CAUSES OF MENTAL ILLNESOVERVIEW OF ETIOLOGY:PANDAS

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Clinical Psychology (PSY401)

LESSON 13

CAUSES OF MENTAL ILLNESOVERVIEW OF ETIOLOGY

The precise causes (etiology) of most mental disorders are not known. But the key word in this

statement is precise. The precise causes of most mental disorders--or, indeed, of mental health--may

not be known, but the broad forces that shape them are known: these are biological, psychological, and

social/cultural factors. What is most important to go over is that the causes of health and disease are

generally viewed as a product of the interplay or interaction between biological, psychological, and

sociocultural factors. This is true for all health and illness, including mental health and mental illness.

For instance, diabetes and schizophrenia alike are viewed as the result of interactions between

biological, psychological, and sociocultural influences. With these disorders, a biological predisposition

is necessary but not sufficient to explain their occurrence (Barondes, 1993). For other disorders, a

psychological or sociocultural cause may be necessary, but again not sufficient.

The brain and behavior are inextricably linked by the plasticity of the nervous system. The brain is the

organ of mental function; psychological phenomena have their origin in that complex organ.

Psychological and sociocultural phenomena are represented in the brain through memories and learning,

which involve structural changes in the neurons and neuronal circuits. Yet neuroscience does not intend

to reduce all phenomena to neurotransmission or to reinterpret them in a new language of synapses,

receptors, and circuits. Psychological and sociocultural events and phenomena continue to have

meaning for mental health and mental illness. It is still meaningful to speak of the interaction of

biological and psychological and sociocultural factors in health and illness.

BIOPSYCHOSOCIAL MODEL OF DISEASE

The modern view that many factors interact to produce disease may be attributed to the seminal work of

George L. Engel, who in 1977 put forward the Biopsychosocial Model of Disease (Engel, 1977).

Engel's model is a framework, rather than a set of detailed hypotheses, for understanding health and

disease. To many scientists, the model lacks sufficient specificity to make predictions about the given

cause or causes of any one disorder. Scientists want to find out what is the specifically contribution of

different factors (e.g., genes, parenting, culture, stressful events) and how they operate. But the purpose

of the biopsychosocial model is to take a broad view, to assert that simply looking at biological factors

alone--which had been the prevailing view of disease at the time Engel was writing--is not sufficient to

explain health and illness.

According to Engel's model, biopsychosocial factors are involved in the causes, manifestation, course,

and outcome of health and disease, including mental disorders. The model certainly fits with common

experience. Few people with a condition such as heart disease or diabetes, for instance, would dispute

the role of stress in aggravating their condition. Research bears this out and reveals many other

relationships between stress and disease (Cohen & Herbert, 1996; Baum & Posluszny, 1999).

One single factor in isolation--biological, psychological, or social--may weigh heavily or hardly at all,

depending on the behavioral trait or mental disorder. That is, the relative importance or role of any one

factor in causation often varies. For example, a personality trait like extroversion is linked strongly to

genetic factors, according to identical twin studies (Plomin et al., 1994). Similarly, schizophrenia is

linked strongly to genetic factors, also according to twin studies.

But this does not mean that genetic factors completely preordain or fix the nature of the disorder and

that psychological and social factors are unimportant. These social factors modify expression and

outcome of disorders. Likewise, some mental disorders, such as post-traumatic stress disorder (PTSD),

Clinical Psychology (PSY401)

are clearly caused by exposure to an extremely stressful event, such as rape, combat, natural disaster etc.

Yet not everyone develops PTSD after such exposure. On average, about 9 percent do (Breslau et al.,

1998), but estimates are higher for particular types of trauma. For women who are victims of crime, one

study found the prevalence of PTSD in a representative sample of women to be 26 percent (Resnick et

al., 1993).

The likelihood of developing PTSD is related to pre-trauma vulnerability (in the form of genetic,

biological, and personality factors), magnitude of the stressful event, preparedness for the event, and the

quality of care after the event (Shalev, 1996). The relative roles of biological, psychological, or social

factors also may vary across individuals and across stages of the life span. In some people, for example,

depression arises primarily as a result of exposure to stressful life events, whereas in others the foremost

cause of depression is genetic predisposition.

