Chapter 5: Genetics, Anatomy, and Biochemistry of Behavior



Like physical health, emotional health is a result of complex interactions among biological, social, and environmental influences. Disorders of health of either type result from aberrations or distortions in one or more of these influences at any time in a person’s life.

Theoretical difficulties exist when trying to separate biological from social and environmental factors in the etiology of psychiatric illness. Therefore, the term organic mental disorder, used in past years to describe behavioral symptoms with causes outside of the emotional range, now is rarely used. Furthermore, over the past few decades, the development of advanced techniques in neuroimaging and neurophysiology have shown that psychiatric function is influenced significantly by neuroanatomical and neurochemical factors. This chapter focuses on the contributions of these and other biological components to the expression of normal behavior and its disorders.

Genetics of Behavior

The role of genetic influences on the development of physical conditions such as heart disease, diabetes, and cancer is well documented. Genetic influences are also important in the display of behavior and its disorders. Because behavioral disorders are expressed in and thus are confounded by the social setting, it is more difficult in behavioral than in physical disorders to isolate genetic from social and environmental etiologies. Research tools that can help separate and identify these factors include family risk, twin, and adoption studies.

Research studies

Family risk studies are used to distinguish between genetic and other risk factors in the etiology of disorders. For a behavioral disorder or trait, the frequency of its occurrence in the relatives of an affected individual, or proband, is compared with its frequency in the general population. If a genetic component is involved in its etiology, a disorder would be expected to have a higher concordance rate (i.e., if concordant, the disorder occurs in both relatives) in close relatives of people with the disorder than in more distant relatives or in the general population.

Twin studies also are used to identify genetic factors in disorders. These studies work on the assumption that, because monozygotic twins have the same genetic makeup, the likelihood of both twins having a disorder will be higher than that of dizygotic twins, who are only as similar genetically as siblings. Furthermore, this assumption should hold true whether the twins are raised in the same home or in separate adoptive homes. For many psychiatric and behavioral traits and disorders, anecdotal and documented findings in twin studies strongly support this hypothesis.

Psychiatric disorders

Research studies provide evidence that genetic factors are involved in the etiology of major psychiatric disorders such as schizophrenia and bipolar disorder (see Chapters 12 and 13). Although each of these disorders occurs in about 1% of the general population, persons with a close genetic relationship to patients with schizophrenia or bipolar disorder are more likely than those with more distant relationships to develop these disorders (Table 5-1). Recent studies suggest also that the volume of brain areas known to be involved in the symptoms of schizophrenia (e.g., gray matter in frontal lobes and language areas) is more similar in monozygotic than in dizygotic twin pairs [Thompson et al., 2001].

Table 5.1 Risk of Developing Schizophrenia and Bipolar Disorder in Relatives of Patients

Relationship to Patient Approximate Risk for Schizophrenia (%) Approximate Risk for Bipolar Disorder (%)
No relationship (general population) 1 1
First-degree relative (sibling, dizygotic twin, child or parent) of a patient with the disorder 10 20
Child of two parents with the disorder 40 60
Monozygotic twin of a patient with the disorder 50 75

Although it has been difficult to link specific chromosomal markers with psychiatric illnesses, in some studies, schizophrenia has been associated with markers on chromosomes 1, 7, 8, and 22. Recently, markers for schizophrenia have also been identified on chromosome 6, a genetic variation in the dysbindin gene [Shi et al., 2009]; [Straub et al., 2002], chromosome 8, a genetic variant of the neureregulin 1 gene [Stefansson et al., 2002], as well as genes on chromosomes 13 and 21 which are associated with disturbed transmission of glutamate [Chumakov et al., 2002]. It is of interest that markers on the long arm of chromosome 22 are also seen in velocardiofacial syndrome, a disorder that has been associated with an increased risk for schizophrenia (Table 5-2). Also, recent evidence suggests that a locus for increased risk for both bipolar disorder and major depressive disorder is present on chromosome 3, particularly 3p21.1 [Bipolar Disorder Genome Study Consortium, 2010].

