Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

Background

Prepulse inhibition (PPI) of the startle reflex is modulated by a complex neural network. Prepulse inhibition impairments are found at all stages of schizophrenia. Previous magnetic resonance imaging (MRI) studies suggest that brain correlates of PPI differ between patients with schizophrenia and healthy controls; however, these studies included only patients with chronic illness and medicated patients. Our aim was to examine the structural brain correlates of PPI in antipsychotic-naive patients with first-episode schizophrenia.

Methods

We performed acoustic PPI assessment and structural MRI (1.5 and 3 T) in men with first-episode schizophrenia and age-matched controls. Voxel-based morphometry was used to investigate the association between PPI and grey matter volumes.

Results

We included 27 patients and 38 controls in the study. Patients had lower PPI than controls. The brain areas in which PPI and grey matter volume correlated did not differ between the groups. Independent of group, PPI was significantly and positively associated with regional grey matter volume in the right superior parietal cortex. Prepulse inhibition and grey matter volume associations were also observed in the left rostral dorsal premotor cortex, the right presupplementary motor area and the anterior medial superior frontal gyrus bilaterally. Follow-up analyses suggested that the rostral dorsal premotor cortex and presupplementary motor area correlations were driven predominantly by the controls.

Limitations

We used 2 different MRI scanners, which might have limited our ability to find subcortical associations since interscanner consistency is low for subcortical regions.

Conclusion

The superior parietal cortex seems to be involved in the regulation of PPI in controls and antipsychotic-naive men with first-episode schizophrenia. Our observation that PPI deficits in schizophrenia may be related to the rostral dorsal premotor cortex and presupplementary motor area, brain areas involved in maintaining relevant sensory information and voluntary inhibition, warrants further study.     

Differential brain glucose metabolic patterns in antipsychotic-naïve first-episode schizophrenia with and without auditory verbal hallucinations

Background

Auditory verbal hallucinations (AVHs) are a core symptom of schizophrenia. Previous reports on neural activity patterns associated with AVHs are inconsistent, arguably owing to the lack of an adequate control group (i.e., patients with similar characteristics but without AVHs) and neglect of the potential confounding effects of medication.

Methods

The current study was conducted in a homogeneous group of patients with schizophrenia to assess whether the presence or absence of AVHs was associated with differential regional cerebral glucose metabolic patterns. We investigated differences between patients with commenting AVHs and patients without AVHs among a group of dextral antipsychotic-naive inpatients with acute first-episode schizophrenia examined with [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) at rest. Univariate and multivariate approaches were used to establish between-group differences.

Results

We included 9 patients with AVHs and 7 patients without AVHs in this study. Patients experiencing AVHs during FDG uptake had significantly higher metabolic rates in the left superior and middle temporal cortices, bilateral superior medial frontal cortex and left caudate nucleus (cluster level p < 0.005, family wise error–corrected, and bootstrap ratio > 3.3, respectively). Additionally, the multivariate method identified hippocampal–parahippocampal, cerebellar and parietal relative hypoactivity during AVHs in both hemispheres (bootstrap ratio < −3.3).

Limitations

The FDG-PET imaging technique does not provide information regarding the temporal course of neural activity. The limited sample size may have increased the risk of false-negative findings.

Conclusion

Our results indicate that AVHs in patients with schizophrenia may be mediated by an alteration of neural pathways responsible for normal language function. Our findings also point to the potential role of the dominant caudate nucleus and the parahippocampal gyri in the pathophysiology of AVHs. We discuss the relevance of phenomenology-based grouping in the study of AVHs.     

Complementary diffusion tensor imaging study of the corpus callosum in patients with first-episode and chronic schizophrenia

Background

Abnormalities in the corpus callosum have long been implicated in schizophrenia. Previous diffusion tensor imaging (DTI) studies in patients with different durations of schizophrenia yielded inconsistent results. By comparing patients with different durations of schizophrenia, we investigated if white matter abnormalities of the corpus callosum emerge at an early stage in the illness or result from pathological progression.

