1. BG Studies of Psychopathology One of the most actively researched areas in recent years It is estimated that 1/3 of the U.S. population suffers from some kind of mental disorder each year and that 50% will do so at some point in their lives Major types of psychopathology that have been studied include schizophrenia, mood disorders, anxiety disorders, autism, and ADHD

2. Schizophrenia Long-term mental disorder involving delusions, hallucinations, and disorganized speech Occurs in approximately 1% of the population (= more than 1,000,000 in the U.S.) Typically strikes in late adolescence or early adulthood Drug therapy can be successful and has reduced the number of schizophrenics who require institutional care

3. BG Studies of Schizophrenia Risk Estimates for Different Kinships Kinships Percent GENERAL POPULATION 1.0 FIRST-DEGREE RELATIVES 9.0 –PARENTS OF SCHIZOPHRENICS 6.0 –SIBS OF SCHIZOPHRENICS 9.0 –DZ TWINS 17.0 –MZ TWINS 48.0 –CHILDREN WITH ONE SCHIZOPHRENIC 12.8 PARENT –APOPTED CHILDREN WITH ONE SCHIZO- 11.0 PHRENIC BIOLOGICAL PARENT –CHILDREN WITH TWO SCHIZOPHRENIC 46.0 PARENTS SECOND-DEGREE RELATIVES (e.g. grandchildren) 4.0 THIRD-DEGREE RELATIVES (e.g. cousins) 2.4 ADOPTIVE RELATIVES OF SCHIZOPHRENICS 1.0

4. Conclusions from BG Studies of Schizophrenia Strong and consistent evidence for genetic influences 48% concordance rate among MZ twins means nongenetic factors are also very important When MZ’s discordant for schizophrenia have been studied, there is some evidence that the schizophrenic twin had birth complications Children of discordant MZ twins are equally likely to develop schizophrenia; among children of discordant DZ twins, those whose parent was schizophrenic are at much greater risk Considerable molecular genetic research has yielded few replicated results to-date: schizophrenia is likely due to multiple genes each of small effect

5. Mood Disorders Two major types: unipolar (depression) and bipolar (depression and mania) Major unipolar depression usually has a slow onset (over weeks or months); each episode may last several months Lifetime risk of unipolar depression approximately 17% in the U.S.; women are twice as much at risk as men after adolescence Bipolar disorder is much less common (approx. 1% of adults, and no difference between males and females)

6. BG Studies of Mood Disorders LESS SEVERE UNIPOLAR DEPRESSION: RISK DZ TWINS 42% MZ TWINS 49% SEVERE UNIPOLAR DEPRESSION: POPULATION 3% 1 ST DEGREE RELATIVES 9% DZ TWINS 11% MZ TWINS 40% RELATIVES OF BIPOLAR 11% DEPRESSIVES BIPOLAR DEPRESSION: POPULATION 1% 1 ST DEGREE RELATIVES 8% DZ TWINS 40% MZ TWINS 72% RELATIVES OF UNIPOLAR DEPRESSIVES 1%

7. Conclusions from BG Studies of Mood Disorders Results are less clear-cut than those for schizophrenia, perhaps because mood disorders are more difficult to diagnose There seems to be some genetic influence on more severe unipolar depression There is clear evidence of genetic influences on bipolar depression Some linkages and gene associations have been reported but require further replication

8. Anxiety Disorders The most common forms of mental illness: lifetime risk is approx. 3% Typically less severe than schizophrenia or major depression May involve short-term, unexpected panic attacks, or a more chronic state of generalized anxiety and uncontrollable worrying Other types include phobias (e.g. claustrophobia) and obsessive compulsive disorder (e.g. anxiety triggered by inability to perform some compulsive act)

9. BG Studies of Anxiety Disorders Less BG research exists here than on schizophrenia or depression Results are mixed: some twin studies suggest a genetic influence but others do not A recent meta-analysis (Hettema et al., 2001) reported that panic, generalized anxiety, phobias, and OCD are familial Recent multivariate BG studies have also reported a sizeable (.53) genetic correlation between different anxiety disorders Molecular genetic research is scarce and inconclusive

10. Childhood Mental Disorders Autism: –marked by abnormalities in social relationships, delayed language development, stereotyped/repetitive behaviors –relatively uncommon: occurs in about 3 to 6 individuals in 10, 000 (0r.03-.06% of the population) –much more common in boys than girls Attention-Deficit Hyperactivity Disorder: –marked by restlessness, poor attention span, impulsive actions –prevalence rate of approx. 4% of N. American school children –also much more common in boys than girls

11. BG Studies of Autism Risk to siblings of an autistic child are 3 to 6% (i.e. 100 times more than the population rate) Several twin studies suggest a genetic influence: Plomin estimates a MZ concordance rate of 60% (i.e. 1000 times the population rate), while DZ concordances are lower Initially, autism was thought to be environmentally determined (cold, rejecting parents) but is now considered one of the most heritable mental disorders Molecular genetic research has yielded some replicated results: loci on chromosomes 7 and 13 appear implicated

12. BG Studies of ADHD Twin studies have consistently shown strong genetic influences (h 2 =.70) Fewer adoption studies exist but also support a genetic influence Considerable molecular genetic research is underway: several replications showing a linkage between ADHD and a long-allele polymorphism in the dopamine D4 receptor gene

13. Multivariate BG Studies of Psychopathology Key Findings No common genetic basis to schizophrenia and bipolar disorder Some evidence that genes predisposing to major depression also contribute to generalized anxiety Other genes appear to co-contribute to phobia, panic disorder, and bulimia As more comorbidity and genetic overlap between disorders are identified, there are important implications for clinical diagnostic systems