Current Medical Diagnosis & Treatment in Psychiatry

Anxiety Disorders

Population Genetics

Family Studies
Family studies provide evidence that some anxiety disorders may be transmitted separately from one another. This is best established for panic disorder and least so for generalized anxiety disorder (GAD). Observations on the increased familial risk for anxiety disorders have been recorded in the literature for over 100 years. Family studies of panic disorder are often complicated by comorbidity with social phobia and GAD. One family study of pure panic disorder probands found a significantly higher risk for panic among first-degree relatives compared to relatives of controls. There was also a fivefold increase in risk for any anxiety disorder. Similarly, an increased risk for agoraphobia (11.6%) has been reported for the relatives of agoraphobic probands, compared to 1.9% for relatives of panic disorder probands and 1.5% for relatives of control probands. A study of simple phobia found an increased risk for simple phobia (31%) among relatives of probands with that diagnosis (but no other anxiety disorder) compared to relatives of control probands (11%). A family history study of social phobia demonstrated that relatives of phobic probands were at increased risk for this disorder (6.6%), compared to relatives of panic disorder probands (0.4%) or relatives of control probands (2.2%).

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Eating Disorders

Population Genetics

Family Studies
The risk of eating disorders in relatives of anorexic patients is higher than that found in control subjects (Table 6-6). Affective illness is also increased in relatives. Even if probands without a major affective illness are considered as a separate group, an excess of affective illness is observed in relatives compared to relatives of control subjects. In one study, 40 bulimic probands were compared to 24 control subjects. Relatives of bulimic probands had a 27.9% risk of major affective illness compared to 8.8% in relatives of control subjects. In comparison, the risk of major affective illness in relatives of bulimic probands without major affective illness was lower (19.1%), but this risk is still higher than for relatives of controls. The same study found that 11.8% of relatives of bulimic probands had an eating disorder, compared to 3.5% of relatives of controls. In the study of bulimia, relatives of probands also showed an excess of alcoholism and ASPD in comparison to relatives of controls.

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Autistic Disorder

Population Genetics

The pooled frequency of autistic disorder in siblings of autistic probands is about 3%, which is 50–100 times the frequency in the general population. A twin study reported an MZ concordance of 36% and a DZ concordance of 0%. When the phenotype was extended to include language and cognitive abnormalities, concordance rates rose to 82% and 10%. This sample of twins, though carefully selected, was small (N = 21), but the essential conclusions regarding heritability were borne out in later studies.

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Antisocial Personality Disorder

Population Genetics

Family Studies
According to one family study of 223 male criminals, 80% were found to have a diagnosis of antisocial personality disorder (ASPD). Of the first-degree male relatives who were interviewed, 16% also received this diagnosis, whereas only 2% of female relatives were so diagnosed. In comparison, 3% of male control subjects and 1% of female control subjects had ASPD. Increased rates of alcoholism and drug abuse were also found among the relatives in this study.

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Alcoholism

Population Genetics

Family Studies
A review of 39 studies on families of 6251 alcoholic subjects and 4083 nonalcoholic subjects reported a 27.0% prevalence of alcoholism in fathers of alcoholic subjects and a 4.9% prevalence in mothers; 30.8% of the alcoholic subjects had at least one alcoholic parent. The same preponderance of alcoholism was not seen in the parents of comparison groups of patients with other psychiatric disorders. The nonpsychiatric control subjects included in the same review showed a 5.2% prevalence of alcoholism in fathers and a 1.2% prevalence in mothers. A recent multicenter study confirmed familial aggregation of alcoholism, with more severe forms showing greater familiality.

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Genetic Counseling

Empirical data for genetic counseling are summarized in Table 6-10. Some illnesses have fairly narrow age-at-onset distributions in the general population. For example, first episodes of bipolar illness almost always occur before age 50. Fully 50% of bipolar individuals develop an initial episode (either depressive or manic) before age 25. Age at onset should be considered in a general way when assessing risk. For example, an unaffected 40-year-old son of a parent with bipolar disorder has already passed through most of the age at risk; thus his risk of developing bipolar disorder is substantially less than 9%. An estimate of approximately 2% would be more accurate in this case.

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Somatization Disorder

Population Genetics

Family Studies
A family history study evaluated first-degree relatives of 49 probands with degree relatives of probands with other somatoform disorders and affective disorder. The risk for a complicated medical history was 8.0% in the first-degree relatives of the somatization disorder probands, compared to 2.3% and 2.5% in the control groups (P < .01).