Methods

We recruited patients with first-episode schizophrenia, patients with chronic schizophrenia and age-, sex-and handedness-matched healthy controls. We used 2 DTI techniques (voxel-based and fibre-tracking DTI) to investigate differences in corpus callosum integrity among the 3 groups.

Results

With both DTI techniques, significantly decreased fractional anisotropy values were identified in the genu of corpus callosum in patients with chronic schizophrenia, but not first-episode schizophrenia, compared with healthy controls.

Limitations

This study was cross-sectional, and the sample size was relatively small.

Conclusion

Abnormalities in the genu of the corpus callosum might be a progressive process in schizophrenia, perhaps related to disease severity and prognosis.     

Is Abnormal Glucose Tolerance in Antipsychotic-Na?ve Patients With Nonaffective Psychosis Confounded by Poor Health Habits?

Introduction:

Some but not all previous studies have found abnormal glucose tolerance or fasting glucose concentrations in antipsychotic-naïve patients with nonaffective psychosis. Our finding of abnormal glucose tolerance in patients with nonaffective psychosis could not be attributed to confounding by age, ethnicity, gender, smoking, socioeconomic status (SES), hypercortisolemia, or body mass index (BMI). However, other factors merit consideration as potential confounders of this association.

Methods:

An extended sample of newly diagnosed, antipsychotic-naive patients with schizophrenia and related disorders and matched controls were administered an oral glucose tolerance test. Confounding factors related to diet, self-care/access to care, and drug abuse were evaluated.

Results:

After accounting for the variance due to age, ethnicity, gender, smoking, SES, morning cortisol concentrations, BMI (or waist–hip ratio), our previous finding of abnormal glucose tolerance in these patients was confirmed. This difference could not be attributed to confounding by substance abuse; blood concentrations of vitamin B12, folate, or homocysteine; aerobic conditioning as measured by resting heart rate; or duration of untreated psychosis.

Discussion:

These results provide further evidence that people with schizophrenia and related disorders have abnormal glucose tolerance and an increased risk of diabetes prior to antipsychotic treatment and independent of health habits and access to care. Other measures should also be examined.     

Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia

Background

Accumulating evidence from postmortem and magnetic resonance imaging (MRI) studies suggests that abnormalities of medial temporal lobe structures are critically involved in the pathogenesis of schizophrenia. It is still unclear, however, whether certain abnormalities are already present in individuals at ultra high-risk (UHR) for transition into psychosis. Recent studies involving patients at UHR showed contradictory results for hippocampal volume, and only 1 study reported that amygdalar volume was unchanged between healthy patients and those at UHR. Furthermore, no subregions of the hippocampus have been investigated in people at UHR.

Methods

We recruited 29 UHR patients, 23 first-episode patients and 29 age-and sex-matched healthy controls. We measured hippocampal and amygdalar volumes from MRI scans by use of BRAINS2 to manually trace the regions of interest. The hippocampi were divided in 2 regions: head and corpus/tail.

Results

Patients at UHR had significantly smaller volumes of the hippocampus corpus and tail bilaterally, but not of the head, compared with healthy controls. Group differences for the right hippocampus corpus and tail volume remained significant after we controlled for whole brain volume and other covariates. We found that UHR patients who later developed psychosis had smaller right hippocampus corpus and tail volumes than did those who did not develop psychosis. First-episode patients had significantly smaller left amygdalar volumes than did healthy individuals or those at UHR.

Limitations

Our study had a small sample size, and we were unable to control for the effects of medication.

Conclusion

Our findings suggest that parts of the hippocampal–amygdalar complex are involved in the pathogenesis of schizophrenia. Reduction of hippocampus corpus and tail volumes may be indicative of the prodromal phase of schizophrenia and represent risk factors for transition into psychosis. Further investigations are needed to determine whether structural changes of the left amygdala play a role during transition from the prodromal phase to the first manifest episode of schizophrenia.     

Associated factors of quality of life in first-episode schizophrenia patients

Objective

Improving quality of life is an important goal in the treatment of schizophrenia. In previous research, quality of life has been reported to be compromised in patients with schizophrenia. The aim of this study was to investigate whether quality of life may be impaired in first-episode schizophrenia patients and to identify the associated factors of quality of life in first-episode schizophrenia.

