Abnormal Psychology

Mood Disorders and Suicide 201

thought that the puzzle of depression was nearly solved. However, we now know that

the story is not that simple—depression is not caused by too much or too little of a

specifi c neurotransmitter. Instead, the disorder arises in part from complex interac-

tions among numerous neurotransmitter substances, which depend on how much of

each is released into the synapses, how long each substance lingers in the synapse,

and how the substances interact with receptors in other areas of the brain that are

involved in the symptoms of depression (Nemeroff, 1998).

One of the early attempts to explain depression in terms of a single neurotrans-

mitter is called the catecholamine hypothesis, which posits that symptoms of depres-

sion arise when levels of norepinephrine fall too low (Schildkraut, 1965). Support

for this hypothesis came from studies showing that people who are depressed

have fewer by-products of norepinephrine in their urine and cerebrospinal fl uid

(Nemeroff, 1998). Perhaps surprisingly, however, autopsies of the brains of people

who were depressed found that many of them had a higherthan normal density

of norepinephrine receptors (Meana, Barturen, & Garcia-Sevilla, 1992). At fi rst

glance, this last fi nding may seem at odds with the fi rst fi nding—why would people

who have lessnorepinephrine have morereceptors that respond to that neurotrans-

mitter? This apparent paradox is resolved by knowing that when the brain doesn’t

produce enough of a neurotransmitter, it often attempts to compensate by increas-

ing the number of receptors that respond to it. An increase in the number of recep-

tors allows a given amount of neurotransmitter to have a larger effect.

Further support for the catecholamine hypothesis came from the fi nding that

depression can be treated by drugs that block norepinephrine reuptake (Brunello &

Racagni, 1998; Schatzberg, 2000). These drugs keep more norepinephrine in the

synapse for a longer period of time, which means that less additional norepineph-

rine needs to be produced to affect the receptors.

But the neurotransmitter norepinephrine and the catecholamine hypothesis

cannot be the whole story. Additional studies have implicated the neurotransmit-

ter serotonin in depression (Booij & Van der Does, 2007; Munafò et al., 2006).

Some researchers hypothesize that serotonin affects depression through its infl uence

on norepinephrine activity (Schildkraut, 1965). However, other researchers have

shown that serotonin directly affects the amygdala (which plays an important role

in emotional expression; LeDoux, 2000), the hypothalamus (which is involved in

vegetative signs of depression; Swaab, 2003), and cortical brain areas involved

in thinking and judgment (Smith & Kosslyn, 2006). Moreover, measurements of

cerebrospinal fl uid and autopsy studies have shown that depressed people have

lower levels of serotonin than normal (Sullivan et al., 2006). And, just as was docu-

mented for norepinephrine, lower levels of serotonin are associated with greater

numbers of certain serotonin receptors, and drugs that block the reuptake of sero-

tonin relieve symptoms of depression (Arroll et al., 2005).

Dopamine also appears to play several roles in depression (Nutt, 2008); too

little of it not only can undermine the effects of reward (and hence can lead to lack

of pleasure), but also can produce psychomotor retardation (Clausius, Born &

Grunz, 2009; Martin-Soelch, 2009; Stein, 2008). In short, depression involves

not only norepinephrine, but also serotonin and dopamine—and perhaps other

neurotransmitters as well.

Stress-Related Hormones

The chemical story doesn’t end with neurotransmitters. Nemeroff (1998, 2008) for-

mulated the stress–diathesis model of depression (which is to be distinguished from the

generaldiathesis–stress model, discussed in Chapter 1). The stress– diathesis model of

depression focuses specifi cally on the hypothalamic-pituitary-adrenal axis (HPA axis;

discussed in Chapter 2) and the role of cortisol, a hormone that is secreted in larger

amounts when an individual experiences stress (see Figure 6.1). According to the

stress–diathesis model, people with depression have an excess of cortisol circulating

in their blood, which makes their brains prone to overreacting when they experience

stress. Moreover, this stress reaction, in turn, alters the serotonin and norepinephrine

systems, which underlie at least some of the symptoms of depression. Antidepressants