Biomedical subjects

Christos Pantelis

Publications and source records attributed to Christos Pantelis.

At least 19 recordsLinked to original sources

PubMed2006

Morphology of the paracingulate sulcus and executive cognition in schizophrenia.

Previous studies have shown that schizophrenia patients display a left-lateralized reduction in cortical folding of the paracingulate cortex, although the functional significance of this anomaly is unclear. We examined the influence of paracingulate sulcus (PCS) asymmetries on cognitive performance in 37 male schizophrenia patients and 43 male controls. Across both groups, a leftward PCS asymmetry was associated with better spatial working memory performance than either a rightward asymmetric or symmetric folding pattern. This suggests that prior reports of impaired performance on such tasks in schizophrenia may be partly explained by the reduced frequency of a leftward PCS asymmetry in this population.

Adult↗

PubMed2006

Generalized and specific cognitive performance in clinical high-risk cohorts: a review highlighting potential vulnerability markers for psychosis.

Cognitive deficits are a core feature of established psychotic illnesses. However, the association between cognition and emerging psychosis is less understood. While there is some evidence that cognitive deficits are present prior to the onset of psychosis, findings are not consistent. In this article we provide an overview of the more general cognitive findings available from genetic high-risk studies, retrospective studies, and birth cohort studies. We then focus the review on neuropsychological performance in clinically "at-risk" groups. Overall, general cognitive ability as assessed by established batteries appears to remain relatively intact in these ultra-high risk cohorts and is a poor predictor close to illness onset relative to other vulnerability factors. Further decline may occur with illness progression, more consistent with state relative to trait factors. In addition, most established cognitive tasks involve several relatively discrete cognitive subprocesses, where findings from general batteries of subtests may mask specific deficits. In this context, our review suggests that relatively specific olfactory identification and spatial working memory deficits exist prior to illness onset and may be more potent trait markers for psychosis than cognitively dense tasks such as verbal memory. Suggestions for further research address the importance of standardization of inclusion criteria and the maintenance of basic neuropsychological assessment to allow better comparison of findings across centers. Further, in order to better understand the aetiopathology of cognitive dysfunction in psychosis, more experimental, hypothesis-driven measures of discrete cognitive processes are required. Delineation of the relationship between specific cognitive ability and symptoms from data-driven approaches may improve our understanding of the role of cognition during psychosis onset.

Cognition Disorders↗

PubMed2006

Evidence of altered prefrontal-thalamic circuitry in schizophrenia: an optimized diffusion MRI study.

MRI diffusion tensor imaging (DTI), optimized for measuring the trace of the diffusion tensor, was used to investigate microstructural changes in the brains of 12 individuals with schizophrenia compared with 12 matched control subjects. To control for the effects of anatomic variation between subject groups, all participants' diffusion images were nonlinearly registered to standard anatomical space. Significant statistical differences in mean diffusivity (MD) measures between the two groups were determined on a pixel-by-pixel basis, using Gaussian random field theory. We found significantly elevated MD measures within temporal, parietal and prefrontal cortical regions in the schizophrenia group (P > 0.001), especially within the medial frontal gyrus and anterior cingulate. The dorsal medial and anterior nucleus of the thalamus, including the caudate, also exhibited significantly increased MD in the schizophrenia group (P > 0.001). This study has shown for the first time that MD measures offer an alternative strategy for investigating altered prefrontal-thalamic circuitry in schizophrenia.

Brain↗

PubMed2006

Neuropathological, neurogenetic and neuroimaging evidence for white matter pathology in schizophrenia.

A wide range of neuropathological abnormalities have been detected in schizophrenia sufferers, and emerging evidence points to neural substrates of connectivity as having a key role in the development of disease. This article reviews the available evidence for white matter pathology in schizophrenia, and examines its possible role as a substrate of impaired connectivity. Neuropathological data is suggestive of abnormalities in glial structure and function, and myelinated structures have also been implicated. A number of studies, particularly using gene array technology, are pointing towards significant disruption in expression of myelination genes. Magnetic resonance imaging has tended to focus on, and detect, more grey than white matter abnormalities, although non-volumetric techniques are suggestive of changes in the microstructure of white matter in schizophrenia. Myelinated structures are an attractive candidate for an anatomical substrate for disconnectivity, and may act synergistically with synaptic changes to result in functional disconnectivity although the relationship between white and grey matter changes in the illness remains unclear.

