Relationships between erythrocyte membrane mono- and poly- unsaturated fatty acid composition and clinical/cognitive indices in antipsychotic-free schizophrenia patients.

Introduction: Membrane phospholipid abnormalities are considered a pathophysiological background for schizophrenia. The aim of the study was to explore in detail the fatty acid (FA) composition in patients with antipsychotic-free schizophrenia and its association with clinical symptoms and cognitive function. Materials and methods: Erythrocyte membrane FAs were measured in 29 antipsychotic-free patients with schizophrenia (male/female = 11/18; mean [standard deviation] age=26.7 [7.9] years) and age and sex-matched 32 healthy volunteers. Clinical symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), and the Schizophrenia Cognition Rating Scale (SCoRS). Results: Eicosapentaenoic acid levels were lower in the schizophrenia group than in the healthy control group. In contrast, arachidonic acid and nervonic acid levels were higher in the schizophrenia group than in the control group. Nervonic acid levels were significantly associated with depression scores as measured by the PANSS. No FA levels were correlated with BACS score; however, oleic acid levels were significantly related to cognitive dysfunction, as measured by the SCoRS. Conclusion: These findings suggest that depressive symptoms along with cognitive dysfunction in daily living in schizophrenia may be linked to the FA composition abnormalities. Further studies will be needed to examine potential longitudinal FA changes during the course of schizophrenia as well as disease specificity.

Analysis of polyunsaturated fatty acids in antipsychotic-free individuals with at-risk mental state and patients with first-episode schizophrenia.

Introduction: Abnormalities in membrane phospholipids are considered one of the pathophysiological backgrounds for schizophrenia. This study, explores the fatty acid composition of erythrocyte membranes and its association with clinical characteristics in two groups: individuals with an at-risk mental state (ARMS) and patients experiencing their first-episode of schizophrenia (FES). Materials and methods: This study measured erythrocyte membrane fatty acids in 72 antipsychotic-free individuals with ARMS, 18 antipsychotic-free patients with FES, and 39 healthy volunteers. Clinical symptoms and cognitive and social functions were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Schizophrenia Cognition Rating Scale (SCoRS), and Social and Occupational Functioning Assessment Scale (SOFAS). Results: Eicosapentaenoic and docosapentaenoic acid levels were lower in the ARMS and FES groups than in the healthy control group. In contrast, nervonic acid (NA) levels were markedly higher in the ARMS and FES groups than in the controls, while only the FES group showed higher levels of arachidonic acid. Oleic acid and NA levels were significantly associated with PANSS scores in both the FES and ARMS groups, particularly for the negative and general subscores. However, the patient groups had no significant associations between the fatty acid composition and the BACS, SCoRS, and SOFAS scores. Furthermore, the baseline fatty acid composition did not differ between the ARMS individuals who later developed psychosis (N = 6) and those who were followed for more than 2 years without developing psychosis onset (N = 30). Discussion: The findings suggest that abnormal fatty acid compositions may be shared in the early stages of schizophrenia and the clinical high-risk state for psychosis and may serve as vulnerability markers of psychopathology.

Creation, effects on embryo quality, and clinical outcomes of a new embryo culture medium with 31 optimized components derived from human oviduct fluid: A prospective multicenter randomized trial.

Purpose: Our aim is to make an ideal embryo culture medium close to human oviduct fluid (HOF) components, and to evaluate the quality of this medium with embryo quality and clinical outcomes in assisted reproductive technology (ART) by a prospective randomized controlled trial (RCT). Methods: Study I: HOF was collected laparoscopically from patients (n = 28) with normal pelvic findings. According to HOF analysis results, the new medium "HiGROW OVIT®" (OVIT) was designed. Study II: Embryos (2 pronuclei (2PN) = 9633) were assigned from 1435 patients. The blastulation rate (BR), good BR (gBR), utilized (transferred/cryo-preserved) BR (uBR), pregnancy rate (PR), and miscarriage rate (MR) were compared between the OVIT and control groups by RCT. Results: The novel medium 'OVIT' was produced according to 31 HOF components. The concentrations of essential amino acids (e-AAs) were lower in OVIT than in current media, yet the opposite was true for ne-AA concentrations. gBR and uBR were higher in the OVIT group than in the control group. In the older female group, gBT and uBR were significantly higher in the OVIT group. Conclusions: The novel medium 'OVIT' was produced according to HOF data. The OVIT had significantly better embryo quality and clinical outcomes than the current media.

Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine.

Accumulating evidence implicates oxidative stress as a potential pathophysiological mechanism of schizophrenia. Accordingly, we synthesized new chemicals using apocynin and tandospirone as lead compounds (A-2, A-3 and A-4). These novel compounds decreased reactive oxygen species (ROS) concentrations in vitro and reversed decreases in glutathione levels in the medial prefrontal cortex of rats transiently exposed to MK-801, an N-methyl-d-aspartate receptor antagonist, in the neonatal period. To determine whether A-2, A-3 and A-4 show behavioral effects associated with antipsychotic properties, the effects of these compounds on methamphetamine (MAP)-induced locomotor and vertical activity were examined in the model rats. A-2 and A-3, administered for 14 days around the puberty period, ameliorated MAP-induced hyperlocomotion in MK-801-treated rats in the post-puberty period, while A-4 suppressed MAP-induced vertical activity. These findings indicate that apocynin-tandospirone derivatives present anti-dopaminergic effects and may alleviate psychotic symptoms of schizophrenia.

Association between olfactory sulcus morphology and olfactory functioning in schizophrenia and psychosis high-risk status.

Olfactory impairment has been reported in patients with schizophrenia and individuals with a high risk of psychosis, but its neural basis is largely unknown. We used magnetic resonance imaging to investigate the morphology of the olfactory sulcus (an indicator of olfactory system development) and its relation to olfactory function in 38 persons with an at-risk mental state (ARMS), 62 patients with schizophrenia, and 61 healthy controls. Odor detection and identification were examined with a T & T olfactometer. Compared with the controls, the olfactory sulcus was significantly shallower and odor identification was inferior among the ARMS and schizophrenia subjects. Across all subjects, but not within each group, the olfactory sulcus depth was significantly related to better identification of odors. Our results support the concept that olfactory sulcus morphology reflects the neurodevelopmental process of the olfactory system.

Endometrial stromal cell attachment and matrix homeostasis in abdominal wall endometriomas.

STUDY QUESTION: How does progesterone alter matrix remodeling in abdominal wall endometriomas compared with normal endometrium? SUMMARY ANSWER: Progesterone may prevent attachment of endometrial cells to the abdominal wall, but does not ameliorate abnormal stromal cell responses of abdominal wall endometriomas. WHAT IS KNOWN ALREADY: Menstruation is a tightly orchestrated physiologic event in which steroid hormones and inflammatory cells cooperatively initiate shedding of the endometrium. Abdominal wall endometriomas represent a unique form of endometriosis in which endometrial cells inoculate fascia or dermis at the time of obstetrical or gynecologic surgery. Invasion of endometrium into ectopic sites requires matrix metalloproteinases (MMPs) for tissue remodeling but endometrium is not shed externally. STUDY DESIGN SIZE, DURATION: Observational study in 14 cases and 19 controls. PARTICIPANTS /MATERIALS, SETTING, METHODS: Tissues and stromal cells isolated from 14 abdominal wall endometriomas were compared with 19 normal cycling endometrium using immunohistochemistry, quantitative PCR, gelatin zymography and cell attachment assays. P values < 0.05 were considered significant and experiments were repeated in at least three different cell preps to provide scientific rigor to the conclusions. MAIN RESULTS AND THE ROLE OF CHANCE: The results indicate that MMP2 and MMP9 are not increased by TGFß1 in endometrioma stromal cells. Although progesterone prevents attachment of endometrioma cells to matrix components of the abdominal wall, it does not ameliorate these abnormal stromal cell responses to TGFß1. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Endometriomas were collected from women identified pre-operatively. Not all endometriomas were collected. Stromal cells from normal endometrium were from different patients, not women undergoing endometrioma resection. WIDER IMPLICATIONS OF THE FINDINGS: This work provides insight into the mechanisms by which progesterone may prevent abdominal wall endometriomas but, once established, are refractory to progesterone treatment. STUDY FUNDING/COMPETING INTEREST(S): Tissue acquisition was supported by NIH P01HD087150. Authors have no competing interests.

Olfactory deficits in individuals at risk for psychosis and patients with schizophrenia: relationship with socio-cognitive functions and symptom severity.

