Stewart A. Shankman

Subthreshold conditions as precursors for full syndrome disorders: a 15-year longitudinal study of multiple diagnostic classes.

BACKGROUND There has been increasing interest in the distinction between subthreshold and full syndrome disorders and specifically whether subthreshold conditions escalate or predict the onset of full syndrome disorders over time. Most of these studies, however, examined whether a single subthreshold condition escalates into the full syndrome form of that disorder. Equally important, though, is whether subthreshold conditions are likely to develop other full syndrome disorders and whether these associations are maintained after adjusting for comorbidity. METHODS A 15-year longitudinal study of subthreshold psychiatric conditions was conducted with 1,505 community-drawn young adults. We examined whether 1) subthreshold major depression, bipolar, anxiety disorders, alcohol use, substance use, conduct disorder and/or ADHD were precursors for the corresponding (homotypic) full syndrome disorder; 2) subthreshold conditions were precursors for other (heterotypic) full syndrome disorders; and 3) these homotypic and heterotypic precursors persisted after adjusting for comorbidity. RESULTS Subthreshold major depression, anxiety, alcohol use, substance use, and conduct all escalated into their corresponding full syndrome and nearly all homotypic developments were maintained after adjusting for comorbid subthreshold and full syndrome conditions. Many heterotypic associations were also observed and most remained after controlling for comorbidity, particularly among externalizing disorders (e.g., alcohol, substance, conduct/antisocial personality disorder). CONCLUSIONS Many subthreshold conditions have predictive validity as they may represent precursors for full syndrome disorders. Alternatively, dimensional conceptualizations of psychopathology which include these more minor conditions may yield greater validity. Subthreshold conditions may represent good targets for preventive interventions.

The relation between depression and anxiety: an evaluation of the tripartite, approach-withdrawal and valence-arousal models.

Epidemiological studies have consistently reported that depressive and anxiety disorders co-occur frequently. This paper reviews the evidence for three models that have been proposed to explain the relation between these two conditions-the tripartite, the approach-withdrawal, and valence-arousal models. Specifically, we focus on predictions that the three models generate for cross-sectional studies, prospective and family/twin studies of personality, and EEG studies. In sum, no model was strongly supported across all types of studies, though specific aspects of each model were. Because of the heterogeneity of depression and anxiety disorders, a model with 2-4 factors or dimensions may not be sufficient to explain the relation between the two conditions.

Reward sensitivity in depression: A biobehavioral study.

The approach-withdrawal model posits 2 neural systems of motivation and emotion and hypothesizes that these systems are responsible for individual differences in emotional reactivity, or affective styles. The model also proposes that depression is characterized by a deficit in reward-seeking behavior (i.e., approach motivation) and is associated with a relative decrease in left frontal brain activity. The authors tested aspects of this model by comparing the electroencephalogram alpha power of depressed and nondepressed individuals during a task that manipulated approach motivation. The study found that control participants and individuals with late-onset depression exhibited the hypothesized increase in left frontal activity during the approach task but individuals with early-onset depression did not. This suggests that early-onset depression may be associated with a deficit in the hypothesized approach motivation system.

Subthreshold Depressive Disorder in Adolescents: Predictors of Escalation to Full-Syndrome Depressive Disorders

OBJECTIVES Subthreshold depressive disorder is one of the best established risk factors for the onset of full-syndrome depressive disorders. However, many youths with subthreshold depressive disorder do not develop full-syndrome depression. We examined predictors of escalation to full-syndrome depressive disorders in a community sample of 225 adolescents with subthreshold depressive disorder. METHOD Criteria for subthreshold depressive disorder were an episode of depressed mood or loss of interest or pleasure lasting at least 1 week and at least two of the seven other DSM-IV-associated symptoms for major depression. Participants were assessed four times from mid-adolescence to age 30 years using semistructured diagnostic interviews. RESULTS The estimated risk for escalation to full-syndrome depressive disorders was 67%. Five variables accounted for unique variance in predicting escalation: severity of depressive symptoms, medical conditions/symptoms, history of suicidal ideation, history of anxiety disorder, and familial loading for depression. Adolescents with three or more risk factors had an estimated 90% chance of escalating to full-syndrome depressive disorder, compared with 47% of adolescents with fewer than three risk factors. CONCLUSIONS These data may be useful in identifying a subgroup of youths with subthreshold depressive disorder who are at especially high risk for escalating to full-syndrome depressive disorders.

What is the association between obsessive-compulsive disorder and eating disorders?

Because eating disorders (EDs) and obsessive compulsive disorder (OCD) co-occur at high rates and can have functionally similar clinical presentations, it has been suggested that both constructs might be part of a common spectrum of disorders. Identifying the relationship between EDs and OCD may lead to the discovery of important shared core disease processes and/or mechanisms for maintenance. The objective of this paper is to understand the relationship between EDs and OCD by systematically reviewing epidemiological, longitudinal and family studies guided by five models of comorbidity posited by Klein and Riso (1993) and others. Though this literature is relatively small, the preponderance of evidence from these studies largely suggests that OCD/ED co-occur because of a shared etiological relationship. Limitations to extant literature, and suggestions for future research are discussed.

