Childhood Maltreatment and Its Association with Cognitive Ability in Young People Suspected to Be at Clinical High Risk of Psychosis.

INTRODUCTION: Childhood maltreatment is associated with both reduced cognitive functioning and the development of psychotic symptoms. However, the specific relationship between childhood maltreatment, cognitive abilities and (pre)psychotic symptoms remains unclear. Therefore, the aim of this study was to investigate the association between childhood maltreatment and tasks of verbal memory and processing speed in a help-seeking sample of an early detection of psychosis service. METHODS: A total of 274 participants consisting of 177 clinical high risk (CHR) for psychosis subjects and 97 clinical controls (CC) with subthreshold CHR underwent a battery of neurocognitive assessments measuring the latent variables verbal memory and processing speed. Additionally, the Trauma and Distress Scale (TADS) was administered to assess varying childhood maltreatment subtypes. Structural equation modeling (SEM) was used to examine associations between verbal memory, processing speed, and maltreatment subtypes. Other factors in the model were age, gender, clinical group (CHR or CC), and the presence of different CHR criteria. RESULTS: Physical abuse was associated with lower scores in verbal memory and processing speed. The explained variance in the SEM reached up to 9.5% for verbal memory and 24.9% for processing speed. Both latent variables were each associated with the presence of cognitive-perceptive basic symptoms. Lower verbal memory was additionally associated with the clinical high-risk group, and processing speed capacity was associated with higher age and female gender. CONCLUSION: Childhood physical abuse in particular was associated with poorer performance on verbal memory and processing speed across both groups of CHR and CC with subthreshold CHR symptoms. This adds to the current literature on reduced cognitive abilities when childhood maltreatment had occurred, albeit subtype dependent. Our findings, together with high prevalence rates of childhood maltreatment in patients with psychosis or CHR states, along with the presence of cognitive deficits in these patients, highlight the importance of not only assessing cognition but also childhood maltreatment in managing these patients. Future research should investigate the specific biological mechanisms of childhood maltreatment on verbal memory and processing speed in CHR subjects, as neurobiological alterations might explain the underlying mechanisms.

The Bern Early Recognition and Intervention Centre for mental crisis (FETZ Bern)-An 8-year evaluation.

AIM: Early detection of, and intervention for, psychosis during its prodromal phase has the potential to alter the course of the disease and has therefore become a major objective of modern clinical psychiatry. An increasing number of early detection and intervention services have been established in Europe and worldwide. This study aims to describe and evaluate an early detection and intervention service for children, adolescents and adults (FETZ Bern) aged from eight to 40 years with a population catchment area of 1.035 million in Bern, Switzerland. METHODS: Routine demographic, diagnostic and service usage data were collected upon admission to the service. Using a retrospective, descriptive and naturalistic study design, data was analysed for different age groups (children, adolescents and adults) and where available, outcome data after 12 and 24 months was evaluated. RESULTS: The FETZ Bern has received 827 referrals with full diagnostic data available for 353 patients. The majority of the assessed patients were young males. While 40% met criteria for a clinical high-risk state of psychosis, 20% were diagnosed with fully manifest psychosis at time of admission, and another 40% had one or more non-psychotic axis-I diagnoses. CONCLUSIONS: The FETZ Bern is the first early detection centre worldwide assessing children aged younger than 12 years, as well as adolescents and young adults in one service. Given that developmental peculiarities are important in understanding and ultimately treating psychosis, the FETZ Bern, with its emphasis on developmental peculiarities, should be considered as a model for other similar services.

Trapped in a Glass Bell Jar: Neural Correlates of Depersonalization and Derealization in Subjects at Clinical High-Risk of Psychosis and Depersonalization-Derealization Disorder.

