The developmental pathways to schizophrenia: Potential moderating effects of stress

Walker, Elaine F.; Neumann, Craig S.; Baum, Kym M.; Davis, Dana; Diforio, Donald; Bergman, Andrea

doi:10.1017/s0954579400007343

Cited by 37 publications

(19 citation statements)

References 101 publications

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“…That females show greater reactivity in some systems but males in others fits with evidence from animal studies that gonadal hormones act differently on different body systems and that estrogen and testosterone tend to have opposite effects (Walker et al, 1996; Spear, 2000; McEwen and Gianaros, 2010). …”

Section: Discussionsupporting

confidence: 76%

Sex differences in physiological reactivity to acute psychosocial stress in adolescence

Ordaz

Luna

2012

Psychoneuroendocrinology

131

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Summary Females begin to demonstrate greater negative affective responses to stress than males in adolescence. This may reflect the concurrent emergence of underlying differences in physiological response systems, including corticolimbic circuitries, the hypothalamic—pituitary— adrenal axis (HPAA), and the autonomic nervous system (ANS). This review examines when sex differences in physiological reactivity to acute psychosocial stress emerge and the directionality of these differences over development. Indeed, the literature indicates that sex differences emerge during adolescence and persist into adulthood for all three physiological response systems. However, the directionality of the differences varies by system. The emerging corti-colimbic reactivity literature suggests greater female reactivity, particularly in limbic regions densely innervated by gonadal hormone receptors. In contrast, males generally show higher levels of HPAA and ANS reactivity. We argue that the contrasting directionality of corticolimbic and peripheral physiological responses may reflect specific effects of gonadal hormones on distinct systems and also sex differences in evolved behavioral responses that demand different levels of peripheral physiological activation. Studies that examine both subjective reports of negative affect and physiological responses indicate that beginning in adolescence, females respond to acute stressors with more intense negative affect than males despite their comparatively lower peripheral physiological responses. This dissociation is not clearly explained by sex differences in the strength of the relationship between physiological and subjective responses. We suggest that females' greater subjective responsivity may instead arise from a greater activity in brain regions that translate stress responses to subjective awareness in adolescence. Future research directions include investigations of the role of pubertal hormones in physiological reactivity across all systems, examining the relationship of corticolimbic reactivity and negative affect, and sex differences in emotion regulation processes.

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Section: Discussionsupporting

confidence: 76%

Sex differences in physiological reactivity to acute psychosocial stress in adolescence

Ordaz

Luna

2012

Psychoneuroendocrinology

131

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“…Several factors could account for the increased attentional disturbance related to negative affective stimuli in schizotypy. This relationship could be mediated by heightened responsivity to stressors in the schizophrenia spectrum as evidenced by personality (Berenbaum and Fujita, 1994), neuroendocrine (Breier et al, 1991;Walker et al, 1996), psychophysiological Kring, 1999;Kring and Neale, 1996;Nuechterlein and Subotnik, 1998;Simons et al, 1993), and experience-sampling (Myin-Germeys et al, 2000 studies. Similar affect processing abnormalities noted in nonpatients with elevated positiveschizotypy scores may account for the cognitive impairment related to negative affective stimuli seen in the present study and elsewhere (Kerns and Berenbaum, 2000).…”

