During their most severe periods, people with schizophrenia live in a private inner world, preoccupied with the strange ideas and images that haunt them. The word itself means “split” (schizo) “mind” (phrenia). It refers not to a multiple-personality split but rather to the mind’s split from reality, as shown in disturbed perceptions, disorganized thinking and speech, and diminished, inappropriate emotions. Schizophrenia is the chief example of a psychotic disorder. This group of disorders is marked by irrationality, distorted perceptions, and lost contact with reality.

As you can imagine, these characteristics profoundly disrupt relationships and work. Given a supportive environment and medication, over 40 percent of people with schizophrenia will have periods of a year or more of normal life experience (Jobe & Harrow, 2010). But only 1 in 7 experience a full and enduring recovery (Jääskeläinen et al., 2013).

43-1 What patterns of perceiving, thinking, and feeling characterize schizophrenia?

Schizophrenia comes in varied forms. Schizophrenia patients with positive symptoms—the presence of inappropriate behaviors—may experience hallucinations, talk in disorganized and deluded ways, and exhibit inappropriate laughter, tears, or rage. Those with negative symptoms—the absence of appropriate behaviors—may have toneless voices, expressionless faces, or mute and rigid bodies.

DISTURBED PERCEPTIONS People with schizophrenia sometimes have hallucinations—they see, feel, taste, or smell things that exist only in their minds. Usually, the hallucinations are sounds, often voices making insulting remarks or giving orders. The voices may tell the person that she is bad or that she must burn herself with a cigarette lighter. Imagine your own reaction if a dream broke into your waking consciousness, making it hard to separate your experience from your imagination. When the unreal seems real, the resulting perceptions are at best bizarre, at worst terrifying.

DISORGANIZED THINKING AND SPEECH Hallucinations are false perceptions. People with schizophrenia also have disorganized, fragmented thinking, which is often distorted by false beliefs called delusions. If they have paranoid tendencies, they may believe they are being threatened or pursued.

Maxine, a young woman with schizophrenia, believed she was Mary Poppins. Communicating with Maxine was difficult because her thoughts spilled out in no logical order. Her biographer, Susan Sheehan (1982, p. 25), observed her saying aloud to no one in particular, “This morning, when I was at Hillside [Hospital], I was making a movie. I was surrounded by movie stars…. I’m Mary Poppins. Is this room painted blue to get me upset? My grandmother died four weeks after my eighteenth birthday.”

Jumbled ideas may make no sense even within sentences, forming what is known as word salad. One young man begged for “a little more allegro in the treatment,” and suggested that “liberationary movement with a view to the widening of the horizon” will “ergo extort some wit in lectures.”

One cause of disorganized thinking may be a breakdown in selective attention. Normally, we have a remarkable capacity for giving our undivided attention to one set of sensory stimuli while filtering out others. People with schizophrenia cannot do this. Thus, tiny, irrelevant stimuli, such as the grooves on a brick or the inflections of a voice, may distract their attention from a bigger event or a speaker’s meaning. As one former patient recalled, “What had happened to me … was a breakdown in the filter, and a hodge-podge of unrelated stimuli were distracting me from things which should have had my undivided attention” (MacDonald, 1960, p. 218). This selective-attention difficulty is but one of dozens of cognitive differences associated with schizophrenia (Reichenberg & Harvey, 2007).

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DIMINISHED AND INAPPROPRIATE EMOTIONS The expressed emotions of schizophrenia are often utterly inappropriate, split off from reality (Kring & Caponigro, 2010). Maxine laughed after recalling her grandmother’s death. On other occasions, she cried when others laughed, or became angry for no apparent reason. Others with schizophrenia lapse into an emotionless flat affect state of no apparent feeling. Most also have an impaired theory of mind—they have difficulty reading other people’s facial emotions and state of mind (Green & Horan, 2010; Kohler et al., 2010). These emotional deficiencies occur early in the illness and have a genetic basis (Bora & Pantelis, 2013).

Motor behavior may also be inappropriate and disruptive. Those with schizophrenia may experience catatonia, characterized by motor behaviors ranging from a physical stupor—motionless for hours—to senseless, compulsive actions, such as continually rocking or rubbing an arm, to severe and dangerous agitation.

43-2 How do chronic and acute schizophrenia differ?

Nearly 1 in 100 people (about 60 percent of them men) will experience schizophrenia this year, joining an estimated 24 million people worldwide (Global, 2015). It typically strikes as young people are maturing into adulthood. It knows no national boundaries. Men tend to be struck earlier, more severely, and slightly more often (Aleman et al., 2003; Eranti et al., 2013; Picchioni & Murray, 2007).

