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). But in this disorder, the mind is not split into multiple personalities. Rather, the mind has suffered a split from reality that shows itself in disturbed perceptions, disorganized thinking and speech, and diminished, inappropriate emotions and actions. Schizophrenia is the chief example of a psychotic disorder, a group of disorders marked by irrationality, distorted perceptions, and lost contact with reality.

As you can imagine, these traits profoundly disrupt relationships and make it difficult to hold a job. When people with schizophrenia live in a supportive environment and receive medication, more than 40 percent will enjoy periods of normal life lasting a year or more (Jobe & Harrow, 2010). But only 1 in 7 will have a full and enduring recovery (Jääskeläinen et al., 2013).

People with schizophrenia display symptoms that are positive (inappropriate behaviors are present) or negative (appropriate behaviors are absent). Those with positive symptoms may have hallucinations or talk in disorganized and deluded ways. They may laugh or cry or lash out in rage at inappropriate times. Those with negative symptoms may have toneless voices, expressionless faces, or mute and rigid bodies.

Disturbed Perceptions and Beliefs

People with schizophrenia sometimes have hallucinations—they see, feel, taste, or smell things that exist only in their minds. Most often, the hallucinations are sounds, usually 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. Stuart Emmons described his experience:

When someone asks me to explain schizophrenia I tell them, you know how sometimes in your dreams you are in them yourself and some of them feel like real nightmares? My schizophrenia was like I was walking through a dream. But everything around me was real. At times, today’s world seems so boring and I wonder if I would like to step back into the schizophrenic dream, but then I remember all the scary and horrifying experiences (Emmons et al., 1997).

When the unreal seems real, the resulting perceptions are at best bizarre, at worst terrifying.

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

Disorganized Speech

Imagine trying to communicate with Maxine, a young woman whose thoughts spill out in no logical order. Her biographer (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 ability to give our undivided attention to one set of sensory stimuli while filtering out others. People with schizophrenia are easily distracted by tiny unrelated stimuli, such as the grooves on a brick or tones in a voice. But dozens of other cognitive differences are also associated with this disorder (Reichenberg & Harvey, 2007).

Diminished and Inappropriate Emotions and Actions

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, a zombielike state of no apparent feeling. For example, monetary perks fail to provide the normal brain reward center activation (Radua et al., 2015). Most also have an impaired theory of mind—they have difficulty reading other people’s facial expressions and state of mind (Green & Horan, 2010; Kohler et al., 2010). These emotional traits occur early in the illness and have a genetic basis (Bora & Pantelis, 2013).

Inappropriate motor behavior takes many forms. Some people with schizophrenia perform senseless, compulsive acts, such as continually rocking or rubbing an arm. Others may remain motionless for hours and then become agitated.

This year, nearly 1 in 100 people (about 60 percent of them men) will join an estimated 24 million others worldwide who have schizophrenia (Global Burden of Disease, 2015). This disorder knows no national boundaries, and it typically strikes as young people are maturing into adulthood. Men tend to be struck earlier, more severely, and slightly more often (Aleman et al., 2003; Eranti et al., 2013; Picchioni & Murray, 2007).

For some, schizophrenia appears suddenly. Recovery is much more likely when a previously well-adjusted person develops the disorder, called acute schizophrenia, seemingly as a rapid reaction to particular life stresses. People with acute schizophrenia often have positive symptoms that respond to drug therapy (Fenton & McGlashan, 1991, 1994; Fowles, 1992).

When schizophrenia is a slow-developing process, called chronic schizophrenia, recovery is doubtful (Harrison et al., 2001). This was the case with Maxine, whose schizophrenia developed gradually, emerging from a long history of social inadequacy and poor school performance (MacCabe et al., 2008). Social withdrawal, a negative symptom, is often found among those with chronic schizophrenia (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).

Schizophrenia is one of the most heavily researched psychological disorders. Most studies now link it with abnormal brain tissue and genetic predispositions. Schizophrenia is a disease of the brain made visible in symptoms of the mind.

Brain Abnormalities

What sorts of brain abnormalities might explain schizophrenia? Biochemical imbalances? Abnormal brain activity? Problems with brain structures or functions? Researchers are taking a close look at all of these.

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Scientists have long known that strange behavior can have strange chemical causes. Have you ever heard the phrase “mad as a hatter”? The saying dates back to the behavior of British hatmakers whose brains were slowly poisoned as they used their mouths to moisten the brims of mercury-laden felt hats (Smith, 1983). Could the hallucinations and other symptoms of schizophrenia have a similar biochemical key?

