Gray matter volume deficits and correlation with insight and negative symptoms in first-psychotic-episode subjects

Bergé D, Carmona S, Rovira M, Bulbena A, Salgado P, Vilarroya O. Gray matter volume deficits and correlation with insight and negative symptoms in first‐psychotic‐episode subjects. Objective: To determine brain areas reduced in first episode of psychotic subjects and its association with lack of insight and negative symptoms. Method: Twenty‐one drug naive first‐episode subjects and 20 controls underwent a structural MRI scan and were clinically assessed. Optimized voxel‐based‐morphometry analysis (VBM) was implemented to find between‐group differences and correlations between GM volume and: (i) lack of insight and (ii) negative symptoms. Results: Patients showed GM reduction in prefrontal and left temporal areas. A significant correlation was found between insight and GM volume in the cerebellum (corrected P = 0.01), inferior temporal gyrus (corrected P = 0.022), medial superior frontal gyrus (corrected P < 0.001), and inferior frontal gyrus (corrected P = 0.012), as the insight decreased, the volume decreased. Negative symptoms correlated with decreased GM volume at cerebellum (corrected P = 0.037) and frontal inferior regions (corrected P < 0.001), the more negative symptoms, the less volume. Conclusion: Our findings support an association between prefrontal, temporal, and cerebellar deficits and lack of insight in schizophrenia and confirm previous findings of GM deficits in patients since the first episode of psychosis.     

青少年精神分裂症首次发病患者脑灰质体积与认知功能的相关性

目的:探讨首发青少年精神分裂症患者脑灰质体积与认知功能的关系。方法:33例首发青少年精神分裂症患者(患者组)和28名性别、年龄、右利手、受教育程度与之相匹配的正常对照组进行神经心理测评,包括连线测验、符号编码、词语流畅性测验、霍普金斯词语学习测验-修订版(HVLT-R)、简易视觉记忆测验-修订版(BVMT-R)、Stroop色词测验(ST-1、ST-2、ST-3)及迷宫测验和结构磁共振扫描(s MRI);用基于体素的形态学方法(VBM))分析比较两组脑灰质体积。结果:患者组除连线测验成绩显著高于正常对照组外(t=2.08,P0.05),符号编码(t=-4.36)、HVLT-R(t=-3.74)、BVMT-R(t=-4.83)、ST-1、ST-2、ST-3(t=-3.08,t=-3.85,t=-3.62)及迷宫测验(t=-3.14)成绩明显低于正常对照组(P0.01或P0.001)。患者组右侧颞上回及右侧颞中回脑灰质体积较正常对照组明显减小(t=-3.868,t=3.964;P均0.001)。Pearson相关分析显示,患者组符号编码(r=0.373,P=0.032)及迷宫测验评分(r=0.356,P=0.042)与右侧颞中回脑灰质体积正相关。结论:首发青少年精神分裂症患者存在脑灰质体积异常;这可能与认知功能广泛损害相关。     

Hippocampal volume deficits associated with exposure to psychological trauma and posttraumatic stress disorder in adults: A meta-analysis

Trauma exposure itself in the absence of posttraumatic stress disorder (PTSD) may be associated with hippocampal volume deficits. We meta-analytically compared hippocampal volumes in PTSD subjects, in trauma-exposed subjects without PTSD, and in trauma-unexposed subjects. Using the words and phrases PTSD, neuroimaging, hippocampus, brain, violence, trauma, abuse, rape, war, combat, accident, and disaster, we searched major computerized databases to obtain candidate studies through 2008 for inclusion. We identified 39 hippocampal volumetric studies in adults with PTSD compared to control groups consisting of either trauma-exposed controls without PTSD or trauma-unexposed controls, or both. We meta-analytically compared left, right, and total hippocampal volumes between 1) PTSD subjects and a trauma-unexposed group, 2) PTSD subjects and a trauma-exposed group without PTSD, and 3) a trauma-unexposed group and a trauma-exposed group without PTSD. Hippocampal volumes were smaller in the PTSD group and trauma-exposed group without PTSD compared to the trauma-unexposed group. Further, the right hippocampus was smaller in the PTSD group compared to the trauma-exposed group without PTSD. Additionally, the right hippocampus was larger than the left in the PTSD and trauma-unexposed groups but not in the trauma-exposed group without PTSD. Hippocampal volume reduction is associated with trauma exposure independent of PTSD diagnosis, albeit additional hippocampal reduction was found in PTSD compared to the trauma-exposed group without PTSD.     