Odor identification deficits are well documented in patients with schizophrenia, but it remains unclear whether individuals at clinical high-risk for psychosis exhibit similar changes and whether their olfactory function is related to social/cognitive functions and symptomatology. In this study, we investigated odor detection sensitivity and identification ability in 32 individuals with at-risk mental state (ARMS), 59 schizophrenia patients, and 169 healthy controls using a T&T olfactometer. The ARMS and schizophrenia subjects were administered the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS) to assess their cognitive and social functions, and the Positive and Negative Syndrome Scale (PANSS) for clinical symptoms. Both the ARMS and schizophrenia subjects had lower odor identification ability when compared with healthy controls, while no significant difference was found in the odor detection sensitivity. The lower odor identification ability in the ARMS group correlated with the severity of negative symptoms and weakly correlated with lower performance on the BACS verbal fluency test. The olfactory measures of schizophrenia patients did not correlate with illness duration, medication, symptom severity, and social and cognitive functions. For the ARMS and schizophrenia groups, the olfactory measures did not correlate with the SOFAS and SCoRS scores. These findings suggest that high-risk subjects for psychosis already show odor identification deficits similar to those observed in schizophrenia patients, which probably reflect a biological trait related to vulnerability to psychosis.

Separation efficiency of a microfluidic sperm sorter to minimize sperm DNA damage.

OBJECTIVE: To evaluate whether microfluidic sperm sorters (MFSSs) allow effective recovery of sorted motile sperm without DNA damage compared with the centrifugation and swim-up procedure. DESIGN: Experimental laboratory study. All participants completed questionnaires regarding previous and/or current diseases, surgery, reproductive experiences, lifestyle factors, and date of the preceding ejaculation. SETTING: University research laboratory. PATIENT(S): Male volunteers were recruited without setting conditions. Semen samples from healthy volunteers (n = 37) were collected in sterile containers by masturbation. INTERVENTION(S): Flow cytometric measurement and sperm chromatin structure assay analysis of DNA damage after sperm preparation using MFSS and the centrifugation and swim-up procedure. MAIN OUTCOME MEASURE(S): Efficacy and efficiency of sperm preparation, correlation between sperm DNA fragmentation index (DFI) and semen parameters, and relationship between basic characteristics and DFI after the centrifugation and swim-up procedure. RESULT(S): Final sperm concentration and motility were significantly different between the centrifugation and swim-up procedure and MFSS sperm preparations. A significantly lower sperm DNA fragmentation rate was detected with MFSS compared with the centrifugation and swim-up procedure use. No correlation was observed between DFI and smoking or drinking, but significant correlations were observed between DFI and medication use and sexual abstinence duration. CONCLUSION(S): MFSSs can be used to efficiently and reliably prepare sperm compared with the centrifugation and swim-up procedure. Further research on the clinical use of MFSSs is required to evaluate the safety and usefulness of this device.

Possible relation between olfaction and anxiety in healthy subjects.

AIMS: While olfaction is a sense closely associated with the limbic system and emotions, the relation between emotional status and olfactory functioning has not been well documented. This study aimed to examine the possible effect of anxiety on olfaction in healthy subjects. METHODS: We investigated the effect of state and trait anxiety on the detection and recognition thresholds for five different odors in 124 healthy subjects (62 men and 62 women, mean age = 27.2 years) using a T&T olfactometer. RESULTS: While the influences of age, socioeconomic status, IQ, and smoking history on olfaction were not significant, women had a lower recognition threshold for the odor of sweet fruit and a higher detection threshold for that of rotten food as compared with men. Both state and trait anxiety ratings were significantly associated with reduced olfactory ability, especially for identification of rose odor. CONCLUSIONS: These findings suggest that emotional status affects olfactory functioning in healthy subjects. Our findings may also partly explain the mild olfactory impairment reported in clinical conditions, such as anxiety disorders.

Neonatal exposure to MK-801 reduces mRNA expression of mGlu3 receptors in the medial prefrontal cortex of adolescent rats.

