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Lesson 2 | Teacher's Guide

The Scientific Understanding of Depression

"Teachers: Nikki neuron reminds you to check the standards tables in the front of the toolkit to see which ones apply for this lesson and your subject area."

The Scientific Study Of Human Behavior and Mental Illness1,2

Scientists in many disciplines, including psychology, psychiatry, neuroscience, biology, pharmacology, sociology, anthropology, and genetics, offer expertise that helps us piece together the puzzle of what accounts for human behavior and its aberrations. Investigators in each specialized field approach the study of mental illness with different research questions and scientific backgrounds. They also use very different kinds of tools and methods. A neuroscientist may use sophisticated, expensive technology such as magnetic resonance imaging (MRI) to produce scans of brain tissue. A social scientist interested in studying human behavior may conduct observations under carefully defined conditions, either in a natural setting or an experimental laboratory. Each discipline contributes uniquely to our understanding of the interplay of biology and environment that shapes human behavior.

The Experimental Method

Regardless of their specific tools and procedures, most scientists involved in research use basically the same approach, known as the experimental or scientific method. Experimental research begins with a hypothesis, a statement formulated from the question that the investigator wants his or her study to answer. An important part of designing a study is starting with a carefully stated hypothesis that can be tested in a way that is measurable. Most experiments involve some kind of comparison of effects between groups or situations. For instance, a psychiatrist interested in finding out about the effects of a new medication for depression might have this as a hypothesis: “This new drug will reduce the number or severity of depressive symptoms as much as, or more than a proven antidepressant.”

To test this hypothesis, the psychiatrist would first carefully define the elements under study, which are called variables. In this case, the variables would be the drugs, at specific dose levels, and the severity and number of depressive symptoms. One approach might be to take two groups of depressed patients and give one group, called the experimental or study group, the new medication, while the other group, called the control group, would be given a proven antidepressant, one that is known to reduce depressive symptoms. If the new medication is effective, the psychiatrist would expect the study group, on average, to show at least as much of a decrease in number or severity of depressive symptoms as the control group.

In a very different kind of research, but also based on the scientific method, a social scientist may conduct direct observations of behavior in varying situations. For instance, a sociologist might want to find out if certain behaviors were associated with gender, age or other variables. He or she might hypothesize that young men in the South behave differently in certain situations than their counterparts in Northern states. The researcher would carefully define the study variables and methods for observing and measuring the subjects’ behaviors. Then the researcher might go to shopping malls in different regions to make observations, perhaps of young men about to enter and exit an elevator to see whether they would go in first or wait to allow someone else to enter first. Data would be analyzed for patterns based on gender, age, or other characteristics.

Careful analysis is critical if we are to respond to mental illness with objectivity and compassion rather than superstition and stigma.

Still another approach is the testing of human subjects under controlled laboratory conditions. For example, a psychologist might hypothesize that depressed persons and non-depressed persons have different personality traits. To test that idea, the researcher might choose to administer a personality test to the two groups. Analysis of test scores might reveal significant ways in which depressed individuals respond differently on these tests, which might suggest that key personality differences are associated with depression.

Clearly, there are many approaches for studying human behavior. A psychopharmacologist may study the effects of medications and other substances on behavior, while a neuropsychologist may study differences in brain function between depressed and non-depressed persons. Suffice it to say, researchers from different disciplines study mental illness using a variety of approaches, but they all agree on one thing: The scientific method is the best way to carry out their work. It requires an ability to think logically and critically rather than simply taking something on faith. This approach requires that a study of any subject is conducted carefully, methodically, and in an unbiased manner, and that the investigator fully explain the methods and results of his/her experiment, so that other scientists and even the public can evaluate the findings. This makes it possible for other researchers to repeat the same experiment to verify the results or apply the findings to new research.

Given the complexity of mental illness and the many unknowns in this field of inquiry, careful analysis is critical if we are to respond to mental illness with objectivity and compassion rather than superstition and stigma. Researchers in all disciplines use some aspect of the scientific method to further scientific understanding about human behavior and mental illness.

Nature-Nurture Model

As we begin to study mental illness in general and depression in particular, we must consider the issue of causation. Over the centuries, there has been much debate about the causes of mental illness. Nature-nurture refers to a long-standing philosophical disagreement over whether a particular behavior or illness is primarily due to nature (biological factors, such as inherited tendencies, brain injury, or medical conditions) or to nurture (environmental factors, or learning that is acquired by a person’s experiences in his or her physical, social and cultural environments, as well as the exercise of the person’s free will).

