At-risk Mental State Subjects Research Articles

Prediction of psychotic disorder in individuals with clinical high-risk state by multimodal machine-learning: A preliminary study

Objective markers which can reliably predict psychosis transition among individuals with at-risk mental state (ARMS) are warranted. In this study, sixty-five ARMS subjects [of whom 17 (26.2%) later developed psychosis] were recruited, and we performed supervised linear support vector machine (SVM) with a variety of combinations of.modalities (clinical features, cognition, structural magnetic resonance imaging, eventrelated.potentials, and polyunsaturated fatty acids) to predict future psychosis onset. While single-modality SVMs showed a poor to fair accuracy, multi-modal SVMs revealed better predictions, up to 0.88 of the balanced accuracy, suggesting the advantage of multi-modal machine-learning methods for forecasting psychosis onset in ARMS.

Resting state hyperconnectivity of the default mode network in schizophrenia and clinical high-risk state for psychosis.

Disrupted functional connectivity (FC) of the default mode network (DMN) may have a pathophysiological role in schizophrenia. However, functional magnetic resonance imaging (fMRI) of the DMN in schizophrenia patients has shown inconsistent results. It also remains unclear whether individuals with at-risk mental state (ARMS) have an altered DMN connectivity and whether it is related to clinical characteristics. This fMRI study examined resting-state FCs of the DMN and its relevance to clinical/cognitive variables in 41 schizophrenia patients, 31 ARMS individuals, and 65 healthy controls. Compared with controls, schizophrenia patients had significantly increased FCs within the DMN and between the DMN and diverse cortical areas, whereas ARMS patients had increased FCs only between the DMN and occipital cortex. FC of the lateral parietal cortex with superior temporal gyrus was positively correlated with negative symptoms in schizophrenia, whereas FC of that with interparietal sulcus was negatively correlated with general cognitive impairment in ARMS. Our findings suggest that increased FCs between the DMN and visual network commonly seen in schizophrenia and ARMS subjects may reflect a network-level disturbance representing a general vulnerability to psychosis. In addition, FC changes related to the lateral parietal cortex may underpin clinical characteristics of ARMS and schizophrenia subjects.

Development and validation of a scale of self-alienation-related attributes for the early diagnosis of schizophrenia

BackgroundThe onset of schizophrenia is often preceded by a prodromal phase. However, it is difficult to predict the future transition to schizophrenia from the prodromal symptoms. Based on the diagnostic significance of Schneider's first rank symptoms (FRS), especially those representing “ego disorders (Ichstörungen)”, we developed a scale of self-alienation-related attributes (Self-A) to assess the psychological characteristics associated with ego disorders for the early diagnosis of schizophrenia. MethodsIn total, 153 schizophrenia (Sz) patients, 83 at-risk mental state (ARMS) subjects, and 154 healthy control (HC) subjects participated in this study. The Self-A scale was constructed by items from the Minnesota Multiphasic Personality Inventory (MMPI) based on the differences between schizophrenia patients with and without FRS representing ego-disorders designated as “self-alienation symptoms”. The Self-A scale was tested for its reliability and validity in a different sample of schizophrenia patients, and was then applied to different cohorts including first-episode schizophrenia (FES) patients, ARMS individuals, and HC subjects. ResultsThe Self-A consisting of 27 items exhibited good internal consistency reliability. The validity was well demonstrated by the high correlation of the Self-A scores with the self-alienation symptom scores. The ARMS and FES groups had higher Self-A scores than the HC group. The Self-A score in the ARMS individuals who later developed schizophrenia was higher than that in the ARMS subjects who did not, and was comparable with that in the FES group. ConclusionsThis study suggests that the newly developed Self-A scale assessing the self-alienation-related attributes can improve the early diagnosis of schizophrenia.

Urinary biopyrrins and free immunoglobin light chains are biomarker candidates for screening at-risk mental state in adolescents.