Methods

Forty-eight patients with first-episode schizophrenia and 20 normal controls were recruited. Quality of life was measured by using the Quality of Life scale (QLS). General and social self-efficacy, perceived social support were measured by using the self-report scales. The clinical assessments and comprehensive neurocognitive battery were also administered.

Results

First-episode group showed significantly decreased QLS total and QLS subscale scores compared to normal controls group. The key associated factors of quality of life in patients with first-episode schizophrenia were the negative symptoms and social self-efficacy.

Conclusion

This finding implies that compromised quality of life may be already emerged in schizophrenia in their first-episode and the psychosocial interventions should be targeting the negative symptoms and the psychosocial protective factors including self-efficacy in addition to simply ameliorating the positive symptoms to foster social reintegration and recovery of first-episode patients.     

Emotion-elicited gamma synchrony in patients with first-episode schizophrenia: a neural correlate of social cognition outcomes

Background

Schizophrenia may be understood as a disorder of neural synchrony. There is also increasing evidence that emotional and social cognitive impairments are central to this disorder. In patients with first-episode schizophrenia, we examined whether emotion perception is associated with disruptions to high-frequency (40 Hz) gamma synchrony and whether these disruptions predict self-regulatory adaptive compensations reflected in social cognitive behaviours.

Methods

We obtained electroencephalography recordings from 28 patients with first-episode schizophrenia and matched healthy controls during perception of facial emotion under both conscious and nonconscious conditions. We extracted gamma-band synchrony from the electroencephalogram. We also used behavioural measures of emotion identification, emotional intelligence, negativity bias and social function, along with ratings of first-episode schizophrenia symptoms. We analyzed group differences and predicted social cognition to assess the potential contribution of medication.

Results

Within 200 ms poststimulus, patients with first-episode schizophrenia showed alterations in gamma synchrony during both conscious and nonconscious emotion perception. Stimulus-locked synchrony was reduced in patients, particularly over the temporal cortex, whereas complementary enhancements in absolute gamma synchrony (independent of stimuli) were more distributed over temporal and left parieto-occipital regions. This pattern of altered synchrony predicted poor performance on each measure of social cognition among these patients. Medication dosage did not correlate significantly with either gamma synchrony or behavioural measures in this group.

Limitations

Limitations to our study include the lack of comparison between medicated and unmedicated patients or between types of medication.

Conclusion

These findings suggest that disruptions in integrative processing of motivationally important stimuli show promise as a potential biological marker of social cognitive impairments, present from the first episode of schizophrenia, and their outcomes.     

Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis

Background

Earlier contributions have documented significant changes in sensory, attention-related endogenous event-related potential (ERP) components and θ band oscillatory responses during working memory activation in patients with schizophrenia. In patients with first-episode psychosis, such studies are still scarce and mostly focused on auditory sensory processing. The present study aimed to explore whether subtle deficits of cortical activation are present in these patients before the decline of working memory performance.

Methods

We assessed exogenous and endogenous ERPs and frontal θ event-related synchronization (ERS) in patients with first-episode psychosis and healthy controls who successfully performed an adapted 2-back working memory task, including 2 visual n-back working memory tasks as well as oddball detection and passive fixation tasks.

Results

We included 15 patients with first-episode psychosis and 18 controls in this study. Compared with controls, patients with first-episode psychosis displayed increased latencies of early visual ERPs and phasic θ ERS culmination peak in all conditions. However, they also showed a rapid recruitment of working memory–related neural generators, even in pure attention tasks, as indicated by the decreased N200 latency and increased amplitude of sustained θ ERS in detection compared with controls.

Limitations

Owing to the limited sample size, no distinction was made between patients with first-episode psychosis with positive and negative symptoms. Although we controlled for the global load of neuroleptics, medication effect cannot be totally ruled out.

