The “Personal Health Budget” intervention model in early psychosis: Preliminary findings from the Parma experience

Objectives Personal Health Budget (PHB) has recently been provided to people with severe mental illness, reflecting a policy shift towards a personalized mental health care based on individual unmet needs. However, evidence on effectiveness of PHB initiatives is still limited. Aim of this research was to provide preliminary data about the beneficial effects of adding PHB to a multicomponent EIP intervention in patients with First-Episode Psychosis (FEP) along a 2-year follow-up period. Methods Participants (n = 49) were FEP patients, aged 18-50 years, entered the “Parma Early Psychosis” program and completing the Health of Nation Outcome Scale (HoNOS), the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF). Friedman test for repeated measure (with Wilcoxon test as post-hoc procedure) was performed to evaluate the longitudinal stability of functioning and clinical parameters. A linear regression analysis was also carried out. Results A significant effect of time on all HoNOS, BPRS and GAF scores along the 2 years of follow-up was found. Regression analysis results specifically showed a relevant association between a PHB multiaxial intervention and the longitudinal decrease in BPRS “Negative Symptoms” subscores, as well as in HoNOS “Behavioral Problems” and “Social Problems” scores. Conclusions Our results support the general applicability of a PHB approach within an “Early Intervention in Psychosis” program for help-seeking adults with FEP

From Computation to the First-Person : Auditory-Verbal Hallucinations and Delusions of Thought Interference in Schizophrenia-Spectrum Psychoses

Schizophrenia-spectrum psychoses are highly complex and heterogeneous disorders that necessitate multiple lines of scientific inquiry and levels of explanation. In recent years, both computational and phenomenological approaches to the understanding of mental illness have received much interest, and significant progress has been made in both fields. However, there has been relatively little progress bridging investigations in these seemingly disparate fields. In this conceptual review and collaborative project from the 4th Meeting of the International Consortium on Hallucination Research, we aim to facilitate the beginning of such dialogue between fields and put forward the argument that computational psychiatry and phenomenology can in fact inform each other, rather than being viewed as isolated or even incompatible approaches. We begin with an overview of phenomenological observations on the interrelationships between auditory-verbal hallucinations (AVH) and delusional thoughts in general, before moving on to review several theoretical frameworks and empirical findings in the computational modeling of AVH. We then relate the computational models to the phenomenological accounts, with a special focus on AVH and delusions that involve the senses of agency and ownership of thought (delusions of thought interference). Finally, we offer some tentative directions for future research, emphasizing the importance of a mutual understanding between separate lines of inquiry

FGF-2 Deficiency Does Not Influence FGF Ligand and Receptor Expression during Development of the Nigrostriatal System

Secreted proteins of the fibroblast growth factor (FGF) family play important roles during development of various organ systems. A detailed knowledge of their temporal and spatial expression profiles, especially of closely related FGF family members, are essential to further identification of specific functions in distinct tissues. In the central nervous system dopaminergic neurons of the substantia nigra and their axonal projections into the striatum progressively degenerate in Parkinson's disease. In contrast, FGF-2 deficient mice display increased numbers of dopaminergic neurons. In this study, we determined the expression profiles of all 22 FGF-ligands and 10 FGF-receptor isoforms, in order to clarify, if FGF-2 deficiency leads to compensatory up-regulation of other FGFs in the nigrostriatal system. Three tissues, ventral mesencephalon (VM), striatum (STR) and as reference tissue spinal cord (SC) of wild-type and FGF-2 deficient mice at four developmental stages E14.5, P0, P28, and adult were comparatively analyzed by quantitative RT-PCR. As no differences between the genotypes were observed, a compensatory up-regulation can be excluded. Moreover, this analysis revealed that the majority of FGF-ligands (18/22) and FGF-receptors (9/10) are expressed during normal development of the nigrostriatal system and identified dynamic changes for some family members. By comparing relative expression level changes to SC reference tissue, general alterations in all 3 tissues, such as increased expression of FGF-1, -2, -22, FgfR-2c, -3c and decreased expression of FGF-13 during postnatal development were identified. Further, specific changes affecting only one tissue, such as increased FGF-16 (STR) or decreased FGF-17 (VM) expression, or two tissues, such as decreased expression of FGF-8 (VM, STR) and FGF-15 (SC, VM) were found. Moreover, 3 developmentally down-regulated FGFs (FGF-8b, FGF-15, FGF-17a) were functionally characterized by plasmid-based over-expression in dissociated E11.5 VM cell cultures, however, such a continuous exposure had no influence on the yield of dopaminergic neurons in vitro