Working memory and attention deficits in adolescent offspring of schizophrenia or bipolar patients: comparing vulnerability markers

Background

Working memory deficits abound in schizophrenia and attention deficits have been documented in schizophrenia and bipolar disorder. Adolescent offspring of patients may inherit vulnerabilities in brain circuits that subserve these cognitive domains. Here we assess impairments in offspring of schizophrenia (SCZ-Offspring) or bipolar (BP-Offspring) patients compared to controls (HC) with no family history of mood or psychotic disorders to the second degree.

Methods

Three groups (n = 100 subjects; range: 10-20 yrs) of HC, SCZ-Offspring and BP-Offspring gave informed consent. Working memory was assessed using a delayed spatial memory paradigm with two levels of delay (2 s & 12 s); sustained attention processing was assessed using the Continuous Performance Task—Identical Pairs version.

Results

SCZ-Offspring (but not BP-Offspring) showed impairments in working memory (relative to HC) at the longer memory delay indicating a unique deficit. Both groups showed reduced sensitivity during attention but only BP-Offspring significantly differed from controls.

Conclusions

These results suggest unique (working memory/dorsal frontal cortex) and potentially overlapping (attention/fronto-striatal cortex) vulnerability pathways in adolescent offspring of patients with schizophrenia and bipolar disorder. Working memory and attention assessments in these offspring may assist in the clinical characterization of the adolescents vulnerable to SCZ or BP.     

Longitudinal alterations of executive function in non-psychotic adolescents at familial risk for schizophrenia

Genetic diathesis to schizophrenia may involve alterations of adolescent neurodevelopment manifesting as cognitive deficits. Brain regions mediating executive function (fronto-striatal circuits) develop during adolescence while those supporting elementary aspects of attention (e.g. sustained focused attention) have a more protracted maturation beginning in childhood. We hence predicted that adolescents at risk for schizophrenia would show a failure of normal maturation of executive function. We prospectively assessed 18 offspring and 6 siblings of schizophrenia patients (HR) and 28 healthy controls at baseline, year-1 and year-2 follow-up using the Continuous Performance Test [visual-d′] and Wisconsin Card Sort Test (WCST). Perseverative errors on the WCST in HR remained stable but decreased in controls over the follow-up (study-group by assessment–time interaction, p = 0.01, controlling for IQ). No significant study-group by assessment-time interactions were seen for sustained attentional performance. HR may not improve while healthy subjects progressively improve on executive function during adolescence and early adulthood. Our results suggest an altered maturational trajectory of executive function during adolescence in individuals at familial risk for schizophrenia.     

Verbal learning contributes to cognitive insight in schizophrenia independently of affective and psychotic symptoms

Objective

Patients with schizophrenia exhibit distorted beliefs and experiences, and their own evaluation of this is labeled cognitive insight. We examined the relationship between cognitive insight and neurocognition, as well as the contribution of neurocognition in explaining cognitive insight.

Method

Clinically characterized patients with schizophrenia (n = 102) were assessed with a measure of cognitive insight, Beck Cognitive Insight Scale (BCIS) and a neuropsychological test battery. The contribution of neurocognition to the explained variance in BCIS components self-reflectiveness (i.e. objectivity and reflectiveness) and self-certainty (i.e. overconfidence in own beliefs) was examined controlling for current affective and psychotic symptoms.

Results

A significant negative correlation was found between self-certainty and verbal learning, whereas no associations were found between self-reflectiveness and any of the neuropsychological tests. Verbal learning was added significantly to the explained variance in self-certainty after controlling for potential confounders.

Conclusion

High self-certainty was associated with poor verbal learning. This suggests that overconfidence in own beliefs is associated with cognitive dysfunction in schizophrenia.     

Gray matter morphology and the level of functioning in one-year follow-up of first-episode schizophrenia patients

Schizophrenia is a condition with a highly variable course that is hard to predict. The aim of the present study was to investigate if local gray matter volume (GMV) can differentiate poor (PF) and good (GF) functioning patients using voxel-wise analysis in a group of first-episode schizophrenia subjects (FES).     

