ABSTRACT
Phospholipid (PL) metabolism is investigated by in vivo 31P magnetic resonance spectroscopy (MRS). Inconsistent alterations of phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) have been described in schizophrenia, which might be overcome by specific editing techniques. The selective refocused insensitive nuclei-enhanced polarization transfer (RINEPT) technique was applied in a cross-sectional study involving 11 schizophrenia spectrum disorder patients (SZP) on stable antipsychotic monotherapy and 15 matched control subjects. Metabolite signals were found to be modulated by cerebrospinal fluid (CSF) content and gray matter/brain matter ratio. Corrected metabolite concentrations of PC, GPC and PE differed between patients and controls in both subcortical and cortical regions, whereas antipsychotic medication exerted only small effects. Significant correlations were found between the severity of clinical symptoms and the assessed signals. In particular, psychotic symptoms correlated with PC levels in the cerebral cortex, depression with PC levels in the cerebellum and executive functioning with GPC in the insular and temporal cortices. In conclusion, after controlling for age and tissue composition, this investigation revealed alterations of metabolite levels in SZP and correlations with clinical properties. RINEPT 31P MRS should also be applied to at-risk-mental-state patients as well as drug-naïve and chronically treated schizophrenic patients in order to enhance the understanding of longitudinal alterations of PL metabolism in schizophrenia.
Subject(s)
Brain/metabolism , Phospholipids/metabolism , Schizophrenia/metabolism , Adult , Antipsychotic Agents/pharmacology , Antipsychotic Agents/therapeutic use , Case-Control Studies , Cerebellum/metabolism , Cerebral Cortex/metabolism , Cross-Sectional Studies , Ethanolamines/metabolism , Female , Glycerylphosphorylcholine/metabolism , Humans , Magnetic Resonance Spectroscopy , Male , Nerve Fibers, Unmyelinated/metabolism , Phosphatidylethanolamines/metabolism , Phosphorus Isotopes , Phosphorylcholine/metabolism , Schizophrenia/cerebrospinal fluid , Schizophrenia/drug therapyABSTRACT
The identification of patients carrying an increased risk of psychosis is one of the most important demands in schizophrenia research. Currently used diagnostic instruments mainly focus on either attenuated psychotic symptoms and brief limited intermittent psychotic symptoms or solely cognitive basic symptoms. The "Early Recognition Inventory based on IRAOS" (ERIraos) has been developed as a comprehensive assessment of both symptom groups within one scale. We compared the results obtained by ERIraos with an international standard instrument, the "Comprehensive Assessment of At Risk Mental States" (CAARMS) and applied both scales in a sample of 121 outpatients positively tested on a screening checklist for at risk mental states (ARMS). Subsamples were classified as first episode of psychosis, late ARMS with prevalent attenuated psychotic symptoms and/or brief limited intermittent psychotic symptoms, earlier stages of ARMS presenting cognitive basic symptoms as well as a vulnerability group, also differing regarding mean age and psychosocial functioning. Our results point to a higher sensitivity of ERIraos compared to scales that mainly focus on attenuated psychotic symptoms and brief limited intermittent psychotic symptoms. A detailed assessment of cognitive basic symptoms seems to be important in early detection, might be an important focus for therapeutic interventions in ARMS patients and might sustain attempts to alleviate cognitive dysfunction in schizophrenia.
Subject(s)
Cognition , Psychotic Disorders/diagnosis , Schizophrenia/diagnosis , Adult , Age Factors , Early Diagnosis , Female , Humans , Male , Personality Inventory , Psychiatric Status Rating Scales , Psychotic Disorders/psychology , Risk Assessment , Risk Factors , Schizophrenic Psychology , Sensitivity and SpecificityABSTRACT
Anxiety is a core symptom of schizophrenia that elicits significant subjective burden of disease and contributes to treatment resistance in schizophrenia. Anxious syndromes might be attributed to incompletely remitted delusions, the negative syndrome, depressive episodes, panic attacks, social phobia, avoidance after hospitalization, and down-tapering of benzodiazepine medication. Pregabalin, an antagonist at the alpha2delta subunit of voltage-gated Ca channels, modulates several neurotransmitter systems and was found to alleviate anxiety in different mental disorders. In schizophrenia, this treatment option has not been evaluated before.Here, we report a case series of 11 schizophrenic patients who had treatment-resistant anxiety and received augmentation with pregabalin. This observational analysis reveals that the strategy was able to significantly reduce scores on the Hamilton anxiety scale; furthermore, we observed improvements of psychotic positive and negative symptoms and mood as assessed by Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, and Calgary Depression Scale for Schizophrenia. After augmentation, both a complete discontinuation of concomitant benzodiazepine treatment as well as a dose reduction of antipsychotics could be achieved. We did not observe pharmacokinetic interactions or adverse events.These observations suggest that treating anxious syndromes in schizophrenia with pregabalin can be effective and tolerable. Further investigations should differentiate schizophrenic subsyndromes of anxiety and evaluate benefits and risks of pregabalin in comparison to placebo and active competitors.