Critical Role of PI3K/Akt/GSK3β in Motoneuron Specification from Human Neural Stem Cells in Response to FGF2 and EGF

Fibroblast growth factor (FGF) and epidermal growth factor (EGF) are critical for the development of the nervous system. We previously discovered that FGF2 and EGF had opposite effects on motor neuron differentiation from human fetal neural stem cells (hNSCs), but the underlying mechanisms remain unclear. Here, we show that FGF2 and EGF differentially affect the temporal patterns of Akt and glycogen synthase kinase 3 beta (GSK3β) activation. High levels of phosphatidylinositol 3-kinase (PI3K)/Akt activation accompanied with GSK3β inactivation result in reduction of the motor neuron transcription factor HB9. Inhibition of PI3K/Akt by chemical inhibitors or RNA interference or overexpression of a constitutively active form of GSK3β enhances HB9 expression. Consequently, PI3K inhibition increases hNSCs differentiation into HB9+/microtubule-associated protein 2 (MAP2)+ motor neurons in vitro. More importantly, blocking PI3K not only enhances motor neuron differentiation from hNSCs grafted into the ventral horn of adult rat spinal cords, but also permits ectopic generation of motor neurons in the dorsal horn by overriding environmental influences. Our data suggest that FGF2 and EGF affect the motor neuron fate decision in hNSCs differently through a fine tuning of the PI3K/AKT/GSK3β pathway, and that manipulation of this pathway can enhance motor neuron generation

Caveolin-1 Plays a Crucial Role in Inhibiting Neuronal Differentiation of Neural Stem/Progenitor Cells via VEGF Signaling-Dependent Pathway

In the present study, we aim to elucidate the roles of caveolin-1(Cav-1), a 22 kDa protein in plasma membrane invaginations, in modulating neuronal differentiation of neural progenitor cells (NPCs). In the hippocampal dentate gyrus, we found that Cav-1 knockout mice revealed remarkably higher levels of vascular endothelial growth factor (VEGF) and the more abundant formation of newborn neurons than wild type mice. We then studied the potential mechanisms of Cav-1 in modulating VEGF signaling and neuronal differentiation in isolated cultured NPCs under normoxic and hypoxic conditions. Hypoxic embryonic rat NPCs were exposed to 1% O2 for 24 h and then switched to 21% O2 for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O2. Compared with normoxic NPCs, hypoxic NPCs had down-regulated expression of Cav-1 and up-regulated VEGF expression and p44/42MAPK phosphorylation, and enhanced neuronal differentiation. We further studied the roles of Cav-1 in inhibiting neuronal differentiation by using Cav-1 scaffolding domain peptide and Cav-1-specific small interfering RNA. In both normoxic and hypoxic NPCs, Cav-1 peptide markedly down-regulated the expressions of VEGF and flk1, decreased the phosphorylations of p44/42MAPK, Akt and Stat3, and inhibited neuronal differentiation, whereas the knockdown of Cav-1 promoted the expression of VEGF, phosphorylations of p44/42MAPK, Akt and Stat3, and stimulated neuronal differentiation. Moreover, the enhanced phosphorylations of p44/42MAPK, Akt and Stat3, and neuronal differentiation were abolished by co-treatment of VEGF inhibitor V1. These results provide strong evidence to prove that Cav-1 can inhibit neuronal differentiation via down-regulations of VEGF, p44/42MAPK, Akt and Stat3 signaling pathways, and that VEGF signaling is a crucial target of Cav-1. The hypoxia-induced down-regulation of Cav-1 contributes to enhanced neuronal differentiation in NPCs