Early diagnosis of individuals' at-risk mental state (ARMS) is important for preventing their pathogenesis or, at least, delaying onset of overt psychosis. Traditional diagnosis of ARMS subjects is mainly based on structured interviews, but future diagnosis would be carried out together with biomarkers. In this study, we report urinary biopyrrins and free immunoglobin light chains κ and λ (κFLC and λFLC) as novel diagnostic biomarker candidates for screening ARMS subjects. Nineteen ARMS subjects and 21 age- and sex-matched healthy controls were enrolled in this study. Inclusion criteria of the ARMS subjects were based on a comprehensive assessment of Structured Interview for Prodromal Syndromes. We compared oxidative stress and immunological markers in the urine of ARMS subjects with those of healthy controls by ELISA protocol. Augmentation of biopyrrins and reduction of κFLC and λFLC were found in the ARMS samples, and their diagnostic performance was evaluated by receiver operating characteristic analysis, of which area under the curve was as large as 0.915 in combination. Our findings suggest that the ARMS subjects were under higher oxidative stress but lower in B cell activation, and that the combined assay of urinary biopyrrins and free immunoglobulin light chains would be useful for the early detection and screening of ARMS subjects among adolescents.

Increased inosine levels in drug-free individuals with at-risk mental state: A serum metabolomics study.

At-risk mental state (ARMS) has been recently attracting attention with respect to the improvement of the management and outcome of psychiatric diseases, such as schizophrenia. Since only a few studies have reported on biological alterations in ARMS, serum metabolomics was carried out in ARMS subjects and healthy controls using liquid chromatography with high-resolution mass spectrometry. Serum samples were collected from ARMS subjects (n=24; male: 12; female 12) and age- and sex-matched healthy controls (n=23 male: 11, female: 12). After serum pre-treatment, liquid chromatography with high-resolution mass spectrometry was performed. Multivariate analyses, such as orthogonal partial least-squares discriminant and volcano plot analyses, were performed. Serum inosine, lactate, taurine, 2,3-dihydroxypropanoate and glutamate levels differed between the two groups. A significant increase in inosine levels was detected in the positive- and negative-ion modes; however, significant differences were not observed in the levels of other purine-related metabolites (hypoxanthine, xanthine and urate) between the two groups. Increased inosine levels may serve as biological markers for ARMS, in addition to alterations in the levels of lactate and certain amino acids.

Potential contribution of pineal atrophy and pineal cysts toward vulnerability and clinical characteristics of psychosis

BackgroundMagnetic resonance imaging (MRI) studies reported pineal gland atrophy in schizophrenia patients and individuals at a clinical high risk of developing psychosis, implicating abnormalities in melatonin secretion in the pathophysiology of psychosis. However, it currently remains unclear whether the morphology of the pineal gland contributes to symptomatology and sociocognitive functions. MethodsThis MRI study examined pineal gland volumes and the prevalence of pineal cysts as well as their relationship with clinical characteristics in 57 at risk mental state (ARMS) subjects, 63 patients with schizophrenia, and 61 healthy controls. The Social and Occupational Functioning Assessment Scale (SOFAS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Brief Assessment of Cognition in Schizophrenia (BACS) were used to assess sociocognitive functions, while the Positive and Negative Syndrome Scale was employed to evaluate clinical symptoms in ARMS subjects and schizophrenia patients. ResultsPineal gland volumes were significantly smaller in the ARMS and schizophrenia groups than in the controls, while no significant differences were observed in the prevalence of pineal cysts. Although BACS, SCoRS, and SOFAS scores were not associated with pineal morphology, patients with pineal cysts in the schizophrenia group exhibited severe positive psychotic symptoms with rather mild negative symptoms. ConclusionThe present results indicate the potential of pineal atrophy as a vulnerability marker in various stages of psychosis and suggest that pineal cysts influence the clinical subtype of schizophrenia.

Features of Duration Mismatch Negativity Around the Onset of Overt Psychotic Disorders: A Longitudinal Study.