UNDERSTANDING CORRELATION, CAUSATION, AND CONSEQUENCES

Any discussion of the etiology of mental health and mental illness needs to distinguish three key terms:

correlation, causation, and consequences. These terms are often confused. All too frequently a

biological change in the brain (a lesion) is purported to be the "cause" of a mental disorder, based on

finding an association between the lesion and a mental disorder. The fact is that any simple

association--or correlation--cannot and does not, by itself, mean causation. The lesion could be a

correlate, a cause of, or an effect of the mental disorder.

When researchers begin to tease apart etiology, they usually start by noticing correlations. A correlation

is an association or linkage of two (or more) events. A correlation simply means that the events are

linked in some way. Finding a correlation between stressful life events and depression would prompt

more research on causation. Does stress cause depression? Does depression cause stress? Or are they

both caused by an unidentified factor? These would be the questions guiding research. But, with co-

relational research, several steps are needed before causation can be established.

If a co-relational study shows that a stressful event is associated with an increased probability for

depression and that the stress usually precedes depression's onset, then stress is called a "risk factor"

for depression. Risk factors are biological, psychological, or sociocultural variables that increase the

probability for developing a disorder and antedate its onset. For each mental disorder, there are likely to

be multiple risk factors, which are woven together in a complex chain of causation. Some risk factors

may carry more weight than others, and the interaction of risk factors may be additive or synergistic.

Establishing causation of mental health and mental illness is extremely difficult. Studies in the form of

randomized, controlled experiments provide the strongest evidence of causation. The problem is that

experimental research in humans may be logistically, ethically, or financially impossible. Co-relational

research in humans has thus provided much of what is known about the etiology of mental disorders.

Yet co-relational research is not as strong as experimental research in permitting inferences about

causality. The establishment of a cause and effect relationship requires multiple studies and requires

judgment about the weight of all the evidence. Multiple co-relational studies can be used to support

causality, when, for example, evaluating the effectiveness of clinical treatments.

But, when studying etiology, co-relational studies are, if possible, best combined with evidence of

biological plausibility. This means that co-relational findings should fit with biological, chemical, and

physical findings about mechanisms of action relating to cause and effect. Biological plausibility is

often established in animal models of disease. That is why researchers seek animal models in which to

study causation. In mental health research, there are some animal models--such as for anxiety and

hyperactivity--but a major problem is the difficulty of finding animal models that simulate what is

often uniquely human functioning. The search for animal models, however, is very important.

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Consequences are defined as the later outcomes of a disorder. For example, the most serious

consequence of depression in older people is increased mortality from either suicide or medical illness.

The basis for this relationship is not fully known.

Putting this all together, the biopsychosocial model holds that biological, psychological, or social factors

may be causes, correlates, and/or consequences in relation to mental health and mental illness. A

stressful life event, such as receiving the news of a diagnosis of cancer, offers a graphic example of a

psychological event that causes immediate biological changes and later has psychological, biological,

and social consequences.

When a patient receives news of the cancer diagnosis, the brain's sensory cortex simultaneously

registers the information (a correlate) and sets in motion biological changes that cause the heart to

pound faster. The patient may experience an almost immediate fear of death that may later escalate to

anxiety or depression. This certainly has been established for breast cancer patients (Farragher, 1998).

Anxiety and depression are, in this case, consequences of the cancer diagnosis, although the exact

mechanisms are not understood. Being anxious or depressed may prompt further changes in behavior,

such as social withdrawal. So there may be social consequences to the diagnosis as well. This example

is designed to lay out some of the complexity of the biopsychosocial model applied to mental health and

mental illness.

BIOLOGICAL INFLUENCES ON MENTAL HEALTH AND MENTAL ILLNESS

There are far-reaching biological and physical influences on mental health and mental illness. The major

categories are genes, infections, physical trauma, nutrition, hormones, and toxins (e.g., lead). We will

focus on the first two categories--genes and infections--for these are among the most exciting and

intensive areas of research relating to biological influences on mental health and mental illness

THE GENETICS OF BEHAVIOR AND MENTAL ILLNESS

That genes influence behavior, normal and abnormal, has long been established. Genes influence

behavior across the animal spectrum, from the lowly fruit-fly all the way to humans. Sorting out which

genes are involved and determining how they influence behavior present the greatest challenge.

Research suggests that many mental disorders arise in part from defects not in single genes, but in

multiple genes. However, none of the genes has yet been pinpointed for common mental disorders

(National Institute of Mental Health [NIMH], 1998). The human genome contains approximately 80,000

genes that occupy approximately 5 percent of the DNA sequences of the human genome. The human

genome project have provided an initial rough draft version of the entire sequence of the human

genome, and in the ensuing years, gaps in the sequence will be closed, errors will be corrected, and the

precise boundaries of genes will be identified.