One possible answer emerged when researchers examined schizophrenia patients’ brains after death. They found an excess number of dopamine receptors (Seeman et al., 1993; Wong et al., 1986). What could this mean? Perhaps a high level of dopamine could intensify brain signals, creating positive symptoms such as hallucinations and paranoia (Grace, 2010). Sure enough, other evidence confirmed this idea. Drugs that block dopamine receptors often lessen the positive symptoms of schizophrenia. Drugs that increase dopamine levels, such as amphetamines and cocaine, sometimes intensify them (Basu & Basu, 2015; Farnia et al., 2014). But there’s more to schizophrenia than abnormal brain chemistry.

Brain scans show that abnormal brain activity and brain structures accompany schizophrenia. Some people with schizophrenia have abnormally low 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). Others have an unusual corpus callosum, the band of nerve fibers through which the right and left hemispheres communicate (Arnedo et al., 2015).

One study took PET scans of brain activity while people were hallucinating (Silbersweig et al., 1995). When patients 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).

In schizophrenia, areas of the brain become enlarged and fill with fluid; cerebral tissue also shrinks (Goldman et al., 2009; van Haren et al., 2015; Wright et al., 2000). These brain differences may be inherited. If one identical twin’s brain shows the abnormalities, the odds are at least 1 in 2 that the other twin’s brain will also have them (van Haren et al., 2012). Some studies have even found brain abnormalities in people who later developed this disorder (Karlsgodt et al., 2010). The greater the shrinkage, the more severe the thought disorder (Collinson et al., 2003; Nelson et al., 1998; Shenton, 1992).

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

What causes brain abnormalities in people with schizophrenia? Some researchers blame mishaps during prenatal development or delivery (Fatemi & Folsom, 2009; Walker et al., 2010). Risk factors include low birth weight, mother’s diabetes, father’s older age, or lack of oxygen during delivery (King et al., 2010). Famine may also increase risks. People conceived during the peak of World War II’s Dutch famine 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, 2014b).

Genetics and Risk

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 their children 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 they have an inherited predisposition to this disorder? Evidence indicates the answer is Yes. For most people, the odds of being diagnosed with schizophrenia are nearly 1 in 100. For those who have a sibling or parent with schizophrenia, the odds increase to about 1 in 10. And if the affected sibling is an identical twin, the odds are close to 1 in 2 (FIGURE 13.13). Those odds are unchanged even when the twins are raised apart (Plomin et al., 1997). (Only about a dozen such cases are on record.)

But wait! Identical twins also share a prenatal environment. So, is it possible that shared germs as well as shared genes produce identical twin similarities? There is some evidence that supports this idea.

About two-thirds of identical twins also share a placenta and the blood it supplies. Other identical twins have two separate placentas. Sharing a placenta raises the odds of later sharing a schizophrenia diagnosis. If identical twins had separate placentas, the chances are 1 in 10. If they shared a placenta, the co-twin’s chances of having the disorder are 6 in 10 (Davis et al., 1995; Davis & Phelps, 1995). A likely explanation: Identical twins who share a placenta are more likely to share the same prenatal viruses (FIGURE 13.14).

How, then, can we untangle the genetic influences from the environmental influences on this disorder? Adoption studies offer some clues. Children adopted by someone who develops schizophrenia do not “catch” the disorder. Rather, adopted children have a higher risk if one of their biological parents has schizophrenia (Gottesman, 1991). Genes matter.

The search is on for specific genes that, in some combination, might lead to schizophrenia-inducing brain abnormalities. (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 this disorder. Some 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.

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Although genes matter, the genetic formula is not as straightforward as the inheritance of eye color. Schizophrenia is a group of disorders, influenced by many genes, each with very small effects (Arnedo et al., 2015; International Schizophrenia Consortium, 2009).

As we have seen again and again, nature and nurture interact. Recall again that epigenetic (literally “in addition to genetic”) factors influence whether 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 only one may develop a disorder (Dempster et al., 2013; Walker et al., 2010). Our heredity and our life experiences work together. Neither hand claps alone.

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Most of us can relate more easily to the ups and downs of anxiety, phobias, and depression than to the strange thoughts, perceptions, and behaviors of schizophrenia. Sometimes our thoughts do 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 therefore continues, more vigorously than ever.