Electrophysiological index of acoustic temporal regularity violation in the middle latency range

Objective

Acoustic violations in temporal regularity have been traditionally indexed by mismatch negativity (MMN). However, recent studies have demonstrated that humans can detect auditory changes in physical sound features, such as frequency, location and intensity, in the first 50 ms after sound onset. Our aim was to examine if temporal regularity violations could be detected in the middle latency range.

Methods

We used an oddball paradigm with 290 ms as standard stimulus onset asynchrony (SOA) and 200 ms as deviant SOA. We also employed a control paradigm that comprised of seven SOAs including 200 and 290 ms, in order to control for differences due to refractoriness.

Results

In the middle latency range, temporal regularity violations led to enhanced Pa and Nb responses, which behaved differently to the corresponding SOAs in the control condition. In the long latency range, temporal regularity violations led to similar behaviours in both oddball and control paradigms.

Conclusions

These findings suggest that with a fast presentation rate, human brains are capable to detect temporal regularity violations in the middle latency range.

Significance

Together with previous studies that found early change detection responses, the current study emphasises that the human brain can encode simple regularity violation as early as approximately 50 ms post-stimulus onset.     

Overweight and obesity in patients with bipolar disorder or schizophrenia compared with a non-psychiatric sample

Objective

Multiple studies suggest an association of overweight and obesity with bipolar disorder (BD) and schizophrenia. The goal of this paper was to determine the magnitude of this association and its relationship with previous course-of-illness and other variables of clinical interest.

Methods

The prevalence of overweight and obesity was compared among patients with BD (n = 108), patients with schizophrenia (n = 250) and a non-psychiatric control group (n = 290). Moreover, within each group we analyzed the variables associated with overweight [including obesity, i.e., body mass index (BMI) ≥ 25] and obesity (BMI ≥ 30) adjusting for a possible confounding effect of sex, age and educational level by logistic regression.

Results

In comparison with the non-psychiatric sample, a strong association of both BMI ≥ 25 and obesity was observed with BD and schizophrenia (adjusted odds ratios between 3.4 and 4.6; P-values < 0.001). Overweight was significantly associated with male sex and increasing age in both control and BD groups; and with female sex among schizophrenia patients. Moreover, for BD patients, earlier onset of first BD symptoms, presence of a non-psychiatric illness, current use of mood-stabilizing medication, and being a non-smoker were significantly associated with overweight; and male sex and the presence of a non-psychiatric illness, with obesity. Within the schizophrenia patients, obesity was significantly associated with female sex, intermediate age range and lower PANSS score.

Conclusions

Among patients with BD or schizophrenia, the chronic course of their illness and their current treatment with psychotropic medication might be more relevant for becoming overweight or obese than the specific psychiatric illness.     

Predictors of symptomatic remission in patients with first-episode schizophrenia: A 16 years follow-up study

Objective

Recent views on schizophrenia outcome and treatment suggest that symptomatic remission is possible, and a definition of remission has been proposed by the Remission in Schizophrenia Working Group (RSWG).This study evaluated whether patients who achieved remission after several years of illness (R) showed psychopathological differences at the onset of their disorder compared to non-remitted (NR) patients.

Method

Forty-eight patients with first-episode schizophrenia were evaluated with the Positive and Negative Symptoms Scale (PANSS) both at the onset of illness and after a mean period of 16 years. Patients were defined as R or NR according to the RSWG criteria.

Results

Eighteen patients (37.5%) were classified as R at follow-up. At onset, R patients showed a lower illness severity, less severe negative and general psychopathology symptoms compared to NR. Furthermore, they underwent fewer psychotic episodes than NR over the course of follow-up. Remission was predicted by lower severity of negative and general psychopathology symptoms at onset and by lesser number of psychotic episodes during follow-up.

Conclusions

The symptomatic remission may be a viable outcome in schizophrenia, particularly for patients with a mild illness and less severe negative symptoms at onset and with few psychotic episodes over time.     

