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The role of polyunsaturated fatty acids and their metabolites for the cause and treatment of psychotic disorders are widely discussed. The efficacy as an augmenting agent in chronic schizophrenia seems to be small or not present, however epidemiological data, as well as some recent controlled studies in emerging psychosis point towards possible preventive effects of long-chain polyunsaturated fatty acids in early and very early stages of psychotic disorders and some potential secondary or tertiary beneficial long-term effects in later, more chronic stages, in particular for metabolic or extra-pyramidal side effects. In this comprehensive review, we describe the physiology and metabolism of polyunsaturated fatty acids, phospholipases, epidemiological evidence and the effect of these fatty acids on the brain and neurodevelopment. Furthermore, we examine the available evidence in indicated prevention in emerging psychosis, monotherapy, add-on therapy and tolerability. The neuroprotective potential of n-3 LC-PUFAs for indicated prevention, i.e. delaying transition to psychosis in high-risk populations needs to be further explored.

Objectives: Intracellular phospholipases A₂ (inPLA₂) are activated during monoaminergic neurotranismision and act as key enzymes in cell membrane repair and remodelling, neuroplasticity, neurodevelopment, apoptosis, synaptic pruning, neurodegenerative processes and neuroinflammation. Several independent studies found increased inPLA₂ activity in drug-naïve first episode and chronic schizophrenia. This study investigates if inPLA₂ activity is associated with symptoms severity and treatment response in first episode schizophrenia (FES)., Methods: InPLA₂ activity was measured in serum of 35 young FES patients (mean age: 19.36 ± 3.32, mean duration of illness: 7.53 ± 6.28 months, 16 neuroleptic-naïve) before and after 12 weeks of treatment with second-generation antipsychotic medications (olanzapine, quetiapine or risperidone), as well as in 22 healthy controls matched for age. Psychopathology and social functioning were assessed at the same time points., Results: Baseline inPLA₂ activity was significantly increased in drug-naïve and treated FES patients compared to healthy controls. Baseline inPLA₂ activity was also associated with severity of negative symptoms and lower functioning at baseline. Furthermore, baseline inPLA₂ activity was associated with improvement in negative symptoms and functioning within the first 12 weeks of treatment., Conclusions: Intracellular PLA₂ activity is increased in first episode schizophrenia and associated with symptom severity and outcome after 12 weeks of treatment. Future studies should investigate the implications of inPLA₂ activity as a potential predictor of treatment response for different antipsychotic agents.

Regional structural brain changes are among the most robust biological findings in schizophrenia, yet the underlying pathophysiological changes remain poorly understood. Recent evidence suggests that abnormal neuronal/dendritic plasticity is related to alterations in membrane lipids. We examined whether serum activity of membrane lipid remodelling/repairing cytosolic phospholipase A(2) (PLA(2)) were related to regional brain structure in magnetic resonance images (MRI). The study involved 24 schizophrenia patients, who were either drug-naïve or off antipsychotic medication, and 25 healthy controls. Using voxel-based morphometry (VBM) analysis of T1-high-resolution MRI-images, we correlated both gray matter and white matter changes with serum PLA(2)-activity. PLA(2) activity was increased in patients, consistent with previous findings. VBM group comparison of patients vs. controls showed abnormalities of frontal and medial temporal cortices/hippocampus, and left middle/superior temporal gyrus in first-episode patients. Group comparison of VBM/PLA(2)-correlations revealed a distinct pattern of disease-related interactions between gray/white matter changes in patients and PLA(2)-activity: in first-episode patients (n=13), PLA(2)-activity was associated with structural alterations in the left prefrontal cortex and the bilateral thalamus. Recurrent-episode patients (n=11) showed a wide-spread pattern of associations between PLA(2)-activity and structural changes in the left (less right) prefrontal and inferior parietal cortex, the left (less right) thalamus and caudate nucleus, the left medial temporal and orbitofrontal cortex and anterior cingulum, and the cerebellum. Our findings demonstrate a potential association between membrane lipid biochemistry and focal brain structural abnormalities in schizophrenia. Differential patterns in first-episode vs. chronic patients might be related to PLA(2)-increase at disease-onset reflecting localized regenerative activity, whereas correlations in recurrent-episode patients might point to less specific neurodegenerative aspects of disease progression., (Copyright 2010 Elsevier Inc. All rights reserved.)

