Parental Secondary Stress: The Often Hidden Consequences of Nonsuicidal Self-Injury in Youth.

OBJECTIVE: This study aims to deepen understanding of the effects on parents of having a self-injuring child by (a) analyzing differences in dimensions of caregiver strain between caregivers of youth with nonsuicidal self-injury (NSSI+) and parents of youth with no known mental health history (MH-); (b) identifying factors that contribute to caregiver strain; and (c) examining parent outcome expectancies. METHOD: Participants were 196 NSSI+ parents and 57 MH- parents. Quantitative measures of psychosocial variables, parent mental health and support variables, and child self-injury characteristics were assessed in relation to caregiver strain, and NSSI+ parental expectancies were assessed via mixed methods. RESULTS: Parents with a NSSI+ youth were more likely to exhibit all forms of objective and subjective strain than parents of youth with no mental health challenges. Despite this, many parents expressed beliefs that their child would experience personal growth as a result of their NSSI experience. CONCLUSION: Findings reveal the important role of mindful parenting practices and informal social support.

Category-Specific Stress Mindsets: Beliefs about the Debilitating versus Enhancing Effects of Specific Types of Stressors among Young Adults.

Recently, research has shown that stress mindsets, or the degree to which people believe that stress is enhancing versus debilitating, impact the ways they process and react to stress. However, young adults encounter various forms of stress, which might elicit different stress mindsets. This study investigated (1) how much young adults think about specific types of stressors as they complete stress mindset measures and (2) how stress mindsets vary across stressor types. METHOD: Participants (n = 182) completed measures of general and category-specific stress mindsets (academic, interpersonal, identity-based, illness, societal, financial) and rated how much they thought of each category when completing the general mindset measure. RESULTS: Academic stress was the most salient, and identity-based discrimination was the least salient as participants completed the stress mindset measure. Academic stress was perceived as the most stress-enhancing, and illness stressors were rated as the least stress-enhancing. Cisgender women reported stronger stress-is-debilitating mindsets for interpersonal and illness/injury-related stressors as compared with cisgender men. CONCLUSION: Stress mindset ratings in research studies might be weighted toward certain types of stressors. Further, young adults' mindsets differ across different stressor categories. This nuance has implications for how we conceptualize stress mindset in interventions and research.

Cingulum and abnormal psychological stress response in schizophrenia.

Stress is implicated in many aspects of schizophrenia, including heightened distress intolerance. We examined how affect and microstructure of major brain tracts involved in regulating affect may contribute to distress intolerance in schizophrenia. Patients with schizophrenia spectrum disorders (n = 78) and community controls (n = 95) completed diffusion weighted imaging and performed psychological stress tasks. Subjective affect was collected pre and post stressors. Individuals who did not persist during one or both stress tasks were considered distress intolerant (DI), and otherwise distress tolerant (DT). Fractional anisotropy (FA) of the dorsal cingulum showed a significant diagnosis x DT/DI phenotype interaction (p = 0.003). Post-hoc tests showed dorsal cingulum FA was significantly lower in DI patients compared with DI controls (p < 0.001), but not different between DT groups (p = 0.27). Regarding affect responses to stress, irritability showed the largest stress-related change (p < 0.001), but irritability changes were significantly reduced in DI patients compared to DI controls (p = 0.006). The relationship between irritability change and performance errors also differed among patients (ρ = -0.29, p = 0.011) and controls (ρ = 0.21, p = 0.042). Further modeling highlighted the explanatory power of dorsal cingulum for predicting DI even after performance and irritability were taken into account. Distress intolerance during psychological stress exposure is related to microstructural properties of the dorsal cingulum, a key structure for cognitive control and emotion regulation. In schizophrenia, the affective response to psychological stressors is abnormal, and distress intolerant patients had significantly reduced dorsal cingulum FA compared to distress intolerant controls. The findings provide new insight regarding distress intolerance in schizophrenia.

Clinical and genetic validity of quantitative bipolarity.