Temperament and character in individuals at ultra-high risk for psychosis and with first-episode schizophrenia: Associations with psychopathology,psychosocial functioning,and aspects of psychological health

Objective

The psychobiological model of temperament and character indicates that personality traits are heritable and, during development, constantly influence one’s susceptibility to schizophrenia. Our objective was to evaluate temperament and character in subjects at ultra-high risk (UHR) for psychosis and individuals with first-episode schizophrenia.

Methods

UHR for psychosis subjects (n = 50), first-episode schizophrenia patients (n = 33), and normal controls (n = 120) were compared on temperament and character dimensions, and correlation analysis of each personality dimension with psychopathologies, global and social functioning, and self-esteem. General and social self-efficacy reports were conducted. UHR subjects were followed-up for 24 months and the baseline personality dimensions were compared between the converted and non-converted groups.

Results

Both clinical groups showed abnormal personality traits in terms of temperament (higher harm avoidance, lower reward dependence and persistence) and character (lower self-directedness and cooperativeness). Psychosocial functioning and psychological health components were found to be correlated with some personality dimensions. The conversion rate of overt psychotic disorder was 25.0% at the 24-month follow-up. Baseline cooperativeness dimension was a significant predictive dimension for conversion into overt psychosis in the UHR group during the follow-up period.

Conclusion

Patients with first episode schizophrenia have a pervasively altered personality profile from normal controls. More importantly, this altered personality profile already emerged in putative prodromal, UHR individuals. The present findings indicate that certain personality traits can play a protective or vulnerable role in developing schizophrenia.     

Relationships between IGF-1, schizophrenia,and treatment of metabolic syndrome

Objectives

The use of atypical antipsychotic drugs in patients with psychiatric illness may result in dyslipidemia, hypertension, glucose intolerance, and abdominal obesity, which are together referred to as metabolic syndrome (MS). To investigate any correlations among insulin-like growth factor-1 (IGF-1), schizophrenia, and MS, we examined the metabolic profiles of patients with schizophrenia taking atypical antipsychotics.

Design

Patients with schizophrenia, their siblings, and controls participated in this study (N = 50 in each group). The Structured Clinical Interview for DSM-IV Axis 1 Disorders (SCID I) and the Brief Psychiatric Rating Scale (BPRS) were administered to patients, and SCID I was administered to patients' siblings. We drew blood to measure IGF-1 levels and to determine the metabolic profiles of all participants; we also conducted anthropometric measurements.

Results

There were no significant differences in IGF-1 levels between groups. By comparing IGF-1 levels with MS-related parameters, we found that IGF-1 levels were negatively correlated with triglyceride levels in the control group, and positively correlated with HDL levels in the patient group (Pearson's correlation: r = −0.291, P = 0.04, and r = 0.328, P = 0.02, respectively). Compared to their siblings, patients with schizophrenia had a significantly different body mass index, waist circumference, and insulin resistance, and showed a trend toward a difference in glucose levels (ANOVA: P = 0.004, P < 0.0001, P = 0.004, P = 0.072, respectively).

Conclusion

A correlation between IGF-1 and MS may significantly influence future therapeutic strategies for MS. In order to determine the role of IGF-1 in schizophrenia, comprehensive longitudinal studies with first-episode drug-naive patients are needed.     

Differentiation of first-episode schizophrenia patients from healthy controls using ROI-based multiple structural brain variables

Background

Brain morphometric measures from magnetic resonance imaging (MRI) have not been used to discriminate between first-episode patients with schizophrenia and healthy subjects.

Methods

Magnetic resonance images were acquired from 34 (17 males, 17 females) first-episode schizophrenia patients and 48 (24 males, 24 females) age- and parental socio-economic status-matched healthy subjects. Twenty-nine regions of interest (ROI) were measured on 1-mm-thick coronal slices from the prefrontal and central parts of the brain. Linear discriminant function analysis was conducted using standardized z scores of the volumes of each ROI.

Results

Discriminant function analysis with cross-validation procedures revealed that brain anatomical variables correctly classified 75.6% of male subjects and 82.9% of female subjects, respectively. The results of the volumetric comparisons of each ROI between patients and controls were generally consistent with those of the previous literature.

Conclusions

To our knowledge, this study provides the first evidence of MRI-based successful classification between first-episode patients with schizophrenia and healthy controls. The potential of these methods for early detection of schizophrenia should be further explored.     

