Causes of depression

Biochemical Factors Low activity of two neurotransmitter chemicals, norepinephrine and

serotonin, has been strongly linked to unipolar depression. In the 1950s, several pieces of
evidence began to point to this relationship. First, medical researchers discovered that certain
medications for high blood pressure often caused depression (Ayd, 1956). As it turned out,
some of these medications lowered norepinephrine activity and others lowered serotonin. A
second piece of evidence was the discovery of the first truly effective antidepressant drugs.
Although these drugs were discovered by accident, researchers soon learned that they relieve
depression by increasing either norepinephrine or serotonin activity. For years it was thought
that low activity of either norepinephrine or serotonin was capable of producing depression, but
investigators now believe that their relation to depression is more complicated (Goldstein et al.,
2011). Research suggests that interactions between serotonin and norepinephrine activity, or
between these and other kinds of neurotransmitters in the brain, rather than the operation of any
one neurotransmitter alone, may account for unipolar depression. Biological researchers have
also learned that the body’s endocrine system may play a role in unipolar depression (Goldstein
et al., 2011). As you have seen, endocrine glands throughout the body release hormones,
chemicals that in turn spur body organs into action (see Chapter 5). People with unipolar
depression have been found to have abnormally high levels of cortisol, one of the hormones
released by the adrenal glands during times of stress (Gao & Bao, 2011; Veen et al., 2011). This
relationship is not all that surprising, given that stressful events often seem to trigger
depression. Another hormone that has been tied to depression is melatonin, sometimes called
the “Dracula hormone” because it is released only in the dark. People who experience a
recurrence of depression each winter (a pattern called seasonal affective disorder) may secrete
more melatonin during the winter’s long nights than other individuals do.Still other biological
researchers are starting to believe that unipolar depression is tied more closely to what happens
within neurons than to the chemicals that carry messages between neurons. They believe that
activity by key neurotransmitters or hormones ultimately leads to deficiencies of certain proteins
and other chemicals within neurons—deficiencies that may impair the health of the neurons and
lead, in turn, to depression (Goldstein et al., 2011). The biochemical explanations of unipolar
depression have produced much enthusiasm, but research in this area has certain limitations.
Some of it has relied on analogue studies, which create depression-like symptoms in laboratory
animals. Researchers cannot be certain that these symptoms do in fact reflect the human
disorder. Similarly, until recent years, technology was limited, and studies of human depression
had to measure brain biochemical activity indirectly. As a result, investigators could never be
certain of the biochemical events that were occurring in the brain. Current studies using newer
technology, such as PET and MRI scans, are helping to eliminate such uncertainties about such
brain activity.causesd

Brain Anatomy and Brain Circuits In earlier chapters, you read that many biological
researchers now believe that emotional reactions of various kinds are tied to brain
circuits—networks of brain structures that work together, triggering each other into action and
producing a particular kind of emotional reaction. Although research is far from complete, a
brain circuit responsible for unipolar depression has also begun to emerge (Brockmann et al.,
2011; Selvaraj et al., 2011). An array of brain-imaging studies point to several brain areas that
are likely members of this circuit, particularly the prefrontal cortex, the hippocampus, the
amygdala, and Brodmann Area 25, an area located just under the brain part called the cingulate
cortex (see Figure 6-1). Research suggests that, among depressed people, activity and blood
flow are low in certain parts of the prefrontal cortex (Lim et al., 2011; Lambert & Kinsley, 2005)
yet high in other parts (Lemogne et al., 2010); the hippocampus is undersized and its production
of new neurons is low (Kubera et al., 2011; Campbell et al., 2004); activity and blood flow are
elevated in the amygdala (Goldstein et al., 2011; Drevets, 2001); and Brodmann Area 25 is
undersized and overactive (Hamani et al., 2011; Mayberg et al., 2005, 2000, 1997).