Section: Discussionmentioning

confidence: 99%

Specificity of emotion-related effects on attentional processing in schizotypy

Mohanty

Heller

Koven

et al. 2008

Schizophrenia Research

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Objectives-In the schizophrenia spectrum, cognitive functions such as perception, language, and attention have been shown to be adversely influenced by negative affect. The present study addressed three issues of specificity and one issue of mechanism regarding affect-related attentional disruption in schizotypy: (1) Is attentional disturbance from negative affective stimuli specific to positive (PS) but not negative schizotypy (NS)? (2) Do positive affective stimuli also foster attentional disturbance? (3) Are anxiety and depression differentially related to PS and NS? (4) Whatever the degree of specificity in these relationships, does anxiety mediate the relationship between schizotypy and attentional disturbance?Methods-Nonpatient participants (N=162) provided responses on scales of schizotypy, anxiety, and depression and performed an emotional Stroop task, judging the ink color of positive, neutral, and negative words.Results-PS but not NS was associated with poorer attentional performance. This attentional disturbance was specific to negative words. PS was associated with anxiety and depression, whereas NS was associated only with depression. Finally, anxiety and depression did not fully mediate the relationship between PS and attentional interference related to negative affective stimuli.* Corresponding author. Tel.: +1 312 503 1749; fax: +1 312 908 8789. Conflict of interestAll authors declare that they have no conflict of interest. ContributorsAll authors were involved in data collection. Aprajita Mohanty designed the study, conducted literature searches and statistical analyses, and was the primary author of the manuscript. Gregory Miller and Wendy Heller contributed to writing it and provided laboratory resources, funding, and oversight. Nancy Koven was also involved in designing the study. All authors contributed to and have approved the final manuscript. Conclusions-Findings of attentional disturbance in the presence of negative affective stimuli, particularly in positive schizotypy, have substantial theoretical implications. They provide a path by which the interplay of cognitive and affective phenomena could lead to the formation, maintenance, and exacerbation of positive symptoms, including delusions and hallucinations. Findings from this study also underscore the importance of examining the differential contribution of comorbid anxiety and depression to cognitive and affective function in the schizophrenia spectrum. NIH Public Access

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“…differences in cortical anatomy remain to be identified. A number of candidate mechanisms exist including gestational and perinatal complications (49) as well as postnatal factors such as head injuries and stressful life events (50). Any of these factors, to the extent that they specifically or preferentially impact one co-twin, may explain clinical as well as neurobiological phenotypic discordance, although each of their influences may depend on specific genetic diatheses.…”

Section: Discussionmentioning

confidence: 99%

Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia

Cannon

Thompson

Erp

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

283

190

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The symptoms of schizophrenia imply disruption to brain systems supporting higher-order cognitive activity, but whether these systems are impacted differentially against a background of diffuse cortical gray-matter deficit remains ambiguous. Some unaffected first-degree relatives of schizophrenics also manifest cortical gray-matter deficits, but it is unclear whether these changes are isomorphic with those in patients, and the answer is critical to understanding the neurobiological conditions necessary for disease expression given a predisposing genotype. Here we report three-dimensional cortical surface maps (probabilistic atlases matching subjects' anatomy point by point throughout cortex) in monozygotic (MZ) and dizygotic (DZ) twins discordant for chronic schizophrenia along with demographically matched control twins. A map encoding the average differences between schizophrenia patients and their unaffected MZ co-twins revealed deficits primarily in dorsolateral prefrontal cortex, superior temporal gyrus, and superior parietal lobule. A map encoding variation associated with genetic proximity to a patient (MZ co-twins > DZ co-twins > control twins) isolated deficits primarily in polar and dorsolateral prefrontal cortex. In each case, the statistical significance was confirmed through analysis of 10,000 Monte Carlo permutations, and the remaining cortex was shown to be significantly less affected by contrast analysis. The disease-related deficits in gray matter were correlated with measures of symptom severity and cognitive dysfunction but not with duration of illness or antipsychotic drug treatment. Genetic and disease-specific influences thus affect gray matter in partially nonoverlapping areas of predominantly heteromodal association cortex, changes that may act synergistically in producing overt behavioral features of the disorder.

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The developmental pathways to schizophrenia: Potential moderating effects of stress

Cited by 37 publications

References 101 publications

Sex differences in physiological reactivity to acute psychosocial stress in adolescence

Sex differences in physiological reactivity to acute psychosocial stress in adolescence

Specificity of emotion-related effects on attentional processing in schizotypy

Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia

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