The effect of ‘two hit’ neonatal and young-adult stress on dopaminergic modulation of prepulse inhibition and dopamine receptor density

Background and purpose:

A combination of early neurodevelopmental insult(s) and young-adult stress exposure may be involved in the development of schizophrenia. We studied prepulse inhibition (PPI) regulation in rats after an early stress, maternal deprivation, combined with a later stress, simulated by chronic corticosterone treatment, and also determined whether changes in brain dopamine receptor density were involved.

Experimental approach:

Rats were subjected to either 24 h maternal deprivation on postnatal day 9, corticosterone treatment from 8 to 10 weeks of age, or both. At 12 weeks of age, the rats were injected with 0.1, 0.3 or 1.0 mg·kg⁻¹ of apomorphine or 0.5 or 2.5 mg·kg⁻¹ of amphetamine and PPI was determined using automated startle boxes. Dopamine D₁ and D₂ receptor levels were assessed in the nucleus accumbens and caudate nucleus using receptor autoradiography.

Key results:

Young-adult treatment with corticosterone resulted in attenuated disruption of PPI by apomorphine and amphetamine. In some rats, maternal deprivation resulted in reduced baseline PPI which added to the effect of corticosterone treatment. There was no down-regulation of dopamine D₁ or D₂ receptors.

Conclusions and implications:

These results confirm and extend our finding of an inhibitory interaction of developmental stress on dopaminergic regulation of PPI. No corresponding changes in dopamine receptor density were observed in brain regions with a major involvement in PPI regulation, suggesting long-lasting desensitization of dopamine receptor signalling or indirect changes in PPI regulation.     

Clinimetric evaluation of the physical mobility scale supports clinicians and researchers in residential aged care

Barker AL, Nitz JC, Low Choy NL, Haines TP. Clinimetric evaluation of the Physical Mobility Scale supports clinicians and researchers in residential aged care.

Objective

To investigate the interrater agreement and the internal construct validity of the Physical Mobility Scale, a tool routinely used to assess mobility of people living in residential aged care.

Design

Prospective, multicenter, external validation study.

Setting

Nine residential aged care facilities in Australia.

Participants

Residents (N=186). Phase 1 cohort (99 residents; mean age, 85.22±5.1y); phase 2 cohort (87 residents; mean age, 81.59±10.69y).

Interventions

Not applicable.

Main Outcome Measures

Kappa statistics, minimal detectable change (MDC₉₀) scores, and Bland-Altman plots were used to assess interrater agreement. Scale unidimensionality, item hierarchy, and person separation were examined with Rasch analysis for both cohorts.

Results

Agreement between raters on 6 of the 9 Physical Mobility Scale items was high (κ>.60). The MDC₉₀ value was 4.39 points, and no systematic differences in scores between raters were found. The Physical Mobility Scale showed a unidimensional structure demonstrated by fit to the Rasch model in both cohorts (phase 1: χ²=23.90, P=.16, person separation index=0.96; phase 2: χ²=22.00, P=.23, person separation index=0.96). Standing balance was the most difficult item in both cohorts (phase 1: logit=2.48, SE, 0.16; phase 2: logit=2.53, SE, 0.15). The person-item threshold map indicated no floor or ceiling effects in either cohort.

Conclusions

The Physical Mobility Scale demonstrated good interrater agreement and internal construct validity with good fit to the Rasch model in both cohorts. The comparative results across the 2 cohorts indicate generality of the findings. The Physical Mobility Scale total raw scores can be converted to Rasch transformed scores, providing an interval measure of mobility. The Physical Mobility Scale may be suited to a range of clinical and research applications in residential aged care.     

Combined neonatal stress and young-adult glucocorticoid stimulation in rats reduce BDNF expression in hippocampus: effects on learning and memory

Epidemiological studies suggest that multiple developmental disruptions are involved in the etiology of psychiatric illnesses including schizophrenia. In addition, altered expression of brain-derived neurotrophic factor (BDNF) has been implicated in these illnesses. In the present study, we examined the combined long-term effect of an early stress, in the form of maternal deprivation, and a later stress, simulated by chronic young-adult treatment with the stress hormone, corticosterone, on BDNF expression in the hippocampus of rats. To assess whether there were behavioral effects, which may correlate with the BDNF changes, learning and memory was tested in the Y-maze test for short term spatial memory, the Morris water maze for long-term spatial memory, and the T-maze test for working memory. Four groups of rats received either no stress, maternal deprivation, corticosterone treatment, or both. Dorsal hippocampus sections obtained from parallel groups were used for BDNF mRNA in situ hybridization. Rats which had undergone both maternal deprivation and corticosterone treatment displayed a unique and significant 25-35% reduction of BDNF expression in the dentate gyrus (DG), and similar trends in the CA1 and CA3 regions of the hippocampus. These "two-hit" animals exhibited a learning delay in the Morris water maze test, a marked deficit in the Y-maze, but little change in the T-maze test. However, some aspects of cognition were also altered in rats with either maternal deprivation or corticosterone treatment. This study demonstrates a persistent effect of two developmental disruptions on BDNF expression in the hippocampus, with parallel, but not completely correlative changes in learning and memory.     

Features of the offensive subtype of Taijin-Kyofu-Sho in US and Korean patients with DSM-IV social anxiety disorder

Taijin-Kyofu-Sho (TKS), an East Asian syndrome of interpersonal fear and avoidance, that has been considered culture-bound, overlaps with social anxiety disorder to an unknown extent. The offensive subtype of TKS is characterized by two features considered atypical of social anxiety disorder: the belief that one displays physical defects and/or socially inappropriate behaviors (offensive TKS symptoms) and fear of offending others (allocentric focus), but no studies have systematically evaluated these two features in patients with social anxiety disorder. The purpose of this study was to assess offensive TKS symptoms and allocentric focus of fear in US (n = 181) and Korean (n = 64) patients with DSM-IV social anxiety disorder, using the newly developed TKS Questionnaire. Seventy-five percent of patients with social anxiety disorder in the US and Korea endorsed at least one of the five offensive TKS symptoms surveyed. The severity of features of offensive TKS was significantly associated with severity of social anxiety symptoms, depressive symptoms, and disability in both samples. These results suggest that features of the offensive subtype of TKS are not uncommon among US patients with social anxiety disorder and may not be as culturally specific as previously believed. They also suggest that Western clinicians should assess patients with social anxiety for features of offensive TKS, and they support further consideration of integrating TKS features into conceptualizations of social anxiety disorder.     

Cross-cultural study of conviction subtype Taijin Kyofu: proposal and reliability of Nagoya-Osaka diagnostic criteria for social anxiety disorder

Conviction subtype Taijin-Kyofu (c-TK) is a subgroup of mental disorder characterized by conviction and strong fear of offending others in social situations. Although the concept of c-TK overlaps with that of social anxiety disorder (SAD), patients with c-TK often may not be diagnosed as such within the current Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria. We propose the Nagoya-Osaka criteria to amend this situation. This study examined the cross-cultural interrater reliability of the proposed criteria. Eighteen case vignettes of patients with a variety of complaints focused around social anxieties were collected from 6 different countries, and diagnosed by 13 independent raters from various nationalities according to the original DSM-IV and the expanded criteria. The average agreement ratio for the most frequent diagnostic category in each case was 61.5% with DSM-IV and 87.6% with the modified DSM-IV with Nagoya-Osaka criteria (p < 0.001). These findings indicate that the Nagoya-Osaka criteria for SAD can improve interrater reliability of SAD.