Conclusion

The present findings support the concept of a blunted electroencephalographic response in patients with first-episode psychosis who recruit the maximum neural generators in simple attention conditions without being able to modulate their brain activation with increased complexity of working memory tasks.     

Grey matter alterations in patients with depersonalization disorder: a voxel-based morphometry study

Background

To our knowledge, no whole brain investigation of morphological aberrations in dissociative disorder is available to date. Previous region-of-interest studies focused exclusively on amygdalar, hippocampal and parahippocampal grey matter volumes and did not include patients with depersonalization disorder (DPD). We therefore carried out an explorative whole brain study on structural brain aberrations in patients with DPD.

Methods

We acquired whole brain, structural MRI data for patients with DPD and healthy controls. Voxel-based morphometry was carried out to test for group differences, and correlations with symptom severity scores were computed for grey matter volume.

Results

Our study included 25 patients with DPD and 23 controls. Patients exhibited volume reductions in the right caudate, right thalamus and right cuneus as well as volume increases in the left dorsomedial prefrontal cortex and right somatosensory region that are not a direct function of anxiety or depression symptoms.

Limitations

To ensure ecological validity, we included patients with comorbid disorders and patients taking psychotropic medication.

Conclusion

The results of this first whole brain investigation of grey matter volume in patients with a dissociative disorder indentified structural alterations in regions subserving the emergence of conscious perception. It remains unknown if these alterations are best understood as risk factors for or results of the disorder.     

Characterization of major depressive disorder using a multiparametric classification approach based on high resolution structural images

Background

Major depressive disorder (MDD) is one of the most disabling mental illnesses. Previous neuroanatomical studies of MDD have revealed regional alterations in grey matter volume and density. However, owing to the heterogeneous symptomatology and complex etiology, MDD is likely to be associated with multiple morphometric alterations in brain structure. We sought to distinguish first-episode, medication-naive, adult patients with MDD from healthy controls and characterize neuroanatomical differences between the groups using a multiparameter classification approach.

Methods

We recruited medication-naive patients with first-episode depression and healthy controls matched for age, sex, handedness and years of education. High-resolution T₁-weighted images were used to extract 7 morphometric parameters, including both volumetric and geometric features, based on the surface data of the entire cerebral cortex. These parameters were used to compare patients and controls using multivariate support vector machine, and the regions that informed the discrimination between the 2 groups were identified based on maximal classification weights.

Results

Thirty-two patients and 32 controls participated in the study. Both volumetric and geometric parameters could discriminate patients with MDD from healthy controls, with cortical thickness in the right hemisphere providing the greatest accuracy (78%, p ≤ 0.001). This discrimination was informed by a bilateral network comprising mainly frontal, temporal and parietal regions.

Limitations

The sample size was relatively small and our results were based on first-episode, medication-naive patients.

Conclusion

Our investigation demonstrates that multiple cortical features are affected in medication-naive patients with first-episode MDD. These findings extend the current understanding of the neuropathological underpinnings of MDD and provide preliminary support for the use of neuroanatomical scans in the early detection of MDD.     

Structural changes in the hippocampus in major depressive disorder: contributions of disease and treatment

Background

Previous magnetic resonance imaging (MRI) studies of patients with major depressive disorder (MDD) have consistently shown bilateral and unilateral reductions in hippocampal volume relative to healthy controls. Recent structural MRI studies have addressed the question of whether changes in the volume of hippocampal subregions may be associated with MDD.

Methods

We used a comprehensive and reliable 3-dimensional tracing protocol that enables delineation of hippocampal subregions (head, body, tail) to study changes in the hippocampus of patients with MDD. We recruited 39 MDD patients (16 medicated, 23 unmedicated) and 34 healthy age- and sex-matched controls. We acquired images using a magnetization-prepared rapid acquisition gradient echo sequence on a 1.5-T scanner with a spatial resolution of 1.5 mm × 0.5 mm × 0.5 mm. We performed volumetric analyses, blinded to diagnosis, using the interactive software package Display. All volumes were adjusted for intracranial volume.