Schizophrenia is considered as a "neurodegenerative" and "neurodevelopmental" disorder, the pathophysiology of which may include hypofunction of the N-methyl-D-aspartate receptor (NMDA-R) or subsequent pathways. Accordingly, administration of NMDA-R antagonists to rodents during the perinatal period may emulate some core pathophysiological aspects of schizophrenia. The effect of 4-day (postnatal day; PD 7-10) administration of MK-801, a selective NMDA-R antagonist, on gene expression in the medial prefrontal cortex (mPFC), hippocampus, and amygdala was evaluated using quantitative polymerase chain reaction methods. Specifically, we sought to determine whether genes related to Glu transmissions, for example those encoding for NMDA-Rs, metabotropic Glu receptors (mGluRs), or Glu transporters, were altered by neonatal treatment with MK-801. Model rats showed downregulation of the mGluR3 subtype in the mPFC around puberty, especially at PD 35 in response to MK-801 or during ontogenesis without pharmacological manipulations. Genes encoding for other mGluRs subtypes, that is NMDA-Rs and Glu transporters, were not affected by the neonatal insult. These results suggest that NMDA-R antagonism in the early course of development modulates the expression of mGluR3 in mPFC around puberty. Thus, mGluR3 may serve as a potential target to prevent the onset and progression of schizophrenia.

Chronic treatment with tandospirone, a 5-HT(1A) receptor partial agonist, suppresses footshock stress-induced lactate production in the prefrontal cortex of rats.

Serotonin 1A receptor (5-HT1A-R) agonists have been demonstrated to elicit antidepressant and anxiolytic effects. Lactate has been considered to play a major role in energy metabolism in the brain. Specifically, extracellular lactate concentrations (eLAC) have been suggested to reflect neural activity. Mild physical (e.g., handling) and non-physical (e.g., psychological) stressors have been shown to increase eLAC in several brain regions, including the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). Using in vivo microdialysis technique, we measured eLAC in the mPFC and BLA of rats under electric footshock stress to clarify the effect of repeated injection procedure (saline, once daily for 14 days) as a stressor on brain energy metabolism. Then, we examined the effect of chronic treatment with tandospirone, a 5-HT1A-R partial agonist, on eLAC during footshock stress in the mPFC. Footshock stress led to an increase in eLAC both in the mPFC and BLA in rats without injections. Repeated saline injection increased basal eLAC in the BLA, while footshock-induced lactate increment was reduced. In the mPFC, repeated saline injection did not affect basal eLAC and footshock-induced eLAC increments. Chronic treatment with tandospirone, at 0.2 and 1.0 mg/kg/day, but not 2.0 mg/kg/day, attenuated footshock stress-induced eLAC elevation in the mPFC. These observations suggest that eLAC in the BLA is sensitive to repeated exposure to physical stress. Data also indicate chronic treatment with tandospirone diminishes acute energy demands during neural activation in the mPFC. The implications of the present findings in relation to clinical efficacy of 5-HT1A agonists are discussed.

Transforming growth factor ß1 (TGFß1) and progesterone regulate matrix metalloproteinases (MMP) in human endometrial stromal cells.

CONTEXT: Menstruation is preceded by progesterone withdrawal and endometrial matrix remodeling predominantly through induction of matrix metalloproteinases (MMP) and recruitment of invading neutrophils. DESIGN: Using endometrial tissues from women during various phases of the menstrual cycle, we found that MMP2, MMP9, and MMP11 were up-regulated in the late secretory phase/premenstrual phase. Because TGFß-responsive genes were also up-regulated in endometrium during this time, we tested the hypothesis that TGFß1 and progesterone regulate expression of MMP in human endometrial stromal cells (HESC). RESULTS: Treatment of HESC with TGFß1 resulted in marked increases in MMP2 and MMP11 mRNA and pro- and active MMP2 activity. Progesterone inhibited TGFß1-induced stimulation of MMP2 and MMP11 through its nuclear hormone receptors. Interestingly, TGFß1 also decreased progesterone receptor (PR)-A and PR-B in HESC with a more pronounced effect on PR-A. CONCLUSIONS: These data support the hypothesis that TGFß1 has endogenous anti-progestational effects in HESC and that the opposing effects of progesterone and TGFß1 are important in regulation of matrix integrity in human endometrium.

T-817MA, a novel neurotrophic agent, ameliorates loss of GABAergic parvalbumin-positive neurons and sensorimotor gating deficits in rats transiently exposed to MK-801 in the neonatal period.