BACKGROUND: Depersonalization (DP) and derealization (DR) are symptoms of a disruption of perceptual integration leading to an altered quality of subjective experiences such as feelings of unreality and detachment from the self (DP) or the surroundings (DR). Both DP and DR often occur in concert with other symptoms, for example in subjects at clinical high-risk (CHR) for psychosis, but also appear isolated in the form of DP/DR disorder. Despite evidence that DP/DR causes immense distress, little is known about their neurobiological underpinnings. Therefore, we investigated the neural correlates of DP/DR using pseudo-continuous arterial spin labeling MRI. METHODS: We evaluated the frequency of DP/DR symptoms in a clinical sample (N = 217) of help-seeking individuals from the Early Detection and Intervention Centre for Mental Crisis (CHR, n = 97; clinical controls (CC), n = 91; and first-episode psychosis (FEP), n = 29). Further, in a subsample of those CHR subjects who underwent MRI, we investigated the resting-state regional cerebral blood flow (rCBF). Here, individuals with (n = 21) and without (n = 23) DP/DR were contrasted. Finally, rCBF was measured in a small independent second sample of patients with DP/DR disorder (n = 6) and healthy controls (HC, n = 6). RESULTS: In the complete clinical sample, significantly higher frequency of DP/DR was found in CHR compared to CC (50.5 vs. 16.5%; χ2 (2) = 24.218, p ≤ 0.001, Cramer's V = 0.359) as well as in FEP compared to CC (37.9 vs. 16.5%; χ2 (2) = 5.960, p = 0.015, Cramer's V = 0.223). In MRI, significantly lower rCBF was detected in the left orbitofrontal cortex in CHR with vs. without DP/DR (x/y/z = -16/42/-22, p < 0.05, FWE corrected). In patients with DP/DR disorder, significantly higher rCBF was detected in the left caudate nucleus (x/y/z = -18/-32/18, p < 0.05) compared to HC. CONCLUSIONS: This study shows that DP/DR symptoms are frequently found in CHR subjects. Investigating two separate DP/DR populations with an identical neuroimaging technique, our study also indicates that there may be divergent pathophysiological mechanisms-decreased neuronal activity in the orbitofrontal cortex, but increased activity within the caudate nucleus-leading to a final common pathway with similar psychopathological symptoms. This suggests that both top-down (orbitofrontal cortex) and bottom-up (caudate nucleus) mechanisms could contribute to the emergence of DP/DR.

Serotonin Transporter and Tryptophan Hydroxylase Gene Variations Mediate Working Memory Deficits of Cocaine Users.

Cocaine users consistently develop working memory (WM) impairments but the mediating molecular mechanisms are unknown so far. Recent evidence suggests that the serotonin (5-HT) system is altered by chronic cocaine use, while also being involved in WM processing. Thus, we investigated the effects of genetic variations impacting 5-HT activity and of peripheral 5-HT transporter (5-HTT) mRNA expression on WM performance in cocaine users and stimulant naive controls. Two hundred twenty participants (126 cocaine users, 94 controls) were assessed with visuospatial, spatial, and verbal WM tasks, genotyped for the length polymorphism in the promoter region of the 5-HTT (5-HTTLPR), the variable number of tandem repeats in the second intron of the 5-HTT (VNTR In2), two single-nucleotide polymorphisms (rs4570625 and rs1386497) in the tryptophan hydroxylase-2 (TPH2) gene and quantified for peripheral 5-HTT mRNA expression in whole-blood samples. Several significant gene × environment interactions between 5-HT genotypes and cocaine use on WM emerged: in cocaine users, the long/long (5-HTTLPR), 9+10/9+10 (VNTR In2) and C/C (TPH2 rs1386497) genotypes were risk alleles for WM impairments, whereas in healthy controls these polymorphisms were associated with improved WM performance. Analogously, high 5-HTT mRNA levels were associated with worse executive WM performance in cocaine users but with increased performance in controls. These gene × environment interactions suggest that the 5-HT system has an important role in the development of cognitive deficits in chronic cocaine users. Hence, pharmacological compounds targeting 5-HT neurotransmission might be promising for the treatment of cognitive deficits in cocaine dependence.