Results

We found a significant reduction in the volume of the hippocampal tail bilaterally, right hippocampal head and right total hippocampus in MDD patients. Medicated MDD patients showed increased hippocampal body volume compared with both healthy controls and unmedicated patients.

Limitations

This study was cross-sectional. Further prospective studies are needed to determine the direct effect of antidepressant treatment.

Conclusion

Our results suggest that decreased hippocampal tail and hippocampal head volumes could be trait changes, whereas hippocampal body changes may be dependent on treatment. We showed that long-term antidepressant treatment may affect hippocampal volume in patients with MDD.     

Alterations in White Matter Evident Before the Onset of Psychosis

Background

Psychotic disorders are associated with widespread reductions in white matter (WM) integrity. However, the stage at which these abnormalities first appear and whether they are correlates of psychotic illness, as opposed to an increased vulnerability to psychosis, is unclear. We addressed these issues by using diffusion tensor imaging (DTI) to study subjects at ultra high risk (UHR) of psychosis before and after the onset of illness.

Methods

Thirty-two individuals at UHR for psychosis, 32 controls, and 15 patients with first-episode schizophrenia were studied using DTI. The UHR subjects and controls were re-scanned after 28 months. During this period, 8 UHR subjects had developed schizophrenia. Between-group differences in fractional anisotropy (FA) and diffusivity were evaluated cross sectionally and longitudinally using a nonparametric voxel-based analysis.

Results

At baseline, WM DTI properties were significantly different between the 3 groups (P < .001). Relative to controls, first-episode patients showed widespread reductions in FA and increases in diffusivity. DTI indices in the UHR group were intermediate relative to those in the other 2 groups. Longitudinal analysis revealed a significant group by time interaction in the left frontal WM (P < .001). In this region, there was a progressive reduction in FA in UHR subjects who developed psychosis that was not evident in UHR subjects who did not make a transition.

Conclusions

People at UHR for psychosis show alterations in WM qualitatively similar to, but less severe than, those in patients with schizophrenia. The onset of schizophrenia may be associated with a progressive reduction in the integrity of the frontal WM.     

Use of the Putamen/Caudate Volume Ratio for Early Differentiation between Parkinsonian Variant of Multiple System Atrophy and Parkinson Disease

Background and purpose

Neuropathological studies have demonstrated that multiple system atrophy (MSA) produces selective atrophy of the putamen with sparing of the caudate nucleus, while both structures are spared in idiopathic Parkinson''s disease (PD). In this study we evaluated the clinical efficacy of using putaminal atrophy in brain MRI to differentiate MSA and PD.

Methods

We measured the putamen/caudate volume ratio on brain MRI in 24 patients with MSA and 21 patients with PD. Two clinicians who were blinded to the patients'' diagnoses and to each other''s assessments measured the volume ratio using a computer program.

Results

The measured volume ratios of the two investigators were highly correlated (r=0.72, p<0.0001). The volume ratio was significantly lower in MSA (1.29±0.28) than PD (1.91±0.29, p<0.0001). Setting an arbitrary cutoff ratio of 1.6 resulted in about 90% of patients with MSA falling into the group with a lower ratio, whereas more than 80% of patients with PD belonged to the other group.

Conclusions

The present results demonstrate that putaminal atrophy in MSA as measured on brain MRI represents an effective tool for differentiating MSA from PD.     

Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls

Background

Patients with schizophrenia show increased brain and cerebrospinal fluid (CSF) concentrations of the endogenous N-methyl-d-aspartate receptor antagonist kynurenic acid (KYNA). This compound is an end-metabolite of the kynurenine pathway, and its formation indirectly depends on the activity of kynurenine 3-monooxygenase (KMO), the enzyme converting kynurenine to 3-hydroxykynurenine.

Methods

We analyzed the association between KMO gene polymorphisms and CSF concentrations of KYNA in patients with schizophrenia and healthy controls. Fifteen single nucleotide polymorphisms (SNPs) were selected covering KMO and were analyzed in UNPHASED.

Results

We included 17 patients with schizophrenia and 33 controls in our study. We found an association between a KMO SNP (rs1053230), encoding an amino acid change of potential importance for substrate interaction, and CSF concentrations of KYNA.

