Stress-Generative Effects of Posttraumatic Stress Disorder: Transactional Associations Between Posttraumatic Stress Disorder and Stressful Life Events in a Longitudinal Sample.

Longitudinal studies have demonstrated transactional associations between psychopathology and stressful life events (SLEs), such that psychopathology predicts the occurrence of new SLEs, and SLEs in turn predict increasing symptom severity. The association between posttraumatic stress disorder (PTSD), specifically, and stress generation remains unclear. This study used temporally sequenced data from 116 veterans (87.9% male) to examine whether PTSD symptoms predicted new onset SLEs, and if these SLEs were associated with subsequent PTSD severity. The SLEs were objectively rated, using a clinician-administered interview and consensus-rating approach, to assess the severity, frequency, and personal dependence (i.e., if the event was due to factors that were independent of or dependent on the individual) of new-onset SLEs. A series of mediation models were tested, and results provided evidence for moderated mediation whereby baseline PTSD severity robustly predicted personally dependent SLEs, B = 0.03, p = .006, and dependent SLEs predicted increases in follow-up PTSD symptom severity, B = -0.04, p = .003, among participants with relatively lower baseline PTSD severity. After we controlled for baseline PTSD severity, personality traits marked by low constraint (i.e., high impulsivity) were also associated with an increased number of dependent SLEs. Our results provide evidence for a stress-generative role of PTSD and highlight the importance of developing interventions aimed at reducing the occurrence of personally dependent stressors.

Negative cognitive styles, dysfunctional attitudes, and the remitted depression paradigm: a search for the elusive cognitive vulnerability to depression factor among remitted depressives.

Results from studies using a behavioral high-risk design and approximations to it generally have corroborated the cognitive vulnerability hypothesis of depression, whereas results from remitted depression studies typically have not. Suspecting that design features of previously conducted remitted designs likely precluded them from detecting maladaptive cognitive patterns, the authors conducted a study featuring the remitted design that has been successful in studies of a biological vulnerability for depression. Participants' current depressive symptoms, negative cognitive styles (hopelessness theory), dysfunctional attitudes (Beck's theory), and lifetime prevalence of clinically significant depression were assessed. Participants who had remitted from an episode of clinically significant depression had more negative cognitive styles, but not greater levels of dysfunctional attitudes, than did never depressed individuals.

Neuropsychological deficits in major depression reflect genetic/familial risk more than clinical history: a monozygotic discordant twin-pair study.

Neuropsychological deficits have been associated with major depression (MD) and persist in some individuals even after symptom remission. However, it is unclear if the deficits are a consequence of MD or are pre-existing and reflect MD vulnerability. We addressed this issue by studying 117 twins from monozygotic (MZ) pairs discordant for lifetime history of DSM-III-R defined MD and 41 twins from MZ pairs in which neither twin had experienced MD. Our assessment included a structured clinical interview and measures from the WMS-III and WAIS-III. The "unaffected" twins from discordant pairs showed the same pattern of performance as their affected cotwins on measures of attention, working memory, verbal memory, and visuo-spatial processing. Compared to twins from pairs with no MD history, twins in discordant pairs had lower performance in the domains of attention, memory, visuo-spatial processing, and general knowledge. However, after adjusting for sex and age, the groups differed only on attention and general knowledge. The similar performance of twins in pairs discordant for MD suggests that familial risk for MD has a greater influence on neuropsychological functioning than individual MD history. Findings of impairment in individuals euthymic for MD are more consistent with pre-existing deficits than scarring effects of MD.

Spit for Science: launching a longitudinal study of genetic and environmental influences on substance use and emotional health at a large US university.

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.

Blue again: perturbational effects of antidepressants suggest monoaminergic homeostasis in major depression.

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.

The Irish Affected Sib Pair Study of Alcohol Dependence: study methodology and validation of diagnosis by interview and family history.

BACKGROUND: This article is the first report of the Irish Affected Sib Pair Study of Alcohol Dependence, whose goal is to detect the genomic location of susceptibility loci for alcohol dependence (AD). This article describes phenotypic characteristics of the probands, siblings, and parents included in the sample and examines agreement among different sources of diagnostic information, including the validity of family history (FH) assessment. METHODS: Structured diagnostic interviews were conducted with 1414 individuals from 591 families ascertained in Ireland. AD was assessed among 1201 probands and affected siblings with use of the Semi-Structured Assessment for the Genetics of Alcoholism and among 213 parents with use of a modified version of the Structured Clinical Interview for DSM. Probands and siblings were also assessed for drinking history, comorbid disorders, and other clinical characteristics. FH reports based on FH-Research Diagnostic Criteria were obtained for 1113 of these individuals as well as for 3652 first-degree relatives who were not interviewed. RESULTS: Sample characteristics confirm the severity of AD among the affected individuals. Agreement between FH ratings and diagnoses based on direct interviews was high for both parent-offspring and sibling-sibling comparisons (e.g., positive and negative predictive values > 80% for a range of cutoffs). Agreement among individuals about their family members was also high for a single item (1 month or more of drinking problems, tetrachoric r = 0.86-0.98), the total number of DSM-IV AD symptoms (polychoric r = 0.86-0.96), and classifications based on a range of cutoffs (kappa = 0.75-0.80). Use of multiple informants improved classification accuracy only slightly (6-10%). CONCLUSIONS: The authors successfully collected data for a large sample of affected sibling pairs for molecular genetic analysis of AD. Individuals with AD were able to provide accurate evaluations of alcoholism symptoms in their parents and adult siblings. A single screening item performed nearly as well as the full scale. Collecting information from multiple informants may not be cost effective for the gain in predictive accuracy. FH information collected from affected informants can be a valuable source of diagnostic information for family studies of alcoholism.