The loudness dependence of the auditory evoked potential (LDAEP) in schizophrenia,bipolar disorder,major depressive disorder,anxiety disorder,and healthy controls

Background

Serotonergic dysfunction in schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, and healthy controls was evaluated by measuring the activity of the loudness dependence of the auditory evoked potential (LDAEP).

Methods

The 357 subjects who were evaluated comprised 55 normal controls, 123 patients with major depressive disorder, 37 with bipolar disorder, 46 with schizophrenia, 37 with panic disorder (PD), 31 with generalized anxiety disorder (GAD), and 28 with post-traumatic stress disorder (PTSD).

Results

LDAEP was significantly stronger in healthy controls than in patients with either bipolar disorder (p = 0.025) or schizophrenia (p = 0.008), and significantly stronger in patients with major depressive disorder than in those with bipolar disorder (p = 0.01) or schizophrenia (p = 0.03). LDAEP did not differ significantly between patients with major depressive disorder and healthy control subjects (p = 0.667), or between healthy control subjects and patients with anxiety disorder, including PD (p = 0.469), GAD (p = 0.664), and PTSD (p = 0.167).

Conclusion

The findings of the present study reveal that patients with major psychiatric disorders exhibit different strengths of LDAEP according to their serotonin-related pathology. Studies controlled for psychotropic medication, menstruation cycle, and smoking are needed.     

An exploratory model for G × E interaction on hippocampal volume in schizophrenia; obstetric complications and hypoxia-related genes

Background

Smaller hippocampal volume has repeatedly been reported in schizophrenia patients. Obstetric complications (OCs) and single nucleotide polymorphism (SNP) variation in schizophrenia susceptibility genes have independently been related to hippocampal volume. We investigated putative independent and interaction effects of severe hypoxia-related OCs and variation in four hypoxia-regulated schizophrenia susceptibility genes (BDNF, DTNBP1, GRM3 and NRG1) on hippocampal volume in schizophrenia patients and healthy controls.

Methods

Clinical assessment, structural MRI scans, and blood samples for genotyping of 32 SNPs were obtained from 54 schizophrenia patients and 53 control subjects. Information on obstetric complications was collected from original birth records.

Results

Severe OCs were related to hippocampal volume in both patients with schizophrenia and healthy control subjects. Of the 32 SNPs studied, effects of severe OCs on hippocampal volume were associated with allele variation in GRM3 rs13242038, but the interaction effect was not specific for schizophrenia. SNP variation in any of the four investigated genes alone did not significantly affect hippocampal volume.

Conclusions

The findings suggest a gene–environment (G × E) interaction between GRM3 gene variants and severe obstetric complications on hippocampus volume, independent of a diagnosis of schizophrenia. Due to the modest sample size, the results must be considered preliminary and require replication in independent samples.     

Increased white matter integrity in the corpus callosum in subjects with high genetic loading for schizophrenia

Objective

White matter abnormalities in the corpus callosum (CC) of schizophrenia have been reported to predate the illness onset. This study aimed to investigate the effect of genetic predisposition on the white matter integrity of the CC, in subjects at genetically high risk for schizophrenia (GHR) and schizophrenia patients.

Method

Fractional anisotropy (FA) of the mid-sagittal CC in 22 young GHR, 15 schizophrenia, and 26 control subjects were examined. GHR subjects were defined as non-prodromal individuals who had more than two relatives with schizophrenia within third-degree relatives, one of whom must be a first-degree relative.

Results

ANCOVA with age and gender as covariates revealed overall difference of FA in the genu and splenium among the three groups. Post-hoc analysis found significantly increased FA in the genu of GHR subjects compared to controls (corrected p < 0.01), whereas schizophrenia patients showed significantly decreased FA in the splenium.

Conclusion

The white matter change of the CC in young GHR subjects was the opposite of that in schizophrenia. To consider previous reports on FA decrease in the CC in schizophrenia and the impaired frontal functioning in GHR group, the increased FA may be an indicator of compensatory alteration in white matter integrity in young GHR people.     