Disorder specificity despite comorbidity: Resting EEG alpha asymmetry in major depressive disorder and post-traumatic stress disorder

The approach-withdrawal and valence-arousal models highlight that specific brain laterality profiles may distinguish depression and anxiety. However, studies remain to be conducted in multiple clinical populations that directly test the diagnostic specificity of these hypotheses. The current study compared electroencephalographic data under resting state, eyes closed conditions in patients with major depressive disorder (MDD) (N=15) and post-traumatic stress disorder (PTSD) (N=14) relative to healthy controls (N=15) to examine the specificity of brain laterality in these disorders. Key findings included (1) reduced left-frontal activity in MDD, (2) a positive correlation between PTSD severity and right-frontal lateralisation, (3) greater activity in PTSD patients relative to MDD within the right-parietotemporal region, and (4) globally increased alpha power in MDD. Findings partially support the diagnostic applicability of the theoretical frameworks. Future studies may benefit from examining task-driven differences between groups.

Does intolerance of uncertainty predict anticipatory startle responses to uncertain threat

Intolerance of uncertainty (IU) has been proposed to be an important maintaining factor in several anxiety disorders, including generalized anxiety disorder, obsessive-compulsive disorder, and social phobia. While IU has been shown to predict subjective ratings and decision-making during uncertain/ambiguous situations, few studies have examined whether IU also predicts emotional responding to uncertain threat. The present study examined whether IU predicted aversive responding (startle and subjective ratings) during the anticipation of temporally uncertain shocks. Sixty-nine participants completed three experimental conditions during which they received: no shocks, temporally certain/predictable shocks, and temporally uncertain shocks. Results indicated that IU was negatively associated with startle during the uncertain threat condition in that those with higher IU had a smaller startle response. IU was also only related to startle during the uncertain (and not the certain/predictable) threat condition, suggesting that it was not predictive of general aversive responding, but specific to responses to uncertain aversiveness. Perceived control over anxiety-related events mediated the relation between IU and startle to uncertain threat, such that high IU led to lowered perceived control, which in turn led to a smaller startle response. We discuss several potential explanations for these findings, including the inhibitory qualities of IU. Overall, our results suggest that IU is associated with attenuated aversive responding to uncertain threat.

Low positive emotionality in young children: Association with EEG asymmetry

Low positive emotionality (PE; e.g., listlessness, anhedonia, and lack of enthusiasm) has been hypothesized to be a temperamental precursor or risk factor for depression. The present study sought to evaluate the validity of this hypothesis by testing whether low PE children have similar external correlates as individuals with depression. This paper focused on the external correlate of EEG asymmetry. Previous studies have reported that individuals at risk for depression exhibited a frontal EEG asymmetry (greater right than left activity). Others have reported an association with posterior asymmetries (greater left than right activity). In the present study, children classified as having low PE at age 3 exhibited an overall asymmetry at age 5-6 with less relative activity in the right hemisphere. This asymmetry appeared to be largely due to a difference in the posterior region because children with low PE exhibited decreased right posterior activity whereas high PE children exhibited no posterior asymmetry. These findings support the construct validity of the hypothesis that low PE may be a temperamental precursor or risk factor for depression.

Biomarkers of Threat and Reward Sensitivity Demonstrate Unique Associations With Risk for Psychopathology

Two emotional/motivational constructs that have been posited to underlie anxiety and depressive disorders are heightened sensitivity to threat and reduced sensitivity to reward, respectively. It is unclear, though, whether these constructs are only epiphenomena or also connote risk for these disorders (and relatedly, whether they connote risk for separate disorders). Using family history of psychopathology as an indicator of risk, the present study examined whether biomarkers of sensitivity to threat (startle potentiation) and reward (frontal EEG asymmetry) were associated with similar or different familial liabilities. In addition, the present study examined whether these biomarkers were associated with risk independent of proband DSM-IV diagnosis. One-hundred and seventy-three individuals diagnosed with panic disorder (PD), early onset major depressive disorder (MDD), both (comorbids), or controls completed two laboratory paradigms assessing sensitivity to predictable/unpredictable threat (measured via startle response) and reward (measured via frontal EEG asymmetry during a gambling task). Results indicated that across all participants: (a) startle potentiation to unpredictable threat was associated with family history of PD (but not MDD); and (b) frontal EEG asymmetry while anticipating reward was associated with family history of MDD (but not PD). Additionally, both measures continued to be associated with family history of psychopathology after controlling for proband DSM-IV diagnosis. Results suggest that the proposed biomarkers of sensitivity to unpredictable threat and reward exhibit discriminant validity and may add to the predictive validity of the DSM-IV defined constructs of PD and MDD, respectively.

Does physical anhedonia play a role in depression? A 20-year longitudinal study

BACKGROUND Anhedonia towards physical or sensory experiences (i.e., physical anhedonia) has most often been examined as a differentia of schizophrenia and not depression, despite the fact that general anhedonia is a core feature of many models of Major Depressive Disorder (MDD). METHODS Forty-nine participants with non-psychotic MDD were recruited from inpatient settings and followed-up six times over 20 years. The three aims of the study was to assess a) the stability of physical anhedonia over time, b) whether physical anhedonia relates to the course of depressive symptoms over time, and c) whether physical anhedonia relates to three domains of functioning - work, social functioning, or re-hospitalizations. RESULTS We found that over time physical anhedonia was relatively stable and related to depressive symptoms (both between and within person). Physical anhedonia was also related to certain aspects of functioning, though less robustly than depressive symptoms. LIMITATIONS Because depressive symptoms, functioning, and physical anhedonia were measured concurrently at each follow-up, the direction of causality among these variables could not be assessed. Additionally, because our sample was recruited from inpatient settings, our findings may not generalize to individuals with less severe depression. CONCLUSIONS A trait tendency to experience decreased pleasure to positive physical stimuli is a clinically meaningful variable for those with MDD and may be a behavioral endophenotype for a more severe form of depression.