In parallel, clinical medicine is studying the aggregation of human disease in families. This effort

includes the study of mental illness, most notably schizophrenia, bipolar disorder (manic depressive

illness), early onset depression, autism, attention-deficit/hyperactivity disorder, anorexia nervosa, panic

disorder, and a number of other mental disorders. From studying how these disorders run in families,

and from initial molecular analyses of the genomes of these families, we have learned that heredity--

that is, genes--plays a role in the transmission of vulnerability of all the aforementioned disorders from

generation to generation.

But we have also learned that the transmission of risk is not simple. Certain human diseases such as

Huntington's disease and cystic fibrosis result from the transmission of a mutation--that is, a

deleteriously altered gene sequence--at one location in the human genome. In these diseases, a single

mutation has everything to say about whether one will get the illness. The transmission of a trait due to a

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single gene in the human genome is called Mendelian transmission, after the Austrian monk, Gregor

Mendel, who was the first to develop principles of modern genetics and who studied traits due to single

genes.

When a single gene determines the presence or absence of a disease or other trait, genes are rather easy

to discover on the basis of modern methods. Indeed, for almost all Mendelian disorders across medicine

that affect more than a few people, the genes already have been identified. In contrast to Mendelian

disorders, to our knowledge, all mental illnesses and all normal variants of behavior are genetically

complex. What this means is that no single gene or even a combination of genes dictates whether

someone will have an illness or a particular behavioral trait.

Rather, mental illness appears to result from the interaction of multiple genes that confer risk, and this

risk is converted into illness by the interaction of genes with environmental factors. The implications for

science are, first, that no gene is equivalent to fate for mental illness. This gives us hope that modifiable

environmental risk factors can eventually be identified and become targets for prevention efforts.

In addition, we recognize that genes, while significant in their aggregate contribution to risk, may each

contribute only a small increment, and, therefore, will be difficult to discover. However, using new

technologies rising from the Human Genome Project, we will know the sequence of each human gene

and the common variants for each gene throughout the human race. With this information, combined

with modern technologies, we will in the coming years identify genes that confer risk of specific mental

illnesses.

This information will be of the highest importance for several reasons. First, genes are the blueprints of

cells. The products of genes, proteins, work together in pathways or in building cellular structures, so

that finding variants within genes will suggest pathways that can be targets of opportunity for the

development of new therapeutic interventions. Genes will also be important clues to what goes wrong in

the brain when a disease occurs. For example, once we know that a certain gene is involved in risk of a

particular mental illness such as schizophrenia or autism, we can ask at what time during the

development of the brain that particular gene is active and in which cells and circuits the gene is

expressed. This will give us clues to critical times for intervention in a disease process and information

about what it is that goes wrong.

Finally, genes will provide tools for those scientists who are searching for environmental risk factors.

Information from genetics will tell us at what age environmental cofactors in risk must be active, and

genes will help us identify homogeneous populations for studies of treatment and of prevention.

Heritability refers to how much genetics contributes to the variation of a disease or trait in a population

at a given point in time (Plomin et al., 1997). Once a disorder is established as running in families, the

next step is to determine its heritability, then its mode of transmission, and, lastly, its location through

genetic

mapping.

One powerful method for estimating heritability is through twin studies. Twin studies often compare the

frequency with which identical versus fraternal twins display a disorder. Since identical twins are from

the same fertilized egg, they share the exact genetic inheritance. Fraternal twins are from separate eggs

and thereby share only 50 percent of their genetic inheritance. If a disorder is heritable, identical twins

should have a higher rate of concordance--the expression of the trait by both members of a twin pair--

than fraternal twins.

Such studies, however, do not furnish information about which or how many genes are involved. They

just can be used to estimate heritability. For example, the heritability of bipolar disorder, according to

the most rigorous twin study, is about 59 percent, although other estimates vary (NIMH, 1998). The

heritability of schizophrenia is estimated, on the basis of twin studies, at a somewhat higher level

(NIMH, 1998). Even with a high level of heritability, however, it is essential to point out that

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environmental factors (e.g., psychosocial environment, nutrition, health care access) can play a

significant role in the severity and course of a disorder.