Animals↗

PubMed2006

Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals.

CONTEXT: Magnetic resonance imaging studies have identified hippocampal volume reductions in schizophrenia and amygdala volume enlargements in bipolar disorder, suggesting different medial temporal lobe abnormalities in these conditions. These studies have been limited by small samples and the absence of patients early in the course of illness. OBJECTIVE: To investigate hippocampal and amygdala volumes in a large sample of patients with chronic schizophrenia, patients with first-episode psychosis, and patients at ultra-high risk for psychosis compared with control subjects. DESIGN: Cross-sectional comparison between patient groups and controls. SETTING: Individuals with chronic schizophrenia were recruited from a mental health rehabilitation service, and individuals with first-episode psychosis and ultra-high risk were recruited from the ORYGEN Youth Health Service. Control subjects were recruited from the community. PARTICIPANTS: The study population of 473 individuals included 89 with chronic schizophrenia, 162 with first-episode psychosis, 135 at ultra-high risk for psychosis (of whom 39 subsequently developed a psychotic illness), and 87 controls. MAIN OUTCOME MEASURES: Hippocampal, amygdala, whole-brain, and intracranial volumes were estimated on high-resolution magnetic resonance images and compared across groups, including first-episode subgroups. We used 1- and 2-way analysis of variance designs to compare hippocampal and amygdala volumes across groups, correcting for intracranial volume and covarying for age and sex. We investigated the effects of medication and illness duration on structural volumes. RESULTS: Patients with chronic schizophrenia displayed bilateral hippocampal volume reduction. Patients with first-episode schizophrenia but not schizophreniform psychosis displayed left hippocampal volume reduction. The remaining first-episode subgroups had normal hippocampal volumes compared with controls. Amygdala volume enlargement was identified only in first-episode patients with nonschizophrenic psychoses. Patients at ultra-high risk for psychosis had normal baseline hippocampal and amygdala volumes whether or not they subsequently developed a psychotic illness. Structural volumes did not differ between patients taking atypical vs typical antipsychotic medications, and they remained unchanged when patients treated with lithium were excluded from the analysis. CONCLUSIONS: Medial temporal structural changes are not seen until after the onset of a psychotic illness, and the pattern of structural change differs according to the type of psychosis. These findings have important implications for future neurobiological studies of psychotic disorders and emphasize the importance of longitudinal studies examining patients before and after the onset of a psychotic illness.

Adolescent↗

PubMed2006

Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions.

Diagnosis in psychiatry increasingly struggles to fulfil its key purposes, namely, to guide treatment and to predict outcome. The clinical staging model, widely used in clinical medicine yet virtually ignored in psychiatry, is proposed as a more refined form of diagnosis which could restore the utility of diagnosis, promote early intervention and also make more sense of the confusing array of biological research findings in psychiatry by organizing data into a coherent clinicopathological framework. A selective review of key papers in clinical medicine and psychiatry which describe clinical and clinicopathological staging, and a range of related issues. Clinical staging has immediate potential to improve the logic and timing of interventions in psychiatry just as it does in many complex and potentially serious medical disorders. Interventions could be evaluated in terms of their ability to prevent or delay progression from earlier to later stages of disorder, and they could be selected on clear-cut risk/benefit criteria. Biological variables and a range of candidate risk factors could be studied within and across stages, and their role, specificity and centrality in risk, onset and progression of disorder could be greatly clarified. A clinicopathological framework could be progressively constructed. Clinical staging with a restructure across and within diagnostic boundaries with the explicit operationalization of criteria for extent and progression of disorder should be actively explored in psychiatry as a heuristic strategy for the development and evaluation of earlier, safer, and more effective clinical interventions, and for clarifying the biological basis of psychiatric disorders.