Facial emotion perception in Chinese patients with schizophrenia and non-psychotic first-degree relatives

Although there is a consensus that patients with schizophrenia have certain deficits in perceiving and expressing facial emotions, previous studies of facial emotion perception in schizophrenia do not present consistent results. The objective of this study was to explore facial emotion perception deficits in Chinese patients with schizophrenia and their non-psychotic first-degree relatives. Sixty-nine patients with schizophrenia, 56 of their first-degree relatives (33 parents and 23 siblings), and 92 healthy controls (67 younger healthy controls matched to the patients and siblings, and 25 older healthy controls matched to the parents) completed a set of facial emotion perception tasks, including facial emotion discrimination, identification, intensity, valence, and corresponding face identification tasks. The results demonstrated that patients with schizophrenia performed significantly worse than their siblings and younger healthy controls in accuracy in a variety of facial emotion perception tasks, whereas the siblings of the patients performed as well as the corresponding younger healthy controls in all of the facial emotion perception tasks. Patients with schizophrenia also showed significantly reduced speed than younger healthy controls, while siblings of patients did not demonstrate significant differences with both patients and younger healthy controls in speed. Meanwhile, we also found that parents of the schizophrenia patients performed significantly worse than the corresponding older healthy controls in accuracy in terms of facial emotion identification, valence, and the composite index of the facial discrimination, identification, intensity and valence tasks. Moreover, no significant differences were found between the parents of patients and older healthy controls in speed after controlling the years of education and IQ. Taken together, the results suggest that facial emotion perception deficits may serve as potential endophenotypes for schizophrenia.     

Cognition and communication dysfunctions in early-onset schizophrenia: Effect of risperidone

Background

Cognitive impairment and formal thought disorder, also referred to as communication disturbances, are considered the core symptoms of schizophrenia, strongly affecting social functioning and long-term outcome. Several studies in adult patients suggest improvement of both functions after the treatment with atypical antipsychotic drugs. Such medications are also used as first line treatment in early-onset schizophrenia, however their efficacy in cognitive and communication domains in this population have not been systematically assessed.

Aim of the study

Evaluation of risperidone efficacy at psychopathological symptoms, cognitive impairment and formal thought disorder in adolescents with schizophrenia spectrum diagnosis.

Material and method

Psychopathological symptoms, cognitive functioning and formal thought disorder were evaluated in 32 hospitalized adolescent patients with schizophrenia spectrum diagnosis at the beginning of risperidone treatment and after clinical improvement and compared to the results of matched healthy control group.

Results

Risperidone treatment was associated with reduction of symptom severity and moderate improvement of formal thought disorder and some aspects of executive functions. Working memory and verbal fluency were not improved. There were few correlations between psychopathological symptoms and results of cognitive tests, mainly between negative symptoms and executive functions.

Discussion

In early-onset schizophrenia spectrum disorders atypical antipsychotic treatment is associated with alleviation of symptoms and only selective and moderate cognitive and communication improvement.     

Elevated noise power in gamma band related to negative symptoms and memory deficit in schizophrenia

Background

There is an increasing consideration for a disorganized cerebral activity in schizophrenia, perhaps relating to a synaptic inhibitory deficit in the illness. Noise power (scalp-recorded electroencephalographic activity unlocked to stimuli) may offer a non-invasive window to assess this possibility.

Methods

29 minimally-treated patients with schizophrenia (of which 17 were first episodes) and 27 healthy controls underwent clinical and cognitive assessments and an electroencephalographic recording during a P300 paradigm to calculate signal-to-noise ratio and noise power magnitudes in the theta and gamma bands.

Results

In comparison to controls, a significantly higher gamma noise power was common to minimally-treated and first episode patients over P3, P4, T5 and Fz electrode sites. Those high values were directly correlated to negative symptom severity and inversely correlated to verbal memory scores in the patients. There were no differences in signal-to-noise ratio magnitudes among the groups. Gamma noise power at Fz discriminated significantly between patients and controls. No significant differences were found in theta noise power or in gamma noise power over the other electrode sites between the groups of patients and controls.

Limitations

We have not assessed phase-locked and non-phase locked power changes, a complementary approach that may yield useful information.

Conclusions

Gamma noise power may represent a useful and non-invasive tool for studying brain dysfunction in psychotic illness. These results suggest an inefficient activation pattern in schizophrenia.     