Introduction: Skin flushing after niacin (methylnicotinate, vitamin B(3)) stimulation is a biological marker of availability of polyunsaturated fatty acids (PUFA). Decreased PUFA levels have been reported in depressive disorder, while add-on supplementation of omega-3 PUFA has been suggested to improve depressive symptoms. This study aimed to clarify whether a disturbance of niacin skin flushing occurs also in depression, and to identify patient characteristics for those who might benefit from PUFA supplementation., Method: We studied 30 patients with recurrent unipolar depressive disorder during a major depressive episode (treated with antidepressants), and 30 healthy volunteers matched for age and gender. Aqueous methylnicotinate was applied in three dilution steps (0.001M, 0.01M, and 0.1M) onto the inner forearm skin. Skin flushing was assessed in three-minute intervals over 15min using optical reflection spectroscopy., Results: While there was no overall difference in skin flushing between patients and controls, niacin sensitivity was inversely correlated with severity of symptoms, and flush deficits were significantly associated with depressed mood, feelings of anxiety and somatic symptoms (loss of appetite and weight loss)., Conclusion: Results are suggestive of a subgroup of depressive patients characterised by a specific symptom cluster and disturbed niacin skin flushing., (Copyright 2009 Elsevier B.V. All rights reserved.)

We applied voxel-based morphometry to high-resolution magnetic resonance images of 99 participants with schizophrenia. Voxel-wise correlations with a score of auditory hallucination severity identified areas in the left and right superior temporal cortex (including Heschl's gyrus), left supramarginal/angular gyrus, left postcentral gyrus and left posterior cingulate cortex. This study extends previous region-of-interest studies demonstrating main effects of auditory hallucinations related to modality-specific superior temporal areas including primary and secondary auditory cortices.

Phospholipase A2 (PLA2) is involved in important aspects of dementia, for example neurotransmission and memory processing, membrane function, choline availability, and antioxidative defense. Reduced PLA2-activity has been reported so far in blood samples and postmortem neuronal tissue in Alzheimer disease. For the first time, we studied PLA2 in cerebrospinal fluid (CSF) in Alzheimer disease (AD), vascular (VD), and mixed Alzheimer/vascular dementia (MD). Intracellular PLA2 was assessed in CSF of 16 AD, 12 VD, 15 MD patients, and 19 healthy control subjects. A fluorometric assay was applied using the PLA2-specific substrate NBDC6-HPC. Significantly reduced PLA2 activity was not only found in AD, but also in VD and MD. This finding was independent of demographic co-variates and medication. PLA2 results in CSF corroborate previous findings of impaired PLA2 function in Alzheimer's disease and extend these to patients with VD. They are likely to reflect an involvement of PLA2 impairment in a variety of pathomechanisms crucial in different dementia subtypes, in which disruption of cholinergic neurotransmission and disturbance of intact membrane function appear to be the key mechanisms.

Topical application of nicotinic acid results in erythema, and in some cases oedema of the skin, supporting a strong relationship between niacin sensitivity and prostaglandin D2. The aim of this study was to examine the inter-rater and intra-rater reliability of a 12-min niacin sensitivity test in healthy adults. Three raters assessed the skin reaction of 12 volunteers, over 3-min intervals across four niacin concentrations (0.1, 0.01, 0.001, and 0.0001), and over six sessions. Inter-rater reliability estimates ranged from 0.85 to 0.97 for the total niacin sensitivity score. Similar inter-rater reliability estimates were found for niacin sensitivity ratings by concentration and time. Intra-rater reliability estimates ranged from 0.63 to 0.93 for the total niacin sensitivity score. These data indicate that the 12-min topical niacin sensitivity test has excellent reliability.

Increasing evidence suggests modulating effects of cannabinoids on time of onset, severity, and outcome of schizophrenia. Efforts to discover the underlying pathomechanism have led to the assumption of gene x environment interactions, including premorbid genetical vulnerability and worsening effects of continuing cannabis use. The objective of this cross-sectional study is to investigate the relationship between delta-9-tetrahydrocannabinol intake and niacin sensitivity in schizophrenia patients and healthy controls. Intensity of niacin skin flushing, indicating disturbed prostaglandin-mediated processes, was used as peripheral marker of lipid-arachidonic acid pathways and investigated in cannabis-consuming and nonconsuming schizophrenia patients and in healthy controls. Methylnicotinate was applied in three concentrations onto the forearm skin. Flush response was assessed in 3-min intervals over 15 min using optical reflection spectroscopy. In controls, skin flushing was significantly decreased in cannabis-consuming as compared to nonconsuming individuals. When comparing the nonconsuming subgroups, patients showed significantly decreased flush response. The populations as a whole (patients and controls) showed an inverse association between skin flushing and sum scores of Symptom Check List 90-R. Results demonstrate an impact of long-term cannabis use on lipid-arachidonic acid pathways. Considering pre-existing vulnerability of lipid metabolism in schizophrenia, observed effects of cannabis use support the notion of a gene x environment interaction.

