The classic model of mental illness in the first half of the 20th century held that stress was the cause of psychiatric illness in an otherwise healthy person (Gershon, 1990, p. 369). In more recent years, we have found biological clues that point to the true root of these mental illnesses.

Insofar as unipolar depression and bipolar disorder (affective disorders) are concerned, as Cicchetti and Toth (1995, p. 409) state, "There is growing consensus that there are multiple pathways to depression. Moreover, not all depressed or manic-depressive individual experience each potential biological or psychological dysfunction that is examined." To this end, I will examine the multiple theories that have been advanced, and the biological states that occur, as possible views into the causes for unipolar depression and bipolar disorder, with the view that one of these theories may be right, or that two or more of these theories may be right, and act in concert in the same person or separately in different people.

Epidemiology

It is estimated that the lifetime prevalence for major depression is 10% for men, and 20% for women. This contrast with only a 1% prevalence for Bipolar (Frude,1998, p. 118).

Genetics

There exists incontrovertible evidence that both unipolar depression and bipolar disorder are genetically linked. However, unlike the color of our eyes or hair, which is based solely upon simple Mendelian genetics, it appears that unipolar and bipolar are expressed as a tendency rather than a simple mathematical model (Cicchetti & Toth, 1995, p. 400).

Many studies have been done to examine the issue of environment versus genes. They found that in monozygotic (MZ), or identical, twins, there was a concordance rate of 54 - 65% for unipolar depression, with the concordance rate even higher in bipolar disorder, at 79%. There was only a concordance rate of 14 - 19% percent in dizygotic (DZ) or fraternal, twins in both cases. This clearly shows a genetic link for both unipolar and bipolar disorders (Frude, 1998, p. 124; Gershon, 1990, p. 377).

Additionally, there is evidence of a cross-link between bipolar and unipolar disorders, as of the 32 MZ twins who were positively concordant for an affective illness, 11 were unipolar, 14 were bipolar, and 7 had one twin unipolar and the other bipolar (Gershon, 1990, p. 377).

Unipolar depression also appears frequently among relatives of those with bipolar disorder, although bipolar disorder does not occur more frequently than normal among family members of those diagnosed with unipolar depression (Feldman, Meyer, & Quenzer, 1997, p. 821).

Gershon (1990, p. 378) further gives evidence against a purely "nurture" Hypothesis for affective disorders through a review of literature regarding adoptees. Of adoptees with affective disorders, their adoptive parents had an affective disorder only 12 percent of the time, while the biological parents manifested an affective disorder 29%.

General Biological Hypotheses of Affective Disorders

Dysregulation Model

The dysregulation model of depression, as proposed by Siever and Davis (1985), suggests that depression is due to inappropriate (i.e. less selective) environmental responsiveness, and defective habituation (i.e. a slower return to baseline functioning following a perturbation). They believe that this is due to a chronic abnormality with the pattern and degree of responsiveness of a neurotransmitter.

Learned Helplessness

Through learned helplessness, first suggested by Seligman in 1975, animals which are exposed to a major stressor (usually an electric shock, or being forced to swim to exhaustion) are subsequently unable to learn to escape that stressor (Willner, 1994, p. 297). This has correlation with the affective disorders, as it was shown that short term treatment (3-7 days) with anti-depressants would reverse the effects, and allow the animals to again be able to learn to "escape" the shock. It is hypothesized that either dopamine or norepinephrine functions are being altered in susceptible individuals. (Willner, 1994, p. 297-298).

Desynchronization of Circadian Rhythms

According to Feldman, Meyer, and Quenzer (1997, p. 823) and Janicak, Davis, Preskorn, and Ayd (1993, p.217), in their reviews of literature, there is sufficient evidence to support the possibility of a desynchronization of biological rhythms as a possible culprit in the affective disorders. This includes: decreased total sleep time, increase sleep onset latency, decreased sleep arousal threshold, increased wakefulness, more frequent changes between sleep stages, and terminal insomnia. Additionally, there is rapid eye movement (REM) sleep effects also associated with affective disorders, including: a decrease in REM onset latency, an increase in REM density, and a redistribution of REM sleep to earlier in the sleep cycle. The abnormalities in sleep patterns are similar to those of a person who has been required to alter their sleep pattern by 12 hours.

The effectiveness of phototherapy in seasonal affective depression (SAD) also is supportive of the theory of a desynchronization of circadian rhythms.

Behavioral Sensitization

When behavior become more severe and occurs more rapidly in response to the same dose of a given psychomotor stimulant, behavioral sensitization is said to have occurred. It is believed to involve dopamine at some point in the process, and can be modified by other neurochemicals such as sex hormones and vasopressin (Goodwin & Jamison, 1990, p.406)

Kindling

In kindling, as in behavioral sensitization, there is an increased response to the same level and duration of stimulation. This can be either a response to a previously unresponded to stimuli, or an increase in response to an already responded to stimuli. (Goodwin & Jamison, 1990, p. 406; Swann, 1993, p. 20).

Summary of Biological Hypotheses of Affective Disorders

While these last two theories do not explain affective disorders directly, they do show parallels with bipolar disorder, according to Goodwin and Jamison (1990, p. 406): that thresholds can be altered; early episodes require a higher level of a precipitant than do later episodes; and that the young are ore vulnerable to sensitization and kindling which is similar to the relatively early age onset of bipolar disorder.

With the theories sensitization and kindling, it is possible to see that those afflicted with bipolar disorder would succumb to spontaneous episodes with no precipitant stress, which is in fact what can occur. Thus, early and vigorous treatment of episodes is mandatory to prevent the changes associated with sensitization and kindling from occurring (Goodwin & Jamison, 1990, p. 407).

If this is true, each episode of an affective illness may leave behind a residue that has the potential to change the neurobiological functioning of the brain, and to potentially alter what medications may be effective.

The first three models examined, on the other hand show how biological changes can affect the mood, and thus either biologically cause the onset of an affective disorder, or exacerbate an already existing disorder.