Table 5.2 Behavioral Manifestations of Chromosomal Neuropsychological Disorders

Chromosome Disorder Behavioral Manifestations
1 Alzheimer’s disease Depression, anxiety, early onset dementia (before age 60)
4 Huntington’s disease Erratic behavior, psychiatric symptoms (e.g., depression), dementia
5 Sotos syndrome Intellectual impairment, phobias, hyperphagia
7 Williams syndrome Hypersociality, intellectual disability, behavioral problems, hypotonia
8 Cohen syndrome Autistic behavior, intellectual disability
9 Dystonia musculorum deformans?/torsion dystonia (DYT1 gene) Major depressive disorder, learning problems
Tuberous sclerosis Seizures, cognitive impairment, autistic behavior
11 Acute intermittent porphyria Manic behavior, psychosis
12 Phenylketonuria Attention deficit/hyperactivity disorder
13 Wilson’s disease Depression, personality changes, thought disorders
14 Alzheimer’s disease Depression, anxiety, early onset dementia
15 Chromosome 15 inversion-duplication syndrome Seizures, autistic behavior, hypotonia
Prader-Willi/Angelman syndrome Intellectual disability, hypotonia, rage, stubborness, self-injury
16 Tuberous sclerosis Seizures, cognitive impairment, autistic behavior
17 Neurofibromatosis-1 Cognitive impairment, autistic behavior
Charcot-Marie–Tooth disease Peripheral neuropathy, neuropathic pain
Smith-Magenis syndrome Intellectual disability, impaired expressive language, stereotyped behavior, clinging and dependency, seizures
18 Tourette’s disorder Discontrol of language and movements May be mistaken for a behavior disorder
19 Alzheimer’s disease (site of the Apo E4 gene) Depression, anxiety, late onset dementia (over 60 years of age)
21 Progressive myoclonic epilepsy Alzheimer’s disease (associated with Down’s syndrome) Cognitive regression, aphasia, intellectual disability Early onset dementia
22 Metachromatic leukodystrophy Personality changes, psychosis, dementia
Neurofibromatosis-2 Hearing impairment
DiGeorge/velocardiofacial syndrome Schizophrenia, bipolar disorder, psychomotor retardation, language delay, ADHD, seizures
X Fragile X syndrome Autistic behavior
Kallman syndrome No sense of smell, lack of sex drive, depression, anxiety, fatigue, insomnia
Lesch-Nyhan syndrome Self-mutilation and other bizarre behavior, intellectual disability
Rett syndrome Autistic behavior, hand-wringing, breathing abnormalities

Genetic factors also play a role in the etiology of personality characteristics. For example, personality features such as responsiveness to stimulation, fearfulness, activity level, and distractibility have a higher concordance rate in monozygotic twins than in dizygotic twins. Such factors also play a role in the etiology of personality disorders, a diagnosis that is made when an individual has significant difficulties in social or occupational functioning because of his or her personality characteristics (see Chapter 24).

The personality disorders are organized in three groups or “clusters” by similarities in their presentations (see Table 24-4). When compared with the general population, relatives of patients in each of the clusters tend to have specific psychiatric problems. For example, patients with cluster A personality disorders (schizoid, schizotypal, and paranoid) are more likely to have relatives with psychotic disorders such as schizophrenia, whereas cluster B (histrionic, narcissistic, antisocial, and borderline) personality disorder patients are more likely to have relatives with major depressive and substance-abuse disorders. Cluster C (avoidant, obsessive-compulsive, and dependent) personality disorders have been associated with anxiety disorders in relatives [Bouchard, 2007].

Neuropsychiatric conditions

There is strong support for genetic factors in the etiology of a number of neuropsychiatric conditions. For example, family risk studies show that, although Alzheimer’s disease is present in only 10% of nonrelatives (see Chapter 18), 25% to 50% of close relatives of Alzheimer’s patients eventually develop the disease. There is also a higher concordance rate for Alzheimer’s in monozygotic than in dizygotic twins.