When schizophrenia is a slow-developing process, called chronic schizophrenia, recovery is doubtful (WHO, 1979). This was the case with Maxine’s schizophrenia, which took a slow course, emerging from a long history of social inadequacy and poor school performance (MacCabe et al., 2008). Those with chronic schizophrenia often exhibit the persistent and incapacitating negative symptom of social withdrawal (Kirkpatrick et al., 2006). Men, whose schizophrenia develops on average four years earlier than women’s, more often exhibit negative symptoms and chronic schizophrenia (Räsänen et al., 2000).

When previously well-adjusted people develop schizophrenia rapidly following particular life stresses, this is called acute schizophrenia, and recovery is much more likely. People with acute schizophrenia often have positive symptoms that respond to drug therapy (Fenton & McGlashan, 1991, 1994; Fowles, 1992).

Schizophrenia is a dreaded psychological disorder. It is also one of the most heavily researched. Most studies now link it with abnormal brain tissue and genetic predispositions. Schizophrenia is a disease of the brain manifested in symptoms of the mind.

BRAIN ABNORMALITIES

43-3 What brain abnormalities are associated with schizophrenia?

Might chemical imbalances in the brain explain schizophrenia? Scientists have long known that strange behavior can have strange chemical causes. Have you ever heard the saying “mad as a hatter”? That phrase dates back to the behavior of British hatmakers whose brains were slowly poisoned as they used their tongue and lips to moisten the brims of mercury-laden felt hats (Smith, 1983). Could schizophrenia symptoms have a similar biochemical key? Scientists continue to track the mechanisms by which chemicals produce hallucinations and other symptoms.

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DOPAMINE OVERACTIVITY One possible answer emerged when researchers examined schizophrenia patients’ brains after death. They found an excess number of dopamine receptors, including a sixfold excess for the dopamine receptor D4 (Seeman et al., 1993; Wong et al., 1986). The resulting hyper-responsive dopamine system could intensify brain signals, creating positive symptoms such as hallucinations and paranoia (Grace, 2010). Drugs that block dopamine receptors often lessen these symptoms. Drugs that increase dopamine levels, such as amphetamines and cocaine, sometimes intensify them (Seeman, 2007; Swerdlow & Koob, 1987).

ABNORMAL BRAIN ACTIVITY AND ANATOMY Abnormal brain activity accompanies schizophrenia. Some people diagnosed with schizophrenia have abnormally low brain activity in the brain’s frontal lobes, which help us reason, plan, and solve problems (Morey et al., 2005; Pettegrew et al., 1993; Resnick, 1992). The brain waves that reflect synchronized neural firing in the frontal lobes decline noticeably (Spencer et al., 2004; Symond et al., 2005).

One study took PET scans of brain activity while people were hallucinating (Silbersweig et al., 1995). When participants heard a voice or saw something, their brain became vigorously active in several core regions. One was the thalamus, the structure that filters incoming sensory signals and transmits them to the brain’s cortex. Another PET scan study of people with paranoia found increased activity in the amygdala, a fear-processing center (Epstein et al., 1998).

Many studies of people with schizophrenia have found enlarged, fluid-filled areas and a corresponding shrinkage and thinning of cerebral tissue (Goldman et al., 2009; Wright et al., 2000). People often inherit these brain differences. If one affected identical twin shows brain abnormalities, the odds are at least 1 in 2 that the other twin will have them (van Haren et al., 2012). Even people who will later develop the disorder may show these symptoms (Karlsgodt et al., 2010). The greater the brain shrinkage, the more severe the thought disorder (Collinson et al., 2003; Nelson et al., 1998; Shenton, 1992).

Two smaller-than-normal areas are the cortex, and the corpus callosum that connects the brain’s two hemispheres (Arnone et al., 2008). Another is the thalamus, which may explain why filtering sensory input and focusing attention can be difficult for people with schizophrenia (Andreasen et al., 1994; Ellison-Wright et al., 2008). The bottom line: Schizophrenia involves not one isolated brain abnormality but problems with several brain regions and their interconnections (Andreasen, 1997, 2001).

PRENATAL ENVIRONMENT AND RISK

43-4 What prenatal events are associated with increased risk of developing schizophrenia?

What causes brain abnormalities in people with schizophrenia? Some scientists point to mishaps during prenatal development or delivery (Fatemi & Folsom, 2009; Walker et al., 2010). Risk factors for schizophrenia include low birth weight, maternal diabetes, older paternal age, and oxygen deprivation during delivery (King et al., 2010). Famine may also increase risks. People conceived during the peak of World War II’s Dutch famine later developed schizophrenia at twice the normal rate. Those conceived during the famine of 1959 to 1961 in eastern China also displayed this doubled rate (St. Clair et al., 2005; Susser et al., 1996).