Combined Modality Therapy↗

PubMed2006

Stress, the hippocampus and the hypothalamic-pituitary-adrenal axis: implications for the development of psychotic disorders.

OBJECTIVE: The experience of stress is commonly implicated in models of the onset of psychotic disorders. However, prospective studies investigating associations between biological markers of stress and the emergence of psychotic disorders are limited and inconclusive. One biological system proposed as the link between the psychological experience of stress and the development of psychosis is the Hypothalamic-Pituitary-Adrenal (HPA) axis. This paper summarizes and discusses evidence supporting a role for HPA-axis dysfunction in the early phase of schizophrenia and related disorders. METHOD: A selective review of psychiatric and psychological research on stress, coping, HPA-axis, the hippocampus and psychotic disorders was performed, with a particular focus on the relationship between HPA-axis dysfunction and the onset of psychotic disorders. RESULTS: Individual strands of past research have suggested that the HPA-axis is dysfunctional in at least some individuals with established psychotic disorders; that the hippocampus is an area of the brain that appears to be implicated in the onset and maintenance of psychotic disorders; and that an increase in the experience of stress precedes the onset of a psychotic episode in some individuals. Models of the onset and maintenance of psychotic disorders that link these individual strands of research and strategies for examining these models are proposed in this paper. CONCLUSIONS: The current literature provides some evidence that the onset of psychotic disorders may be associated with a higher rate of stress and changes to the hippocampus. It is suggested that future research should investigate whether a relationship exists between psychological stress, HPA-axis functioning and the hippocampus in the onset of these disorders. Longitudinal assessment of these factors in young people at 'ultra' high risk of psychosis and first-episode psychosis cohorts may enhance understanding of the possible interaction between them in the early phases of illness.

Animals↗

PubMed2005

Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis.

BACKGROUND: We examined pituitary volume before the onset of psychosis in subjects who were at ultra-high risk (UHR) for developing psychosis. METHODS: Pituitary volume was measured on 1.5-mm, coronal, 1.5-T magnetic resonance images in 94 UHR subjects recruited from admissions to the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia and in 49 healthy control subjects. The UHR subjects were scanned at baseline and were followed clinically for a minimum of 1 year to detect transition to psychosis. RESULTS: Within the UHR group, a larger baseline pituitary volume was a significant predictor of future transition to psychosis. The UHR subjects who later went on to develop psychosis (UHR-P, n = 31) had a significantly larger (+12%; p = .001) baseline pituitary volume compared with UHR subjects who did not go on to develop psychosis (UHR-NP, n = 63). The survival analysis conducted by Cox regression showed that the risk of developing psychosis during the follow-up increased by 20% for every 10% increase in baseline pituitary volume (p = .002). Baseline pituitary volume of the UHR-NP subjects was smaller not only compared with UHR-P (as described above) but also compared with control subjects (-6%; p = .032). CONCLUSIONS: The phase before the onset of psychosis is associated with a larger pituitary volume, suggesting activation of the HPA axis.

Adolescent↗

PubMed2005

Structural brain imaging evidence for multiple pathological processes at different stages of brain development in schizophrenia.

The underlying neurobiology of emerging psychotic disorders is not well understood. While there is evidence from structural imaging and other studies supporting the popular notion that schizophrenia arises as a consequence of an "early neurodevelopmental" lesion, more recent findings challenge this notion. Evidence, including our own data, suggests that dynamic brain changes occur during the earliest stages of a psychotic illness, including around the time of transition to illness. In this article we review the available longitudinal and relevant cross-sectional structural neuroimaging studies focusing on both the very early neurodevelopmental markers (pre- or perinatal origin) and the later markers (late neurodevelopmental) around the period of transition to illness. Based on our review of recent findings, we suggest that the onset of psychosis is a time of active brain changes, wherein, for a proportion of individuals, (i) an early (pre- and perinatal) neurodevelopmental lesion renders the brain vulnerable to anomalous late (particularly postpubertal) neurodevelopmental processes, as indicated by evidence for accelerated loss of gray matter and aberrant connectivity particularly in prefrontal regions; and (ii) these anomalous neurodevelopmental processes interact with other causative factors associated with the onset of psychosis (e.g., substance use, stress, and dysregulation of the hypothalamic-pituitary-adrenal axis function), which together have neuroprogressive sequelae involving medial temporal and orbital prefrontal regions, as suggested by imaging studies around transition to active illness. However, the pathological processes underlying such progressive changes during "late neurodevelopment" remain unclear but may reflect anomalies of synaptic plasticity, abnormal brain maturation, the adverse effects of stress, or other environmental factors. In this context, the features of schizophrenia, including the neuropsychological deficits and behavioral manifestations, can be understood as direct effects of these multiple pathological processes at various neurodevelopmental stages, including genetic and nongenetic etiological factors.

