Physiological Evidence of the Disease Process in the Brain

Many persons with schizophrenia and their families attribute the illness to psychological stress alone, a conclusion that is inconsistent with psychiatric research (Holzinger, Kilian, Lindenbach, Petscheleit, & Angermeyer, 2003). However, why would we assume that individuals who experience or observe a condition would necessarily know its origins? Does being bald give you insight into the hormonal changes that have taken place to bring about hair loss? Certainly not.

Summarizing all available evidence on the etiology of schizophrenia, Walker, Kestler, Bollini, and Hochman (2004) reached the conclusion that both genetic and prenatal factors can influence vulnerability to this illness. The same can be said for mental illnesses in general. Subsequent processes, including brain development, that occur during adolescence and exposure to stressful events can trigger the onset of what is known as a major mental illness.

The evidence is overwhelming that schizophrenia and similar conditions are due to changes in the structure and functioning of the brain (Buchanan & Carpenter, 1997; Frith, 1997; Walker et al., 2004). Today, very sophisticated neuroimaging techniques, such as magnetic resonance imaging (MRI), computerized axial tomography (CAT) scans, and positron emissions tomography (PET) scans, provide a window for viewing living, working brains. Developed with the help of high-speed computers, MRI and CAT scans provide pictures of the brain's structure, whereas PET scans provide snapshots of its functioning.

Using these various brain scans, the living brains of people with serious mental illnesses have been compared to other individuals, of the same age and sex, without mental illnesses. Based on the differences found between people with serious mental illnesses and those without them, it has become increasingly clear that the brains of people who have a serious mental illness have both a different neuroanatomy and different neural functioning than people who do not have a major psychiatric disorder (Buchanan & Carpenter, 1997).

An MRI scan provides images of the tissue, structure, and spaces (ventricles and sulci) in the brain. In the MRI scans shown in Figure 2.1, the lighter gray areas are the brain tissue cells, or neurons, and the darker gray areas are the ventricles. The ventricles are large fluid-filled enclosures and the sulci are the spaces or folds in the brain's cortex. These are part of the normal anatomy or structure of the brain. Normally, ventricles and sulci become enlarged as part of the aging process. In the MRI scans pictured in Figure 2.1, note that the person with schizophrenia, on the right, has less brain tissue and enlarged ventricles compared to the peer of the same age, on the left.

People diagnosed with schizophrenia, compared to others their own age, often have larger spaces in their brain in the form of enlarged ventricles and sulci, indicating they have less brain tissue (Gur & Pearlson, 1993). MRI and CAT scans have consistently found that these spaces are enlarged in the brains of people with schizophrenia (Heckers, 1997). Based on this evidence, it appears that some people with schizophrenia have suffered a type of physical dementia (e.g., enlarged ventricles), perhaps as early as adolescence or young adulthood.

The brains of people with schizophrenia, and perhaps other mental illnesses, have other significant structural differences when compared to people of the same age and sex, and even differ from those of their family. People with schizophrenia have a significantly smaller brain region, known as the hippocampus, in comparison to their peers (Schulze et al., 2003). Studies have shown that reductions in the size of the hippocampus occur during the first psychotic episode. In addition, there are differences in the frontal and temporal lobe regions of the brains of people with schizophrenia. Parts of the temporal and frontal lobes have less volume and are smaller than they should be (Conklin & Iacona, 2002; Kurachi, 2003a, 2003b). Raine and colleagues (2002) found that there are also

Psychiatric Rehabilitation

FIGURE 2.1 MRI scans of 28-year-old identical twins discordant for schizophrenia, showing enlarged cerebral ventricles in the affected twin. (Courtesy of Dr. E. Fuller Torrey and Dr. Daniel Weinberger, Clinical Brain Disorders Branch, National Institute of Mental Health.) OK.

Weil twin Affected twin

FIGURE 2.1 MRI scans of 28-year-old identical twins discordant for schizophrenia, showing enlarged cerebral ventricles in the affected twin. (Courtesy of Dr. E. Fuller Torrey and Dr. Daniel Weinberger, Clinical Brain Disorders Branch, National Institute of Mental Health.) OK.

frontal lobe differences in persons with schizophrenia spectrum disorders, that is, individuals with symptoms similar to schizophrenia who do not experience severe episodes of psychosis. Many of the problems people with schizophrenia experience, such as problems with auditory (hearing) processing in the form of hallucinations, understanding concepts and abstract ideas, and other cognitive or thinking problems, are associated with these regions of the brain. Differences can also be seen in a nearby region known as the amygdala.

The causes for the differences in brain structure are not known but a number of theories are emerging. One involves neurotrophins, which are the hormone-like growth factors that help neurons to grow, arrange themselves properly, and develop synaptic connections with other neurons. People with schizophrenia have an abnormally low level of neurotrophins. One major neurotrophin, brain-derived neurotrophic factor (BDNF), has been found to be significantly lower in people with schizophrenia (Pitiladar, Gonul, Taneli, & Akdeniz, 2004). These abnormal levels lead to abnormal neuronal development and abnormal development of both the dendrites (branches of brain cells) and synapses (small spaces where different brain cells meet).

Another theory is based on the evidence that the stress response of persons who have serious mental illnesses, which is the release of a set of brain hormones called glucocor-ticoids, is poorly regulated. The response to stress is therefore unduly prolonged. Gluco-corticoids are known to interact with the hypothalamus-pituitary axis (HPA). The hypothalamus is a brain structure associated with many human appetites and drives. It is directly connected to a very important gland, the pituitary. High levels of glucocorticoids and prolonged response to stress have been found among people who have a serious mental illness. This prolonged stress reaction may lead both to the experience of escalating symptoms, relapses, and the deterioration of certain brain structures (Cotter & Pariante, 2002). In animal studies, the prolonged release of glucocorticoids is associated with the development of a smaller hippocampus, a problem specifically found in schizophrenia.

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