Historically, scientific thought was strongly influenced by 17th century French philosopher René Descartes’ notion of the separation of mind and body; as a result, scientists tended to adopt one stance or the other nature or nurture. But for many years now, the dichotomous nature-nurture model has been considered out of date. Today, most behavioral scientists believe that almost always some combination of nature-nurture determines behavior and the presence or absence of mental illness.2,3 We will now look at the model upon which the nature-nurture model is based, as well as others that have been developed to explain human behavior and mental illness.

Cartesian Dualism Model4,5

René Descartes developed the notion of mind-body dualism to help resolve a dispute between scientists and church officials over scientific findings that seemed to conflict with some church teachings. Descartes, in an attempt to resolve the matter and allow both sides to proceed without getting in each other’s way, simply declared that in the universe, there are two types of elements: 1) physical matter, which belongs in the realm of science and can be measured by scientists, and 2) spiritual or mental matter, which has no physical properties and can not be measured by science, but is in the domain of religion and the church.

Descartes’ idea gained wide acceptance and came to be known as Cartesian dualism. Although the concept helped settle the dispute between religious leaders and scientists of the 1600s, its legacy was a somewhat artificial dichotomy that unfortunately, to this day, still influences the way many view mental illness. We now know that all events, whether physical or mental, can potentially be measured and studied scientifically. This does not necessarily conflict with religion as a separate way to approach knowledge of reality and the world.

Diathesis-Stress Model2,6

Most behaviors and illnesses, mental and physical, are the result of a combination of biological and environmental influences. One model often used to describe how illnesses develop is the diathesis-stress model. This model of illness simply says that illness generally arises from a combination of stress and an inherited (genetic) weakness or vulnerability to a particular type of disease (stress + genetic/biological vulnerability = illness). Almost never is a disease or behavior produced by only one or the other factor. Whether a virus causes you to get sick will depend not only on the biological characteristics of the virus itself and of the body that you inherited, but also your current health status, which is related to your behavior and history of choices, stress level, and cultural influences.

Stress can be defined as anything, physical or psychological, that requires an organism to expend extra energy in order to adapt to a stress-causing event. When enough or the right kind of stress occurs, a weak link in a person’s biological or psychological makeup may give way, causing disease. For instance, a person may inherit relatively weak bones in the feet. As long as no serious stress on the feet occurs, there may be no problem despite the inborn weakness. However, with a significant stress to the feet, such as a fall from a high place, the genetically weakened bones may fracture, whereas this same stress would not cause breaks in “healthier” feet.

In a similar way, genetic vulnerability can predispose an individual to a mental disorder. A person may inherit a tendency for major depression, but may never experience it, if he or she grows up in a stable home with many resources and few stressors. Yet, if several highly stressful things occur within a short period of time and the stress persists, the person may become depressed.

The more genetically vulnerable a person is, the less stress is required for an illness to manifest. Most any individual, even someone with no particular weakness, could become depressed if enough bad things (stressors) happen at the same time or in rapid succession. Clearly, genetics has a strong influence on the development of illness and many other aspects of human behavior. Nevertheless, the environment is also a powerful influence, as demonstrated by a study of identical twins that were reared apart by separate parents (same genes, different environments). Researchers found that twins born to parents with depression were more likely to become depressed even when raised apart, but not always, suggesting that even the most highly inherited behavioral tendencies are significantly influenced by environmental or learned factors.

A solid body of scientific evidence documents the interaction of genetic vulnerabilities and environmental stress that results in depression. Some of the most compelling research linking stress and depression investigated the action of a circuit of brain structures and organs called the Hypothalamic-Pituitary-Adrenal (HPA) axis. More on this topic will be covered in a later lesson, but it is important to know that mental health researchers have determined that chronic stress causes the HPA axis to work overtime and to stop functioning properly.8 This dysfunction of the HPA axis changes hormonal and chemical levels in a person’s body, which seems associated with the development of depression.

Integrative Models of Mental Illness

It is now clear that the either-or approach of Cartesian dualism to the study of human behavior is narrow and outdated. But even with widespread rejection of this model, debate is ongoing among scientists about the relative roles of biological and environmental factors. The emphasis in theory often shifts back and forth between two perspectives: that mental illness results from diseased brain processes (biological causation), and that mental illness results from traumatic experiences and unstable social relationships (environmental causation). However, many top researchers now believe that various factors influence each other, resulting in a behavior or illness.9

