First-episode Psychosis Group Research Articles

Association of Hippocampal Atrophy With Duration of Untreated Psychosis and Molecular Biomarkers During Initial Antipsychotic Treatment of First-Episode Psychosis

ImportanceDuration of untreated psychosis (DUP) has been associated with poor outcomes in schizophrenia, but the mechanism responsible for this association is not known.ObjectivesTo determine whether hippocampal volume loss occurs during the initial 8 weeks of antipsychotic treatment and whether it is associated with DUP, and to examine molecular biomarkers in association with hippocampal volume loss and DUP.Design, Setting, and ParticipantsA naturalistic longitudinal study with matched healthy controls was conducted at Shanghai Mental Health Center. Between March 5, 2013, and October 8, 2014, 71 medication-naive individuals with nonaffective first-episode psychosis (FEP) and 73 age- and sex-matched healthy controls were recruited. After approximately 8 weeks, 31 participants with FEP and 32 controls were reassessed.ExposuresThe participants with FEP were treated according to standard clinical practice with second-generation antipsychotics.Main Outcomes and MeasuresHippocampal volumetric integrity (HVI) (an automated estimate of the parenchymal fraction in a standardized hippocampal volume of interest), DUP, 13 peripheral molecular biomarkers, and 14 single-nucleotide polymorphisms from 12 candidate genes were determined.ResultsThe full sample consisted of 71 individuals with FEP (39 women and 32 men; mean [SD] age, 25.2 [7.7] years) and 73 healthy controls (40 women and 33 men; mean [SD] age, 23.9 [6.4] years). Baseline median left HVI was lower in the FEP group (n = 57) compared with the controls (n = 54) (0.9275 vs 0.9512; difference in point estimate, −0.020 [95% CI, −0.029 to −0.010]; P = .001). During approximately 8 weeks of antipsychotic treatment, left HVI decreased in 24 participants with FEP at a median annualized rate of −.03791 (–4.1% annualized change from baseline) compared with an increase of 0.00115 (0.13% annualized change from baseline) in 31 controls (difference in point estimate, −0.0424 [95% CI, −0.0707 to −0.0164]; P = .001). The change in left HVI was inversely associated with DUP (r = −0.61; P = .002). Similar results were found for right HVI, although the association between change in right HVI and DUP did not achieve statistical significance (r = −0.35; P = .10). Exploratory analyses restricted to the left HVI revealed an association between left HVI and markers of inflammation, oxidative stress, brain-derived neurotrophic factor, glial injury, and markers reflecting dopaminergic and glutamatergic transmission.Conclusions and RelevanceAn association between longer DUP and accelerated hippocampal atrophy during initial treatment suggests that psychosis may have persistent, possibly deleterious, effects on brain structure. Additional studies are needed to replicate these exploratory findings of molecular mechanisms by which untreated psychosis may affect hippocampal volume and to determine whether these effects account for the known association between longer DUP and poor outcome.

Gray and white matter changes and their relation to illness trajectory in first episode psychosis

Previous works have studied structural brain characteristics in first-episode psychosis (FEP), but few have focused on the relation between brain differences and illness trajectories. The aim of this study is to analyze gray and white matter changes in FEP patients and their relation with one-year clinical outcomes. A sample of 41 FEP patients and 41 healthy controls (HC), matched by age and educational level was scanned with a 3T MRI during the first month of illness onset. One year later, patients were assigned to two illness trajectories (schizophrenia and non-schizophrenia). Voxel-based morphometry (VBM) was used for gray matter and Tract-based spatial statistics (TBSS) was used for white matter data analysis. VBM revealed significant and widespread bilateral gray matter density differences between FEP and HC groups in areas that included the right insular Cortex, the inferior frontal gyrus and orbito-frontal cortices, and segments of the occipital cortex. TBSS showed a significant lower fractional anisotropy (FA) in 8 clusters that included segments of the anterior thalamic radiation, the left body and forceps minor of corpus callosum, the right anterior segment of the inferior fronto-occipital fasciculus and the anterior segments of the cingulum. The sub-groups comparison revealed significant lower FA in the schizophrenia sub-group in two clusters: the anterior thalamic radiation and the anterior segment of left cingulum. These findings are coherent with previous morphology studies. The results suggest that gray and white matter abnormalities are present at early stages of the disease, and white matter differences may distinguish different illness prognosis.