Abnormal regional spontaneous neural activity in first-episode,treatment-naive patients with late-life depression: A resting-state fMRI study

Background

The previous resting perfusion or task-based studies have provided evidence of functional changes in the brains of patients with late-life depression (LLD). Little is known, so far, about the changes in the spontaneous brain activity in LLD during the resting state. The aim of this study was to investigate the spontaneous neural activity in first-episode, treatment-naive patients with LLD by using resting-state functional magnetic resonance imaging (fMRI).

Methods

A novel analytical method, coherence-based regional homogeneity (Cohe-ReHo), was used to assess regional spontaneous neural activity during the resting state in 15 first-episode, treatment-naive patients with LLD and 15 age- and gender-matched healthy controls.

Results

Compared to the healthy controls, the LLD group showed significantly decreased Cohe-ReHo in left caudate nucleus, right anterior cingulate gyrus, left dorsolateral prefrontal cortex, right angular gyrus, bilateral medial prefrontal cortex, and right precuneus, while significantly increased Cohe-ReHo in left cerebellum posterior lobe, left superior temporal gyrus, bilateral supplementary motor area, and right postcentral gyrus (p < 0.005, corrected for multiple comparisons).

Conclusions

These findings indicated abnormal spontaneous neural activity was distributed extensively in first-episode, treatment-naive patients with LLD during the resting state. Our results might supply a novel way to look into the underlying pathophysiology mechanisms of patients with LLD.     

Association of the manganese superoxide dismutase gene Ala–9Val polymorphism with clinical phenotypes and tardive dyskinesia in schizophrenic patients

Objective

Several recent studies that have investigated the genetic association between the manganese superoxide dismutase (MnSOD) gene Ala–9Val single-nucleotide polymorphism (SNP) and tardive dyskinesia (TD) have produced conflicting results. This study was to investigate whether this SNP was associated with clinical phenotypes and antipsychotic-induced tardive dyskinesia (TD) in schizophrenia in a genetically homogeneous Han Chinese inpatient population.

Methods

Genotyping was performed for the MnSOD gene Ala–9Val SNP in Chinese schizophrenia patients with (n = 176) and without TD (n = 346). The severity of TD was assessed using the abnormal involuntary movement scale (AIMS), and psychopathology using the Positive and Negative Syndrome Scale (PANSS).

Results

The frequencies of genotypes and alleles did not differ significantly between schizophrenic patients with and without TD (both p > 0.05). Also, there was no significant difference in the AIMS total score between the Val/Val and Ala allele carrier groups (p > 0.05). However, the PANSS negative symptom subscore was significantly higher in patients with Val/Val genotype (21.8 ± 7.3) than those with Ala alleles (20.1 ± 7.7) (t = 2.32, p = 0.03).

Conclusion

While the MnSOD gene Ala–9Val polymorphism did not play a major role in the susceptibility to TD in schizophrenic patients, it might be associated with negative symptoms of schizophrenia.     

Insulin resistance and metabolic profile in antipsychotic naïve schizophrenia patients

Objectives

Several studies have suggested insulin resistance related to dyslipidemia and body weight in drug treated schizophrenia patients. Although, insulin resistance or impaired glucose tolerance is also reported in antipsychotic naïve schizophrenia patients, their relationship with dyslipidemic changes and body weight is not well established. The present study was undertaken to examine insulin resistance in antipsychotic naïve schizophrenia patients of this region and to evaluate any association between lipid parameters and body weight with their insulin resistance, if any.

Method

Plasma glucose, total serum cholesterol and its LDL, HDL fractions, and serum insulin levels were measured from fasting blood samples of newly diagnosed, antipsychotic naïve schizophrenia patients (n = 30) and matched control group (n = 25) in a hospital based case control study. Homoeostatic model assessment (HOMA) was done to evaluate insulin resistance.

Results

Means of plasma glucose, total serum cholesterol and its LDL, HDL fractions did not vary significantly (p > 0.05) between cases and control. Insulin resistance was significantly increased (p < 0.05) in drug naïve cases. Multiple linear regression analyses did not show any association (p > 0.05) between insulin resistance and lipid parameters.

