Merel Prikken

The effect of raloxifene augmentation in men and women with a schizophrenia spectrum disorder: a systematic review and meta-analysis

Recognizing the robust sex differences in schizophrenia prevalence, the selective estrogen receptor modulator (SERM) raloxifene is a likely candidate for augmentation therapy in this disorder. Therefore, a systematic search was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Randomized controlled trials investigating the effect of raloxifene in schizophrenia spectrum disorders were included in the quantitative analyses. Outcome measures were psychotic symptom severity, depression, and cognition. Meta-analyses were performed using Comprehensive Meta-Analysis software. A random-effects model was used to compute overall weighted effect sizes in Hedges’ g. Nine studies were included, investigating 561 patients with a schizophrenia spectrum disorder. Raloxifene was superior to placebo in improving total symptom severity (N = 482; Hedge’s g = .57, p = 0.009), as well as positive (N = 561; Hedge’s g = 0.32, p = 0.02), negative (N = 561; Hedge’s g = 0.40, p = 0.02), and general (N = 526; Hedge’s g = 0.46, p = 0.01) subscales, as measured by the Positive and Negative Syndrome Scale. No significant effects were found for comorbid depression and cognitive functioning. Altogether, these results confirm the potential of raloxifene augmentation in the treatment of schizophrenia.

Abnormal agency experiences in schizophrenia patients: Examining the role of psychotic symptoms and familial risk

Experiencing self-agency over ones own action outcomes is essential for social functioning. Recent research revealed that patients with schizophrenia do not use implicitly available information about their action-outcomes (i.e., prime-based agency inference) to arrive at self-agency experiences. Here, we examined whether this is related to symptoms and/or familial risk to develop the disease. Fifty-four patients, 54 controls, and 19 unaffected (and unrelated) siblings performed an agency inference task, in which experienced agency was measured over action-outcomes that matched or mismatched outcome-primes that were presented before action performance. The Positive and Negative Syndrome Scale (PANSS) and Comprehensive Assessment of Symptoms and History (CASH) were administered to assess psychopathology. Impairments in prime-based inferences did not differ between patients with symptoms of over- and underattribution. However, patients with agency underattribution symptoms reported significantly lower overall self-agency experiences. Siblings displayed stronger prime-based agency inferences than patients, but weaker prime-based inferences than healthy controls. However, these differences were not statistically significant. Findings suggest that impairments in prime-based agency inferences may be a trait characteristic of schizophrenia. Moreover, this study may stimulate further research on the familial basis and the clinical relevance of impairments in implicit agency inferences.

Efficacy of different types of cognitive enhancers for patients with schizophrenia: a meta-analysis

Cognitive impairment is a core feature of schizophrenia, which is predictive for functional outcomes and is, therefore, a treatment target in itself. Yet, literature on efficacy of different pharmaco-therapeutic options is inconsistent. This quantitative review provides an overview of studies that investigated potential cognitive enhancers in schizophrenia. We included pharmacological agents, which target different neurotransmitter systems and evaluated their efficacy on overall cognitive functioning and seven separate cognitive domains. In total, 93 studies with 5630 patients were included. Cognitive enhancers, when combined across all different neurotransmitter systems, which act on a large number of different mechanisms, showed a significant (yet small) positive effect size of 0.10 (k = 51, p = 0.023; 95% CI = 0.01 to 0.18) on overall cognition. Cognitive enhancers were not superior to placebo for separate cognitive domains. When analyzing each neurotransmitter system separately, agents acting predominantly on the glutamatergic system showed a small significant effect on overall cognition (k = 29, Hedges’ g = 0.19, p = 0.01), as well as on working memory (k = 20, Hedges’ g = 0.13, p = 0.04). A sub-analysis of cholinesterase inhibitors (ChEI) showed a small effect on working memory (k = 6, Hedges’ g = 0.26, p = 0.03). Other sub-analyses were positively nonsignificant, which may partly be due to the low number of studies we could include per neurotransmitter system. Overall, this meta-analysis showed few favorable effects of cognitive enhancers for patients with schizophrenia, partly due to lack of power. There is a lack of studies involving agents acting on other than glutamatergic and cholinergic systems, especially of those targeting the dopaminergic system.

O2.5. MULTISENSORY INTEGRATION UNDERLYING BODY OWNERSHIP IN SCHIZOPHRENIA AND INDIVIDUALS AT FAMILIAL RISK TO DEVELOP PSYCHOSIS: A STUDY USING THE RUBBER HAND ILLUSION PARADIGM

Abstract Background Patients with schizophrenia suffer from fundamental self-disturbances and have difficulties integrating and distinguishing between the self and others. For example, they experience that bodily boundaries vanish, that body parts are located at the wrong part of the body or that they are not the subject of their own movements. Such experiences are referred to as disturbances in the sense of body ownership. Although these are well-described psychotic symptoms, surprisingly little is known about their etiology and development. Our aim was to replicate a more flexible sense of body ownership in patients, thereby using a well-controlled experimental procedure (with proprioceptive drift and subjective strength of the illusion. Second, we examine whether increased familial risk to develop psychosis (i.e., offspring of patients with schizophrenia), relative to increased familial risk to develop mood disorders or the absence of familial risk, is related to alterations in RHI measures. Methods With a Rubber Hand Illusion (RHI) paradigm, body ownership was assessed in two different cohorts: 1) 54 patients with schizophrenia and 56 age and gender matched controls and 2) 24 children/adolescents with at least one parent with schizophrenia, 33 children/adolescents with at least one parent with bipolar disorder, and 18 age and gender matched controls. In this paradigm, a visible rubber hand and the invisible real hand were stroked either synchronously or asynchronously. Subsequently, proprioceptive drift and subjective RHI were measured. Results All groups showed the rubber hand illusion, i.e., a stronger proprioceptive drift and higher subjective ratings of the RHI after synchronous compared with asynchronous stroking (all p<0.001). The effect of synchronicity on subjective RHI was significantly stronger in patients with schizophrenia as compared with healthy individuals (p=0.03). No significant differences were found between children/adolescents with and without increased familial risk to develop psychosis. Last, in patients the subjective RHI was related to severity of delusions (rho=0.36). Discussion This study confirms alterations in embodied ownership experiences in patients with schizophrenia, but no evidence was found for impairments in children/adolescence with increased familial or clinical risk to develop psychosis. Longitudinal data are needed to reveal whether impairments in body ownership are predictive of psychosis onset, however, our findings provide suggestive evidence that this is not the case. In addition, that group differences were found in multisensory integration processes related to the embodiment, but not proprioceptive drift, implicates different underlying mechanisms. A possible explanation might come from the distinction between bottom-up (i.e., sensory input) and top-down (i.e., cognitive representation of body schema) mechanisms that influence multisensory integration, that is, altered cognitive representations may influence embodiment but not proprioceptive drift.