Uma Vaidyanathan

Validating female psychopathy subtypes: differences in personality, antisocial and violent behavior, substance abuse, trauma, and mental health.

Recent empirical investigations utilizing male prisoners have begun to validate clinical conceptualizations of primary and secondary psychopathy subtypes. We extended this literature by identifying similar psychopathic subtypes in female prisoners on the basis of personality structure using model-based cluster analysis. Secondary psychopaths (n = 39) were characterized by personality traits of negative emotionality and low behavioral constraint, an early onset of antisocial and criminal behavior, greater substance use and abuse, more violent behavior and institutional misconduct, and more mental health problems, including symptoms of posttraumatic stress disorder and suicide attempts. Primary psychopaths (n = 31) exhibited few distinguishing personality features but were prolific criminals especially in regards to nonviolent crime, and exhibited relatively few mental health problems despite substantial exposure to traumatic events. The results support alternative etiological pathways to antisocial and criminal behavior that are evident in personality structure as well as gender similarities and differences in the manifestation of psychopathic personalities.

Linking dimensional models of internalizing psychopathology to neurobiological systems: affect-modulated startle as an indicator of fear and distress disorders and affiliated traits.

Integrative hierarchical models have sought to account for the extensive comorbidity between various internalizing disorders in terms of broad individual difference factors these disorders share. However, such models have been developed largely on the basis of self-report and diagnostic symptom data. Toward the goal of linking such models to neurobiological systems, we reviewed studies that have employed variants of the affect-modulated startle paradigm to investigate emotional processing in internalizing disorders as well as personality constructs known to be associated with these disorders. Specifically, we focused on four parameters of startle reactivity: fear-potentiated startle, inhibition of startle in the context of pleasant stimuli, context-potentiated startle, and general startle reactivity. On the basis of available data, we argue that these varying effects index differing neurobiological processes related to mood and anxiety disorders that are interpretable from the standpoint of dimensional models of the internalizing spectrum. Further, we contend that these empirical findings can feed back into and help reshape conceptualizations of internalizing disorders in ways that make them more amenable to neurobiological analysis.

Startle Reflex Potentiation During Aversive Picture Viewing as an Indicator of Trait Fear

Measures of fearfulness and measures of psychopathy show positive and negative associations, respectively, with startle reflex potentiation during unpleasant picture viewing. We tested the hypothesis that a common bipolar trait dimension underlies these differing associations. Blink responses to noise probes were recorded during pleasant, neutral, and unpleasant pictures in 88 undergraduates assessed with a battery of self-report scales indexing fear and psychopathy/fearlessness. A significant positive association was found between an omnibus index of fear, consisting of scores on the first component from a principal components analysis of these various scales, and startle potentiation during aversive picture viewing. This association was most robust, across participants overall and within gender subgroups, for scenes that were most directly threatening. Implications for psychophysiological research on individual differences and psychopathology are discussed.

Clarifying the role of defensive reactivity deficits in psychopathy and antisocial personality using startle reflex methodology.

Prior research has demonstrated deficits in defensive reactivity (indexed by potentiation of the startle blink reflex) in psychopathic individuals. However, the basis of this association remains unclear, as diagnostic criteria for psychopathy encompass two distinct phenotypic components that may reflect differing neurobiological mechanisms-an affective-interpersonal component and an antisocial deviance component. Likewise, the role of defensive response deficits in antisocial personality disorder (APD), a related but distinct syndrome, remains to be clarified. In the current study, the authors examined affective priming deficits in relation to factors of psychopathy and symptoms of APD using startle reflex methods in 108 adult male prisoners. Deficits in blink reflex potentiation during aversive picture viewing were found in relation to the affective-interpersonal (Factor 1) component of psychopathy, and to a lesser extent in relation to the antisocial deviance (Factor 2) component of psychopathy and symptoms of APD-but only as a function of their overlap with affective-interpersonal features of psychopathy. These findings provide clear evidence that deficits in defensive reactivity are linked specifically to the affective-interpersonal features of psychopathy and not to the antisocial deviance features represented most strongly in APD.

Clarifying domains of internalizing psychopathology using neurophysiology.

Current initiatives such as the National Institute of Mental Healths Research Domain Criteria project aim to reorganize classification of mental disorders along neurobiological lines. Here, we describe how consideration of findings from psychiatric research employing two physiological measures with distinct neural substrates--the startle blink reflex and the error-related negativity (ERN)--can help to clarify relations among disorders entailing salient anxiety or depressive symptomatology. Specifically, findings across various studies and reviews reveal distinct patterns of association for both the startle blink reflex and the ERN with three key domains of psychopathology: (1) Fear (or phobic) disorders (distinguished by increased startle to unpleasant stimuli, but normal-range ERN). (2) Non-phobic anxiety disorders and negative affect (associated with increased ERN, increased startle across all types of emotional stimuli and increased baseline startle) and, more tentatively (3) Major depression (for which patterns of response for both startle and ERN appear to vary, as a function of severity and distinct symptomatology). Findings from this review point to distinct neurobiological indicators of key psychopathology domains that have been previously demarcated using personality and diagnostic data. Notably, these indicators exhibit more specificity in their relations with these three domains than has been seen in quantitative-dimensional models. Implications of these findings are discussed.