Background: Disruption of arachidonic acid pathways and prostaglandin signalling has been implicated in the pathophysiology of schizophrenia., Aims: We intended to study prostaglandin signalling in groups of young schizophrenia patients, first-degree relatives, and healthy controls in order to assess effects of heritability on this biological marker-one important endophenotype criterion., Method: Namely, we assessed intensity of methylnicotinate skin flushing using optical reflection spectroscopy. Tests were applied to 19 adolescent first-episode schizophrenia patients, 21 first-degree relatives, and groups of age and gender matched healthy controls., Results: Compared to healthy controls, attenuation of skin flushing at low niacin concentrations was found only in schizophrenia patients, but not in first-degree relatives., Conclusion: While our results indicate niacin hyposensitivity as reliable biological marker in schizophrenia, they do not provide clear evidence for its heritability. Particularly, the results in adolescent schizophrenia patients are suggestive for the perception of attenuated niacin flushing as secondary to the pathophysiology at the onset of schizophrenic illness, namely increased oxidative stress, alterations of unspecific immune-response or inflammation-like processes.

(31)Phosphorus magnetic resonance spectroscopy ((31)P-MRS) allows in vivo investigation of cerebral phospholipid and energy metabolism. Using 2D chemical shift imaging, this method can be applied to study multiple brain areas and to assess concentrations of both phospholipids and high-energy phosphates. The purpose of our study was to assess multiregional metabolic profiles in schizophrenia using a 2D-resolved MRS technique, and to assess the intercorrelation of findings. We applied (31)P-MRS chemical shift imaging in 31 schizophrenia patients (12 antipsychotic-naïve first-episode and 19 antipsychotic-free multi-episode patients) and 31 healthy age- and sex-matched controls. Spatially resolved maps were compared for the main metabolites of the (31)P spectrum. Metabolites of phospholipid (PME and PDE) and energy (PCr and Pi) metabolism were significantly reduced in bilateral prefrontal and medial temporal (including hippocampal) brain regions, caudate nucleus, thalamus and anterior cerebellum as compared to controls. Moreover, factor analysis of these changes showed a characteristic spatial pattern of changes, which demonstrates significant associations between alterations of phospholipid and energy metabolism, and between metabolic alterations and severity of symptoms (BPRS total score, but not SANS or SAPS scores). This suggests a pattern of intercorrelated changes of these metabolic markers. Results support the notion of disturbed phospholipid turnover in schizophrenia, probably unrelated to prior pharmacological treatment, and associated with increased energy demand.

Bioactive lipids, in particular arachidonic acid (AA), are vital for monoaminergic neurotransmission, brain development and synaptic plasticity. Phospholipases A2 (PLA2) are key-enzymes in AA metabolism and are activated during monoaminergic neurotransmission. Reduced membrane AA levels, and an altered activity of PLA2 have been found in peripheral membranes of drug-naïve patients with schizophrenia with some conflicting results in more chronic patient populations. Furthermore, in vivo brain phosphorus-31 magnetic resonance spectroscopy suggests reduced lipid membrane precursors (phosphomonoesters) and increased membrane breakdown products (phosphodiesters) in drug-naïve or early treated first-episode schizophrenia patients compared to age-matched controls or chronic populations and these changes were correlated with peripheral red blood cell membrane AA levels. We postulate that processes modulating membrane lipid metabolism are associated with psychotic illnesses and might partially explain the mechanism of action of antipsychotic agents, as well as experimental agents such as purified ethyl-eicosapentaenoic acid (E-EPA). Recent supplementation trials suggest that E-EPA is a modestly effective augmentation treatment resulting in reduced doses of antipsychotic medication in acutely ill patients with schizophrenia (but not in residual-type schizophrenia). This review investigates the role of bioactive lipids in schizophrenia and its treatment, as well as its potential use in prevention.

