ABSTRACT
Schizophrenia is a severe mental condition in which several lipid abnormalities-either structural or metabolic-have been described. We tested the hypothesis that an abnormality in membrane lipid composition may contribute to aberrant dopamine signaling, and thereby symptoms and cognitive impairment, in schizophrenia (SCZ) patients. Antipsychotic-medicated and clinically stable SCZ outpatients (n=74) were compared with matched healthy subjects (HC, n=40). A lipidomic analysis was performed in red blood cell (RBC) membranes examining the major phospholipid (PL) classes and their associated fatty acids (FAs). Clinical manifestations were examined using the positive and negative syndrome scale (PANSS). Cognitive function was assessed using the Continuous Performance Test, Salience Attribution Test and Wisconsin Card Sorting Test. Sphingomyelin (SM) percentage was the lipid abnormality most robustly associated with a schizophrenia diagnosis. Two groups of patients were defined. The first group (SCZ c/SM-) is characterized by a low SM membrane content. In this group, all other PL classes, plasmalogen and key polyunsaturated FAs known to be involved in brain function, were significantly modified, identifying a very specific membrane lipid cluster. The second patient group (SCZ c/SM+) was similar to HCs in terms of RBC membrane SM composition. Compared with SCZ c/SM+, SCZ c/SM- patients were characterized by significantly more severe PANSS total, positive, disorganized/cognitive and excited psychopathology. Cognitive performance was also significantly poorer in this subgroup. These data show that a specific RBC membrane lipid cluster is associated with clinical and cognitive manifestations of dopamine dysfunction in schizophrenia patients. We speculate that this membrane lipid abnormality influences presynaptic dopamine signaling.
Subject(s)
Cognitive Dysfunction/physiopathology , Dopamine/physiology , Lipid Metabolism/physiology , Membrane Lipids/physiology , Schizophrenia/physiopathology , Schizophrenic Psychology , Signal Transduction/physiology , Adult , Case-Control Studies , Chronic Disease , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Erythrocytes/metabolism , Fatty Acids/metabolism , Female , Humans , Male , Middle Aged , Neuropsychological Tests/statistics & numerical data , Phospholipids/metabolism , Psychometrics , Schizophrenia/diagnosis , Sphingomyelins/metabolism , Statistics as Topic , Synaptic Transmission/physiologyABSTRACT
BACKGROUND: Epidemiological studies suggest a positive but controversial correlation between the major mental disorders, particularly schizophrenia and delinquent or criminal acting out. aim : To study the occurrence of violence in patients with schizophrenia according to demographic, clinical and disease progression features. METHODS: This retrospective study included all out-patients, consulting during a period of one month, suffering from schizophrenia for at least five years. The clinical and forensic history was obtained owing to a semi-structured interview with patients and their families, medical records and the passing of different scales. RESULTS: Sixty patients were included. 46.7% (n=28) of patients had a violent behavior in the pre morbid period. Aggressiveness was noted as the first prodrome in 13.3% (n=8) of cases. 28 major acts of violence were committed by 30% (n=18) of patients regardless of the active period of disease. In 13.3% (n=8) of cases, these acts announced the disease. The majority of acts have been committed against a non-foreign person. Recurrence was noted in 44.4% (n=8) of patients. Several risk factors of violent behavior were found. Only prodromal aggression was associated with a poor prognosis. CONCLUSION: Violences committed by patients with schizophrenia are attributed to a particular group of patients and do not have necessarily a pejorative prognostic value.