Longitudinal volume changes of the pituitary gland in patients with schizotypal disorder and first-episode schizophrenia

An enlarged volume of the pituitary gland has been reported in the schizophrenia spectrum, possibly reflecting the hypothalamic-pituitary-adrenal (HPA) hyperactivity. However, it remains largely unknown whether the pituitary size longitudinally changes in the course of the spectrum disorders. In the present study, longitudinal magnetic resonance imaging (MRI) data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The pituitary volume was measured at baseline and follow-up (mean, 2.7 years) scans and was compared across groups. The pituitary volume was larger in the schizophrenia patients than controls at baseline, and both patient groups had significantly larger pituitary volume than controls at follow-up. In a longitudinal comparison, both schizophrenia (3.6%/year) and schizotypal (2.7%/year) patients showed significant pituitary enlargement compared with controls (− 1.8%/year). In the schizophrenia patients, greater pituitary enlargement over time was associated with less improvement of delusions and higher scores for thought disorders at the follow-up. These findings suggest that the pituitary gland exhibits ongoing volume changes during the early course of the schizophrenia spectrum as a possible marker of state-related impairments.     

Patterns of cerebral white matter damage and cognitive impairment in adolescents born very preterm

There is increasing evidence about the presence of white matter damage in subjects with a history of premature birth, even in those classified as good outcome because of an apparently normal development. Although intellectual performance is within normal limits in premature children it is significantly decreased compared to paired controls. The purpose of this study was to investigate the relationship between a lower performance intelligence quotient and white matter damage in preterm adolescents. The sample comprised 44 adolescents (mean age ± S.D.: 14.4 ± 1.6 years) born before 32 weeks of gestational age and 43 term-born adolescents (14.5 ± 2.1 years). Individual voxel-based morphometry analyses demonstrated that 35/44 (80%) preterm subjects had white matter abnormalities. The centrum semiovale and the posterior periventricular regions were the most frequently affected areas. Correlation analysis showed that in preterms the performance intelligence quotient correlated with the whole-brain white matter volume (r = 0.32; P = 0.036) but not with grey matter volume. Complementary analysis showed that low scores in the Digit Symbol subtest, a measure of processing speed, in the preterm group correlated with reductions in white matter concentration. These results suggest that white matter damage is highly common and that it persists until adolescence. Hence, diffuse white matter loss may be responsible for performance intelligence quotient and processing speed decrements in subjects with very preterm birth.     

Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls

Background

Similar patterns of subcortical brain abnormalities and neurocognitive dysfunction have been demonstrated in schizophrenia and bipolar disorder, with more extensive findings in schizophrenia. It is unknown whether relationships between subcortical volumes and neurocognitive performance are similar or different between schizophrenia and bipolar disorder.

Methods

MRI scans and neuropsychological test performance were obtained from 117 schizophrenia or 121 bipolar spectrum disorder patients and 192 healthy control subjects. Using the FreeSurfer software, volumes of 18 selected subcortical structures were automatically segmented and analyzed for relationships with results from 7 neurocognitive tests.

Results

In schizophrenia, larger left ventricular volumes were related to poorer motor speed, and bilateral putamen volumes were related to poorer verbal learning, executive functioning and working memory performance. In bipolar disorder, larger left ventricular volumes were related to poorer motor speed and executive functioning. The relationship between left putamen volume and working memory was specific to schizophrenia. The relationships between left inferior lateral ventricles and motor speed and between right putamen volumes and executive functioning were similar in schizophrenia and bipolar disorder, and different from healthy controls. The results remained significant after corrections for use of antipsychotic medication. Significant structure-function relationships were also found when all subjects were combined into one group.

Conclusion

The present findings suggest that there are differences as well as similarities in subcortical structure/function relationships between patients with schizophrenia or bipolar disorder and healthy individuals. The observed differences further suggest that ventricular and putamen volume sizes may reflect severity of cognitive dysfunction in these disorders.     

Associations of serum brain-derived neurotrophic factor with cognitive impairments and negative symptoms in schizophrenia

Brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations of serum BDNF levels with the cognition and clinical characteristics in patients with schizophrenia. Sixty-three patients with schizophrenia and 52 age- and sex-matched healthy controls were examined with neuropsychological tests. Serum BDNF levels were determined by enzyme-linked immunosorbent assay (ELISA). There were no significant differences in serum BDNF levels between normal controls and patients with schizophrenia. Serum BDNF levels of normal controls showed negative correlations with verbal working memory, but this was not the case with schizophrenic patients. Meanwhile, serum BDNF levels of schizophrenic patients showed positive correlations with the scores of the Scale for the Assessment of Negative Symptoms (SANS) and the Information subtest scores of Wechsler Adult Intelligence Scale Revised (WAIS-R). Serum BDNF levels are related with the impairment of verbal working memory and negative symptoms in patients with schizophrenia.     