Reduced amplitude of duration mismatch negativity (dMMN) has been reported in psychotic disorders and at-risk mental state (ARMS); however, few longitudinal MMN studies have examined the amplitude changes during the course of psychosis. We compared dMMN amplitude between ARMS individuals with later psychosis onset and those without, and we longitudinally examined potential dMMN changes around psychosis onset. Thirty-nine ARMS subjects and 22 healthy controls participated in this study. Of the 39 ARMS subjects, 11 transitioned to psychosis (at-risk mental state with later psychosis onset [ARMS-P]) during follow-up and 28 did not (at-risk mental state without later psychosis onset [ARMS-NP]). dMMN was measured twice using an auditory oddball paradigm with a mean interval of 2years. Follow-up dMMN data were available for all but four ARMS-P subjects. dMMN amplitude at baseline was smaller in ARMS-P subjects compared with control and ARMS-NP subjects. Additionally, ARMS-P subjects displayed a longitudinal decline in dMMN amplitude, which was not present in control and ARMS-P subjects. We also observed a progressive decline in dMMN amplitude during the transition period, suggesting dynamic brain changes associated with the psychosis onset. Our findings implicate dMMN amplitude as a biological predictor of future psychosis onset in high-risk individuals, which may be used for early detection and intervention of psychosis.

Structural MRI Study of the Planum Temporale in Individuals With an At-Risk Mental State Using Labeled Cortical Distance Mapping.

Background: Recent studies have demonstrated brain structural changes that predate or accompany the onset of frank psychosis, such as schizophrenia, among individuals with an at-risk mental state (ARMS). The planum temporale (PT) is a brain region involved in language processing. In schizophrenia patients, gray matter volume reduction and lack of normal asymmetry (left > right) of PT have repeatedly been reported. Some studies showed progressive gray matter reduction of PT in first-episode schizophrenia patients, and in ARMS subjects during their development of psychosis.Methods: MRI scans (1.5 T field strength) were obtained from 73 ARMS subjects and 74 gender- and age-matched healthy controls at three sites (University of Toyama, Toho University and Tohoku University). Participants with ARMS were clinically monitored for at least 2 years to confirm whether they subsequently developed frank psychosis. Cortical thickness, gray matter volume, and surface area of PT were estimated using FreeSurfer-initiated labeled cortical distance mapping (FSLCDM). PT measures were compared among healthy controls, ARMS subjects who later developed overt psychosis (ARMS-P), and those who did not (ARMS-NP). In each statistical model, age, sex, intracranial volume, and scanning sites were treated as nuisance covariates.Results: Of 73 ARMS subjects, 18 developed overt psychosis (12 schizophrenia and 6 other psychoses) within the follow-up period. There were no significant group differences of PT measures. In addition, significant asymmetries of PT volume and surface area (left > right) were found in all diagnostic groups. PT measures did not correlate with the neurocognitive performance of ARMS subjects.Discussion: Our results suggest that the previously-reported gray matter reduction and lack of normal anatomical asymmetry of PT in schizophrenia patients may not emerge during the prodromal stage of psychosis; taken together with previous longitudinal findings, such PT structural changes may occur just before or during the onset of psychosis.

Subcortical Brain Volume Abnormalities in Individuals With an At-risk Mental State.

Previous structural magnetic resonance imaging studies of psychotic disorders have demonstrated volumetric alterations in subcortical (ie, the basal ganglia, thalamus) and temporolimbic structures, which are involved in high-order cognition and emotional regulation. However, it remains unclear whether individuals at high risk for psychotic disorders with minimal confounding effects of medication exhibit volumetric changes in these regions. This multicenter magnetic resonance imaging study assessed regional volumes of the thalamus, caudate, putamen, nucleus accumbens, globus pallidus, hippocampus, and amygdala, as well as lateral ventricular volume using FreeSurfer software in 107 individuals with an at-risk mental state (ARMS) (of whom 21 [19.6%] later developed psychosis during clinical follow-up [mean = 4.9 years, SD = 2.6 years]) and 104 age- and gender-matched healthy controls recruited at 4 different sites. ARMS individuals as a whole demonstrated significantly larger volumes for the left caudate and bilateral lateral ventricles as well as a smaller volume for the right accumbens compared with controls. In male subjects only, the left globus pallidus was significantly larger in ARMS individuals. The ARMS group was also characterized by left-greater-than-right asymmetries of the lateral ventricle and caudate nucleus. There was no significant difference in the regional volumes between ARMS groups with and without later psychosis onset. The present study suggested that significant volume expansion of the lateral ventricle, caudate, and globus pallidus, as well as volume reduction of the accumbens, in ARMS subjects, which could not be explained only by medication effects, might be related to general vulnerability to psychopathology.