Let’s consider another possible culprit. Might a midpregnancy viral infection impair fetal brain development (Brown & Patterson, 2011)? To test this fetal-virus idea, scientists have asked these questions:

These converging lines of evidence suggest that fetal-virus infections contribute to the development of schizophrenia. This finding strengthens the U.S. government recommendation that “pregnant women need a flu shot” (CDC, 2014).

Why might a second-trimester maternal flu bout put fetuses at risk? Is the virus itself the culprit? The mother’s immune response to it? Medications taken (Wyatt et al., 2001)? Does the infection weaken the fetal brain’s supportive glial cells, leading to reduced synaptic connections (Moises et al., 2002)? In time, answers may become available.

GENETIC INFLUENCES

43-5 How do genes influence schizophrenia?

Fetal-virus infections may increase the odds that a child will develop schizophrenia. But many women get the flu during their second trimester of pregnancy, and only 2 percent of them bear children who develop schizophrenia. Why does prenatal exposure to the flu virus put some children at risk but not others? Might some people be more vulnerable because of an inherited predisposition? The evidence indicates that, Yes, some may inherit a predisposition to schizophrenia. For most people, the odds of being diagnosed with schizophrenia are only 1 in 100. For those who have a sibling or parent with the disorder, the odds increase to about 1 in 10. And if the affected sibling is an identical twin, the odds increase to nearly 1 in 2 (FIGURE 43.1). Those odds are unchanged even when the twins are reared apart (Plomin et al., 1997). (Only about a dozen such cases are on record.)

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Remember, though, that identical twins share more than their genes. They also share a prenatal environment. About two-thirds also share a placenta and the blood it supplies; the other one-third have separate placentas. Shared placentas matter. If the co-twin of an identical twin with schizophrenia shared the placenta, the chances of developing the disorder are 6 in 10. If the identical twins had separate placentas, the co-twin’s chances of developing schizophrenia drop to 1 in 10 (Davis & Phelps, 1995; Davis et al., 1995; Phelps et al., 1997). Twins who share a placenta are more likely to share the same prenatal viruses. So perhaps shared germs as well as shared genes produce identical twin similarities.

Adoption studies help untangle genetic and environmental influences. Children adopted by someone who develops schizophrenia do not “catch” the disorder. Rather, adopted children have a higher risk if a biological parent has schizophrenia (Gottesman, 1991). Genes matter.

The search is on for specific genes that, in some combination, predispose schizophrenia-inducing brain abnormalities (FIGURE 43.2). (It is not our genes but our brains that directly control our behavior.) In the biggest-ever study of the genetics of psychiatric disorder, scientists from 35 countries pooled data from the genomes of 37,000 people with schizophrenia and 113,000 people without (Schizophrenia Working Group, 2014). They found 103 genome locations linked with the disorder. Some of these genes influence the activity of dopamine and other brain neurotransmitters. Others affect the production of myelin, a fatty substance that coats the axons of nerve cells and lets impulses travel at high speed through neural networks.

Although genes matter, the genetic formula is not as straightforward as the inheritance of eye color. The new result confirms other genome studies which show that schizophrenia is a group of disorders that are influenced by many genes, each with very small effects (Arnedo et al., 2015; International Schizophrenia Consortium, 2009).

As we have seen in so many different contexts, nature and nurture interact. Recall that epigenetic (literally “in addition to genetic”) factors influence whether or not genes will be expressed. Like hot water activating a tea bag, environmental factors such as viral infections, nutritional deprivation, and maternal stress can “turn on” the genes that put some of us at higher risk for this disorder. Identical twins’ differing histories in the womb and beyond explain why they may show differing gene expressions (Dempster et al., 2013; Walker et al., 2010). Our heredity and our life experiences work together. Neither hand claps alone.

Thanks to our expanding understanding of genetic and brain influences on maladies such as schizophrenia, the general public increasingly attributes psychiatric disorders to biological factors (Pescosolido et al., 2010).

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Few of us can relate to the strange thoughts, perceptions, and behaviors of schizophrenia. Sometimes our thoughts jump around, but we rarely talk nonsensically. Occasionally we feel unjustly suspicious of someone, but we do not believe the world is plotting against us. Often our perceptions err, but rarely do we see or hear things that are not there. We feel regret after laughing at someone’s misfortune, but we rarely giggle in response to our own bad news. At times we just want to be alone, but we do not live in social isolation. However, millions of people around the world do talk strangely, suffer delusions, hear nonexistent voices, see things that are not there, laugh or cry at inappropriate times, or withdraw into private imaginary worlds. The quest to solve the cruel puzzle of schizophrenia continues, more vigorously than ever.

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