regions, your internal organs, and external sensory systems, such as your eyes and ears. The amygdala integrates this information with various internal drives, such as whether you are hungry or thirsty or in pain; it then assigns a level of emotional significance to whatever is going on. For example, when the amygdala becomes aware that you are alone and hearing unfamiliar sounds in the dark, it initiates a fear response, such as panic or anxiety. It then activates the appropriate body systems, the release of hormones, and specific behaviors to respond to the (real or imagined) threat. The amygdala also is activated by sensory stimuli that seem ambiguous or unfamiliar to us, such as unfamiliar sounds or people. In response to ambiguous or unfamiliar stimuli, we become vigilant and pay closer attention to what is happening in our immediate environment. If you were a dog, your ears would perk up. Your amygdala gathers as much sensory information as possible, compares it to what you already know, and then instructs other brain regions to respond.

Almost without fail, and regardless of the nature of the information gathered by your vigilant brain, the amygdala usually comes to the same conclusion: be afraid. If a sensory event, such as a sight or sound or taste, is unfamiliar; your limbic system almost always assumes that the situation is potentially dangerous and should be treated as such. If everything p. 24is assumed to be dangerous until proven otherwise, you are much more likely to survive the experience and pass on your be-fearful-first genes. Thus, humans fear everything that is unfamiliar or not-like-me: we fear unfamiliar dogs, people who look or dress differently, unfamiliar places, unfamiliar odors, things that go bump in the night, people who stare at us for too long, heights, enclosed small spaces, dark alleys, unknown people who follow us, etc. You get the idea. We all have witnessed the consequences of fear: we hide behind closed doors, we hide in protected or gated communities, we keep a loaded gun by every door and under the pillow, we hire bodyguards, we install security systems, we build walls. Brains evolved to perform one primary function: survival of the individual and the species; fear plays a critical role in survival. Unfortunately, your fear-inducing amygdala occasionally overreacts to trivial or harmless stimuli. Sometimes the amygdala induces behaviors that may get a person mentioned on the evening news.

Consider the following scenario: You are walking in an unfamiliar wooded area and you are aware of recent reports that snakes have been spotted along your current route. Then, without warning, you spot something brown, round, and coiled up on the ground next to a fallen tree. Your flight-or-fight response to this potential threat is activated immediately, quickly increasing your heart rate, respiration, and blood pressure; then, you realize that it is only a coil of discarded rope. Was your physiological response reasonable and appropriate? Yes, it was, because it prepared you to escape or defend yourself from a perceived danger. Your physiological response was so fast that it preceded recognition of the actual stimulus, the rope, due to the fact that your amygdala appears to receive partially processed sensory information before the more complex parts of your brain have had a chance to identify the true nature of the threat. Your brain evolved to help you survive to pass on your genes to the next generation. The best way to achieve this goal is to induce a response immediately to p. 25imagined threats regardless of whether that response is appropriate or not. Whether you are walking down a dark alley or are in a landscape full of snakes does not make any difference to your brain; you need to prepare yourself for fight or flight to defend your be-fearful-first genes so that you can pass those be-fearful-first genes along to your offspring.

By now you have clearly gotten the point that being frightened of everything all of the time is a safe and effective way to maintain your species. Unfortunately, it is also quite stressful, and chronic stress ultimately will have negative consequences upon your health. The brain, due to the impact of evolution, does not concern itself with the long-term effects of chronic stress on the body because these negative consequences usually appear long after you have finished reproducing and passing on your be-fearful-first genes to the next generation.

Due to its control over your emotional response, the amygdala plays a critical role in the decision-making processes in your brain. In order to achieve this goal, the amygdala influences the function of many other brain regions. It activates the frontal lobes of your brain to increase your vigilance to potential threats. The amygdala also controls how your brain processes sensory inputs that are associated with emotional experiences. This is an extremely important function because it determines whether you will remember the details of fearful events. For example, mugging victims tend to distort the details of the tragic event by “remembering” that the mugger was bigger and uglier, the gun was bigger, the alley was darker, etc. Recall my point from Chapter 1, the brain is not an accurate recording device; the influence of the amygdala makes memories more interesting or frightening than the events truly were. The influence of the amygdala, however, also makes it less likely that you will walk down that alley alone again. Your amygdala has succeeded again and your be-fearful-first genes live to breed another day!