T-817MA [1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate] is a newly synthesized neuroprotective agent for the treatment of psychiatric disorders characterized by cognitive disturbances, such as Alzheimer's disease. Cognitive impairment has also been suggested to be a cardinal feature of schizophrenia. We sought to determine whether T-817MA would ameliorate sensorimotor gating deficits and loss of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) neurons in the brain of rats transiently exposed to MK-801, an N-methyl-d-aspartate receptor blocker, in the neonatal stage, as an animal model of schizophrenia. Prepulse inhibition (PPI) was examined in rats treated neonatally with MK-801 (postnatal day; PD 7-10, 0.2 mg/kg/day, s.c.) or vehicle at PD 35 and PD 63. The number of PV-positive GABAergic neurons in the medial prefrontal cortex (mPFC) and the hippocampus was measured after the behavioral assessments. T-817MA (10 or 20 mg/kg) or vehicle was administered for 14 days (on PD 49-62). Administration of T-817MA at 20 mg/kg, but not 10 mg/kg, ameliorated PPI deficits and completely reversed the decrease in the number of PV-positive GABAergic neurons in rats given MK-801. These results indicate that T-817MA may provide a novel therapeutic approach for the treatment of cognitive deficits of schizophrenia.

Effect of transient blockade of N-methyl-D-aspartate receptors at neonatal stage on stress-induced lactate metabolism in the medial prefrontal cortex of adult rats: role of 5-HT1A receptor agonism.

Decreased activity of the medial prefrontal cortex (mPFC) has been considered a basis for core symptoms of schizophrenia, an illness associated with a neurodevelopmental origin. Evidence from preclinical and clinical studies indicates that serotonin (5-HT)1A receptors play a crucial role in the energy metabolism of the mPFC. This study was undertaken to determine (1) if transient blockade of N-methyl-D-aspartate receptors during the neonatal stage inhibit energy demands in response to stress, as measured by extracellular lactate concentrations, in the mPFC at the young adult stage, and (2) if tandospirone, a 5-HT1A partial agonist, reverses the effect of the neonatal insult on energy metabolism. Male pups received MK-801 (0.20 mg/kg) on postnatal days (PDs) 7-10. On PD 63, footshock stress-induced lactate levels were measured using in vivo microdialysis technique. Tandospirone (0.1, 1.0, and 5.0 mg/kg) was administered once daily for 14 days before the measurement of lactate levels. Neonatal MK-801 treatment suppressed footshock stress-induced lactate production in the mPFC, but not caudate-putamen, whereas basal lactate levels were not significantly changed in either brain region. The MK-801-induced suppression of footshock stress-induced lactate production in the mPFC was attenuated by tandospirone at 1.0mg/kg/day, but not 0.1 or 5.0 mg/kg/day, which is an effect antagonized by coadministration of WAY-100635, a selective 5-HT1A antagonist. These results suggest a role for impaired lactate metabolism in some of the core symptoms of schizophrenia, for example, negative symptoms and cognitive deficits. The implications for the ability of 5-HT1A agonism to ameliorate impaired lactate production in the mPFC of this animal model are discussed.

T-817MA, but Not Haloperidol and Risperidone, Restores Parvalbumin-Positive γ -Aminobutyric Acid Neurons in the Prefrontal Cortex and Hippocampus of Rats Transiently Exposed to MK-801 at the Neonatal Period.

The number of parvalbumin (PV)-positive γ -aminobutyric acid (GABA) neurons is decreased in the brain of rats transiently exposed to MK-801, an N-methyl-D-aspartate (NMDA) receptor blocker, in the neonatal stage (Uehara et al. (2012)). T-817MA [1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate] is a neuroprotective agent synthesized for the treatment of psychiatric disorders characterized by cognitive disturbances, such as dementia. We herein sought to determine whether T-817MA, haloperidol (HPD), or risperidone (RPD) would ameliorate the decrease in the number of PV-positive GABA neurons in the medial prefrontal cortex (mPFC) and hippocampus of the model animals. Rats were treated with MK-801 (0.2 mg/kg/day) or vehicle on postnatal days (PD) 7-10, and the number of PV-positive neurons in the mPFC and hippocampus were measured on PDs 63. T-817MA (20 mg/kg), HPD (1 mg/kg), or RPD (1 mg/kg) were administered during PDs 49-62. Fourteen-day administration of T-817MA reversed the decrease in the number of PV-positive neurons in the above brain regions of rats given MK-801, whereas HPD and RPD were ineffective. These results indicate that T-817MA provides a novel pharmacologic strategy to enhance cognitive function in patients with schizophrenia.

Membrane fatty acid levels as a predictor of treatment response in chronic schizophrenia.