Background: Increased activity of calcium independent phospholipase A2 (iPLA2) has repeatedly been found in the serum of unmedicated first-episode schizophrenia patients and assumed to reflect a pertubation of phospholipid metabolism. Previous studies in chronic schizophrenia were less conclusive. To explore whether iPLA2 changes are stage dependent, we investigated serum iPLA2 activity in various stages of schizophrenia., Methods: iPLA2 activity was assessed in the serum of 30 first-episode and 23 multiepisode schizophrenia patients and 53 healthy control subjects matched for age and gender. A fluorimetric assay was applied using the PLA2 specific substrate NBDC6-HPC, thin-layer chromatography of reaction products, and digital image scanning for signal detection., Results: Group comparison between first-episode and multiepisode patients and corresponding control groups revealed significantly increased iPLA2 activity only in first-episode patients. Enzyme activity in first-episode patients was also markedly increased, compared with chronic patients. iPLA2 changes observed were irrespective of neuroleptic medication, age, or gender., Conclusions: Our results suggest increased lipid turnover in the acute early phase of schizophrenia that is less obvious in chronic stages. Future longitudinal studies involving iPLA2 activity and phosphorous magnetic resonance spectroscopy need to address the relation between perturbed brain lipid metabolism and iPLA2 increment in the course of schizophrenia.

The mismatch negativity (MMN) as an auditory evoked potential is thought to reflect an early, preconscious attention process. While this component has gained great importance in studies on clinical populations and in basic research on auditory information processing, the involvement of different neurotransmitters in the generation of this component is less well understood. We investigated the impact of the benzodiazepine lorazepam as a GABA agonist on the neuromagnetic MMN (MMNm) and auditory evoked field component N100m. A group of 12 healthy subjects was studied in single blind trials under the following three conditions: after the intake of 1.25 mg lorazepam, 100 mg caffeine or placebo. Neuromagnetic recordings were obtained before drug intake and three times after it. Controlled visual attention was tested additionally using a version of the Continuous Performance Test (CPT). The neuromagnetic activity was reconstructed by a single moving dipole, and the dipole moment and its latency were compared between conditions and time points of measurement. Lorazepam diminished the signal detection performance in the CPT 25 min after drug intake. The source of the field component N100m was attenuated, most significantly in the recording 105 min after lorazepam intake. The attenuation of the MMNm under lorazepam became significant at 105 min, but was visually less apparent, because in all conditions a decrease of the MMNm dipole moment within the course of a session was observed. Besides the already known effects of benzodiazepines on controlled attention functions, preconscious attention functions as reflected in the MMN are impaired by acute benzodiazepine intake. MMN studies on clinical populations have to be controlled for the recording time because of the strong habituation of this component.

Investigation of abnormal skin response to niacin (vitamin B3) stimulation has gained increasing interest in schizophrenia research during last years. However, current efforts to implement niacin tests in routine diagnostics are jeopardised by wide inter-individual variations of skin response. We investigated age and gender as potential factors of influence on niacin sensitivity in 117 healthy subjects (63 male, 54 female). Niacin was applied in three dilution steps (0.1, 0.01, 0.001 M) onto the inner forearm skin. Skin reaction was assessed in three minute intervals over 15 min using optical reflection spectroscopy. Males displayed a significantly weaker flush response than females. The rate of non-responders at the lowest concentration was about twice as high in men than women. Significant negative correlations between age and niacin sensitivity were revealed for both sexes. Age and gender considerably influence niacin sensitivity, possibly due to the effects of sex hormones on vasomotor function and prostaglandin metabolism. Consideration of gender and age is strongly recommended for further clinical niacin studies.

Spontaneous intracranial hypotension (SIH) is known to cause postural headache, often combined with auditory, and vestibular symptoms, nausea, vomiting, and diplopia. We report a 63-year-old male patient who for the first time developed a depressive episode followed by acute manic symptoms during the course of SIH, both relieved after treatment of the underlying organic disturbance.