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Tourette's Syndrome

Population Genetics

Twin Studies
One study evaluated 43 pairs of same-sex twins, including 30 MZ pairs and 13 DZ pairs. MZ twin concordance was 77% for any tics, compared to 23% for DZ twins. For Tourette’s syndrome per se, the MZ twin concordance was 53%, compared to the DZ twin concordance of 8%. These differences are significant.

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Schizophrenia

Population Genetics

Family Studies
Pooled family study data from Europe show an age-corrected morbid risk for schizophrenia of 5.6% in parents, 10.1% in siblings, and 12.8% in children. It is thought that the lower rate in parents is related to a relative decrease in fertility among schizophrenic patients. Because general population figures for morbid risk for schizophrenia are around 1%, all classes of first-degree relatives have a clear increase in prevalence. The risk for offspring of two schizophrenic parents is difficult to estimate because of the small number of cases but probably runs between 35% and 45% (in the pooled data it is 46.3%). Among second-degree relatives (eg, uncles, aunts, nephews, nieces, grandchildren), half-siblings, and cousins, the risk ranges from 2% to 4%.

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Mental Retardation

Mental retardation is defined by subnormal scores on standardized testing. Intelligence quotient (IQ) cutoffs of 90, 70, and 50 are commonly considered to be the boundaries for mild, moderate, and severe mental retardation.

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Obsessive-Compulsive Disorder

Population Genetics

Family Studies
One study evaluated 145 first-degree relatives of 46 children with obsessive-compulsive disorder (OCD). The investigators found that of the 90 parents evaluated in person, 15 (17%) received a diagnosis of OCD, compared to 1.5% of the parents of 34 children with conduct disorder who served as a control group. This 17% rate is also significantly higher than the prevalence rate of 2% in the general population. Fathers were three times as likely as mothers to receive a diagnosis of OCD. Of the 56 siblings evaluated personally, three (5%) met criteria for OCD. When data were corrected for age, the morbid risk was 35% in siblings. This result should be viewed with caution because of the magnitude of the age correction for siblings. The probands all had severe childhood-onset OCD and were referred to the investigators for treatment protocols. It is possible that childhood-onset OCD represents a more severe form of the illness. Nevertheless, this carefully conducted family study reveals an increased risk for OCD among the first-degree relatives of OCD probands.

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Drug Abuse

Population Genetics

Family Studies
Considerable comorbidity has been reported for alcoholism and other Axis I disorders in individuals who abuse drugs, and a relationship has been found between the type of comorbid disorder (eg, alcoholism or affective disorder) in probands and the rate of that same disorder in relatives. Relatives of opiate-dependent probands are at significantly increased risk for substance abuse, alcoholism, antisocial personality disorder, and major depression, compared to control subjects.

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Attention-Deficit/Hyperactivity Disorder

Population Genetics

Early family studies of ADHD noted alcoholism and sociopathy in male relatives of children with ADHD and hysteria in female relatives. This same constellation was not manifest in the adoptive parents of adopted children with ADHD.

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Alzheimer's Disease

Population Genetics

Genetic etiologies for some forms of Alzheimer’s disease have been found, and specific genes that influence vulnerability have been identified (Table 6-5). A review of epidemiologic studies, however, is remarkable in that it does not show high heritability of the disorder. This observation is partly attributable to multiple environmental and genetic etiologic factors. It is also related to the variable age at onset for the condition. Early-onset causes are more likely to be heritable and may be determined by single genes. Late-onset cases are more likely to be multifactorial. Important genetic factors in late-onset cases may be obscured by the fact that mortality from other causes decreases familial aggregation.

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Affective Disorders

Population Genetics

Family Studies
Family studies of affective disorders have continually demonstrated aggregation of illness in relatives (Table 6-2). In a study at the National Institute of Mental Health, 25% of relatives of bipolar probands were found to have bipolar disorder or unipolar illness (depression) themselves, compared to 20% of relatives of unipolar probands and 7% of relatives of control subjects. In the same study, 40% of the relatives of schizoaffective probands demonstrated affective illness at some point in their lives. These data demonstrate increased risk in relatives of patients; they also show that the various forms of affective illness appear to be related in a hierarchical way. Relatives of schizoaffective probands may have schizoaffective illness themselves but are more likely to have bipolar or unipolar illness. Relatives of bipolar probands have either bipolar or (more likely) unipolar illness.

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