Mapping prodromal psychosis: A critical review of neuroimaging studies

Institute of Psychiatry, Department of Psychosis Studies, London, UK.
European Psychiatry (Impact Factor: 3.44). 09/2011; 27(3):181-91. DOI: 10.1016/j.eurpsy.2011.06.006
Source: PubMed


The onset of schizophrenia is usually preceded by a prodromal phase characterized by functional decline and subtle prodromal symptoms, which include attenuated psychotic phenomena, cognitive deterioration and a decline in socio-occupational function. Preventive interventions during this phase are of great interest because of the impressive clinical benefits. However, available psychopathological criteria employed to define a high risk state for psychosis have low validity and specificity. Consequently there is an urgent need of reliable neurocognitive markers linked to the pathophysiological mechanisms that underlie schizophrenia. Neuroimaging techniques have rapidly developed into a powerful tool in psychiatry as they provide an unprecedented opportunity for the investigation of brain structure and function. This review shows that neuroimaging studies of the prodromal phases of psychosis have the potentials to identify core structural and functional markers of an impending risk to psychosis and to clarify the dynamic changes underlying transition to psychosis and to address significant correlations between brain structure or function and prodromal psychopathology. Additionally, neurochemical methods can address the key role played by neurotransmitters such as dopamine and glutamate during the psychosis onset. To conclude, multimodal neuroimaging may ultimately clarify the neurobiology of the prodromal phases by the integration of functional, structural and neurochemical findings.

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    • "However, conversion rates vary across studies applying these criteria (Simon et al., 2011; Fusar-Poli et al., 2012a). Therefore, additional parameters have been investigated, including neuroimaging (Fusar-Poli et al., 2012b), neuropsychological (Becker et al., 2010; Fusar-Poli et al., 2012c; Pukrop and Ruhrmann, 2012), and neurophysiological measures (Shin et al., 2011). Particularly, event related potentials have been identified as potential biological predictors of psychosis, e.g. "
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    ABSTRACT: Background Prediction studies in subjects at Clinical High Risk (CHR) for psychosis are hampered by a high proportion of uncertain outcomes. We therefore investigated whether quantitative EEG (QEEG) parameters can contribute to an improved identification of CHR subjects with a later conversion to psychosis. Methods This investigation was a project within the European Prediction of Psychosis Study (EPOS), a prospective multicenter, naturalistic field study with an 18-month follow-up period. QEEG spectral power and alpha peak frequencies (APF) were determined in 113 CHR subjects. The primary outcome measure was conversion to psychosis. Results Cox regression yielded a model including frontal theta (HR = 1.82; [95% CI 1.00–3.32]) and delta (HR = 2.60; [95% CI 1.30–5.20]) power, and occipital–parietal APF (HR = .52; [95% CI .35–.80]) as predictors of conversion to psychosis. The resulting equation enabled the development of a prognostic index with three risk classes (hazard rate 0.057 to 0.81). Conclusions Power in theta and delta ranges and APF contribute to the short-term prediction of psychosis and enable a further stratification of risk in CHR samples. Combined with (other) clinical ratings, EEG parameters may therefore be a useful tool for individualized risk estimation and, consequently, targeted prevention.
    Schizophrenia Research 03/2014; 153(1-3). DOI:10.1016/j.schres.2014.01.019 · 3.92 Impact Factor
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    • "This incorporates information obtained from other modalities as regressors for whole-brain analyses and also allows voxel-wise multimodal correlation. BPM has been used widely for integrative analysis of different neuroimaging modalities (19–21). On the basis of our previous findings (17), we expected a direct relationship between perfusion and GM within the areas with the most marked hypoperfusion during the acute effects of heroin. "
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    ABSTRACT: Structure and function in the human healthy brain are closely related. In patients with chronic heroin exposure, brain imaging studies have identified long-lasting changes in gray matter (GM) volume. More recently, we showed that acute application of heroin in dependent pa-tients results in hypoperfusion of fronto-temporal areas compared with the placebo condition. However, the relationship between structural and cerebral blood flow (CBF) changes in heroin addiction has not yet been investigated. Moreover, it is not known whether there is any interaction between the chronic structural changes and the short and long term effects on per-fusion caused by heroin. Using a double-blind, within-subject design, heroin or placebo (saline) was administrated to 15 heroin-dependent patients from a stable heroin-assisted treat-ment program, in order to observe acute short-term effects. Arterial spin labeling (ASL) was used to calculate perfusion quantification maps in both treatment conditions, while Voxel Based Morphometry (VBM) was conducted to calculate regional GM density. VBM and ASL data were used to calculate homologous correlation fields by Biological Parametric Mapping (BPM). We correlated each perfusion condition (heroin and placebo) separately with a VBM sample that was identical for the two treatment conditions. It was assumed that heroin-associated perfusion is manifested in short term effects, while placebo-associated perfusion is more related to long term effects. Correlation analyses revealed a significant positive correlation in frontal and temporal areas between GM and both perfusion conditions (heroin and placebo). The heroin-associated perfusion was also negatively correlated with GM in the left thalamus and right cuneus. These findings indicate that, in heroin-dependent patients, low GM volume is positively associated with low perfusion within fronto-temporal regions.
    Frontiers in Psychiatry 10/2013; 4:135. DOI:10.3389/fpsyt.2013.00135
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    • "Before a first onset of psychosis, a prodromal period occurs in over 70% of schizophrenia cases (Häfner et al., 2003), which is characterized by attenuated psychotic symptoms, anxiety, social and role dysfunction, and affective symptoms. In the hope of reducing morbidity and preventing or delaying onset through early intervention, current efforts aim at identifying young people at risk during this prodromal stage (e.g., Corcoran et al., 2010; Fusar-Poli et al., 2012b). Little is known, however, about the underlying pathophysiology of emerging psychosis. "
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    ABSTRACT: Smell identification deficits (SIDs) are relatively specific to schizophrenia and its negative symptoms, and may predict transition to psychosis in clinical high-risk (CHR) individuals. Moreover, event-related potentials (ERPs) to odors are reduced in schizophrenia. This study examined whether CHR patients show SIDs and abnormal olfactory N1 and P2 potentials. ERPs (49 channels) were recorded from 21 CHR and 20 healthy participants (13 males/group; ages 13-27 years) during an odor detection task using three concentrations of hydrogen sulfide (H2S) or blank air presented unilaterally by a constant-flow olfactometer. Neuronal generator patterns underlying olfactory ERPs were identified and measured by principal components analysis (unrestricted Varimax) of reference-free current source densities (CSD). Replicating previous findings, CSD waveforms to H2S stimuli were characterized by an early N1 sink (345 ms, lateral-temporal) and a late P2 source (600 ms, mid-frontocentroparietal). N1 and P2 varied monotonically with odor intensity (strong > medium > weak) and did not differ across groups. Patients and controls also showed comparable odor detection and had normal odor identification and thresholds (Sniffin' Sticks). However, olfactory ERPs strongly reflected differences in odor intensity and detection in controls, but these associations were substantially weaker in patients. Moreover, severity of negative symptoms in patients was associated with reduced olfactory ERPs and poorer odor detection, identification and thresholds. Three patients who developed psychosis had poorer odor detection and thresholds, and marked reductions of N1 and P2. Thus, despite the lack of overall group differences, olfactory measures may be of utility in predicting transition to psychosis among CHR patients.
    International journal of psychophysiology: official journal of the International Organization of Psychophysiology 07/2013; 90(2). DOI:10.1016/j.ijpsycho.2013.07.003 · 2.88 Impact Factor
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