The rationale of this study was to understand the complexity of kinetics of fluorogenic phospholipid substrates as well as contradictory findings of clinical papers measuring phospholipase A2 (PLA2) activity using different methodologies. The aim was to recommend to clinicians and researchers what substrate in conjunction with what assay should be used. Two methods, (i) continuous fluorometric assay and (ii) high performance thin layer chromatography (HPTLC) on microplates combined with quantitative image scanning, were studied with three different substrates (bis-BODIPY FL C11-PC, NBDC6-HPC, PED6). The study demonstrates that NBD-PC is not a suitable substrate to measure PLA2 activity using a spectrofluorometer. On the other hand, NBD-PC gives the highest and most reproducible integrated light intensities (ILls) in HPTLC studies. Slow time-dependent increases in fluorescence intensities recorded with biological samples in fluorometers, but not caused by substrate splitting, had to be classified as "perturbation kinetics". PLA2 activities in blood samples of 26 unmedicated schizophrenia patients and 26 age-matched healthy controls were measured by the spectrofluorometric method and then compared with the activity data obtained with the HPTLC method. A significant group difference was found only with the HPTLC. In order to get more reliable results, we recommend that clinicians and researchers use NBD-phosphatidylcholines as PLA2 substrates in biological samples and start with an analytical separation of reaction products followed by image analysis of the fluorescent spots.

The niacin skin phenomenon reflects a prostaglandin (PG) mediated flush and oedema reaction. As PG metabolism is linked to breakdown of membrane lipids, diminished sensitivity to niacin application suggests potential disturbance in membrane phospholipid-arachidonic acid-PG pathways. We aimed to evaluate and quantify topical niacin skin reaction in early psychosis using optical reflection spectroscopy (ORS) and a new descriptive assessment scale integrating time course, redness, and oedema. Niacin skin tests were performed on 25 medicated first-episode psychosis patients fulfilling DSM-IV criteria for schizophreniform psychosis or schizophrenia and on 25 healthy controls. Nicotinic acid was applied in four dilution steps to the subjects inner forearm skin and skin reaction was consecutively assessed using ORS and a seven point rating scale. Both descriptive ratings and spectroscopic measures revealed significant group differences at the lower niacin concentrations (0.001 and 0.0001 M). At higher concentrations (0.01 and 0.1 M) only descriptive ratings were capable to show significant group effects. Data of both methods showed moderate to strong correlation (r=0.605) as long as the erythema was not affected by the oedema. The data suggest that niacin sensitivity is inversely correlated with negative symptoms. Both methods demonstrate that niacin sensitivity is impaired in a group of first episode psychosis patients and are therefore able to distinguish a subgroup of patients with metabolic impairment. Niacin sensitivity in high risk populations and the specificity of impaired skin response are subjects of further investigation.

The intracellular pH value has a profound influence on cerebral metabolism. Thus, inadequate pH control may intensify local metabolic deficits. To investigate the influence of neuroleptics on cerebral intracellular pH, we retrospectively evaluated the findings from three independent phosphorous-31 magnetic resonance spectroscopy ((31)P-MRS) studies on schizophrenic patients. A total sample of 72 patients and 32 healthy controls was investigated. A modified pH value was found only in those schizophrenic patients treated with the atypical neuroleptic clozapine.

Optical reflection spectroscopy is a simple and quick method for the quantification of colour intensity, and is thus suitable for the determination of changes in skin reddening (erythema) due to local vasodilatation. To quantify the time course of this erythema, the oxyhaemoglobin absorption double peak with maxima at 542 and 577 nm is an appropriate parameter. A compact handheld optical spectrometer makes the technique applicable to clinical use, an example being the niacin patch test described herein. This noninvasive test provides information about the cell membrane metabolism via the skin flush induced by niacin (vitamin B3) and mediated by prostaglandin. The aim of this study was to adapt optical reflection spectroscopy to the requirements of the clinical niacin patch test. To that end, we investigated 60 healthy volunteers. Analysis of the spectroscopic data with regard to physiological covariables of niacin sensitivity revealed faster and more intense erythema in females--a gender effect that to our knowledge has not previously been reported. In the light of these results, the findings of other researchers based on semi-quantitative test methods should be reassessed, with consideration given to the gender effect.

Functional neuroimaging findings of "hypofrontality" in schizophrenic patients - as tested with the Wisconsin Card Sorting Test (WCST) - are still controversial, mainly due to methodological aspects and the heterogeneity of the patient samples. To measure WCST specific and reproducible reduced cerebral activations in schizophrenic patients, we revised the study design and patient recruitment, respectively. For this purpose, we used an adequate active control task instead of an undefined rest condition to determine exclusively WCST specific cerebral activations. In addition, we focused on the investigation of modified activations between a selected group of neuroleptic-naive schizophrenic patients and carefully matched healthy controls by means of functional magnetic resonance imaging. The results indicate that neuroleptic-naive schizophrenic patients show reduced activations in the right frontal and left temporal lobe, as well as in the left cerebellum. By utilizing an active control task all unwanted activations are suppressed. Furthermore the influence of different task performances is reduced. The findings are in line with previous PET and SPECT studies and confirm the "hypofrontality" hypothesis. The findings suggest that "hypofrontality" is not caused by neuroleptic medication.