O10.1. DISORGANIZED GYRIFICATION NETWORK PROPERTIES DURING THE TRANSITION TO PSYCHOSIS

BackgroundThere is urgent need to improve the limited prognostic accuracy of psychopathology-based classifications to predict the onset of psychosis in clinical high-risk (CHR) subjects for psychosis. However, as yet no reliable biological marker has been established to differentiate CHR subjects who will develop psychosis from those who will not. This study investigated abnormalities in graph-based gyrification connectome in CHR subjects and patients with first-episode psychosis (FEP) and tested the accuracy of this systems-based approach to predict the transition to psychosis among CHR individuals.Methods44 healthy controls (HC), 63 at-risk mental state (ARMS) subjects without later transition to psychosis (ARMS-NT), 16 ARMS subjects with later transition (ARMS-T), and 38 antipsychotic-free patients with FEP were recruited from the specialized clinic for the early detection of psychosis at the Department of Psychiatry, University of Basel, Basel, Switzerland. Gyrification-based structural covariance networks (connectomes) were constructed to quantify global integration, segregation and small-worldness. Extremely randomized trees with repeated, nested cross-validation was performed to differentiate ARMS-T from ARMS-NT individuals. Permutation testing was used to assess the significance of classification performance measures.ResultsSmall-worldness is reduced in both ARMS-T and FEP patients, secondary to reduced integration and increased segregation in both groups. In addition, we also found that transitivity (segregation) was significantly higher in ARMS-T and FEP groups compared to both ARMS-NT and healthy controls. Using the connectome properties as features, we obtained a high classification accuracy of 90% (balanced accuracy: 81%, positive predictive value: 85%, negative predictive value: 92%.) All performance measures were highly significant as indicated by permutation tests (all p < 0.01).DiscussionOur findings suggest that there is poor integration in the coordinated development of cortical folding in patients who develop psychosis. This study further indicates that gyrification-based connectomes might be a promising means to generate systems-based measures from anatomical data that improves individual prediction of psychosis transition in CHR subjects.

Early Intervention and a Direction of Novel Therapeutics for the Improvement of Functional Outcomes in Schizophrenia: A Selective Review.

A recent review reported that the median proportion of patients recovering from schizophrenia was 13.5% and that this did not change over time. Various factors including the duration of untreated psychosis, cognitive impairment, negative symptoms, and morphological changes in the brain influence the functional outcome of schizophrenia. The authors herein reviewed morphological changes in the brain of schizophrenia patients, effects of early intervention, and a direction of developing novel therapeutics to achieve significant improvement of the functional outcome. A selective review of the literature including studies from our department was performed. Longitudinal structural neuroimaging studies on schizophrenia revealed that volume reductions in the peri-Sylvian regions (e.g., superior temporal gyrus and insula), which are related to positive psychotic symptoms, progress around the onset (critical stage) of schizophrenia, but become stable in the chronic stage. On the other hand, morphological changes in the fronto-thalamic regions and lateral ventricle, which are related to negative symptoms, neurocognitive dysfunction, and the functional outcome, progress during both the critical and chronic stages. These changes in the peri-Sylvian and fronto-thalamic regions may provide a pathophysiological basis for Crow's two-syndrome classification. Accumulated evidence from early intervention trials suggests that the transition risk from an at-risk mental state (ARMS) to psychosis is approximately 30%. Differences in the cognitive performance, event-related potentials (e.g., mismatch negativity), and brain morphology have been reported between ARMS subjects who later developed psychosis and those who did not. Whether early intervention for ARMS significantly improves the long-term recovery rate of schizophrenia patients remains unknown. With respect to the development of novel therapeutics, animal models of schizophrenia based on the N-methyl-d-aspartate receptor hypofunction hypothesis successfully mimicked behavioral changes associated with cognitive impairments characteristic of the disease. Furthermore, these animal models elicited histological changes in the brain similar to those observed in schizophrenia patients, i.e., decreased numbers of parvalbumin-positive interneurons and dendritic spines of pyramidal neurons in the frontal cortex. Some antioxidant compounds were found to ameliorate these behavioral and histological abnormalities. Early intervention coupled with novel therapeutics may offer a promising approach for substantial improvement of the functional outcome of schizophrenia patients.