The amygdala also becomes quite active when other people are looking at us. This response underlies why public p. 26speaking is usually rated as people’s number-one fear; even more feared than heights, deep water, death, bugs, loneliness, and darkness. Neurons in the amygdala pay attention to the eyes of other people in order to inform you whether someone is staring at you. Staring at one’s prey is a challenging action that is often a prelude to an attack. If someone in a crowded room, even if it was only a little girl holding her doll, started staring at you, how would that make you feel? She is following you, keeping her eyes trained on your every move; even her doll’s eyes now seem focused on you. What does she want from you? Why is she following you? Feeling threatened yet? Yes, indeed! We all would respond with fear to a similar situation, no matter how innocent the “attacker” might seem.

Children with autism do not respond to staring; magnetic resonance imaging (MRI) scanning studies of their amygdalae indicate that these children primarily pay attention to the mouths of other people and, therefore, miss critical social cues. The amygdala in older people is less responsive to social cues, threatening or not, than it is in younger people. Why? Possibly because as we get older and experience numerous and varied emotional and fearful events, our frontal lobes gain more control over how the amygdala responds to incoming sensory information. Studies have shown that the frontal lobe is responsible for turning off the amygdala. Indeed, humans with a thicker frontal cortex (specifically, the bottom middle of the brain) have a greater ability to reduce activation of their amygdala that is prompted by strongly emotional stimuli. You might remember the television show Star Trek and the planet of Vulcans who were always in complete control of their emotions; possibly the Vulcans had big frontal lobes.

Studies of brains from preterm babies have shown that the amygdala is wired up to the rest of the brain prior to birth and is, therefore, capable of helping the brain store strong, usually fearful, emotional memories. This might explain why some adults have inexplicable fears. Possibly, at this very early stage of brain development, the amygdala was able to record p. 27a negative memory while the hippocampus was still unable to form a memory of the event associated with the unpleasant experience.

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Why are close-talkers so frightening?

During the fifth season of the long-running and very popular sitcom Seinfeld, we were introduced to a person who was a “close-talker,” a person who stands unusually close to others when speaking. We have all met this person. A colleague of mine used to stand so close when talking to me that his hand gestures actually occurred behind my head; they only could be appreciated by someone standing behind me! Is there an explanation for this behavior? Studies have found that bilateral damage to the amygdala reduces a person’s need for interpersonal distance when talking to others. Although numerous social and cultural differences might explain why some people do not acknowledge your personal space when talking to you, some of these “close-talkers” might have a poorly functioning amygdala due to injury, mild hypoxia, or inheritance. Bilateral damage to the amygdala also may reduce a person’s ability to produce a normal fear response to dangerous stimuli. In humans, one peculiar consequence of bilateral amygdala injury is the loss of the ability to laugh at other people’s jokes; in contrast, these individuals are capable of laughing at their own jokes. Age-related changes in the amygdala thus might explain why your grandfather never laughs at your jokes; rest assured, however, you really are very funny.

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What is depression?

Given the important role of the amygdala and hippocampus in the control of emotion, it is not surprising that scientists have discovered a connection between impaired function in the amygdala and hippocampus and symptoms of depression. Numerous studies have discovered that the hippocampus p. 28is smaller in patients with major depression as compared to those without the illness. The degree of brain shrinkage is influenced by how long the depression has been untreated. Imaging studies have shown that the activity of neurons within the amygdala also is significantly altered in patients with major depressive disorder. One day, noninvasive monitoring of the activity of these brain regions might offer better diagnostic accuracy for major depression and provide insight into whether specific treatments are truly helpful for this devastating brain disorder. A cure for depression is badly needed.