Limitations

Given the limited sample size, the results are tentative until replication.

Conclusion

Our results suggest that the nonsynonymous KMO SNP rs1053230 influences CSF concentrations of KYNA.     

Brain volumes in psychotic youth with schizophrenia and mood disorders

Background

We sought to test the hypothesis that deficits in grey matter volume are characteristic of psychotic youth with early-onset schizophrenia-spectrum disorders (EOSS) but not of psychotic youth with early-onset mood disorders (EOMD).

Methods

We used magnetic resonance imaging to examine brain volume in 24 psychotic youth (13 male, 11 female) with EOSS (n = 12) or EOMD (n = 12) and 17 healthy controls (10 male, 7 female). We measured the volume of grey and white matter using an automated segmentation program.

Results

After adjustment for age and intracranial volume, whole brain volume was lower in the EOSS patients than in the healthy controls (p = 0.001) and EOMD patients (p = 0.002). The EOSS patients had a deficit in grey matter volume (p = 0.005), especially in the frontal (p = 0.003) and parietal (p = 0.006) lobes, with no significant differences in white matter volume.

Limitations

The main limitations of our study were its small sample size and the inclusion of patients with depression and mania in the affective group.

Conclusion

Adolescents with EOSS have grey matter deficits compared with healthy controls and psychotic adolescents with EOMD. Our results suggest that grey matter deficits are not generally associated with psychosis but may be specifically associated with schizophrenia. Larger studies with consistent methods are needed to reconcile the contradictory findings among imaging studies involving psychotic youth.     

A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder

Background

Some, although not all, studies report small hippocampal volume in patients with major depressive disorder (MDD) relative to healthy controls. Here, we explore the contribution of key demographic and clinical variables to this difference.

Methods

We used meta-analytic techniques to provide an updated analysis of data from 32 magnetic resonance imaging studies of hippocampal volume in patients with MDD.

Results

Our analysis confirmed the difference in hippocampal volume, but only among patients with MDD whose duration of illness was longer than 2 years or who had more than 1 disease episode. We found no such effect in studies that included patients who did not fit these criteria. The effect was limited to children and middle-aged or older adults. Analyzed collectively, studies including young adult patients showed equivalent hippocampal volumes across MDD patients and controls, a result that may be attributable to a reduced burden of illness in this population. Age at onset of disease, severity of depression at the time of scanning, sex and slice thickness did not contribute to differences in hippocampal volume between patients with MDD and controls.

Limitations

The small size of many of the clinical and demographic subgroups may have limited statistical power to detect between-group differences.

Conclusion

Although all studies were cross-sectional, our results suggest that hippocampal volume reductions generally occur after disease onset in patients with MDD. These findings have implications for the timing of clinical interventions aimed at reducing the impact of MDD on neuronal structure and function.     

Oxidative damage to RNA but not DNA in the hippocampus of patients with major mental illness

Background

Oxidative damage in the central nervous system is increasingly recognized as an important pathological process in many diseases. Previously, our laboratory found that oxidative damage to lipids and proteins was increased in postmortem brain tissue from patients with bipolar disorder and schizophrenia. In the current study, we analyzed oxidative damage to nucleic acids in the CA1, CA3 and dentate gyrus regions of postmortem hippocampus tissue from patients with bipolar disorder, schizophrenia and major depression.

Methods

We examined oxidative damage to nucleic acids by performing immunohistochemistry with a monoclonal antibody that recognizes both 8-hydroxyguanosine in RNA and 8-hydroxy-2’-deoxyguanosine in DNA.

Results

We found that the amount of oxidative damage to nucleic acids was elevated in the CA1, CA3 and dentate gyrus regions of the hippocampus among patients with bipolar disorder, schizophrenia and major depressive disorder. This damage was predominantly in the cytoplasm, suggesting that the damage was primarily to RNA. Compared with oxidative damage in control samples, the magnitude of damage was high in patients with schizophrenia, modest in patients with bipolar disorder and lower in patients with major depression.

