Minor physical anomalies and vulnerability in prodromal youth

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Abstract

Because both the brain and craniofacial/limb features originate from the same germinal layer during early gestation, the postnatal presence of minor physical anomalies (MPAs) involving these physical features may be indicative of defects in prenatal neural migration and consequent brain abnormalities among individuals with psychosis. However, to date it is unknown what symptoms and characteristics MPAs may be associated with, or how these markers may reflect vulnerability among adolescents at high-risk for developing psychosis. This information is particularly vital for understanding susceptibility and informing etiological conceptualizations such as the neural diathesis–stress model. In this study, 50 adolescents with a prodromal syndrome were evaluated for MPAs, salivary cortisol, auditory and visual memory function, and attenuated positive, negative, and disorganized symptoms. Results indicated that the participants showing elevated MPAs (n = 25) were distinguished by elevated cortisol, deficit immediate and delayed visual memory, and higher levels of disorganized prodromal symptoms when compared with those participants exhibiting a lower incidence of MPAs. This was supported by supplementary correlational analyses examining the entire sample. These findings provide preliminary support for a theory that MPAs may reflect hippocampal system vulnerability among prodromal patients.

Introduction

Minor physical anomalies (MPAs) are dysmorphic characteristics that are of little functional or cosmetic consequence (e.g., high-steepled or a cleft palate) (Weinberg et al., 2007), but nonetheless, the signs have been of interest to researchers since early conceptualizations of schizophrenia (Kraepelin, 1896). In recent years, investigators have viewed the heightened occurrence of MPAs among individuals in the schizophrenia spectrum through the lens of a neurodevelopmental framework (Weinberger, 1995), specifying that these markers serve as an enduring representation of early gestational insult (e.g., maternal exposure to viral teratogen, stress, and hypoxia) (Mittal et al., 2008a, Mittal et al., 2008b, Mittal et al., 2009) and may elucidate etiological processes, improving understanding of susceptibility among youth at high-risk for developing psychosis. However, to date it has been unclear what symptoms and characteristics MPAs may be associated with, how these markers may reflect vulnerability in the psychosis prodrome (McNeil et al., 2000, Waddington et al., 1999). This is critical as measuring MPAs and vulnerability in the prodromal period, a time less confounded by the effects and consequences of illness, stands to provide a unique perspective for understanding susceptibility in the etiology of psychosis.

The prodromal period is characterized by the emergence of a constellation of subthreshold psychotic-like symptoms and progressive social/functional impairments that precede the onset of an Axis I psychotic disorder, and is of interest both as a window for investigating processes involved in disease onset and also as a potential point of intervention and prevention (Haroun et al., 2006). Within this framework, it is particularly noteworthy that prodromal adolescents have been found to exhibit a range of characteristics including elevations in resting cortisol (Walder et al., 2000, Walker et al., 2008), and deficits in verbal fluency and declarative verbal memory (Simon et al., 2007). Prodromal youth also show elevated positive (e.g., suspiciousness, grandiosity, unusual thoughts, perceptual abnormalities, and disorganized communication), negative symptoms (e.g., feeling disconnected from self and others) and disorganized symptoms (e.g., odd behavior, bizarre thinking, and trouble with focus and attention) (Miller et al., 1999). However, to date, it is unclear to what degree these characteristics and symptoms may reflect an early prenatal insult, as indexed by the presence of MPAs.

The present investigation examines the relations among MPAs, salivary cortisol, memory function, and symptom profiles in a group of adolescent with a prodromal syndrome. Specifically, it is hypothesized that high-risk participants with elevated MPAs will show significant elevations in cortisol, deficits in domains of immediate and delayed auditory and visual memory, and higher levels of attenuated positive, negative and disorganized symptoms when compared to those high-risk participants with lower levels of MPAs.

Section snippets

Methods

Participants were recruited from the Atlanta, Georgia area for a prospective study conducted at Emory University. Recruitment announcements focused on youth with subclinical signs of risk for psychosis and described prodromal and schizotypal symptoms in lay terminology. The present sample includes those who met symptom criteria for a schizotypal personality disorder or a prodromal syndrome (Miller et al., 1999). This report presents data on 50 adolescents, ranging in age from 12 to 18 years for

Results

The MPA scores ranged from 9 to 63 (median = 19); the sample was split at the median and a total of 25 high-risk patients fell into the Low-MPA category and 25 high-risk participants fit in the High-MPA group. Analyses were conducted to test for demographic differences between the groups. Independent t-tests indicated no group differences in age [t(48) = .08, p = .93] or parental education [t(45) = −.54, p = .59], and Chi Square tests revealed no significant differences between the Low-MPA and High-MPA

Discussion

This report suggests that those high-risk individuals with elevated MPAs exhibit a distinct series of characteristics and symptoms. Taken together, findings that the High-MPA group showed increased levels of salivary cortisol, deficit immediate/delayed visual memory, and significantly more disorganized symptoms are consistent with a neural diathesis–stress conceptualization of schizophrenia (Walker and Diforio, 1997, Walker et al., 2008, Weinberger, 1995) and to our knowledge, represent the

Role of funding source

This research was supported by National Institute of Mental Health (NIMH) grant MH4062066 to Dr. Walker and grant MH087258-01 to Dr. Mittal. Dr. Mittal was also supported by seed funds from the University of Colorado Boulder.

Contributors

Dr. Mittal conceptualized the study, conducted analyses, and drafted the manuscript. Dr. Walker attained funding for the study, directed data collection, conceptualized the study, and drafted the manuscript.

Conflict of interest

There are no conflicts of interest to report.

Acknowledgments

There are no acknowledgements.

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