Brain↗

PubMed2005

Hippocampal and anterior cingulate morphology in subjects at ultra-high-risk for psychosis: the role of family history of psychotic illness.

BACKGROUND: While structural brain imaging abnormalities have been identified in schizophrenia and related disorders, it is unclear when they arise. Some appear to predate the illness and may be genetic in origin, while others are associated with the onset of the disorder. METHODS: We examined the hippocampal volumes and anterior cingulate morphology from the MRI scans of 79 male subjects at ultra-high-risk (UHR) for developing psychosis, 35 of whom had a family history of schizophrenia, and compared them with 49 healthy male volunteers. RESULTS: Analysis of covariance demonstrated that left hippocampal volumes were significantly smaller in the UHR group without a family history of schizophrenia, when compared to the UHR group with such history. A similar pattern was found for the left anterior cingulate region, both in terms of reduced paracingulate folding and cingulate sulcus interruptions, although this did not reach significance. CONCLUSIONS: We found that a family history of schizophrenia was not associated with a greater degree of structural brain abnormalities in an ultra-high-risk group, and in fact it was those UHR patients without such history who displayed greater abnormalities, although this only reached significance for the left hippocampus. Thus, it appears that the mechanisms that result in gross morphological anomalies in the hippocampus and anterior cingulate in psychosis are driven more by environmental than genetic factors.

Adult↗

PubMed2005

The FOCIS international survey on psychiatrists' opinions on cognition in schizophrenia.

BACKGROUND: The goal of this project was to develop an interview to evaluate psychiatrists' views on the nature of cognitive dysfunction in schizophrenia, its importance as a potential treatment target, and its relative importance as a treatment target across different phases of schizophrenia. MATERIALS AND METHODS: A survey (available in paper or on-line) consisting of 27 questions, was developed by the Focus on Cognition in Schizophrenia (FOCIS) group, and distributed in a single wave mailing to 63,295 psychiatrists in 21 countries worldwide. RESULTS: The overall response rate was 4.7% (n=2975). The surveyed psychiatrists perceived cognition as a high treatment priority in stabilized schizophrenia patients, but less so for first episode or acute schizophrenia patients. The potential of atypical antipsychotics to improve cognitive dysfunction in schizophrenia was identified by 81% of the respondent psychiatrists. CONCLUSIONS: Cognitive deficits in people with schizophrenia are seen by clinical psychiatrists as relevant to treatment and rehabilitation plans. They were, however, regarded as a higher treatment priority in stabilized chronic rather than in first episode patients. The results suggest clinical psychiatrists need additional education regarding the nature of cognitive dysfunction in schizophrenia and its importance for psychosocial rehabilitation and community re-entry.

Attitude of Health Personnel↗

PubMed2005

A manual and automated MRI study of anterior cingulate and orbito-frontal cortices, and caudate nucleus in obsessive-compulsive disorder: comparison with healthy controls and patients with schizophrenia.