Limitations

The interpretation of our results is limited by a number of factors, including the retrospective review of patient history, the relatively small sample size and the inclusion of patients who had substance abuse and were undergoing various drug treatments at the time of death.

Conclusion

Our results suggest that oxidative damage to RNA, rather than to DNA, occurs in vulnerable neurons of the brain in patients with major mental illness and may contribute to the pathology of these disorders. The magnitude of RNA oxidative damage may be associated with the severity of mental illness.     

Electroencephalographic Abnormalities and 5-Year Outcome in First-Episode Psychosis

Objective:

To examine the relation of electroencephalographic abnormalities to 5-year outcomes in first-episode psychosis (FEP).

Methods:

Patients (n = 103) had their baseline electroencephalogram (EEG) classified by modified Mayo Clinic criteria. Symptoms and psychosocial functioning were rated after 5 years of treatment.

Results:

Dysrhythmic EEG was associated with persistence in positive and negative symptoms of psychoses and poorer psychosocial functioning at 5-year follow-up, independently of other characteristics, such as duration of untreated illness or premorbid adjustment. A higher percentage of people with comorbid substance use disorder had normal EEG.

Conclusions:

Abnormal baseline EEG in FEP is associated with poorer 5-year symptomatic and functional outcome.     

Orbitofrontal volume reductions during emotion recognition in patients with major depression

Background

Major depressive disorder is associated with both structural and functional alterations in the emotion regulation network of the central nervous system. The relation between structural and functional changes is largely unknown. Therefore, we sought to determine the relation between structural differences and functional alterations during the recognition of emotional facial expressions.

Methods

We examined 13 medication-free patients with major depression and 15 healthy controls by use of structural T₁-weighted high-resolution magnetic resonance imaging (MRI) and functional MRI during 1 session. We set the statistical threshold for the analysis of imaging data to p < 0.001 (uncorrected).

Results

As shown by voxel-based morphometry, depressed patients had reductions in orbitofrontal cortex volume and increases in cerebellar volume. Additionally, depressed patients showed increased activity during emotion recognition in the middle frontal cortex, caudate nucleus, precuneus and lingual gyrus. Within this cerebral network, the orbitofrontal volumes were negatively correlated in depressed patients but not in healthy controls with changes in blood oxygen level–dependent signal in the middle frontal gyrus, caudate nucleus, precuneus and supplementary motor area.

Limitations

Our results are limited by the relatively small sample size.

Conclusions

This combined functional and structural MRI study provides evidence that the orbitofrontal cortex is a key area in major depression and that structural changes result in functional alterations within the emotional circuit. Whether these alterations in the orbitofrontal cortex are also related to persistent emotional dysfunction in remitted mental states and, therefore, are related to the risk of depression needs further exploration.     

Methamphetamine Enhances the Development of Schizophrenia in First-Degree Relatives of Patients With Schizophrenia

Objective:

Although there is some evidence that methamphetamine (MA) abuse may play a causative role in the development of schizophrenia, studies directly linking these 2 are rare.

Methods:

In our study, the effect of MA abuse on the development of schizophrenia was investigated in 15 MA abusers who are offspring of patients with schizophrenia and 15 siblings of MA abusers without a history of drug abuse. Cognitive deficits and resting-state brain function were evaluated in all participants. Correlations between cognitive deficits and schizophrenia development were investigated.

Results:

Significantly more cognitive impairments were observed in MA abusers, compared with their siblings without a history of drug use. Significant abnormalities in regional homogeneity (ReHo) signals were observed in resting brain in MA abusers. Decreased ReHo was found to be distributed over the bilateral cingulate gyrus, right Brodmann area 24, and bilateral anterior cingulate cortex. Seven MA abusers were diagnosed with schizophrenia, while 1 control sibling was diagnosed with schizophrenia during the 5-year follow-up. The cognitive scores correlated with the development of schizophrenia in MA abusers.

Conclusion:

Our study provides direct evidence for the causative role of MA use in the etiology of schizophrenia and highlights the role of MA-induced brain abnormalities in cognitive deficiency and development of schizophrenia.