Genetic Contributions

The massive literature on the genetics of schizophrenia can be assimilated into a multifactorial polygenic model but cannot be made to fit a single-major-locus model with high penetrance (Faraone & Tsuang 1985; Gottesman, 1991; Moldin & Got-tesman, 1997; Risch, 1990). There is no clear evidence against a simple multifactorial polygenic model, but Gottesman (e.g., 1991) notes the possibility of a mixed model. This model includes a small number of mostly genetic cases (a few single rare genes with high penetrance), a small number of cases due primarily to environmental factors, and a large number of cases falling within one of two polygenic models (one simply polygenic, the other a specific major gene of small effect embedded in a polygenic etiology). Thus, the vast majority of cases involve a polygenic etiology.

Heterogeneity in schizophrenia in the form of a chronic versus an episodic course is, at least as a first approximation, easy to conceptualize in a polygenic model. In the polygenic model with a threshold at which total liability produces symptoms of schizophrenia, a chronic course will (on average) be associated with greater genetic liability because there is an inverse relationship between the amount of genetic liability and the amount of environmental liability needed to reach threshold (Gottesman & Shields, 1982, pp. 63-69, 220-221). At high genetic loading, most environments will bring total liability above the threshold, making a chronic course likely. As the genetic loading decreases and more stressful environments are required to reach the threshold for symptom onset, the probability of encountering such environments diminishes, and an episodic course is more likely.

The polygenic model articulated by Gottesman includes environmental influences in the multifac-torial etiology of schizophrenia (general environmental liability) and thus falls within the diathesis-stress model in which genetic vulnerability and environmental stress combine to produce an episode of schizophrenia. Additionally, the polygenic model includes both specific and general genetic liability. Specific genetic liability increases the risk of schizophrenia per se. The sources of general genetic liability have not been specified other than to indicate that they have nothing to do with schizophrenia per se. Presumably, they represent modifiers or potentiators of the specific liability— that is, they are nonspecific contributors to etiology. As such, they are not part of the schizophrenia spectrum and will segregate independently of schizophrenia in family studies.

Fowles (1992b) proposed that the general genetic liability includes factors relevant to the stress component in the diathesis-stress model. Two broad categories of such factors are obvious. First, some genetically influenced characteristics may increase stress indirectly by making the environment objectively more stressful. For example, low IQ contributes to educational and occupational disadvantages, and temperament factors may interfere with one's ability to reach an adequate social and occupational adjustment (e.g., such behavioral deficit traits as anhedonia, shyness, social withdrawal, etc.). Second, any factor that increases stress reactivity will directly increase sensitivity to stressful environments (see Gottesman & Moldin, 1998). This second group of influences is especially relevant to motivational theories.

Because the BIS is an anxiety system and it has been suggested that it contributes to GAD, a genetic contribution to the BIS is an obvious potential contributor to general genetic liability. The BAS, with its accompanying positive affect, is less obvious but nonetheless also relevant. First, as noted before, the BAS is involved in many aspects of actively coping with threats. Consequently, it is likely to be activated strongly in stressful situations. Additionally, the finding that dopaminergic activity is increased during stressful events (Brier, Wolkowitz, & Pickar, 1991; Gray, 1987, p. 337; Healey, 1989) implicates the bAs in stress responses. This train of thought suggests that there might be two dimensions of arousal associated with heterogeneity in schizophrenia: (1) BAS activation involving behavioral activation, dopamin-ergic activity, and (sometimes) positive affect; and (2) BIS activation involving behavioral inhibition and aversive arousal (anxiety).

Stress Management

Stress Management

Stressed and feel like pulling your hair out? Discover How To Remove The Shackles And Burdens From Your Life To Become Stress-Free! Do you feel tense and uptight most of the time? Is there a choke hold on your life? Are you more than ready to relive pressure and frustration from everyday problems? Well, look no further...

Get My Free Ebook

Post a comment