Abnormal fatty acid composition in neural membranes, that is, the balance between essential polyunsaturated fatty acids (EPUFAs) and saturated fatty acids, has been suggested to be related to the psychotic symptoms and cognitive impairment of schizophrenia. This study was conducted to test the hypothesis that the ability of atypical antipsychotic drugs to ameliorate positive symptoms and cognitive function relevant to daily living would be predicted by baseline EPUFAs concentrations in the erythrocyte membrane in subjects with schizophrenia. A total of 24 actively psychotic patients with schizophrenia participated in the study. After blood drawing, they were treated with olanzapine or perospirone. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative symptoms (SANS), as well as the script tasks, a measure of event schema recognition, were administered at baseline and 3months after the start of treatment. Erythrocyte membrane fatty acid levels were analysed using a gas chromatography system. Scores of SAPS and SANS, as well as script task performance, were improved during treatment with either antipsychotic drug. Regression analysis indicates baseline EPUFAs concentrations were positively and negatively related with percent improvement of positive symptoms and script task performance, respectively. The results of this study suggest composition of phospholipids in the erythrocyte membrane provide a feasible marker to predict treatment response in patients with schizophrenia.

Change in the expression of myelination/oligodendrocyte-related genes during puberty in the rat brain.

Age-dependent changes of gene expression in the prefrontal cortex (PFC) of rats around the time of puberty were investigated by means of microarray and quantitative polymerase chain reaction (qPCR). About 127 and 138 genes were increased and decreased, respectively, in the PFC of rats at post-puberty (PD56) compared with those at pre-puberty (PD35). Functional analysis showed significant associations of these genes with aging, cellular development, and neuropsychological disorders. qPCR analysis confirmed down-regulation of seven genes related to myelination. As these genes have been reported to be diminished in the brain of patients with schizophrenia, the results of this study suggest an exaggerated maturation process may contribute to the pathogenesis of psychotic disorders.

Neonatal exposure to MK-801, an N-methyl-D-aspartate receptor antagonist, enhances methamphetamine-induced locomotion and disrupts sensorimotor gating in pre- and postpubertal rats.

Administration of non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists (e.g. phencyclidine, MK-801) has been shown to elicit behavioral abnormalities related to symptoms of schizophrenia, such as spontaneous locomotor activity and impaired sensorimotor gating, as represented by deficits of prepulse inhibition (PPI). We sought to determine whether transient blockade of NMDA receptors at the neonatal stage would produce dopamine supersensitivity around puberty, as manifested by these behavioral measures. For this purpose, we examined methamphetamine (MAP; 1.0mg/kg, i.p.)-induced locomotor activity and PPI in pre- (postnatal day; PD 36-38) or post- (PD 64-66) puberty in rats administered MK-801 (0.2mg/kg/day, s.c.) between PD 7 and PD 10. Neonatal MK-801 treatment augmented MAP-induced hyperlocomotion especially in the early adulthood, whereas spontaneous locomotor activity and rearing were not changed. MK-801 administration also disrupted PPI without affecting startle amplitudes around puberty. These findings suggest that transient exposure to MK-801 in the neonatal stage causes exaggerated dopamine transmission and cognitive deficits, particularly in the post-puberty stage.

Serotonin-1A receptor gene polymorphism and the ability of antipsychotic drugs to improve attention in schizophrenia.

INTRODUCTION: The purpose of this study was to determine if the functional single nucleotide polymorphisms of rs6259 C(-1019)G in the promoter region, which regulates serotonin 5-HT(1A) receptor transcription, affects the ability of antipsychotic drugs to improve attention in patients with schizophrenia. METHODS: Subjects were neuroleptic-free and meeting DSM-IV-TR criteria for schizophrenia. Psychopathology and attention were evaluated with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) at baseline and 3 months after treatment with atypical antipsychotic drugs (AAPDs). DNA was extracted from peripheral blood following standard procedures. Genotyping was performed with HS-Taq assay (LaboPass). RESULTS: Data were available from 30 subjects (male/female=19/11), in which 17 had the CC genotype, three had the GG genotype, and 10 were heterozygous. The 3-month treatment with AAPDs was associated with significant improvements in positive and negative symptoms, but not attention as measured by SANS-Attention subscale in the entire subject group. There were no significant differences in the degree of improvements of SAPS and SANS scores between the CC genotype group and the (C/G plus G/G) combined group. On the other hand, improvement of attention was significantly greater for the former group compared to the latter group (P<0.016), suggesting a detrimental influence of the G-allele. CONCLUSION: These results provide additional support to the role of 5-HT(1A) receptors in some of the cognitive disturbances of schizophrenia. Further studies with a larger number of subjects are warranted.