Functional imaging and neuropsychological data suggest that interconnected brain structures including the orbito-frontal cortex (OFC), anterior cingulate cortex (ACC) and caudate nucleus (CN) are involved in the pathophysiology of obsessive-compulsive disorder (OCD), but structural imaging studies investigating these regions have yielded inconclusive results. This may be due to inconsistencies in the identification of anatomical boundaries and methodologies utilised (i.e. automated vs. manual tracing). This magnetic resonance imaging study used manual tracing to measure volumes of selected brain regions (OFC, ACC and CN) in OCD patients and compared them with samples of healthy (HC) and psychiatric (schizophrenia; SCZ) controls (n=18 in each group). Concurrently, automated voxel-based analysis was also used to detect subtle differences in cerebral grey and white matter. For the OCD vs. HC comparison, there were no significant volumetric differences detected using the manual or the automated method (although the latter revealed a deficit in the subcortical white matter of the right temporal region). A direct comparison of the two patient groups showed no significant differences using the manual method. However, a moderate effect size was detected for OFC grey matter (reduced in SCZ), which was supported by findings of reduced OFC volume in the automated analysis. Automated analyses also showed reduced volumes in the dorsal (white matter) and ventral ACC (grey and white matter), as well as the left posterior cingulate (grey and white matter) in SCZ. The findings suggest that in contrast to findings in SCZ, there are very few (if any) gross structural anomalies in OCD.

Adult↗

PubMed2005

Functional connectivity during Stroop task performance.

Using covariance-based multivariate analysis, we examined patterns of functional connectivity in rCBF on a practice-extended version of the Stroop color-word paradigm. Color-word congruent and incongruent conditions were presented in six AB trials to healthy subjects during 12 H2(15)O PET scans. Analyses identified two reproducible canonical eigenimages (CE) from the PET data, which were converted to a standard Z score scale after cross-validation resampling and correction for random subject effects. The first CE corresponded to practice-dependent changes in covarying rCBF that occurred over early task repetitions and correlated with improved behavioral performance. This included many regions previously implicated by PET and fMRI studies of this task, which we suggest may represent two "parallel" networks: (i) a cingulo-frontal system that was initially engaged in selecting and mapping a task-relevant response (color naming) when the attentional demands of the task were greatest; and (ii) a ventral visual processing stream whose concurrent decrease in activity represented the task-irrelevant inhibition of word reading. The second CE corresponded to a consistent paradigmatic effect of Stroop interference on covarying rCBF. Coactivations were located in dorsal and ventral prefrontal regions as well as frontopolar cortex. This pattern supports existing evidence that prefrontal regions are involved in maintaining attentional control over conflicting response systems. Taken together, these findings may be more in line with theoretical models that emphasize a role for practice in the emergence of Stroop phenomena. These findings may also provide some additional insight into the nature of anterior cingulate- and prefrontal cortical contributions to implementing cognitive control in the brain.

Arousal↗

PubMed2005

Early processing deficits in object working memory in first-episode schizophreniform psychosis and established schizophrenia.

BACKGROUND: While there are many studies showing working-memory deficits in schizophrenia there are only a few that disentangle impairments for working-memory subprocesses such as perceptual, attentional, mnemonic and executive function. METHOD: In this study of delay-dependent memory, 55 patients with schizophreniform psychosis, 50 with established schizophrenia and 56 healthy controls were investigated. Using the delayed matching-to-sample task from the Cambridge Neuropsychological Test Automated Battery (CANTAB), performance deficits were found in both patient groups after controlling for age and pre-morbid IQ. RESULTS: Even after controlling for simultaneous matching-to-sample ability (i.e. perceptual matching), impaired performance in both patient groups was found as soon as the stimuli were no longer present. Impaired performance was not due to different types of errors in patients versus controls. Performance in both patient groups was comparable, except for a slight decrease of overall task performance. This suggests that the deficit is relatively stable during the course of the illness. CONCLUSIONS: Our results suggest a deficit in patients with psychotic illness in the initial processes necessary to actively maintain information, such as the ability to form an internal representation of complex objects.

Adolescent↗

PubMed2005

Increased pituitary volume in antipsychotic-free and antipsychotic-treated patients of the AEsop first-onset psychosis study.