Research has yet to provide a comprehensive understanding of the genetic basis of bipolar disorder (BP). In genetic studies, defining the phenotype by diagnosis may miss risk-allele carriers without BP. The authors aimed to test whether quantitatively detected subclinical symptoms of bipolarity identifies a heritable trait that infers risk for BP. The Quantitative Bipolarity Scale (QBS) was administered to 310 Old Order Amish or Mennonite individuals from multigenerational pedigrees; 110 individuals had psychiatric diagnoses (20 BP, 61 major depressive disorders (MDD), 3 psychotic disorders, 26 other psychiatric disorders). Familial aggregation of QBS was calculated using the variance components method to derive heritability and shared household effects. The QBS score was significantly higher in BP subjects (31.5 ± 3.6) compared to MDD (16.7 ± 2.0), other psychiatric diagnoses (7.0 ± 1.9), and no psychiatric diagnosis (6.0 ± 0.65) (all p < 0.001). QBS in the whole sample was significantly heritable (h2 = 0.46 ± 0.15, p < 0.001) while the variance attributed to the shared household effect was not significant (p = 0.073). When subjects with psychiatric illness were removed, the QBS heritability was similar (h2 = 0.59 ± 0.18, p < 0.001). These findings suggest that quantitative bipolarity as measured by QBS can separate BP from other psychiatric illnesses yet is significantly heritable with and without BP included in the pedigrees suggesting that the quantitative bipolarity describes a continuous heritable trait that is not driven by a discrete psychiatric diagnosis. Bipolarity trait assessment may be used to supplement the diagnosis of BP in future genetic studies and could be especially useful for capturing subclinical genetic contributions to a BP phenotype.

Elevated allostatic load early in the course of schizophrenia.

Stress plays a significant role in schizophrenia from disease onset to exacerbation of psychotic symptoms. Allostatic load (AL) is a measure of cumulative stress to the organism. This study is an extension of our previous work on AL and its relationship to brain structures. Here, we further determined whether elevated AL is a function of illness chronicity, or if it is already present early in the course of schizophrenia. AL was compared in schizophrenia patients early in the illness (within 5 years of disease onset), patients with chronic schizophrenia (more than 5 years of illness), and two groups of healthy controls that were age-and sex-matched to the two patient groups. This work is presented with an expanded sample and includes about two-thirds of the participants who were previously reported. We found that patients with early psychosis had significantly elevated AL score compared with their age-matched controls (p = 0.005). Chronic course patients also had elevated AL compared with age-matched controls (p = 0.003). Immune and stress hormone AL subcomponents were nominally higher in early-stage patients compared with controls (p = 0.005 and 0.04, respectively). Greater AL was also associated with more severe positive psychotic symptoms in early-stage patients (r = 0.54, p = 0.01). Elevated levels of allostatic load are already present in the early years of the schizophrenia illness, particularly in patients with more severe psychotic symptoms. AL may be a useful evaluation for the need of early intervention on psychosomatic comorbidity.

Allostatic load and reduced cortical thickness in schizophrenia.

Structural imaging studies have consistently found reduced gray matter thickness of the cerebral cortex in schizophrenia, a finding that is evident in first episode psychosis and may be progressive in some cases. Although genetic predisposition and medication effects may contribute to cortical thinning, we hypothesize that the cumulative effects of stress may represent an environmental factor impacting brain morphology in schizophrenia. We examined the relationship between allostatic load, an index of peripheral biomarkers representing the cumulative effects of stress, and cortical thickness. Allostatic load was calculated for 44 patients with schizophrenia spectrum disorders (SSD) and 33 normal controls (NC) based on 13 cardiovascular, neuroendocrine, immune, and metabolic measurements. Controlling for age, SSD had significantly elevated allostatic load as compared with NC (p=0.008). Controlling for age, whole brain average cortical thickness was lower in SSD patients compared to NC (p=0.008). However, once allostatic load was accounted for, the group difference in cortical thickness became marginal (p=0.058). Exploratory analyses on subcomponents of allostatic load suggested that elevated immune marker C-reactive protein, stress hormones, and cardiovascular indices within allostatic load were more strongly associated with reduced cortical thickness in SSD. In NC, only the association between immune marker C-reactive protein and cortical thickness was replicated. These results support the hypothesis that allostatic load may account for some of the gray matter deficits observed in schizophrenia. Among the allostatic indices, the inflammatory mechanism appears particularly relevant to cortical thickness in both schizophrenia patients and normal controls.

