Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics

Khan, Mohammad M.; Evans, Denise; Gunna, Vijayasudha; Scheffer, Russell E.; Parikh, Vinay; Mahadik, Sahebarao P.

doi:10.1016/s0920-9964(01)00334-6

Cited by 242 publications

(140 citation statements)

References 35 publications

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“…48,52 (b) AA changes are present in drug naïve patients indicates that the relationship is independent of drug treatment and associated with the onset of disease. [49][50][51] (c) Chronic haloperidol administration in rats reduced AA levels specifically in dopaminergic neurons, possibly due to interactions with dopamine receptors and their downstream targets, the PLA2 enzymes. 57 (d) Increased calcium-independent PLA2 activity has been replicated in both peripheral and CNS tissue, and in drug naïve patients (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…Red blood cell (RBC) and CNS cell membranes of medicated and drug naïve patients with schizophrenia have significantly lower levels of PUFAs, in particular AA [48][49][50][51][52] suggesting that this is not only a drug effect. The change in AA levels correlates to decreased membrane fluidity and to psychosis severity 12,13,49,51,53 with some conflicting results.…”

Section: Pla2s and Reduced Pufas In Schizophreniamentioning

confidence: 99%

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The role of phospholipases A2 in schizophrenia

Law¹,

Cotton²,

Berger

2006

Mol Psychiatry

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A range of neurotransmitter systems have been implicated in the pathogenesis of schizophrenia based on the antidopaminergic activities of antipsychotic medications, and chemicals that can induce psychotic-like symptoms, such as ketamine or PCP. Such neurotransmitter systems often mediate their cellular response via G-protein-coupled release of arachidonic acid (AA) via the activation of phospholipases A2 (PLA2s). The interaction of three PLA2s are important for the regulation of the release of AA -phospholipase A2 Group 2 A, phospholipase A2 Group 4A and phospholipase A2 Group 6A. Gene variations of these three key enzymes have been associated with schizophrenia with conflicting results. Preclinical data suggest that the activity of these three enzymes are associated with monoaminergic neurotransmission, and may contribute to the differential efficacy of antipsychotic medications, as well as other biological changes thought to underlie schizophrenia, such as altered neurodevelopment and synaptic remodelling. We review the evidence and discuss the potential roles of these three key enzymes for schizophrenia with particular emphasis on published association studies.

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Section: Discussionmentioning

confidence: 99%

Section: Pla2s and Reduced Pufas In Schizophreniamentioning

confidence: 99%

The role of phospholipases A2 in schizophrenia

Law¹,

Cotton²,

Berger

2006

Mol Psychiatry

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“…There is also substantial evidence for altered free radical metabolism and associated free radical pathology, lipid peroxidation (Mahadik and Mukherjee, 1996;Reddy and Yao, 1996;Tsai et al, 1998;Mahadik et al, 1999), and altered lipid metabolism (Peet et al, 1999) in schizophrenia. Some studies have also found that treatment with atypical antipsychotics, but not HAL, reduces the free radical pathology and improves membrane lipid integrity with parallel improvements in psychopathology (Horrobin, 1999;Khan et al, 2002;Arvindakshan et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Haloperidol, Risperidone, and Clozapine Exposure on Cholinergic Markers and Spatial Learning Performance in Rats

Terry

Hill

Parikh

et al. 2002

Neuropsychopharmacol

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Haloperidol (HAL), a potent typical antipsychotic, continues to be a frequently prescribed medication for behavioral disturbances associated particularly with schizophrenia despite well-documented adverse effects associated with its chronic use. Animal experiments have even indicated that HAL can damage cholinergic pathways and thus could be especially deleterious to those experiencing cognitive deficits. However, several recent clinical studies indicate that atypical antipsychotics may actually improve cognitive function in some patients, although this assertion requires further investigation. The purpose of this study was to compare the effects of prior chronic (45-or 90-day) oral exposure to HAL and the atypical antipsychotics risperidone (RISP) and clozapine (CLOZ) on cognitive performance and central cholinergic markers in rats. All analyses were done after 4 days of drug washout in order to minimize direct drug effects. Learning performance and choline acetyltransferase (ChAT) levels were assessed in a water maze task and with immunofluorescence staining, respectively. HAL significantly impaired learning performance after 90 but not after 45 days of treatment when compared to both vehicle controls and the atypical agents, while RISP slightly improved task performance. Both 45 and 90 days of previous HAL exposure reduced ChAT staining in several brain regions, including the cortex, caudate-putamen, and hippocampus. ChAT staining in the caudate-putamen and hippocampus was also decreased after 90 days of RISP exposure, raising the possibility of deleterious cognitive effects after exposure to this dosage for longer periods of time. The results suggest that antipsychotic drugs exert differential and temporally dependent effects on central cholinergic neurons and learning performance.

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“…(1994) (191) C schizophrenia EM, mol/ml Treated C v. controls (192) C schizophrenia (193) C schizophrenia Brain C v. controls with mental disorders (91) C schizophrenia (194) C schizophrenia (195) C schizophrenia (196) C schizophrenia (197) C schizophrenia (81) C schizophrenia (198) C Indian schizophrenia (199) C schizophrenia and schizoaffective disorder (200) C schizophrenia…”

Section: Other Mood and Behavioural Disordersmentioning

confidence: 99%

“…Smoking and alcohol consumption, often also associated with psychiatric conditions, have also been found to impact on n-3PUFA synthesis resulting in reductions in levels (217,218) . Traditional medications for a number of psychiatric conditions may also impact on n-3PUFA status, although work on first-episode schizophrenics suggests that medications are unlikely to explain low levels of n-3PUFA in these individuals (194,199) . Evidence suggesting that both n-3PUFA status and mood may be explained by a third party is also available.…”

Section: Other Mood and Behavioural Disordersmentioning

confidence: 99%

Is there a role forn-3 long-chain polyunsaturated fatty acids in the regulation of mood and behaviour? A review of the evidence to date from epidemiological studies, clinical studies and intervention trials

2008

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Selected biochemical evidence suggests a potential role for n-3 long-chain PUFA (n-3PUFA) in the regulation of mood and behaviour. The present paper reviews the relevant evidence, to date, from epidemiological studies, clinical studies and intervention trials. Most evidence is available investigating a role for n-3PUFA in depression, depressive illness and suicidal behaviour, but work is also available on anxiety and anxiety-related disorders, fatigue and fatigue-related disorders, aggression, hostility and anti-social behaviour, inattention, impulsivity and attention deficit hyperactivity disorder and schizophrenic disorders. For all these aspects of mood and behaviour, the evidence available is currently limited and highly inconsistent, both in terms of study methodology and study findings. There is a clear need for further work in this area.

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Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics

Cited by 242 publications

References 35 publications

The role of phospholipases A2 in schizophrenia

The role of phospholipases A2 in schizophrenia

Differential Effects of Haloperidol, Risperidone, and Clozapine Exposure on Cholinergic Markers and Spatial Learning Performance in Rats

Is there a role forn-3 long-chain polyunsaturated fatty acids in the regulation of mood and behaviour? A review of the evidence to date from epidemiological studies, clinical studies and intervention trials

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