Longitudinal study examining abnormal white matter integrity using a tract-specific analysis in individuals with a high risk for psychosis.

Although volume reductions in the grey matter have been previously observed in individuals with an at-risk mental state (ARMS) for psychosis, the features of white matter integrity and their correlation with psychiatric symptoms remain unclear. Forty-six ARMS subjects were examined using magnetic resonance imaging (MRI) to acquire diffusion tensor imaging (DTI); the subjects were also evaluated using the Scale of Prodromal Symptoms at baseline and at 52 weeks. Sixteen healthy controls also underwent MRI scanning. The DTI results were longitudinally analyzed using a tract-specific analysis to measure the fractional anisotropy (FA) values of the entire corpus callosum (CC), as well as its genu, trunk, and splenium. During the 52-week study period, seven patients developed psychosis (ARMS-P) and 39 did not (ARMS-NP). In the entire CC and the genu, trunk, and splenium of the CC, the FA values of the ARMS subjects were each significantly smaller than the respective values of the healthy controls at baseline. In the genu and trunk, the baseline FA values in the ARMS-NP group were, paradoxically, smaller than those of the ARMS-P group at baseline. Regarding the association between the FA values and psychiatric symptoms, a reduction in the FA value in the genu was significantly correlated with a deterioration of negative symptoms among the ARMS subjects. Abnormal white matter integrity in the CC may predict the long-term outcome of patients with prodromal psychosis, since negative symptoms are associated with poor functioning.

Reduced Thickness of the Anterior Cingulate Cortex in Individuals With an At-Risk Mental State Who Later Develop Psychosis.

Despite the fact that only a part of the individuals with at-risk mental state (ARMS) for psychosis do develop psychosis, biological markers of future transition to psychosis have not been well documented. Structural abnormality of the anterior cingulate gyrus (ACG), which probably exists prior to the onset of psychosis, could be such a risk marker. We conducted a multicenter magnetic resonance imaging (MRI) study of 3 scanning sites in Japan. 1.5-T 3D MRI scans were obtained from 73 ARMS subjects and 74 age- and gender-matched healthy controls. We measured thickness, volume, and surface area of the ACG using labeled cortical distance mapping and compared these measures among healthy controls, ARMS subjects who later converted to overt psychosis (ARMS-C), and those who did not (ARMS-NC). Seventeen of 73 (23%) ARMS subjects developed overt psychosis within the follow-up period. The thickness of the left ACG was significantly reduced in ARMS-C relative to healthy subjects (P = .026) while both ARMS-C (P = .001) and ARMS-NC (P = .01) had larger surface areas of the left ACG compared with healthy controls. Further studies will be needed to identify potential markers of future transition to psychosis though cortical thinning of the ACG might be one of the candidates.

