ArticlePsychopharmacology2012
Effects of chronic clozapine administration on markers of arachidonic acid cascade and synaptic integrity in rat brain.
Article in Psychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02272010 (Targeted Alterations in n-3 and n-6 Fatty Acids for the Management of Mood Variability in the Maintenance Phase of Bipolar Disorder), which is not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Targeted Alterations in n-3 and n-6 Fatty Acids for the Management of Mood Variability in the Maintenance Phase of Bipolar Disorder
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Arachidonic acid in aging: New roles for old players.Journal of advanced research · 2025Review
- Third-Generation Antipsychotics: The Quest for the Key to Neurotrophism.Life (Basel, Switzerland) · 2025Review
- Impact of neuroinflammation on brain glutamate and dopamine signalling in schizophrenia: an update.Metabolic brain disease · 2025Review
- Antipsychotics-Induced Changes in Synaptic Architecture and Functional Connectivity: Translational Implications for Treatment Response and Resistance.Biomedicines · 2022Review
- Serotonin Receptor 5-HTCells · 2022Article
- Moderate blood alcohol and brain neurovulnerability: Selective depletion of calcium-independent phospholipase A2, omega-3 docosahexaenoic acid, and its synaptamide derivative as a potential harbinger of deficits in anti-inflammatory reserve.Alcoholism, clinical and experimental research · 2021Article
- Plasma Lysophosphatidylcholine and Lysophosphatidylethanolamine Levels Were Associated With the Therapeutic Response to Olanzapine in Female Antipsychotics-naïve First-episode Patients With Schizophrenia.Frontiers in pharmacology · 2021Article
- Ageing: Is there a role for arachidonic acid and other bioactive lipids? A review.Journal of advanced research · 2018Review
- Studies on Prostaglandin-Endoperoxide Synthase 1: Lower Levels in Schizophrenia and After Treatment with Antipsychotic Drugs in Conjunction with Aspirin.The international journal of neuropsychopharmacology · 2018Article
- Immediate-Early Genes Modulation by Antipsychotics: Translational Implications for a Putative Gateway to Drug-Induced Long-Term Brain Changes.Frontiers in behavioral neuroscience · 2017Review
- Plasma linoleic acid partially mediates the association of bipolar disorder on self-reported mental health scales.Journal of psychiatric research · 2015Article
- Peripheral BDNF: a candidate biomarker of healthy neural activity during learning is disrupted in schizophrenia.Psychological medicine · 2015Article
- Is schizophrenia a neurodegenerative disease? Evidence from age-related decline of brain-derived neurotrophic factor in the brains of schizophrenia patients and matched nonpsychiatric controls.Neuro-degenerative diseases · 2015Article
- Does Systemic Inflammation Play a Role in Pediatric Psychosis?Clinical schizophrenia & related psychoses · 2015Article
- Existing and novel biological therapeutics in suicide prevention.American journal of preventive medicine · 2014Article
- RETRACTED: Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in the postmortem frontal cortex from schizophrenia patients.Schizophrenia research · 2013Article
- Chronic clozapine reduces rat brain arachidonic acid metabolism by reducing plasma arachidonic acid availability.Journal of neurochemistry · 2013Article
- Effect of repetitive daily ethanol intoxication on adult rat brain: significant changes in phospholipase A2 enzyme levels in association with increased PARP-1 indicate neuroinflammatory pathway activation.Alcohol (Fayetteville, N.Y.) · 2013Article
- Elevated immune-inflammatory signaling in mood disorders: a new therapeutic target?Expert review of neurotherapeutics · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe mode of action of clozapine, an atypical antipsychotic approved for treating schizophrenia (SZ) and used for bipolar disorder (BD) mania, remains unclear. We tested for overlap with the actions of the mood stabilizers, lithium, carbamazepine and valproate, which downregulate arachidonic acid (AA) cascade markers in rat brain and upregulate BDNF. AA cascade markers are upregulated in BD and SZ postmortem BD brain in association with neuroinflammation and synaptic loss, while BDNF is decreased.
methodsRats were injected intraperitoneally with a therapeutically relevant dose of clozapine (10 mg/kg/day) or with saline for 30 days, and AA cascade and synaptic markers and BDNF were measured in the brain.
resultsCompared with saline-injected rats, chronic clozapine increased brain activity, mRNA and protein levels of docosahexaenoic acid (DHA)-selective calcium-independent phospholipase A₂ type VIA (iPLA₂), mRNA and protein levels of BDNF and of the postsynaptic marker, drebrin, while decreasing cyclooxygenase (COX) activity and concentration of prostaglandin E₂ (PGE₂), a proinflammatory AA metabolite. Activity and expression of AA-selective calcium-dependent cytosolic cPLA₂ type IVA and of secretory sPLA₂ Type II were unchanged.
conclusionsThese results show overlap with effects of mood stabilizers with regard to downregulation of COX activity and PGE₂ and to increased BDNF and suggest a common action against the reported neuropathology of BD and SZ. The increased iPLA₂ expression following clozapine suggests increased production of anti-inflammatory DHA metabolites, and, with increased BDNF and drebrin, clear neuroprotective action.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.