To provide a more powerful test of the diathesis-stress component of the reformulated theory of depression (Abramson, Seligman, & Teasdale, 1978), we extended and refined the Metalsky, Abramson, Seligman, Semmel, and Peterson (1982) study and examined whether the content of college students' attributional styles (hypothesized attributional diathesis) as measured at Time 1 interacted with the outcomes students received on a class midterm exam to predict their subsequent depressive mood responses. In addition, to test the mediation component of the theory, we examined whether the relation between the hypothesized attributional diathesis and failure students' subsequent depressive mood responses to their low midterm grades was mediated by the particular causal attributions these students made for their low grades. The results partially corroborated the current statement (Abramson, Alloy, & Metalsky, 1986; Abramson, Metalsky, & Alloy, 1986a, 1986b) of the diathesis-stress component of the theory. Whereas students' immediate depressive mood reactions were predicted solely by the outcomes they received on the class midterm exams, their enduring depressive mood reactions were predicted solely by the hypothesized Attributional Diathesis X Outcome on Midterm Exam interaction. The direction and form of the interaction were in line with prediction. The results fully corroborated predictions derived from the mediation component of the theory as they applied to students' enduring mood responses.

Finding genes involved in complex behavioral outcomes, and understanding the pathways by which they confer risk, is a challenging task, necessitating large samples that are phenotypically well characterized across time. We describe an effort to create a university-wide research project aimed at understanding how genes and environments impact alcohol use and related substance use and mental health outcomes across time in college students. Nearly 70% of the incoming freshman class (N = 2715) completed on-line surveys, with 80% of the students from the fall completing spring follow-ups. 98% of eligible participants also gave DNA. The participants closely approximated the university population in terms of gender and racial/ethnic composition. Here we provide initial results on alcohol use outcomes from the first wave of the sample, as well as associated predictor variables. We discuss the potential for this kind of research to advance our understanding of genetic and environment influences on substance use and mental health outcomes.

Alcoholism is a relatively common, chronic, disabling and often treatment-resistant disorder. Evidence from twin and adoption studies indicates a substantial genetic influence, with heritability estimates of 50-60%. We conducted a genome scan in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD). Most probands were ascertained through alcoholism treatment settings and were severely affected. Probands, affected siblings and parents were evaluated by structured interview. A 4 cM genome scan was conducted using 474 families of which most (96%) were comprised by affected sib pairs. Nonparametric and quantitative linkage analyses were conducted using DSM-IV alcohol dependence (AD) and number of DSM-IV AD symptoms (ADSX). Quantitative results indicate strong linkage for number of AD criteria to a broad region of chromosome 4, ranging from 4q22 to 4q32 (peak multipoint LOD = 4.59, P = 2.1 Â 10 À6, at D4S1611). Follow-up analyses suggest that the linkage may be due to variation in the symptoms of tolerance and out of control drinking. There was evidence of weak linkage (LODs of 1.0-2.0) to several other regions, including 1q44, 13q31, and 22q11 for AD along with 2q37, 9q21, 9q34 and 18p11 for ADSX. The location of the chromosome 4 peak is consistent with results from prior linkage studies and includes the alcohol dehydrogenase gene cluster. The results of this study suggest the importance of genetic variation in chromosome 4 in the etiology and severity of alcoholism in Caucasian populations.

Some evolutionary researchers have argued that current diagnostic criteria for major depressive disorder (MDD) may not accurately distinguish true instances of disorder from a normal, adaptive stress response. According to disorder advocates, neurochemicals like the monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) are dysregulated in major depression. Monoamines are normally under homeostatic control, so the monoamine disorder hypothesis implies a breakdown in homeostatic mechanisms. In contrast, adaptationist hypotheses propose that homeostatic mechanisms are properly functioning in most patients meeting current criteria for MDD. If the homeostatic mechanisms regulating monoamines are functioning properly in these patients, then oppositional tolerance should develop with prolonged antidepressant medication (ADM) therapy. Oppositional tolerance refers to the forces that develop when a homeostatic mechanism has been subject to prolonged pharmacological perturbation that attempt to bring the system back to equilibrium. When pharmacological intervention is discontinued, the oppositional forces cause monoamine levels to overshoot their equilibrium levels. Since depressive symptoms are under monoaminergic control, this overshoot should cause a resurgence of depressive symptoms that is proportional to the perturbational effect of the ADM. We test this prediction by conducting a meta-analysis of ADM discontinuation studies. We find that the risk of relapse after ADM discontinuation is positively associated with the degree to which ADMs enhance serotonin and norepinephrine in prefrontal cortex, after controlling for covariates. The results are consistent with oppositional tolerance, and provide no evidence of malfunction in the monoaminergic regulatory mechanisms in patients meeting current diagnostic criteria for MDD. We discuss the evolutionary and clinical implications of our findings.

An inference from the cognitive theories of depression is that only a subset of depressed individuals should exhibit distinctively negative cognitive styles. Although this inference has been supported by previous research, attempts to characterize these depressives have yielded few identifying variables. This study of psychiatric inpatients and normal control subjects identified several characteristics of depressives with very negative cognitive styles by (a) examining traditional depression subtypes, (b) grouping depressives on the basis of clinical observations, and (c) asking whether sex, developmental events, and history and severity of depression predict cognitive styles. We found that borderline personality disorder, negative family dynamics during childhood, a history of sexual abuse, and severity of depression predict cognitive styles. We speculate that aversive developmental events may contribute to cognitive vulnerability to depression.