In this retrospective study the efficacy of tumor dispensaire in patients with superficial transitional cell carcinoma of the bladder was investigated in a population of 246 patients. Special attention was payed to follow up cystoscopy. Furthermore our goal was to identify and confirm prognostic factors relevant to recurrence rate and tumor progression. After transurethral resection 241 patients suffering from superficial bladder cancer were enclosed. The first of them were diagnosed in 1984 with a mean follow up range of 6.1 years and a minimum of 1 year. The evaluation was closed in 1995. The 1-year recurrence free rate of all cases amounts to 60%, whereas 42% of patients with a pT1-primary tumor and 45% with a pTa-primum developed a relapse within 2 years after the first diagnosis. All in all more than 50% of all recurrent tumors occurred within the first two years if illness. Patients with pTa and pT1 tumor are progressed in 10.7% and 18%. In 8% we saw lymphogen metastases in patients with pT1 carcinoma. 149 patients (62%) were followed up exactly (+/- 1 cystoscopy) according to the investigation schedule. More than +/- 3 aberrant cystoscopies contrary to the follow up instructions happened very seldom. Prognostic factors to be found of significance for tumor progression and recurrence risk are: tumor staging and grading, multiplicity in occurrence, period of time between first diagnosis and first relapse, associated dysplasia or carcinoma in situ. Chest X-ray and urography should be performed in accordance to the patients individual clinical situation, not routinely (2 cases of pulmonary metastasis occurred after pT1G2-3 tumor progression in 496 regular chest X-rays and 1 ureter tumor was diagnosed by routine urography). As a main result of our investigation we defined two groups of patients with superficial bladder cancer: a "low risk" group (pTa, G1-2, late recurrence (> 2 yrs.) and a "high risk" group (pT1, G3, early recurrence (< 2 yrs.), multifocal occurrence). Group 1 ("low risk") should be followed up for 5 years and group 2 ("high risk") for 10 years. Cystoscopic investigations are scheduled with regard to the group risk of recurrence and tumor progression. For patients of both groups the need of chest X-ray and urography should be evaluated individually.

During the last few years analyses of the lipidmetabolism have been performed on schizophrenic patients. Anabolic and katabolic metabolite-concentrations from blood and cell samples have been measured. By means of new investigation techniques, such as 31P-magnetic-resonance-spectroscopy, it is nowadays even possible to determine membrane metabolites non-invasively in vivo. Arachidonic acid deficits in peripheral cell membranes, turnover of phosphodiesters in the brain, increased phospholipase A2 (PLA2)-activity in serum and blood cells, disturbed niacin-response and abnormalities of the PLA2-gene are summarised as phospholipid-membrane-hypothesis of schizophrenia. Although there is some evidence for correlations between those findings and psychotic symptoms, the connection to the pathogenesis of schizophrenia still has speculative character. Furthermore it has to be confirmed that peripheral biochemical findings acquired in schizophrenics are transferable to the metabolism of the central nervous system. Actual results of enzyme and metabolite measurements reported in literature and current findings of our own 31P-MR-spectroscopic studies are surveyed and summarised. To point out possible connections between the phospholipid-metabolism of the central nervous system and of peripheral blood-cells, systemic approaches are considered.

31Phosphorus nuclear magnetic resonance spectroscopy (31P-MRS) has gained much interest in schizophrenia research in the last years, since it allows noninvasive measurement of high energy phosphates and phospholipids of the human brain in vivo. Thus, several studies have reported cerebral metabolic differences between patients and healthy controls as well as on lateralization effects and influences of epidemiological and psychopathological factors. This review gives a survey of the potential of 31P-MRS in schizophrenia research and summarizes and comments on the results of preceding studies. The discussion covers the reduction of phospholipids in patients in the context of the membrane phospholipid hypotheses, the question of an energetic hypometabolism in schizophrenics, and the influence of neuroleptic medication.