The road not taken: life experiences in monozygotic twin pairs discordant for major depression.

In an effort to understand how environmental experiences contribute to risk for major depression (MD), we conducted joint autobiographical interviews with 14 pairs of monozygotic twins (mean age 51.2) rigorously discordant for a lifetime history of MD. Twelve of the pairs could be sorted into four broad categories. In two pairs, discordance was associated with a single traumatic event occurring to the affected twin. In seven pairs, the well twin had one stable, long-term, successful romantic relationship, whereas the affected co-twin had romantic reversals one or more of which precipitated depressive episodes. These pairs varied in the degree to which the romantic problems seemed to arise from bad luck or poor choices. In one pair, occupational difficulties were strongly related to discordance in experiences with MD. In two pairs, several mechanisms seemed to be at work. Discordance in the quality of intimate love relationships was the most common etiological factor revealed by interview in these discordant pairs, with single dramatic events and occupational problems being considerably rarer. Even in this best of natural experiments, the causal interrelationship between personality, environment and depressive episodes was not always clear. Many pairs illustrated the protective effects of planfulness and the malignant effect of cumulative continuity where early difficulties in relationships shaped the subsequent life course. These results speak both to the importance of environmental influences on human well-being and psychopathology, and the complexity of the causal paths underlying their effects.

Do reasons for major depression act as causes?

We make sense of human behavior using reasons, which produce understanding via a subjective empathy-based first-person perspective and causes, which leads to explanations utilizing objective facts about the world assessed scientifically. We evaluate the common sense hypothesis that for episodes of major depression (MD), reasons act as causes. That is, individuals who have highly understandable depressive episodes will have, on average, fewer objective scientifically validated causes than those who have un-understandable episodes. The understandability of a MD as defined by the Diagnostic and Statistical Manual, 4th Edition (DSM IV) experienced in the past year in 630 personally interviewed twins from a population-based registry was rated, with high reliability, from rich contextual information. We predicted, from these understandability ratings, via linear and logistic regression, 12 validated risk factors for MD reflecting genetic and long-term environmental liability. No significant association was observed between 11 of these indices and the understandability of the depressive episode. The only significant finding-higher cotwin risk for MD associated with greater understandability-was opposite that predicted by the reasons-as-causes hypothesis. Our results do not support the hypothesis that reasons for MD act as causes. These findings, unlikely to result from low power, may be explicable from an empirical and/or philosophical perspective. Our results are, however, consistent with 'the trap of meaning' hypothesis, which suggests that understanding does not equal explanation and that while reasons may be critical to help us empathize with our patients, they are unreliable indices of objective risk factors for illness.

Should the diagnosis of major depression be made independent of or dependent upon the psychosocial context?

BACKGROUND: The diagnosis of certain psychiatric syndromes (e.g. panic attacks, post-traumatic stress disorder) is crucially dependent on the psychosocial context in which they arise. For other syndromes (e.g. schizophrenia), the context is generally irrelevant. Should the diagnosis of major depression (MD) be made dependent upon or independent of the psychosocial context in which it occurs? METHOD: Twins were selected from a population-based registry who, on personal interview, reported developing a full depressive syndrome either 'out of the blue' or in response to stressful life events (SLEs) rated objectively as having mild, low moderate, high moderate or severe long-term contextual threat (LTCT). RESULTS: In these depressed subjects, no relationship was found between the level of adversity associated with onset and most indices of liability to depression, including risk of MD in co-twin and parents, level of neuroticism, risk for future depressive episodes, co-morbidity with other internalizing disorders and history of sexual abuse. Compared to the remainder of this epidemiologic cohort, subjects developing depression in response to the severe threat events had substantially elevated levels of all the examined indices of liability to MD. CONCLUSIONS: Individuals who develop a full depressive syndrome in response to high-threat events do not have an appreciably lower liability to MD than those developing depression after exposure to low adversity and have much higher liability to depression than observed in their population cohort. These results support the hypothesis that, in general, MD can be diagnosed independently of the psychosocial context in which it arises.

The similiarity of facial expressions in response to emotion-inducing films in reared-apart twins.

BACKGROUND: While the role of genetic factors in self-report measures of emotion has been frequently studied, we know little about the degree to which genetic factors influence emotional facial expressions. METHOD: Twenty-eight pairs of monozygotic (MZ) and dizygotic (DZ) twins from the Minnesota Study of Twins Reared Apart were shown three emotion-inducing films and their facial responses recorded. These recordings were blindly scored by trained raters. Ranked correlations between twins were calculated controlling for age and sex. RESULTS: Twin pairs were significantly correlated for facial expressions of general positive emotions, happiness, surprise and anger, but not for general negative emotions, sadness, or disgust or average emotional intensity. MZ pairs (n=18) were more correlated than DZ pairs (n=10) for most but not all emotional expressions. CONCLUSIONS: Since these twin pairs had minimal contact with each other prior to testing, these results support significant genetic effects on the facial display of at least some human emotions in response to standardized stimuli. The small sample size resulted in estimated twin correlations with very wide confidence intervals.

Genomewide linkage study in the Irish affected sib pair study of alcohol dependence: evidence for a susceptibility region for symptoms of alcohol dependence on chromosome 4.

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 x 10(-6), 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.

Vulnerability to depressive mood reactions: toward a more powerful test of the diathesis-stress and causal mediation components of the reformulated theory of depression.

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.