Lipid Metabolism, Abdominal Adiposity, and Cerebral Health in the Amish.

OBJECTIVE: To assess the association between peripheral lipid/fat profiles and cerebral gray matter (GM) and white matter (WM) in healthy Old Order Amish (OOA). METHODS: Blood lipids, abdominal adiposity, liver lipid contents, and cerebral microstructure were assessed in OOA (N = 64, 31 males/33 females, ages 18-77). Orthogonal factors were extracted from lipid and imaging adiposity measures. GM assessment used the Human Connectome Project protocol to measure whole-brain average cortical thickness. Diffusion-weighted imaging was used to derive WM fractional anisotropy and kurtosis anisotropy measurements. RESULTS: Lipid/fat measures were captured by three orthogonal factors explaining 80% of the variance. Factor one loaded on cholesterol and/or low-density lipoprotein cholesterol measurements; factor two loaded on triglyceride/liver measurements; and factor three loaded on abdominal fat measurements. A two-stage regression including age/sex (first stage) and the three factors (second stage) examined the peripheral lipid/fat effects. Factors two and three significantly contributed to WM measures after Bonferroni corrections (P < 0.007). No factor significantly contributed to GM. Blood pressure (BP) inclusion did not meaningfully alter the lipid/fat-WM relationship. CONCLUSIONS: Peripheral lipid/fat indicators were significantly and negatively associated with cerebral WM rather than with GM, independent of age and BP level. Dissecting the fat/lipid components contributing to different brain imaging parameters may open a new understanding of the body-brain connection through lipid metabolism.

Association of White Matter With Core Cognitive Deficits in Patients With Schizophrenia.

Importance: Efforts to remediate the multiple cognitive function impairments in schizophrenia should consider white matter as one of the underlying neural mechanisms. Objective: To determine whether altered structural brain connectivity is responsible for 2 of the core cognitive deficits in schizophrenia- reduced information processing speed and impaired working memory. Design, Setting, and Participants: This cross-sectional study design took place in outpatient clinics from August 1, 2004, to August 31, 2015. Participants included 166 patients with schizophrenia and 213 healthy control individuals. These participants were from 3 independent cohorts, each of which had its own healthy control group. No participant had current or past neurological conditions or major medical conditions. Patients were diagnosed with either schizophrenia or schizoaffective disorder as defined by the DSM-IV. Controls had no Axis I psychiatric disorder. Main Outcomes and Measures: Mediation analyses and structural equation modeling were used to analyze the associations among processing speed, working memory, and white matter microstructures. Whole-brain and regional diffusion tensor imaging fractional anisotropy were used to measure white matter microstructures. Results: Of the study participants, the 166 patients with schizophrenia had a mean (SD) age of 38.2 (13.3) years and the 213 healthy controls had a mean (SD) age of 39.2 (14.0) years. There were significantly more male patients than controls in each of the 3 cohorts (117 [70%] vs 91 [43%]), but there were no significant differences in sex composition among the 3 cohorts. Patients had significantly reduced processing speed (Cohen d = 1.24; P = 6.91 × 10-30) and working memory deficits (Cohen d = 0.83; P = 1.10 × 10-14) as well as a significant whole-brain fractional anisotropy deficit (Cohen d = 0.63; P = 2.20 × 10-9). In schizophrenia, working memory deficit was mostly accounted for by processing speed deficit, but this deficit remained when accounting for working memory (Cohen d = 0.89; P = 2.21 × 10-17). Mediation analyses showed a significant association pathway from fractional anisotropy to processing speed to working memory (P = 5.01 × 10-7). The strength of this brain-to-cognition pathway in different white matter tracts was strongly associated with the severity of schizophrenia-associated fractional anisotropy deficits in the corresponding white matter tracts as determined by a meta-analysis (r = 0.85-0.94; all P < .001). The same pattern was observed in patients and controls either jointly or independently. Conclusions and Relevance: Study findings suggest that (1) processing speed contributes to the association between white matter microstructure and working memory in schizophrenia and (2) white matter impairment in schizophrenia is regional tract-specific, particularly in tracts normally supporting processing speed performance.