Each year, more than 100 million people worldwide develop clinically recognizable depression. The incidence of depression is 10 times greater than schizophrenia. Nearly twice as many women than men will report at least one major depressive episode during their lifetime. Depression is the leading cause of disability for women aged 15–44 years across all nations and cultures. The diagnosis of depression depends on three main factors: etiology, severity, and duration. Etiology refers to the cause of the depression. For example, depression may appear as a normal reaction to grief or as a primary affective disorder, as a reaction to the withdrawal of a drug, or as a component of a wide variety of medical problems, such as cancer or liver disease. Severity is a measure of how debilitating the symptoms are to the person’s lifestyle. Everyone experiences occasional feelings of sadness that may last a few days; in contrast, major depression is characterized by long-term (usually longer than two weeks) feelings of hopelessness, irritability, and loss of interest or pleasure in most activities. In addition to these symptoms, depression often is associated with significant changes in appetite or weight, poor sleep quality, excessive feelings of guilt, feelings of worthlessness, lethargy, and recurrent thoughts of death or suicide attempts.

Over the past century, younger and younger people are being diagnosed with major depression. There are many possible reasons for this trend, such as increased life stressors, more sensitive diagnostic methods that are catching p. 29previously undiagnosed cases, and an increase in the number of patients, particularly males, willing to seek medical care at earlier ages. Depression has many causes; this has necessitated many different, and sometimes quite dangerous, treatments.

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How is depression treated?

In 1786, the Italian physician Luigi Galvani recognized that our brains communicate by electrical signals; this led to the development of ways to utilize electricity to manipulate brain function. Electroconvulsive therapy (ECT) was first introduced in 1938 and involves applying a brief electrical pulse to the scalp while the patient is unconscious (we hope) under anesthesia. ECT was found effective for treating multiple psychiatric illnesses, especially depression. The experience of ECT sounds horrifying and the treatment still carries a highly negative stigma. Following the introduction of safer antidepressant medications, the use of ECT treatment declined during the 1960s. Its use has increased since the late 1970s because of improved delivery methods and increased safety and comfort measures. ECT most commonly is administered to patients who fail to respond to medications or who do not tolerate the side effects of standard medications. Most important, when patients demonstrate symptoms that increase the risk of harm to themselves or others, ECT may be the treatment of choice because its benefits are almost immediate.

In comparison, the non-ECT treatments currently available for the treatment of depression are only modestly effective, and treatment resistance remains a significant problem. Unfortunately, according to recent analyses, our current antidepressant medications are no more effective than those introduced over 50 years ago, although the newer drugs usually have fewer unpleasant or dangerous side effects. Because most patients show spontaneous recovery from their depression, especially when it is a reaction to life events, it is estimated p. 30that today’s medications only provide for about 20%–30% more recoveries than if no drug were administered at all! Consider that statistic for a moment: Doing nothing works for almost 80% of people diagnosed with depression. The problem is that healthcare providers are not able to predict which patients fall into that 20%–30%; thus, today virtually all depressed patients are medicated.

Most drugs prescribed today to reduce the symptoms of depression (there is no cure) act by enhancing the action of the neurotransmitters serotonin, dopamine, or norepinephrine. These neurotransmitters are produced in your brain from the components of your diet. They are used by neurons to communicate with each other; serotonin, dopamine, and norepinephrine all play a role in determining how you feel. Current antidepressant medications block the inactivation of serotonin, norepinephrine, or dopamine within the synapse by blocking reuptake; thus, they are called selective reuptake inhibitors. If the drug selectively prevents the reuptake of serotonin, for example, it is given the acronym SSRI (selective serotonin reuptake inhibitor). Selective reuptake inhibitors slow the inactivation of neurotransmitters once they are released from neurons; this prolongs the time that they are available to act upon other neurons. Think of these drugs as door locks and the neurotransmitters as cats. You open the door and your cats run outside and interact with other cats in the neighborhood; you put an end to this playtime by opening the door and allowing the cats to rush back inside. Selective reuptake inhibitors keep the door locked so that the cats are forced to stay outside and play for a longer period of time. Ultimately, the neighborhood (your brain) is full of cats (e.g., serotonin) running around between the houses (neurons). However, simply because this is how these drugs can act within the brain does not offer any insight into how the drugs actually do reduce the symptoms of depression. Fortunately, the U.S. Food and Drug Administration (FDA) does not require that the therapeutic mechanism of a p. 31drug be understood, only that the drug works and is safe. The modern selective reuptake inhibitors are considered relatively safe and effective for most patients.