Conclusions

Newly diagnosed schizophrenia patients were more prone to insulin resistance in our study population. This was not associated with any dyslipidemic changes as the lipid parameters were not elevated in them compared to the healthy controls. It was not dyslipidemia, but some other common genetic or risk factors that might be responsible for the increased insulin resistance in antipsychotic naïve schizophrenia patients in our study population.     

Pain conditions among veterans with schizophrenia or bipolar disorder

Objective

The purpose of this study was to assess the rates of chronic, noncancer pain conditions in patients with schizophrenia or bipolar disorder within the Veterans Health Administration (VHA) System.

Method

This cross-sectional study used administrative data extracted from VHA treatment records of all individuals receiving VHA services in fiscal year 2008 (N= 5,195,551). The associations between severe psychiatric disorders (schizophrenia and bipolar disorder) and chronic pain (arthritis, back pain, chronic pain, migraine, headache, psychogenic and neuropathic) were evaluated using a series of logistic regression analyses.

Results

Veterans with schizophrenia [odds ratio (OR)=1.21] and bipolar disorder (OR=2.17) were significantly more likely to have chronic pain overall relative to veterans without these psychiatric conditions. These associations were slightly lower than for the association between depression and pain in this sample (OR=2.61). The highest associations between specific psychiatric diagnosis and pain condition were found with chronic pain, headache and psychogenic pain.

Conclusions

Noncancer pain conditions occur in elevated rates among patients with schizophrenia and bipolar disorder. Future research could further examine possible barriers to adequate pain treatment among people with serious mental illness, as well as the extent to which chronic pain might impact mental health recovery.     

Resting brain perfusion in alcohol-induced psychotic disorder: A comparison in patients with alcohol dependence,schizophrenia and healthy controls

Introduction

Alcohol-induced psychotic disorder (AIPD), also known as alcohol hallucinosis, is a rare complication of alcohol abuse. The underlying pathophysiology is poorly understood, and the disorder needs to be differentiated from alcohol withdrawal delirium and schizophrenia. No brain-imaging studies in AIPD have been reported to date. Case reports of brain imaging in AIPD suggest possible dysfunction in the thalamus, basal ganglia, frontal lobes and cerebellum. Our aim was to prospectively compare resting brain perfusion (rCBF) in patients with AIPD, uncomplicated alcohol dependence, schizophrenia and healthy volunteers.

Methods

Single photon emission computed tomography (SPECT) was utilized to compare rCBF in patients with AIPD (n = 19), schizophrenia (n = 16), uncomplicated alcohol dependence (n = 20) and healthy volunteers (n = 19).

Results

Increased rCBF was demonstrated in the right calcarine area in patients with AIPD compared to healthy volunteers, with a trend towards increased rCBF to the frontal and temporal lobes and the right pallidum. Decreased left sided rCBF to the putamen, parietal, mid-frontal and mid-temporal lobes and heterogenous flow to the cerebellum were demonstrated in patients with AIPD when compared to patients with uncomplicated alcohol dependence. The left posterior cingulate and right cerebellum showed higher and lower rCBF respectively in patients with AIPD compared to patients with schizophrenia.

Conclusion

Our findings implicate the right occipital lobe and possibly the cerebellum in the pathogenesis of AIPD and have similarities with those previously reported in alcohol withdrawal. Reduced rCBF to the frontal lobes, thalamus and basal ganglia in AIPD as suggested in previous case reports could not be confirmed.     

A genetic schizophrenia-susceptibility region located between the ANKK1 and DRD2 genes

Background

The gene coding for the D2 dopamine receptor (DRD2) is considered to be one of the most pertinent candidate genes in schizophrenia. However, genetic studies have yielded conflicting results whereas the promising TaqIA variant/rs1800497 has been mapped in a novel gene, ANKK1.

Methods

We investigated eleven single nucleotide polymorphisms (SNPs) spanning the DRD2 and ANKK1 genes, using both a case–control association study comparing 144 independent patients to 142 matched healthy subjects, and a transmission disequilibrium test in 108 trios. This classical genetic study was coupled with a cladistic phylogeny-based association test of human variants, and with an interspecies evolution study of ANKK1.