Like the diathesis-stress model, but more comprehensive in the factors considered, integrative models view illness as the product of complex interactions among a variety of influences. The biological or neurological processes underlying mental illness (such as genetic or inherited causes) are only part of the explanation for how an illness develops. A behavioral scientist using an integrated model to understand why a person has become mentally ill would also consider environmental factors, such as upbringing and education, as well as the impact of culture and interpersonal relationships. Each of these factors can influence the others in a complex process that ultimately determines the development of an illness. For example, even though we now have good evidence that the tendency to develop depression is at least sometimes genetically transmitted, we also have evidence of how culture can overcome this and other influences. The close-knit Kaluli tribe of New Guinea is strongly supportive of all members, especially in times of personal crisis. As a result, depression is virtually nonexistent. Even the death of a loved one is not the trauma for the Kaluli that it is for other social groups, in which bereaved individuals often become depressed.10

A key concept for integrative models is bidirectional causation,2 which holds that biological processes determine behavior, but that psychosocial and environmental processes can produce biological effects on the brain, the endocrine and immune systems, and the rest of the body. According to this dynamic model, either kind of process can cause changes in the other. Research findings support this idea. For example, in a study using brain imaging, people with obsessive-compulsive disorder who were treated with a psychological approach (behavior modification therapy) showed subsequent changes in their brain activity. Similar changes in brain activity also occurred after treatment with medication.11 Animal research has deepened our understanding of the environment’s effects on brain development and the bidirectional relationship between physiology and behavior. Numerous studies have demonstrated that rats raised in an “enriched” environment, in which they have access to lots of “rat toys,” grow more cortex tissue (a part of the brain that deals with higher types of learning and problem-solving) than rats which don’t have access to such toys.12 The differences in brain physiology between the two experimental groups of rats resulted in significant differences in their abilities. As the “enriched” rats grew, they mastered learning tasks more easily than rats that did not develop in an enriched environment.

Another experiment demonstrated the opposite effect. Cats that had one of their eyelids sewn shut at birth were never able to see out of that eye when it was later reopened, even though all the anatomical parts were intact. Researchers concluded that permanent damage had been caused by the extended deprivation of sensory input to areas of the brain that deal with vision during a critical stage of the kittens’ development, when the brain requires stimulation through experience in order to mature and function properly.13 These and similar studies demonstrate how environmental conditions can cause both positive and negative biological changes, even to the brain. Comprehending the interaction of myriad biological, psychological, and socialenvironmental factors is essential to behavioral science research, yielding invaluable insights that ultimately may lessen the economic, social and emotional burdens of mental illness.


1. Coon D. Introduction to Psychology: Gateways to Mind and Behavior. Belmont, Calif: Wadsworth; 2001.

2. Basic Behavioral Science Research as a Resource for Mental Health. National Institute of Mental Health. Available at: publicat/basintro.cfm. Accessed July 25, 2002.

3. Genetics and Mental Disorders: Report of the National Institute of Mental Health’s Genetics Workgroup. National Institute of Mental Health, National Institutes of Health. Available at http:
. Accessed July 25, 2002.

4. Pinel JP. Biopsychology. 3rd ed. Boston, Mass: Allyn and Bacon; 1997.

5. Damasio AR. Descartes’ Error: Emotion, Reason, and the Human Brain. New York, NY: Grosset/ Putnam; 1994.

6. Meehl P. Toward an integrated theory of schizotaxia, schizotypy, and schizophrenia. Journal of Personality Disorders. 1990;4:1-99.

7. Cadoret RJ, Stewart MA. An adoption study of attention defi cit/hyperactivity/aggression and their relationship to adult antisocial personality. Comprehensive Psychiatry. 1991;32(1):73-82.
8. Ritchie JC, Nemeroff CB. Stress, the hypothalamicpituitary-adrenal axis, and depression. In:
McCubbin JA, Kaufmann PG, eds. Stress, Neuropeptides, and Systemic Disease. San Diego, Calif: Academic Press Inc; 1991:181-197.

9. Barlow DH, David VM. Abnormal Psychology: An Integrative Approach. 2nd ed. Belmont, Calif:
Wadsworth/Thomson Learning; 2001.

10. Schieffelin E. The cultural analysis of depressive affect: an example from New Guinea. In Kleinman A, Good B, eds. Culture and Depression. Berkeley, Calif: University of California Press; 1985:101-133.

11. Baxter L. Positron emission tomography studies of cerebral glucose metabolism in obsessivecompulsive disorder. Journal of Clinical Psychiatry. 1994;55(10):54-59.

12. Rosenzweig MR, Bennett EL. Psychobiology of plasticity: effects of training and experience on brain and behavior. Behavioural Brain Research. 1996;78(1):57-65. 13. Sillito AM. Plasticity in the visual cortex. Nature. 1983;303:477-478.

Sponsored by the UAMS College of Medicine, Department of Psychiatry’s Partners in Behavioral Health Sciences program which is made possible by support from a Science Education Partnership Award (R25 RR15976) from the National Center for Research Resources at the National Institutes of Health.