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Why do you sleep so poorly when you are depressed?

Depression is often inherited and also can develop in association with other common mental or physical disorders. For example, depression, sleep disorders, and migraine headaches may all have similar underlying neural mechanisms; they often co-occur, more often in women than in men. In a recent study of patients with migraine, 58% reported also suffering anxiety regularly, 19% had chronic long-standing depression, and 83% had poor sleep quality with excessive daytime sleepiness. The connection between sleep and depression is fascinating because it might offer clues to understanding both phenomena. Let us take a look at one of these clues: nondepressed people start dreaming about two hours after falling asleep; depressed people start dreaming almost immediately. When depressed people start taking antidepressant medications, the time it takes for them to enter their first dream episode lengthens toward a normal duration. If this does not happen, the prognosis for recovery on that medication is poor. Sleep deprivation has a well-known antidepressant effect but only if one is depressed. As many of us learned during college, skipping a night of sleep will not make a nondepressed person happier. Indeed, it tends to make people anxious and irritable, reactions which are often symptoms of depression. The same applies to antidepressant medications; that is, if you are not depressed, taking an antidepressant drug will not make you happier. For many migraine sufferers, depression typically begins with the onset of their migraine and coincides with bouts of insomnia and anxiety. About 25% of patients with migraine have depression, and almost 50% of these patients also have anxiety. People with migraine, depression, and anxiety are more sensitive to subtle shifts in hormonal levels as p. 32well as to air travel, sleep loss, or specific foods; many of these act as triggers for one or more of these symptoms. The genes that link these various disorders have not been discovered.

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Why is depression so common?

Depression has been called the common cold of mental illnesses because all of us catch it at some point in our lives. This is a fitting metaphor given what is now known about one potential cause of depression. An imbalance in gut bacteria and viruses may underlie depression. Therefore, depression may be so common because an imbalance in the variety of gut bacteria is so easy to induce. Lifestyle choices, such as shift work or smoking, the overuse of antibiotics, or disease conditions such as irritable bowel syndrome, are associated with depression and a reduction in the variety of gut bacteria.

Recent investigations of humans and locusts have focused upon the effects of bacterial infection, the development of body and brain inflammation, and the appearance of sickness behavior or depression. Recent studies show that the level of proinflammatory proteins in the blood increase during depression. Most of these proinflammatory proteins can cross the blood–brain barrier easily and influence brain function. In addition, the current antidepressant medications exhibit anti-inflammatory proclivities. Moreover, obese humans produce significant amounts of proinflammatory proteins. Taken together, these findings may explain why obesity and depression occur so often in advanced industrial economies and often are inherited together. Furthermore, obese humans do not respond well to most antidepressant drugs, as compared to nonobese depressed patients. More on this later.

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What is the role of serotonin in depression?

Humans and locusts use the neurotransmitter serotonin for apparently similar functions. When serotonin levels are too p. 33low due to the content of their diet or stress from overcrowding, both locusts and humans display solitary behaviors and make an effort to become isolated from others. When humans consume diets that are low in tryptophan, a condition often seen when someone first goes on a vegetarian or vegan diet, the brain produces much less serotonin and humans display many of the symptoms of depression such as anxiety, irritability, and difficulty thinking. When locusts eat grain containing tryptophan, their brains make more serotonin and they become gregarious and spend time in the company of large crowds of other locusts aggressively eating tryptophan-containing fields of crops. When depressed humans take medications that enhance serotonin function in their brains, they become happier and enjoy the company of friends and family. Depression and sickness behavior (malaise, failure to concentrate, sleepiness, fatigue, coldness, muscle and joint aches, and reduced appetite) share many features that are regulated by infection status, level of inflammatory proteins being produced, and availability of specific nutrients in the diet that lead to the production of serotonin. Sickness behaviors are initiated by our immune system in response to infection or injury; their goal is to remove us from potential harm while we heal.

