Metabolomic analysis of biochemical changes in the plasma and urine of first-episode neuroleptic-naïve schizophrenia patients after treatment with risperidone.

Early findings propose that impaired neurotransmission in the brain plays a key role in the pathophysiology of schizophrenia. Recent advances in understanding its multiple etiologies and pathogenetic mechanisms provide more speculative hypotheses focused on even broader somatic systems. Using a targeted tandem mass spectrometry (MS/MS)-based metabolomic platform, we compared metabolic signatures consisting of monoamine and amino acid neurotransmitter (NT) metabolites in plasma/urine simultaneously between first-episode neuroleptic-naïve schizophrenia patients (FENNS) and healthy controls before and after a 6-week risperidone monotherapy, which suggest that the patient NT profiles are restoring during treatment. To detect and identify potential biomarkers associated with schizophrenia and risperidone treatment, we also performed a combined ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) and 1H nuclear magnetic resonance (NMR)-based metabolomic profiling of the same samples, indicating a further deviation of the patients' global metabolic profile from that of controls. The NTs and their metabolites together with the 32 identified biomarkers underpin that metabolic pathways including NT metabolism, amino acid metabolism, glucose metabolism, lipid metabolism, energy metabolism, antioxidant defense system, bowel microflora and endocrine system are disturbed in FENNS. Among them, pregnanediol, citrate and α-ketoglutarate (α-KG) were significantly associated with symptomatology of schizophrenia after Bonferroni correction and may be useful biomarkers for monitoring therapeutic efficacy. These findings promise to yield valuable insights into the pathophysiology of schizophrenia and may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.

Abnormal plasma monoamine metabolism in schizophrenia and its correlation with clinical responses to risperidone treatment.

Abnormalities in plasma monoamine metabolism reflect partly the illness of schizophrenia and sometimes the symptoms. Such studies have been repeatedly reported but have rarely taken both metabolites and parent amines or inter-amine activity ratios into account. In this study, the monoamines, their metabolites, turnovers and between-metabolite ratios in plasma were measured longitudinally in 32 schizophrenic patients treated with risperidone for 6 weeks, to examine possible biochemical alterations in schizophrenia, and to examine the association between treatment responses and psychopathology assessed according to the Positive and Negative Syndrome Scale (PANSS). The results showed lower level of plasma 3,4-dihydroxyphenylacetic acid (DOPAC) in relapsed versus first-episode schizophrenic patients, higher norepinephrine (NE) turnover rate (TR) in undifferentiated in comparison to paranoid schizophrenic patients and relatively higher metabolic activity of dopamine (DA) to serotonin (5-HT) in first-episode versus relapsed schizophrenic patients. Risperidone treatment induced a decrement of plasma DA levels and increments of plasma DOPAC and DA TR in the total group of schizophrenic patients. The turnover rate of 5-HT was was reduced in undifferentiated and relapsed subgroups of schizophrenic patients. The linkages between 5-HT TR, DA/NE relative activity and clinical symptomatology were also identified. These findings are consistent with an involvement of these systems in the pathogenesis of schizophrenia as well as in the responses to treatment, and the usefulness of certain biochemical indices as markers for subgrouping.

Elevated plasma γ-aminobutyrate/glutamate ratio and responses to risperidone antipsychotic treatment in schizophrenia.

BACKGROUND: γ-aminobutyrate (GABA) and Glutamate (Glu) are respectively two major inhibitory and excitatory neurotransmitters in the central nervous system and recent theories propose that both of their signaling complexes are compromised in patients with schizophrenia. METHODS: The changes in plasma GABA, Glu and GABA/Glu ratio in schizophrenia have been studied and may be potential clinical markers. Here, we examined if plasma GABA, Glu and GABA/Glu ratio are altered in 32 schizophrenics, including a comprehensive investigation of their involvements with clinical course of a 6-week risperidone antipsychotic treatment. RESULTS: Plasma levels of GABA and Glu were significantly lower in patients than in controls, while plasma GABA/Glu ratio was significantly elevated. During treatment, a non-significant further decrease of plasma GABA, a significant increase of plasma Glu and a significant reduction of plasma GABA/Glu ratio were observed. The ratio returned to the control level at week 6 even though concentrations of GABA and Glu were still distant from normal. After the Bonferroni correction, partial correlation analyses showed that plasma GABA and GABA/Glu ratio were positively correlated with the dose of risperidone and plasma concentration of 9-hydroxyrisperidone. The reduction of plasma GABA/Glu ratio was positively correlated with the improvement of activation symptom cluster. CONCLUSIONS: The elevated plasma GABA/Glu ratio reinforces the idea of an abnormal GABA-Glu interaction in schizophrenia. The ratio may be a good peripheral state-like marker in schizophrenia research.

[Prevalence of psychiatric disorders in primary and middle school students in Hunan Province].

OBJECTIVE: To investigate the prevalence of psychiatric disorders in a representative sample of primary and middle school students in Hunan Province. METHODS: A total of 9 495 children aged 5-17 years from Hunan urban and rural schools were enrolled by a cluster sampling and a two-phase design. The students' psychiatric status was assessed using the Investigation Screening Inventory for Child Mental Disorder and a semi-structured interview designed based on the DSM-IV criteria. RESULTS: The overall prevalence of psychiatric disorders was 16.22%. Attention-deficit and disruptive behavior disorders were the commonest in the diagnostic categories of psychiatric disorders (10.69%). Regarding specific disorders, the most prevalent was attention-deficit/hyperactivity disorder (5.95%). Psychiatric disorders were more prevalent in boys than in girls (20.49% vs 11.16%; p<0.01). The prevalence of attention-deficit and disruptive behavior disorders in boys was higher than in girls (14.76% vs 5.87%; p<0.01). The prevalence of psychiatric disorders in middle school students (12-17 years) was significantly higher than in primary students (5-11 years) (18.38% vs 14.64%; p<0.01). There were no significant differences in the prevalence of psychiatric disorders between urban and rural students. CONCLUSIONS: Psychiatric disorders are common among primary and middle school students in Hunan Province. The prevalence of this disorder in boys is higher than in girls. The middle school students have higher prevalence than primary students.

[A case-control study on family environment related factors in attention deficit hyperactivity disorder with anxiety disorder].

OBJECTIVE: To study the family rearing pattern of attention deficit hyperactivity disorder (ADHD) with or without anxiety disorder and to explore its risk factors. METHODS: 9495 children and their parents were sampled at random in Hunan province, using two-stage investigation. Those who were diagnosed ADHD and the normal control filled out Egna Minnen av Barndoms Uppfostran and family adaptability and cohesion scale by themselves. RESULTS: The comparison of factors as: actual family cohesion, parents' punishments, rejection, mother's excessive protection, intervention and father's excessive protection were significantly different between ADHD with or without anxiety disorder and normal children (P < 0.05). The comparison of parents' punishments, rejection, excessive protection and intervention were obviously different between ADHD with anxiety disorder and simple ADHD (P < 0.05). Mother's rejection was the influencing factor of simple ADHD, with OR as 1.122. Ideal family cohesion, mother's rejection and father's punishments were the influencing factors of ADHD with anxiety disorder, with OR as 0.966, 1.215 and 1.089 respectively. CONCLUSION: There were some problems in the parental rearing pattern of ADHD with or without anxiety disorder. Mother's rejection, father's punishments and ideal family cohesion were suggested to be correlated with ADHD and anxiety disorder.