Bringing the "self" into focus: conceptualising the role of self-experience for understanding and working with distressing voices

A primary goal of cognitive behavior therapy for psychosis (CBTp) is to reduce distress and disability, not to change the positive symptoms of psychosis, such as hearing voices. Despite demonstrated associations between beliefs about voices and distress, the effects of CBTp on reducing voice distress are disappointing. Research has begun to explore the role that the psychological construct of “self” (which includes numerous facets such as self-reflection, self-schema and self-concept) might play in causing and maintaining distress and disability in voice hearers. However, attempts to clarify and integrate these different perspectives within the voice hearing literature, or to explore their clinical implications, are still in their infancy. This paper outlines how the self has been conceptualised in the psychosis and CBT literatures, followed by a review of the evidence regarding the proposed role of this construct in the etiology of and adaptation to voice hearing experiences. We go on to discuss some of the specific intervention methods that aim to target these aspects of self-experience and end by identifying key research questions in this area. Notably, we suggest that interventions specifically targeting aspects of self-experience, including self-affection, self-reflection, self-schema and self-concept, may be sufficient to reduce distress and disruption in the context of hearing voices, a suggestion that now requires further empirical investigation

The comprehensive assessment of at-risk mental states : from mapping the onset to mapping the structure

BACKGROUND: Improving the identification of clinical vulnerability to psychosis in help-seeking subjects is crucial for refining risk stratifications and implementing intervention strategies. AIMS: To define underlying dimensions of subclinical psychopathology in Ultra-High-Risk (UHR) subjects; to test their temporal stability and association with baseline clinical and functional features; and to evaluate their predictive value for subsequent transition to psychosis. METHOD: 223 subjects meeting the Personal Assessment and Crisis Evaluation (PACE) criteria for UHR were assessed with the Comprehensive Assessment of At-Risk Mental States (CAARMS) and monitored for a period of up to three years. Data were analysed via principal component analysis (PCA), Spearman correlation analysis and Cox regression. RESULTS: PCA of the CAARMS yielded three orthogonal symptom clusters (negative, disorganized and perceptual-affective instability) with substantial temporal stability over a one-month time span. These clusters were strongly related to global functioning, quality of life, baseline major psychopathology and duration of symptoms before referral. The severity of the CAARMS disorganized component was the strongest predictor of transition to frank psychosis at follow-up. CONCLUSIONS: A dimensional approach to CAARMS-measured symptoms may refine current early identification heuristics and provide an alternative way to characterize UHR profiles complementary to the current categorical one

Hallucination-like experiences in the nonclinical population

Unusual subjective experiences are relatively common in the general population and have been associated with an increased level of vulnerability to psychosis. The current study aimed to a) determine the distribution of hallucination-like experiences (HLEs) in a community sample of young adults, b) investigate their dimensional subtypes, and c) test the association of HLEs with indicators of poor mental health. Four hundred thirty-seven participants (men, 41%) completed a battery of questionnaires including the 16-item Launay-Slade Hallucination Scale (LSHS), the 12-item General Health Questionnaire (GHQ-12) and the 21-item Peters et al. Delusions Inventory (PDI). The LSHS correlated significantly with GHQ-12 and PDI. Individuals with higher levels of psychological distress were found to report higher frequencies of the HLEs compared with those in the reference range. Exploratory factor analysis of LSHS produced a four-factor solution: a) "auditory and visual HLEs," b) "multisensory HLEs," c) "intrusive thoughts," and d) "vivid daydreams." The current results provide further support for the multidimensional nature of hallucination proneness in the general population and indicate that some HLEs (particularly those related to intrusiveness of thought) are associated with a lower level of perceived well-bein