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naïve), 26 were receiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls (+22%, p< 0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15% larger in antipsychotic-free patients (p=0.028), 17% larger in patients receiving atypicals (p=0.01), and 30% larger in patients receiving typicals (p<0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together (+11%, p=0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24% larger in patients with schizophrenia/schizophreniform disorder (n=40, p<0.001), 19% larger in depressed patients (n=13, p=0.022), 16% larger in bipolar patients (n=16, p=0.037), and 12% larger in those with other psychoses (n=9, p=0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effect on pituitary volume, likely to be related to activation of prolactin-secreting cells. This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis.

Adolescent↗

PubMed2005

Diseases of white matter and schizophrenia-like psychosis.

OBJECTIVE: To analyse the available data regarding the presentation of psychosis in diseases of central nervous system (CNS) white matter. METHOD: The available neurological and psychiatric literature on developmental, neoplastic, infective, immunological and other white matter diseases was reviewed. RESULTS: A number of diseases of the white matter can present as schizophrenia-like psychoses, including leukodystrophies, neoplasms, velocardiofacial syndrome, callosal anomalies and inflammatory diseases. CONCLUSIONS: Production of psychotic symptoms may result from functional asynchrony of interdependent regions, due to alterations in critical circuits as a result of pathology. The nature, location and timing of white matter pathology seem to be the key factors in the development of psychosis, especially during the critical adolescent period of association area myelination. Diseases that disrupt the normal formation of myelin appear to cause psychosis at higher rates than those that disrupt mature myelinated structures. Diffuse rather than discrete lesions, in particular those affecting frontotemporal zones, are also more strongly associated with schizophrenia-like psychosis. These illnesses point to the central role that white matter plays in maintaining CNS connectivity and to how pathology of the white matter may contribute to the neurobiology of psychosis.

Brain Diseases↗

PubMed2005

Memory impairments identified in people at ultra-high risk for psychosis who later develop first-episode psychosis.

OBJECTIVE: While cognitive deficits are frequently reported in psychotic disorders, it is unclear whether these impairments predate the onset of illness and to what extent they are predictive of later transition to psychosis. METHOD: The authors studied 37 healthy volunteers and 98 symptomatic, help-seeking patients meeting the inclusion criteria of a treatment program for people at ultra-high risk for psychosis. Of the ultra-high-risk patients, 34 (34.7%) developed psychosis over the course of the investigation. Premorbid and current IQ, attention, memory, and executive functioning were measured with instruments including subtests from the Wechsler Memory Scale-Revised (WMS-R). Analyses compared the ultra-high-risk patients who became psychotic, those who did not become psychotic, and the comparison subjects. RESULTS: Overall, the ultra-high-risk subjects had significantly lower performance IQs than the comparison subjects. Further, impairments were also found in the visual reproduction subtest and the verbal memory index (predominantly owing to lower logical memory scores) of the WMS-R that were specific to the ultra-high-risk-patients who developed psychosis. No other memory, attentional, or executive tasks discriminated between any of the groups. CONCLUSIONS: These findings suggest that visuospatial processing impairment and some memory deficits were apparent before the full expression of psychotic illness. Cognitive performance on more complex tasks requiring rapid registration and efficient recall may be compromised before development of first-episode psychosis. Further experimental tasks that challenge these cognitive domains are required to clarify the predictive value of these results.

Adolescent↗

PubMed2005

Neurobiology of early psychosis.

BACKGROUND: Neurobiological studies of the early course of psychoses, such as schizophrenia, allow investigation of pathophysiology without the confounds of illness chronicity and treatment. AIMS: To review the recent literature on the biology of the early course of psychoses. METHOD: We carried out a critical appraisal of the recent findings in the neurobiology of early psychoses, using structural, functional and neurochemical imaging techniques. RESULTS: Brain structural alterations are present early in the illness and may predate symptom onset. Some changes, notably those in frontal and temporal lobes, can progress during the early phases of the illness. Functional and neurochemical brain abnormalities can also be seen in the premorbid and the early phases of the illness. Some, although not all, changes can be trait-like whereas some others might progress during the early years. CONCLUSIONS: A better understanding of such changes, especially during the critical periods of the prodrome, around the transition to the psychotic phase and during the early phases of the illness is crucial for continued research into preventive intervention strategies.

Brain↗