Structural Network Disorganization in Subjects at Clinical High Risk for Psychosis

Previous network studies in chronic schizophrenia patients revealed impaired structural organization of the brain’s rich-club members, a set of highly interconnected hub regions that play an important integrative role for global brain communication. Moreover, impaired rich-club connectivity has also been found in unaffected siblings of schizophrenia patients, suggesting that abnormal rich-club connectivity is related to familiar, possibly reflecting genetic, vulnerability for schizophrenia. However, no study has yet investigated whether structural rich-club organization is also impaired in individuals with a clinical risk syndrome for psychosis. Diffusion tensor imaging and probabilistic tractography was used to construct structural whole-brain networks in 24 healthy controls and 24 subjects with an at-risk mental state (ARMS). Graph theory was applied to quantify the structural rich-club organization and global network properties. ARMS subjects revealed a significantly altered structural rich-club organization compared with the control group. The disruption of rich-club organization was associated with the severity of negative psychotic symptoms and led to an elevated level of modularity in ARMS subjects. This study shows that abnormal structural rich-club organization is already evident in clinical high-risk subjects for psychosis and further demonstrates the impact of rich-club disorganization on global network communication. Together with previous evidence in chronic schizophrenia patients and unaffected siblings, our findings suggest that abnormal structural rich-club organization may reflect an endophenotypic marker of psychosis.

Deficits of cognitive theory of mind and its relationship with functioning in individuals with an at-risk mental state and first-episode psychosis

Disturbance of theory of mind (ToM) and its relationship with functioning in schizophrenia is well documented; however, this is unclear in spectrum disorders like at-risk mental state (ARMS) and first-episode psychosis (FEP). To assess mental state reasoning ability, the total score of the Theory of Mind Picture Stories Task questionnaire was compared among 36 Japanese individuals with ARMS, 40 with FEP, and 25 healthy controls (HC). Pearson's correlations between ToM performance and global and social functioning indices were examined. ToM performance for FEP and ARMS subjects was significantly lower than that for HC, though the significance of the difference between the ARMS and HC disappeared when controlling for premorbid IQ. ToM deficits in ARMS subjects were confirmed only in the comprehension of higher-order false belief. Only among FEP subjects were ToM performance and global functioning significantly correlated, though the significance disappeared when controlling for neurocognitive performance or dose of antipsychotics. No significant correlation between ToM performance and social functioning was observed in the FEP and ARMS groups. The current findings suggest that ToM deficits emerge in ARMS subjects confined within a higher-order domain, and that the relationship between ToM impairment and functional deterioration might be established after psychosis onset.

COMT Val158Met genotype and cannabis use in people with an At Risk Mental State for psychosis: Exploring Gene x Environment interactions

BackgroundEpidemiological and retrospective studies suggest a cannabis x catechol-O-methyltransferase (COMT) Val158Met interaction effect on development of psychosis. The aim of this study was to examine this interaction and its association with severity of subclinical symptoms in people with an At Risk Mental State (ARMS) for psychosis. MethodsSeverity of symptoms, cannabis use and genotype were assessed at baseline in 147 help-seeking young adults who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. ResultsCannabis use and COMT Val-allele showed an interaction effect in ARMS subjects. Subjects who were weekly cannabis users at some point prior to entering the study showed more severe positive symptoms. This effect increased if they were carriers of the COMT Val-allele and even more so if they were homozygous for the Val-allele. ConclusionsOur results suggest that the COMT Val158Met polymorphism moderates the effect of regular cannabis use on severity of subclinical psychotic symptoms.

Sensorimotor gating, cannabis use and the risk of psychosis

Sensorimotor gating, measured as the modification of eye blink startle reflexes to loud acoustic stimuli by quieter preceding stimuli, is altered in those with psychosis, their relatives and those at high clinical risk for psychosis. Alterations have also been shown in cannabis users, albeit to a lesser extent, and cannabis is a known risk factor for the onset of psychosis in clinically and genetically susceptible individuals.We examined the interaction between clinical risk for psychosis and cannabis use on sensorimotor gating, both Prepulse Inhibition (PPI) and Prepulse Facilitation (PPF). We tested PPI and PPF in participants with an At Risk Mental State (ARMS) for psychosis and a matched control group. Both groups included a proportion of subjects who had recently used cannabis, as confirmed by urinary drug screening (UDS) on the day of testing. We found that ARMS participants showed reduced PPF and PPI relative to controls, the latter driven by a group by cannabis use interaction, with recent use reducing PPI in ARMS participants but not in controls. When the analysis was limited to UDS-negative participants there was significantly reduced PPF in ARMS subjects relative to controls, but no differences in PPI. Within the ARMS group reduced sensorimotor gating, measured by both PPI and PPF, related to reduced overall level of function.Cannabis use in clinical high risk individuals may increase the risk of psychosis in part through worsening PPI, while PPF is altered in ARMS individuals irrespective of cannabis use. This develops our understanding of cognitive mechanisms leading to the experience of aberrant perceptual phenomena and the subsequent development of psychotic symptoms.