Taken together, these similarities suggest that depressive behaviors are so common because they evolved as a universally needed survival mechanism that was passed on from generation to generation as an effective method of surviving in a dangerous world teeming with opportunities for injury and infection. All species, from locusts to humans, may have evolved the ability to suffer depression because it has survival value for the individual, and, therefore, the species. However, due to the negative health consequences of long-term inflammation in the brain and body, the symptoms of depression must be aggressively treated because untreated depression increases the risk of cancer and reduced lifespan. Ironically, depression-related behaviors may be evolved physiological p. 34reactions that are healthful in the short term but harmful if allowed to continue for a long time.

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What is bipolar disorder?

Patients with bipolar disorder show many of the same symptoms of depression as described earlier. In addition to the symptoms of major depression, in order to be diagnosed with bipolar disorder a person must display at least one episode of mania. Mania is characterized by inflated self-esteem or grandiosity, decreased need for sleep, pressure to keep talking, racing thoughts, easy distractibility, excessive irritability, agitation, and attention to pleasurable activities that often have a high probability for negative consequences, such as unrestrained buying sprees, sexual indiscretions, or foolish investments. Many artists, writers, poets, and composers, such as Virginia Woolf, Jack London, Jackson Pollock, and Ernest Hemingway, who suffered with bipolar disorder produced some of their most iconic works during manic episodes.

The initial symptoms of bipolar illness usually begin in late adolescence, often presenting as depression during the teen years or even earlier. Children with bipolar parents have a significantly increased risk of developing the illness. Too often, the symptoms in children are difficult to recognize because they can be mistaken for normal age-appropriate behaviors. No single genetic marker has been identified; however, recent studies suggest some genetic similarities among bipolar illness, schizophrenia, and autism. Bipolar disorder is a collection of symptoms that represent a disruption in how multiple brain regions communicate with one another. An error in how some brain regions wired themselves together during development makes some people susceptible to bipolar disorder. Possibly as a consequence of these wiring problems, some brain regions are too small and some areas of cortex are too thin.

Noninvasive investigations of the brains of patients with bipolar illness have shown that a portion of the frontal lobe p. 35is reduced in size. Preliminary studies suggest that electrical stimulation of this part of the brain can compensate for the atrophy and reduce the symptoms of depression in bipolar patients who are otherwise treatment resistant. The drug treatments for patients with bipolar disorder are known collectively as mood-stabilizing drugs and include lithium salts and the anticonvulsants valproate, carbamazepine, and lamotrigine. For more than five decades the primary treatment for bipolar disorder has been lithium salts. Lithium increases the time between manic episodes; it has minimal effects upon the depression phase of this illness. However, by reducing the incidence of mania, the incidence of depression also is reduced. This discovery suggests that the cycling between mania and depression involves neural mechanisms that are somehow interconnected with each other in the brain. Lithium has many known actions within the brain; whether any of these is responsible for its antimanic proclivities is unknown. In general, lithium treatment alone is insufficient to treat all of the symptoms of the disorder; the majority of patients are given a combination therapy of lithium and other medications such as antidepressants. Unfortunately, many patients cannot tolerate the unpleasant side effects of lithium therapy, including changes in weight and appetite, tremor, blurred vision, metallic tastes, and dizziness. Obviously, treatments that are more effective, act faster, and are tolerated better are needed badly. Newer classes of drugs that modulate the action of the neurotransmitter glutamate are now being actively investigated. In addition, a recent report claimed that deep brain stimulation, similar to that used on patients with Parkinson’s disease, might be quite effective for patients with bipolar disorder.

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 p. 36appearance 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.

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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 p. 37neurons 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 p. 38of symptoms, as well as which are not likely to show significant remission. This information allows psychiatrists to make informed judgments regarding patient therapy.

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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, p. 39schizophrenia 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.

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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.

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p. 40How 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.