Another point is that environmental factors may even protect against the disorder developing in the first

place. Even with the relatively high heritability of schizophrenia, the median concordance rate among

identical twins is 46 percent (NIMH, 1998), meaning that in over half of the cases, the second twin does

not manifest schizophrenia even though he or she has the same genes as the affected twin. This implies

that environmental factors exert a significant role in the onset of schizophrenia.

INFECTIOUS INFLUENCES

It has been known since the early part of the 20th century that infectious agents can penetrate into the

brain where they can cause mental disorders. A highly common mental disorder of unknown etiology at

the turn of the century, termed "general paresis," turned out to be a late manifestation of syphilis.

The sexually transmitted infectious agent--Treponema pallidum--first caused symptoms in

reproductive organs and then, sometimes years later, migrated to the brain where it led to neurosyphilis.

Neurosyphilis was manifest by neurological deterioration (including psychosis), paralysis, and later

death. With the wide availability of penicillin after World War II, neurosyphilis was virtually eliminated

(Barondes, 1993).

Neurosyphilis may be thought of as a disease of the past (at least in the developed world), but dementia

associated with infection by the human immunodeficiency virus (HIV) is certainly not. HIV-associated

dementia continues to encumber HIV-infected individuals worldwide. HIV infection penetrates into the

brain, producing a range of progressive cognitive and behavioral impairments.

Early symptoms include impaired memory and concentration, psychomotor slowing, and apathy. Later

symptoms, usually appearing years after infection, include global impairments marked by mutism,

incontinence, and paraplegia (Navia et al., 1986).

The prevalence of HIV-associated dementia varies, with estimates ranging from 15 percent to 44

percent of patients with HIV infection (Grant et al., 1987; McArthur et al., 1993). The high end of this

estimate includes patients with subtle neuropsychological abnormalities. What is remarkable about HIV-

associated dementia is that it appears to be caused not by direct infection of neurons, but by infection of

immune cells known as macrophages that enter the brain from the blood. The macrophages indirectly

cause dysfunction and death in nearby neurons by releasing soluble toxins (Epstein & Gendelman,

1993).

Besides HIV-associated dementia and neurosyphilis, other mental disorders are caused by infectious

agents. They include herpes simplex encephalitis, measles encephalomyelitis, rabies encephalitis, and

chronic meningitis(Kaplan & Sadock, 1998). More recently, research has uncovered an infectious

etiology to one form of obsessive-compulsive disorder, as explained below.

PANDAS

In the late 1980s, it was discovered that some children with obsessive-compulsive disorder (OCD)

experienced a sudden onset of symptoms soon after a streptococcal pharyngitis (Garvey et al., 1998).

The symptoms were classic for OCD--concerns about contamination, spitting compulsions, and

extremely excessive hoarding--but the abrupt onset was unusual. Further study of these children led to

the identification of a new classification of OCD called PANDAS. This acronym stands for pediatric

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autoimmune neuropsychiatric disorders associated with streptococcal infection. PANDAS are

distinct from classic cases of OCD because of their episodic clinical course marked by sudden symptom

exacerbation linked to streptococcal infection, among other unique features.

The exacerbation of symptoms is correlated with a rise in levels of antibodies that the child produces to

fight the strep infection. Consequently, researchers proposed that PANDAS are caused by antibodies

against the strep infection that also manage to attack the basal ganglia region of the child's brain

(Garvey et al., 1998). In other words, the strep infection triggers the child's immune system to develop

antibodies, which, in turn, may attack the child's brain, leading to obsessive and compulsive behaviors.

Under this proposal, the strep infection does not directly induce the condition; rather, it may do so

indirectly by triggering antibody formation. How the antibodies are so damaging to a discrete region of

the child's brain and how this attack ignites OCD-like symptoms are two of the fundamental questions

guiding research.

PSYCHOSOCIAL INFLUENCES ON MENTAL HEALTH AND MENTAL ILLNESS

Stressful life events, affect (mood and level of arousal), personality, and gender are prominent

psychological influences. Social influences include parents, socioeconomic status, racial, cultural, and

religious background, and interpersonal relationships.

Since these psychosocial influences are familiar to the general reader, detailed description of each is

beyond the scope of our study here. Instead, we will summarize the sweeping theories of individual

behavior and personality that inspired a vast body of psychosocial research: psychodynamic theories,

behaviorism, and social learning theories.

PSYCHODYNAMIC THEORIES

Psychodynamic theories of personality assert that behavior is the product of underlying conflicts over

which people often have scant awareness. Sigmund Freud (18561939) was the towering proponent of

psychoanalytic theory, the first of the 20th-century psychodynamic theories.