Results

Case–control study, followed by a 108 trios family-based association analysis for replication, revealed an association between schizophrenia and the ANKK1 rs1800497 (p = 0.01, Odds Ratio = 1.5, 95% Confidence Interval = 1.1–2.2), and the intergenic rs2242592 (p = 2 · 10^− 4, OR = 1.8, 95%CI = 1.3–2.5). A significant SNP–SNP interaction was also found (p < 10^− 5, OR = 2.0, 95%CI = 1.6–2.5). The phylogeny-based association test also identified an association between both these polymorphisms and schizophrenia. Finally, interspecies comparison of the sequences from chimpanzee, orangutan, rhesus macaque and human species suggested specific involvement of ANKK1 in the human lineage.

Conclusions

Intergenic rs2242592 appears to be involved in the genetic vulnerability to schizophrenia, whereas the ANKK1 rs1800497 appears to have a modifying rather than causative effect. Finally, ANKK1 may be a specific human lineage-trait involved in a specific human disease, schizophrenia.     

The wide variability of perospirone metabolism and the effect of perospirone on prolactin in psychiatric patients

Background

Perospirone was developed in Japan and is used for the treatment of schizophrenia and related illnesses. The authors investigated the relationship between the dosage of perospirone and the plasma levels of perospirone and its active metabolite, ID15036, and also evaluated the impact of the plasma concentrations of perospirone and ID15036 on the plasma prolactin level to examine whether perospirone or ID15036 affected the dopamine D₂ blockade, in psychiatric patients treated with perospirone.

Methods

The subjects consisted of 21 adults treated with perospirone (4–60 mg/day). The plasma perospirone and ID15036 levels were measured in 21 patients and serum prolactin levels were investigated in 10 male patients with schizophrenia.

Results

The plasma ID15036 level was higher than the plasma perospirone, and a positive correlation was observed between the dosage of perospirone and the ID15036 levels (p = 0.032). The 10 male patients showed a positive correlation between the plasma perospirone levels and plasma prolactin levels (r = 0.688, p = 0.028) and between the plasma ID15036 levels and prolactin levels (r = 0.775, p = 0.009).

Conclusion

The plasma levels of ID15036 may have a greater impact on the dopamine D₂ blockade than perospirone in patients treated with perospirone.     

Serum brain-derived neurotrophic factor predicts responses to escitalopram in chronic posttraumatic stress disorder

Introduction

Some studies have found that antidepressants increase serum brain-derived neurotrophic factor (BDNF) levels in patients with major depression and the expression of BDNF mRNA in limbic structures of rats.

Objectives

This study addressed whether the SSRI escitalopram increases serum BDNF levels in subjects with PTSD and whether BDNF levels are associated with treatment response.

Methods

Medically healthy male subjects (N = 16) with chronic PTSD completed a 12 week open-label trial of flexible dose (5–20 mg/day) escitalopram monotherapy. BDNF levels were obtained at baseline, and at weeks 4, 8 and 12.

Results

PTSD symptoms significantly declined over the course of the 12 week escitalopram treatment. Despite a substantial improvement in PTSD symptoms, there was virtually no change in BDNF levels over time. Nevertheless, mean BDNF levels across the trial were strongly correlated with the slope of PTSD symptoms over the 12 weeks (r = 0.58, p = 0.018). Lower mean BDNF was associated with a greater decrease in PTSD symptoms over the course of the trial.

Conclusions

PTSD subjects with low BDNF levels demonstrated the largest treatment response from an agent with putative neurotrophic effects.     

Religious involvement is associated with greater purpose,optimism, generosity and gratitude in persons with major depression and chronic medical illness

Objective

Religious involvement may help individuals with chronic medical illness cope better with physical disability and other life changes. We examine the relationships between religiosity, depressive symptoms, and positive emotions in persons with major depression and chronic illness.

Methods

129 persons who were at least somewhat religious/spiritual were recruited into a clinical trial to evaluate the effectiveness of religious vs. secular cognitive behavioral therapy. Reported here are the relationships at baseline between religious involvement and depressive symptoms, purpose in life, optimism, generosity, and gratefulness using standard measures.