Several chromosomes have been linked to the development of Alzheimer’s disease. The most well-known association is that of Alzheimer’s disease with chromosome 21 (amyloid precursor protein gene) since individuals with Down’s syndrome (trisomy 21) who live beyond the age of 40 ultimately develop behavioral and neuroanatomical evidence of Alzheimer’s disease. Chromosomes 1 (presenilin 1 gene) and 14 (presenilin 2 gene) have also been linked to Alzheimer’s disease, particularly in the early onset type that is evident before the age of 60. Also, the presence on chromosome 19 of the apolipoprotein E2 (Apo E2?) allele appears to decrease while the presence of E4 allele (Apo E4?) appears to increase the likelihood of developing Alzheimer’s disease, particularly in women [Bartrés-Faz et al., 2002]. Specific chromosomal associations for other neuropsychiatric symptoms and disorders can be found in Table 5-2.

Case 5.1

The Patient

A physician confirms that a 26-year-old woman is in her first trimester of pregnancy. During the discussion after the examination, the woman tells the doctor that her identical twin sister recently entered a psychiatric hospital. The patient explains that over the past few months her sister reported hearing the voice of God telling her that she was chosen for a special “mission.” The patient does not know her sister’s diagnosis but expresses concern that her own unborn child will develop the same illness


Although more information must be gained to make a definitive diagnosis of the sister’s illness, the presence of auditory hallucinations (hearing voices) lasting over several months suggests schizophrenia (see Chapter 12). Alternatively, the patient’s sister may be showing the manic phase of bipolar disorder characterized by delusions of grandeur (being chosen for a special mission) (see Chapter 13). Although other factors are involved in their etiology, there is a significant genetic component to the development of both of these disorders. Because the patient has the same genetic makeup as her monozygotic twin sister, the risk to her own child is the same as it would be to her sister’s child or any first-degree relative


The patient should be advised that there are other nongenetic factors involved in the etiology of major psychiatric illness; however, if her sister has schizophrenia, her own child’s genetic risk for developing the illness is about 10%. Bipolar disorder has a higher concordance rate and her child’s genetic risk is about 20%. Counseling should be provided to help the patient understand the two disorders and their managements.

Other neuropsychiatric disorders with strong genetic components include Huntington’s disease and Tourette’s disorder (see Chapter 2). Offspring of one affected parent with Huntington’s disease, a fatal autosomal-dominant disorder associated with an abnormal gene on the short arm of chromosome 4, have a 50% chance of developing the disorder. Huntington’s disease (and Fragile X syndrome) also shows genetic anticipation, a phenomenon in which the disease has an earlier onset and more severe symptoms with each succeeding generation. A high percentage of patients with Tourette’s disorder have a family member who is also affected by the illness, and its concordance rate is higher in monozygotic than in dizygotic twins.

Substance-abuse disorders

Many people believe that substance-abuse disorders are caused by an individual’s weak self-control or poor choice of social peers. Although such social difficulties clearly exist among abusers, much recent evidence suggests that substance-abuse disorders such as alcoholism also have a genetic component. Evidence of genetic associations in alcoholism includes the following findings:

  • The concordance rate for alcoholism is about twice as high for monozygotic twins as it is for dizygotic twins.
  • Adopted children in adulthood tend to show the drinking patterns characteristic of their biological rather than their adoptive parents.
  • Alcoholism is about four times more prevalent in the biological children of alcoholics than of nonalcoholics.

Furthermore, the genetic component of alcoholism is related to both sex and age of onset; sons of alcoholics are at greater risk than their daughters, particularly if the sons begin to abuse alcohol before the age of 20.

Cocaine abuse is also associated with genetic factors. Early in this century, [McHugh et al., 2002], a polymorphism in the promoter region of the prodynorphin gene was shown to be associated with protection against cocaine abuse.