Impact on the Onset of Psychosis of a Polygenic Schizophrenia-Related Risk Score and Changes in White Matter Volume

Background: Reductions in the volume of brain white matter are a common feature in schizophrenia and bipolar disorder while the association between white matter and polygenic schizophrenia-related risk is unclear. To look at the intermediate state between health and the full-blown disorder, we investigated this aspect in groups of patients before and after the onset of psychosis. Methods: On a 3 Tesla scanner, total and regional white matter volumes were investigated by structural magnetic resonance imaging (MRI) in the following groups: 37 at-risk mental state patients (ARMS), including 30 with no transition to psychosis (ARMS-NT) and 7 with a transition to psychosis (ARMS-T) pooled with 25 first episode psychosis (FEP) patients. These T1-weighted images were automatically processed with the FreeSurfer software and compared with an odds-ratio-weighted polygenic schizophrenia-related risk score (PSRS) based on the publicly available top white matter single-nucleotide polymorphisms. Results: We found no association, only a trend, between PSRS and white matter volume over all groups (β = 0.24, p = 0.07, 95% confidence interval = [-0.02 – 0.49]). However, a higher PSRS was significantly associated with a higher probability of being assigned to the ARMS-T + FEP group rather than to the ARMS-NT group (β = 0.70, p = 0.02, 95% confidence interval = [0.14 – 1.33]); there was no such association with white matter volume. Additionally, a positive association was found between PSRS and the Brief Psychiatric Rating Scale (BPRS) total score for the pooled ARMS-NT/ARMS-T+FEP sample and for the ARMS-T + FEP group also, but none for the ARMS-NT group only. Conclusion: These findings suggest that at-risk mental state patients with a transition and first-episode psychosis patients have a higher genetic risk for schizophrenia than at-risk mental state patients with no transition to psychosis; this risk was associated with psychopathological symptoms. Further analyses may allow polygenic schizophrenia-related risk scores to be used as biomarkers to predict psychosis.

Stress hormones and verbal memory in young people over the first 12 weeks of treatment for psychosis

AimsMemory impairment in psychosis may be mediated through detrimental effects of hypothalamic-pituitary-adrenal (HPA) axis function. This study prospectively investigated the relationship between cortisol, sulphate dehydroepiandrosterone (DHEA(S) and cortisol: DHEA(S) ratio and memory in 35 first-episode psychosis (FEP) patients during the first 12 weeks of treatment and 23 healthy controls (HC). MethodsMorning blood sampling and tests of attention, working memory and verbal memory occurred at baseline and 12-week follow-up. ResultsFEP and HC groups did not significantly differ in levels of cortisol, DHEA(S) or their ratio at baseline or over 12-weeks. The FEP group performed significantly below HC on all cognitive measures at baseline and over 12-weeks. Cortisol levels were unrelated to cognition in both groups. At baseline, DHEA(S) was positively associated with attention in HCs, but negatively associated with attention in FEP participants. Change in DHEA(S) was negatively associated with change in memory over 12-weeks in both groups. At 12-weeks, there was a negative correlation between the cortisol: DHEA(S) ratio and attention in both groups. ConclusionsThese findings are mostly in contrast to findings in chronic schizophrenia. Investigation at different illness phases and over longer-follow-up periods is required to determine the complex relationship between HPA-axis and memory functioning in psychosis.

Impaired action self-monitoring and cognitive confidence among ultra-high risk for psychosis and first-episode psychosis patients

BackgroundSelf-monitoring biases and overconfidence in incorrect judgments have been suggested as playing a role in schizophrenia spectrum disorders. Little is known about whether self-monitoring biases may contribute to early risk factors for psychosis. In this study, action self-monitoring (i.e., discrimination between imagined and performed actions) was investigated, along with confidence in judgments among ultra-high risk (UHR) for psychosis individuals and first-episode psychosis (FEP) patients. MethodsThirty-six UHR for psychosis individuals, 25 FEP patients and 33 healthy controls (CON) participated in the study. Participants were assessed with the Action memory task. Simple actions were presented to participants verbally or non-verbally. Some actions were required to be physically performed and others were imagined. Participants were asked whether the action was presented verbally or non-verbally (action presentation type discrimination), and whether the action was performed or imagined (self-monitoring). Confidence self-ratings related to self-monitoring responses were obtained. ResultsThe analysis of self-monitoring revealed that both UHR and FEP groups misattributed imagined actions as being performed (i.e., self-monitoring errors) significantly more often than the CON group. There were no differences regarding performed actions as being imagined. UHR and FEP groups made their false responses with higher confidence in their judgments than the CON group. There were no group differences regarding discrimination between the types of actions presented (verbal vs non-verbal). ConclusionsA specific type of self-monitoring bias (i.e., misattributing imagined actions with performed actions), accompanied by high confidence in this judgment, may be a risk factor for the subsequent development of a psychotic disorder.

Deterioration of visuospatial associative memory following a first psychotic episode: a long-term follow-up study.

Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset. In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5-11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised. Visuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up. Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.

Increased Striatal and Reduced Prefrontal Cerebral Blood Flow in Clinical High Risk for Psychosis.