Results

Although religiosity was unrelated to depressive symptoms (F = 0.96, p = 0.43) and did not buffer the disability–depression relationship (B = − 1.56, SE 2.90, p = 0.59), strong relationships were found between religious indicators and greater purpose, optimism, generosity, and gratefulness (F = 7.08, p < 0.0001).

Conclusions

Although unrelated to depressive symptoms in the setting of major depression and chronic medical illness, higher religious involvement is associated with positive emotions, a finding which may influence the course of depression over time.     

Comparison of the density of gamma-aminobutyric acid in the ventromedial prefrontal cortex of patients with first-episode psychosis and healthy controls

Background

Abnormality in the concentration and functioning of gamma-aminobutyric acid (γ-aminobutyric acid, GABA) in the brain is not only an important hypothetical link to the cause of schizophrenia but it may also be correlated with the cognitive decline and negative symptoms of schizophrenia. Studies utilizing high field magnetic resonance spectroscopy (MRS) report abnormal density of GABA in the ventromedial prefrontal cortex (vmPFC) of patients with chronic schizophrenia, but these results may be confounded by study participants’ prior use of antipsychotic medications.

Aim

Compare the density of GABA in the vmPFC of patients with first-episode psychosis to that in healthy controls and assess the relationship of GABA density in the vmPFC to the severity of psychotic symptoms.

Methods

Single-voxel ¹H-MRS was used to assess the concentration of GABA and other metabolites in the vmPFC of 22 patients with first-episode psychosis (10 with schizophrenia and 12 with schizophreniform disorder) and 23 healthy controls. Thirteen of the 22 patients were drug-naïve and 9 had used antipsychotic medication for less than 3 days. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the severity of psychotic symptoms in the patient group.

Results

The mean (sd) GABA density in the vmPFC was significantly higher in patients than in controls (2.28 [0.54] v. 1.93 [0.32] mM, t=2.62, p=0.012). The densities of other metabolites – including N-acetylaspartic acid (NAA), glutamic acid (GLU), and glutamine (GLN) – were not significantly different between patients and controls. Among the patients, GABA density in the vmPFC was not significantly correlated with PANSS total score or with any of the three PANSS subscale scores for positive symptoms, negative symptoms, and general psychopathology. GABA concentration was not associated with the duration of illness, but it was significantly correlated with patient age (r=0.47, p=0.026).

Conclusion

Elevation of GABA density in the vmPFC of patients with first-episode psychosis confirms that this abnormality is independent of medication use. The failure to find a correlation of GABA density in the vmPFC with the severity of psychotic symptoms needs to be confirmed in larger studies, but it suggests that there are several intervening steps between brain pathology and clinical symptoms.     

Deficient inhibition of return in schizophrenia-further evidence from an independent sample

Previous studies on spatial orienting of attention in schizophrenia demonstrated a deficit of Inhibition of Return (IOR). However, other studies reported a delay in the manifestation, but an overall normal amount of IOR in patients with schizophrenia. However, the latter studies used a cue-back manipulation which is known to reinstate or speed up IOR. Hence, it is not clear whether even very long cue target intervals would allow IOR to develop in patients with schizophrenia in the absence of a cue-back manipulation. The aim of the present study was to study IOR in patients with schizophrenia using a single cue paradigm and a very long cue target interval of >1 s in order to differentiate between blunted and delayed IOR. We examined 32 inpatients with schizophrenia and 16 healthy controls with a covert orienting of attention task (COVAT) with non-predictive peripheral cues and three stimulus onset asynchronies (SOA: 100 ms, 800 ms and 1050 ms). We found a lack of Inhibition of Return (IOR) in patients with schizophrenia with both long SOAs of 800 and 1050 ms. As in a previous study of our group, the IOR deficit was unrelated to psychopathology, length of illness, number of previous psychotic episodes and type of neuroleptic medication. In summary, our study confirms and extends previous reports of deficient IOR in patients with schizophrenia. IOR seems to be not just delayed, but rather profoundly disturbed in schizophrenia. Deficient IOR in patients with schizophrenia might be viewed as a trait or alternatively as a vulnerability marker of the disorder.