Cannabis induces different cognitive changes in schizophrenic patients and in healthy controls

It is known that 60 to 80% of schizophrenic patients show deficits in cognition. There may be an increase in these deficits as a result of additional regular use of cannabis. The aim of the study was to evaluate the effect of chronic cannabis consumption on the cognitive functions of schizophrenic patients and healthy control subjects after a minimum abstinence time of 28 days. The study sample consisted of 39 schizophrenics (19 cannabis-abusers and 20 non-abusers) and 39 healthy controls (18 cannabis-abusers, 21 non-abusers). In a 2x2-factorial design (Diagnostic Groups [healthy controls, schizophrenic patients]xCannabis abuse [without, with]) with diagnostic group and cannabis consumption considered between-subject factors) we tested the hypothesis that dually diagnosed patients (i.e. suffering both from schizophrenia and cannabis abuse) perform worse in neuropsychological tests than schizophrenic patients without cannabis abuse. On the whole, schizophrenic patients performed worse than healthy control subjects. Surprisingly, rather than deteriorating neuropsychological performance, regular cannabis abuse prior to the first psychotic episode improved cognition in some tests. This was even more pronounced when regular consumption started before the age of 17. On the other hand, cannabis use deteriorated test performance in healthy controls, especially in cases when regular consumption started before the age of 17. To sum up, regular cannabis abuse has a different effect on cognitive function in schizophrenic patients and healthy controls.     

Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: a preliminary study

Objectives

We evaluated the efficacy of bimodal repetitive transcranial magnetic stimulation (rTMS) in treating pharmacologically non-responsive patients with schizophrenia.

Methods

Ten patients with DSM-IV schizophrenia, unresponsive to pharmacological treatment, underwent treatment with 15 rTMS sessions, as an adjunctive therapy, for three weeks. Each session comprised 40 trains, beginning every 30 s: 20 trains of 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC) with a 3-s duration and 20 trains of 1 Hz rTMS to the left temporoparietal cortex (TPC) with a 30-s duration. We assessed patients via the Positive and Negative Syndrome Scale (PANSS) and Korean Version of the Calgary Depression Scale for Schizophrenia (K-CDSS), at five time points: baseline, Days 8, 15, and 22, and 1 week after final treatment (Day 29). Patients who agreed to take neurocognitive tests underwent neurocognitive function evaluations at baseline and 1 week after final treatment.

Results

At Day 29, all PANSS subscale scores in had decreased significantly compared to baseline (Z = − 2.214, p = 0.027, positive; Z = − 2.132, p = 0.033, negative; Z = − 2.023, p = 0.043, general pathology; Z = − 2.371, p = 0.018, total). Effect over time was significant for the PANSS positive and negative subscale scores and total score (χ² = 13.35, p = 0.010; χ² = 10.27, p = 0.036; and χ² = 16.50, p = 0.002, respectively) but not for the general pathology subscale. Among the neurocognitive tests, the fourth and fifth trials and total K-AVLT scores showed significant increases (Z = − 2.041, p = 0.041; Z = − 2.251, p = 0.024; and Z = − 2.201, p = 0.028, respectively), suggesting improvement in short-term auditory verbal memory.

Conclusions

Bimodal rTMS stimulation of left DLPFC and left TPC induced clinical improvement in pharmacologically non-responsive schizophrenia patients and may have improved their short-term verbal memories.     

Anterior insular volume is larger in patients with obsessive-compulsive disorder

There has been increasing evidence indicating gray matter abnormalities in patients with obsessive-compulsive disorder (OCD). Several voxel-based morphometry (VBM) studies have reported volume changes in the insular cortex. Although there are distinct differences in the connectivity and functions in the anterior and posterior insular cortices, these two regions have never been distinguished in previous VBM studies. In this study, we adopted a region of interest (ROI) method to measure insular volume separately. We investigated insular volume in 32 drug-free patients with OCD and in 34 healthy controls using magnetic resonance imaging (MRI). Repeated measures multivariate analysis of covariance (MANCOVA) was conducted to examine the difference between the patients and the controls. Compared with the healthy controls, the patients had a significantly larger gray matter volume in the anterior insular cortex bilaterally (post hoc test, p = 0.036; left, p = 0.047; right). This is the first volumetric MRI study to separately investigate the anterior and posterior insular cortex volumes in non-medicated patients with OCD. The results suggest that the anterior insular cortex may be related to the pathophysiology of OCD.     