Brain Diffusion Changes in Emerging Psychosis and the Impact of State-Dependent Psychopathology

Background/Aims: Previous diffusion tensor imaging (DTI) studies have shown microstructural changes in the brain white matter of at-risk mental state (ARMS) subjects for psychosis and patients with first-episode psychosis (FEP). However, only a few studies have been conducted in clinical high-risk samples and findings in both groups are inconsistent, in particular along the superior longitudinal fasciculus (SLF). Methods: This DTI study used tract-based spatial statistics (TBSS) to compare fractional anisotropy (FA) and mean diffusivity (MD) between ARMS subjects, untreated and antipsychotic-treated FEP patients and healthy controls (HC) across the whole brain and the SLF. Results: Compared to HC, ARMS and FEP patients showed increased FA and decreased MD in diverse regions across the whole brain including the SLF. FA in the SLF was positively correlated with positive psychotic symptoms in ARMS and FEP individuals. Furthermore, untreated but not treated FEP patients showed increased FA in the left inferior longitudinal fasciculus and right SLF. Conclusion: This study revealed increased FA and decreased MD in early stages of psychosis in widespread white matter tracts including the SLF. Our findings further suggest that microstructural changes in the SLF are probably related to state-dependent psychopathology.

Event-related potentials and biomarkers of psychiatric diseases: the necessity to adopt and develop multi-site guidelines.

Higuchi et al. (2014) published a paper comparing healthy controls, schizophrenic patients and subjects with at-risk mental state (ARMS) during an event-related potential (ERP) auditory oddball task. Results showed that ARMS subjects who transitioned to schizophrenia (Converters) disclosed diminished duration mismatch negativity amplitudes (dMMN) as compared with non-Converters before onset of illness. As the reduction of dMMN is a common finding when schizophrenic patients are compared with healthy controls (e.g., Umbricht and Krljes, 2005), the authors concluded that decreased dMMN amplitudes are a trait biomarker of psychosis, present before and after the development of the disease.

Stress biomarkers as predictors of transition to psychosis in at-risk mental states: Roles for cortisol, prolactin and albumin

Stress and inflammation are thought to play a role in the risk of developing a psychotic disorder. We aimed to identify stress-related biomarkers for psychosis transition in help-seeking individuals with an at-risk mental state (ARMS). We studied 39 ARMS subjects who were attending an Early Intervention Service. We included a control group of 44 healthy subjects (HS) matched by sex and age. Stressful life events and perceived stress were assessed. Stress-related biomarkers were determined in serum (cortisol, prolactin, C-reactive protein and albumin), plasma (fibrinogen) or saliva (morning cortisol, cortisol awakening response). All ARMS were followed-up at our Unit for at least one year. We divided the ARMS group into two subgroups based on the development of a psychotic disorder (ARMS-P, N = 10) or not (ARMS-NP, N = 29). ARMS-P reported more stressful life events and perceived stress than HS and ARMS-NP groups. In relation to baseline stress biomarkers, ARMS-P subjects had increased prolactin and lower albumin levels in serum, when compared to ARMS-NP and HS groups. These results did not change when repeated in a subsample of antipsychotic-naïve ARMS subjects. We also found significant differences between groups in the cortisol secretion after awakening. In a multinomial logistic regression adjusting for age, sex and life stress, prolactin was a predictor of psychosis transition whereas albumin levels had a protective effect. Our study underscores the role of stress and stress-related biomarkers (cortisol awakening response, prolactin and albumin) in the pathogenesis of psychosis.