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Rationale: While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges. Objectives: Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders. Methods: The relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed (N = 3,373) and pharmacokinetic influences investigated. Results: Fifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120–270 ng/ml and 180–380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders. Conclusions: High interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers. [ABSTRACT FROM AUTHOR]

Recent research suggests that embodiment sensations (sense of body ownership and sense of body agency) are altered in schizophrenia. Using a mirror box illusion setup, we tested if the anomalous embodiment experience depends on deficient processing of visuomotor synchrony, disrupted processing of movement mode, or both. The task required participants to press a lever with their index while looking at the image of the experimenter’s hand moving on a similar lever. The illusion of embodiment could arise because looking toward the direction of their own hand the participant saw the reflection of the experimenter’s hand visually superimposed to his own one through a mirror. During the illusion induction, we systematically varied visuomotor asynchrony (4 delays were imposed on the movement of the experimenter’s hand) and the mode of movement (the participant could perform active vs. passive movements). The strength of the illusion of embodiment of the external hand was assessed with explicit judgments of ownership and agency. Patients’ data showed an anomalous modulation of ownership with respect to visuomotor synchrony manipulation and an altered modulation of agency with respect to both visuomotor synchrony and movement mode manipulations. Results from the present study suggest that impairments affecting both the processing of temporal aspects of visuomotor signals and the processing of type of movement underlie anomalous embodiment sensations in schizophrenia. Hypotheses about potential deficits accounting for our results are proposed. [ABSTRACT FROM AUTHOR]

There is abundant evidence that the cerebral white matter and in particular the corpus callosum show several structural abnormalities in both schizophrenia (SCZ) and bipolar disease (BD). However, which cognitive functions are impaired as a result of these anomalies is still unclear. Previous behavioural tests of interhemispheric crosstalk have shown a differential impairment in SCZ with interhemispheric transmission time, as tested with the Poffenberger paradigm, essentially normal but with an abnormally enhanced interhemispheric summation effect, as tested with the redundant signal effect. The present study was inspired by this discrepancy and by the more general question of a possible overlap between the pathophysiology of SCZ and BD. We tested both SCZ and BD patients in the Poffenberger paradigm and redundant signal effect and found a similar dissociation, namely a normal interhemispheric transfer time and an abnormal redundant signal effect. The only difference between the two groups was a selective slowing of speed of response of the dominant right hand in the SCZ group suggesting an impairment of left hemisphere functions. These results cast further light on the question of common and differential impairments of basic psychological functions in the two diseases. [ABSTRACT FROM AUTHOR]