Abnormal Psychology

Schizophrenia and Other Psychotic Disorders 545

neurotransmitter serotonin), they report schizophrenia-like experiences (Syvalathi,

1994). (As noted in Chapter 9, LSD affects both serotonin and dopamine activity.)

Clearly, dopamine is involved in schizophrenia, but research has defi nitively

documented that the dopamine hypothesis was an oversimplifi cation (McDermott &

de Silva, 2005). Rather than being a primary cause of the disorder, dopamine affects,

and is affected by, other neurotransmitters whose activity, along with the structural

and functional abnormalities of various brain areas, gives rise to some of the symp-

toms of schizophrenia (Laruelle et al., 1993; Nestler, 1997; Syvalathi, 1994; Vogel

et al., 2006; Walker & Diforio, 1997; Weinberger & Lipska, 1995).

Serotonin and Glutamate

Medications that affect serotonin levels can decrease both positive and negative symp-

toms in people with schizophrenia. Research studies suggest complex interactions

among serotonin, dopamine, and glutamate (Andreasen, 2001). For example, sero-

tonin has been shown to enhance the effect of glutamate, which is the most common

fast-acting excitatory transmitter in the brain (Aghajanian & Marek, 2000). This is

relevant to understanding schizophrenia because the N-methyl-D-aspartate (NMDA)

glutamate receptor has been shown to play a crucial role in learning and memory,

and hence abnormalities in its functioning may explain some of the defi cits associated

with schizophrenia, such as defi cits in working memory. In particular, studies have

found unusually high levels of glutamate in people with schizophrenia, particularly in

the frontal lobe (Abbott & Bustillo, 2006; van Elst et al., 2005); such an excess of glu-

tamate may disrupt the timing of neural activation in the frontal lobe, which in turn

may impair cognitive activities that depend on the smooth coordination of different

operations, such as working memory, where information a must be actively retained

in short-term memory as it is operated upon (Lewis & Moghaddam, 2006).

Stress and Cortisol

Research fi ndings suggest that stress can contribute to schizophrenia, because stress

affects cortisol production, which in turn affects the brain; the effects of stress proba-

bly start well before the fi rst episode of schizophrenia emerges. The relationship with

cortisol appears even in childhood. Children who are at risk for schizophrenia react

more strongly to stress, and their baseline levels of cortisol are higher than those of

other children (Walker, Logan, & Walker, 1999). The relationship between stress,

cortisol, and symptoms of schizophrenia has also been noted during adolescence, the

time when prodromal symptoms often emerge: A 2-year longitudinal study of adoles-

cents with schizotypal personality disorder found that cortisol levels—and symptoms

of schizophrenia—increased over the 2 years (Walker, Walder, & Reynolds, 2001).

Thus, people who develop schizophrenia appear to be more biologically reactive

to stressful events. A hypothesized mechanism for this relationship is that the biolog-

ical changes and stressors of adolescence promote higher levels of cortisol, which is

thought to affect dopamine activity. Even after adolescence, people with schizophre-

nia have higher levels of stress-related hormones, including cortisol (Zhang et al.,

2005). In one study, the siblings of people with schizophrenia exhibited a larger

stress response than did healthy control participants but a smaller stress response

than did participants with schizophrenia; these fi ndings not only provide evidence

that genes play a role in how strongly a person will respond to stress, but also sug-

gest that the genetic contribution to the stress response may play a role in the devel-

opment of schizophrenia (Brunelin et al., 2008).

Effects of Estrogen

We noted earlier that when women develop schizophrenia, they often have different

symptoms than men do and tend to function better. Such fi ndings have led to the estro-

gen protection hypothesis (Seeman & Lang, 1990). According to this hypothesis, the

hormone estrogen, which occurs at higher levels in women, protects against symptoms

of schizophrenia through its effects on serotonin and dopamine activity. This protec-

tion may explain why women are likely to have a later onset of the disorder than do

men. Evidence for the estrogen protection hypothesis comes from two sources. One is

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