Patterns of comorbidity among mental disorders: a person-centered approach

OBJECTIVE Comorbidity poses a major challenge to conventional methods of diagnostic classification. Although dimensional models of psychopathology have shed some light on this issue, the reason for interrelationships among dimensions is unclear. The current study employed an alternative approach to characterizing patterns of comorbidity among common mental disorders by modeling them instead as clusters by using latent class analysis (LCA). METHOD Latent class analyses of Diagnostic and Statistical Manual of Mental Disorders diagnoses from two nationally representative epidemiological samples--the National Comorbidity Survey and National Comorbidity Survey--Replication datasets--were undertaken. RESULTS Within each dataset, LCA yielded 5 latent classes exhibiting distinctive profiles of diagnostic comorbidity: a fear class (all phobias and panic disorder), a distress class (depression, generalized anxiety disorder, dysthymia), an externalizing class (alcohol and drug dependence, conduct disorder), a multimorbid class (highly elevated rates of all disorders), and a few-disorders class (very low probability of all disorders). Whereas some disorders were relatively specific to certain classes, others (major depression, posttraumatic stress disorder, social phobia) appeared to be evident across all classes. Profiles for the five classes were highly similar across the two samples. When bipolar I disorder was added to the LCA models, in both samples, it occurred almost exclusively in the multimorbid class. CONCLUSIONS Comorbidity among mental disorders in the general population appears to occur in a finite number of distinct patterns. This finding has important implications for efforts to refine existing diagnostic classification schemes, as well as for research directed at elucidating the etiology of mental disorders.

Knowns and unknowns for psychophysiological endophenotypes: Integration and response to commentaries

We review and summarize seven molecular genetic studies of 17 psychophysiological endophenotypes that comprise this special issue of Psychophysiology, address criticisms raised in accompanying Perspective and Commentary pieces, and offer suggestions for future research. Endophenotypes are polygenic, and possibly influenced by rare genetic variants. Because they are not simpler genetically than clinical phenotypes, they are unlikely to assist gene discovery for psychiatric disorder. Once genetic variants for clinical phenotypes are identified, associated endophenotypes are likely to provide valuable insights into the psychological and neural mechanisms important to disorder pathology. This special issue provides a foundation for informed future steps in endophenotype genetics, including the formation of large sample consortia capable of fleshing out the many genetic variants contributing to individual differences in psychophysiological measures.

Heritability and Molecular-Genetic Basis of Resting EEG Activity: A Genome-Wide Association Study

Several EEG parameters are potential endophenotypes for different psychiatric disorders. The present study consists of a comprehensive behavioral- and molecular-genetic analysis of such parameters in a large community sample (N = 4,026) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric heritability estimates ranged from .49 to .85, with a median of .78. The additive effect of all SNPs (SNP heritability) varied across electrodes. Although individual SNPs were not significantly associated with EEG parameters, several genes were associated with delta power. We also obtained an association between the GABRA2 gene and beta power (p < .014), consistent with findings reported by others, although this did not survive Bonferroni correction. If EEG parameters conform to a largely polygenic model of inheritance, larger sample sizes will be required to detect individual variants reliably.

Heritability and molecular genetic basis of acoustic startle eye blink and affectively modulated startle response: A genome‐wide association study

Acoustic startle responses have been studied extensively in relation to individual differences and psychopathology. We examined three indices of the blink response in a picture-viewing paradigm-overall startle magnitude across all picture types, and aversive and pleasant modulation scores-in 3,323 twins and parents. Biometric models and molecular genetic analyses showed that half the variance in overall startle was due to additive genetic effects. No single nucleotide polymorphism was genome-wide significant, but GRIK3 produced a significant effect when examined as part of a candidate gene set. In contrast, emotion modulation scores showed little evidence of heritability in either biometric or molecular genetic analyses. However, in a genome-wide scan, PARP14 produced a significant effect for aversive modulation. We conclude that, although overall startle retains potential as an endophenotype, emotion-modulated startle does not.

In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes

Whole genome sequencing was completed on 1,325 individuals from 602 families, identifying 27 million autosomal variants. Genetic association tests were conducted for those individuals who had been assessed for one or more of 17 endophenotypes (N range = 802-1,185). No significant associations were found. These 27 million variants were then imputed into the full sample of individuals with psychophysiological data (N range = 3,088-4,469) and again tested for associations with the 17 endophenotypes. No association was significant. Using a gene-based variable threshold burden test of nonsynonymous variants, we obtained five significant associations. These findings are preliminary and call for additional analysis of this rich sample. We argue that larger samples, alternative study designs, and additional bioinformatics approaches will be necessary to discover associations between these endophenotypes and genomic variation.