Many of Freud's followers pioneered their own psychodynamic theories, but we will cover only

psychoanalytic theory. A brief discussion of Freud's work contributes to a historical perspective of

mental health theory and treatment approaches.

Freud's theory of psychoanalysis holds two major assumptions: (1) that much of mental life is

unconscious (i.e., outside awareness), and (2) that past experiences, especially in early childhood, shape

how a person feels and behaves throughout life (Brenner, 1978).

Freud's structural model of personality divides the personality into three parts--the id, the ego, and the

superego. The id is the unconscious part that is the cauldron of raw drives, such as for sex or aggression.

The ego, which has conscious and unconscious elements, is the rational and reasonable part of

personality. Its role is to maintain contact with the outside world in order to help keep the individual in

touch with society. As such, the ego mediates between the conflicting tendencies of the id and the

superego.

The superego is a person's conscience that develops early in life and is learned from parents, teachers,

and others. Like the ego, the superego has conscious and unconscious elements (Brenner, 1978).

When all three parts of the personality are in dynamic equilibrium, the individual is thought to be

mentally healthy. However, according to psychoanalytic theory, if the ego is unable to mediate between

the id and the superego, an imbalance would occur in the form of psychological distress and symptoms

of mental disorders.

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Psychoanalytic theory views symptoms as important only in terms of expression of underlying conflicts

between the parts of personality. The theory holds that the conflicts must be understood by the

individual with the aid of the psychoanalyst who would help the person unearth the secrets of the

unconscious. This was the basis for psychoanalysis as a form of treatment.

BEHAVIORISM AND SOCIAL LEARNING THEORY

Behaviorism (also called learning theory) posits that personality is the sum of an individual's observable

responses to the outside world (Feldman, 1997). As charted by J. B. Watson and B. F. Skinner in the

early part of the 20th century, behaviorism stands in opposition with psychodynamic theories, which

strive to understand underlying conflicts.

Behaviorism rejects the existence of underlying conflicts and an unconscious. Rather, it focuses on

observable, overt behaviors that are learned from the environment (Kazdin, 1996, 1997). Its application

to treatment of mental problems is known as behavior modification. Learning is seen as behavior change

molded by experience. Learning is accomplished largely through either classical or operant

conditioning.

Classical conditioning is grounded in the research of Ivan Pavlov, a Russian physiologist. It explains

why some people react to formerly neutral stimuli in their environment, stimuli that previously would

not have elicited a reaction. Pavlov's dogs, for example, learned to salivate merely at the sound of the

bell, without any food in sight. Originally, the sound of the bell would not have elicited salvation. But

by repeatedly pairing the sight of the food (which elicits salvation on its own) with the sound of the bell,

Pavlov taught the dogs to salivate just to the sound of the bell by itself.

Operant conditioning, a process described and coined by B. F. Skinner, is a form of learning in which a

voluntary response is strengthened or attenuated, depending on its association with positive or negative

consequences (Feldman, 1997). The strengthening of responses occurs by positive reinforcement, such

as food, pleasurable activities, and attention from others. The attenuation or discontinuation of responses

occurs by negative reinforcement in the form of removal of a pleasurable stimulus. Thus, human

behavior is shaped in a trial and error way through positive and negative reinforcement, without any

reference to inner conflicts or perceptions. What goes on inside the individual is irrelevant, for humans

are equated with "black boxes."

Mental disorders represented maladaptive behaviors that were learned. They could be unlearned through

behavior modification (behavior therapy) (Kazdin, 1996, 1997).

SOCIAL LEARNING THEORY

The movement beyond behaviorism was spearheaded by Albert Bandura (1969, 1977), the originator of

social learning theory (also known as social cognitive theory). Social learning theory has its roots in

behaviorism, but it departs in a significant way. While acknowledging classical and operant

conditioning, social learning theory places far greater emphasis on a different type of learning,

particularly observational learning. Observational learning occurs through selectively observing the

behavior of another person, a model. When the behavior of the model is rewarded, children are more

likely to imitate the behavior. For example, a child who observes another child receiving candy for a

particular behavior is more likely to carry out similar behaviors.

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Social learning theory asserts that people's cognitions--their views, perceptions, and expectations

toward their environment--affect what they learn. Rather than being passively conditioned by the

environment, as behaviorism proposed, humans take a more active role in deciding what to learn as a

result of cognitive processing. Social learning theory gave rise to cognitive-behavioral therapy.

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