Neurocognitive dysfunction in strategic and non-strategic gamblers

Objective

It has been theorized that there may be subtypes of pathological gambling, particularly in relation to the main type of gambling activities undertaken. Whether or not putative pathological gambling subtypes differ in terms of their clinical and cognitive profiles has received little attention.

Method

Subjects meeting DSM-IV criteria for pathological gambling were grouped into two categories of preferred forms of gambling — strategic (e.g., cards, dice, sports betting, stock market) and non-strategic (e.g., slots, video poker, pull tabs). Groups were compared on clinical characteristics (gambling severity, and time and money spent gambling), psychiatric comorbidity, and neurocognitive tests assessing motor impulsivity and cognitive flexibility.

Results

Seventy-seven subjects were included in this sample (45.5% females; mean age: 42.7 ± 14.9) which consisted of the following groups: strategic (n = 22; 28.6%) and non-strategic (n = 55; 71.4%). Non-strategic gamblers were significantly more likely to be older, female, and divorced. Money spent gambling did not differ significantly between groups although one measure of gambling severity reflected more severe problems for strategic gamblers. Strategic and non-strategic gamblers did not differ in terms of cognitive function; both groups showed impairments in cognitive flexibility and inhibitory control relative to matched healthy volunteers.

Conclusion

These preliminary results suggest that preferred form of gambling may be associated with specific clinical characteristics but are not dissociable in terms of cognitive inflexibility and motor impulsivity.     

Brain activation associated with motor skill practice in children with developmental coordination disorder: an fMRI study

Children with developmental coordination disorder (DCD) have difficulty in learning new motor skills. At present, it is not known whether these children employ a different set of brain regions than typically developing (TD) children during skilled motor practice. Using functional magnetic resonance imaging, we mapped brain activity associated with skilled motor practice of a trail-tracing task in 7 children with DCD and 7 age-matched controls (aged 8-12 years). We indexed change in motor performance as a reduction in tracing error from early practice to retention. Children with DCD showed less blood-oxygen-level-dependent signal as compared to TD children in a network of brain regions associated with skilled motor practice: bilateral inferior parietal lobules (Brodmann Area (BA) 40), right lingual gyrus (BA 18), right middle frontal gyrus (BA 9), left fusiform gyrus (BA 37), right cerebellar crus I, left cerebellar lobule VI, and left cerebellar lobule IX. While no statistically significant differences were detected, effect size testing revealed that children with DCD demonstrated poorer tracing accuracy than TD children at retention (d = 0.48). Our results suggest that, compared to TD peers, children with DCD demonstrate under-activation in cerebellar-parietal and cerebellar-prefrontal networks and in brain regions associated with visual-spatial learning. These data suggest a neurobiological correlation with impaired learning of motor skills in children with DCD, which will need to be confirmed with a larger sample.     

Investigating the neuropsychological and neuroanatomical changes that occur over the first 2-3 years of illness in patients with first-episode schizophrenia

OBJECTIVE: This study explored the concurrent courses of the neuroanatomical and neuropsychological changes that occurred over the first 2-3 years of illness in patients with first-episode schizophrenia (FES). METHODS: Fifty-two patients with FES underwent neuropsychological testing and a structural magnetic resonance imaging (sMRI) scan within three months of their first presentation to mental health services with psychotic symptoms (time1). Patients' cognitive performance was evaluated via an extensive neuropsychological test battery, which assessed 9 cognitive domains. Of the 52 patients at time1, 32 returned 2-3 years later (time2) for follow-up neuropsychological testing, and 20 of these also underwent follow-up sMRI. MR images were preprocessed in SPM99. Grey matter volumes of patients' whole-brain, frontal lobes and temporal lobes were calculated by convolving the preprocessed images with manually-drawn binary masks. RESULTS: Patients exhibited longitudinal improvements in full-scale IQ, performance IQ and visual memory. In contrast, concurrent reductions in grey matter were observed for the whole-brain (3% reduction) and the frontal lobe (3.65% reduction). Furthermore, the extent of patients' whole-brain and frontal-lobe grey matter changes were positively correlated with longitudinal changes in verbal learning and memory. DISCUSSION: The results of this study suggest that while the early stages of schizophrenia are associated with a mild improvement in patients' overall cognitive functioning, they are also associated with progressive grey matter atrophy.