Increased striatal dopaminergic activity and decreased prefrontal functioning have been reported in individuals at clinical high risk (CHR) for psychosis. Abnormal metabolic rate might affect resting-state cerebral blood flow (rCBF) in the respective regions. Here, we examined if striatal and prefrontal rCBF differ between patients with CHR, first-episode psychosis (FEP), chronic schizophrenia-spectrum disorder (SZ) and controls. Two cohorts with a total of 122 participants were included and analyzed separately: 32 patients with SZ and 31 healthy controls (HC) from the University Hospital of Psychiatry, and 59 patients from the Bern Early Recognition and Intervention Center (29 with CHR, 12 with FEP, and 18 clinical controls [CC]). Ultra-high risk criteria were assessed with the Structured Interview for Psychosis-Risk Syndromes, basic symptom criteria with the Schizophrenia Proneness Instrument. rCBF was measured with pseudo-continuous arterial spin labeling 3T-Magnetic Resonance Imaging. Striatal rCBF was significantly increased and prefrontal rCBF significantly decreased in the SZ group compared to HC group and in the CHR and FEP groups compared to CC group. Striatal rCBF correlated significantly with positive symptom scores in SZ and CHR. An inverse correlation between striatal and frontal rCBF was found in controls (HC, CC), but not in patient groups (SZ, FEP, CHR). This is the first study to demonstrate increased neuronal activity within the striatum, but reduced prefrontal activity in patients with CHR, FEP, and SZ compared to the respective controls. Our results indicate that alterations in striatal and prefrontal rCBF are reflecting metabolic abnormalities preceding the onset of frank psychosis.

Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis

Reduced amplitude of mismatch negativity (MMN) is one of the more promising biological markers of schizophrenia. This finding holds true in both early and chronic phases of the disorder, and is compatible with the glutamatergic dysfunction hypothesis. To further establish MMN as a biomarker of aberrant glutamatergic neurotransmission, an exploration for an association with blood levels of glutamatergic amino acids is an important next step. Despite a large body of work investigating MMN in schizophrenia, no previous studies have undertaken this endeavor. Nineteen patients with first-episode psychosis (FEP), 21 ultra-high risk individuals (UHR), and 16 healthy controls (HC) participated in the study. The MMNs in response to duration change (dMMN) and frequency change (fMMN) were measured. The fasting plasma levels of glutamate, glutamine, glycine, D-serine, and L-serine were measured. dMMN amplitudes were significantly reduced in FEP and UHR, compared to HC. The plasma levels of glutamate of FEP were significantly higher than those of HC. Higher plasma levels of glutamate were associated with smaller dMMN amplitudes in the FEP and HC groups. These findings are compatible with the hypothesis that MMN is a useful biological marker of aberrant glutamatergic neurotransmission in the early stages of schizophrenia.

Does co-occurring borderline personality disorder influence acute phase treatment for first-episode psychosis?

This aims of this study were: (1) to determine the prevalence of co-occurring borderline personality disorder (BPD) in a first-episode psychosis (FEP) sample; (2) to determine differences between patients with and without BPD on demographics, comorbidities and clinical risks and other variables; and (3) to examine whether BPD comorbidity influenced treatment received by patients for FEP during their first 3 months after service entry to a specialist early psychosis service. A file audit was conducted for 100 consecutive admissions to an early psychosis service. Patients with a clinician-rated co-occurring diagnosis of BPD were compared with patients without clinician-rated BPD on a range of variables. Twenty-two percent of the FEP sample was diagnosed with co-occurring BPD by clinician ratings. The FEP group with co-occurring BPD was found to be younger, more likely to have other comorbidities, and were at higher risk of suicide and violent behaviour. Group differences were found in treatment received for FEP, whereby patients with co-occurring BPD had poorer access to standard treatment, including guideline concordant antipsychotic medication prescription. Young people with co-occurring clinician-rated BPD and FEP experienced greater difficulty accessing standard care for FEP and received relatively different treatment, including different pharmacotherapy, compared with those FEP patients without BPD. There is a need to develop new clinical guidelines and effective treatments for this specific subgroup with early psychosis and co-occurring BPD that take into account interpersonal and "premorbid" aspects of their presenting problems.

Identifying neurocognitive markers for outcome prediction of global functioning in individuals with first-episode and ultra-high-risk for psychosis.

There is an increasing need for identifying neurocognitive predictors of global functional outcome in early psychosis toward optimizing an early intervention strategy. We conducted a longitudinal observational study to investigate an association between neurocognitive assessments at baseline and global functional outcome at an average of 1-year follow up. Participants included ultra-high-risk for psychosis (UHR) individuals who had not converted to psychosis during the follow-up period (UHR-NP) and those with first-episode psychosis (FEP). We evaluated neurocognition at baseline using the Brief Assessment of Cognition in Schizophrenia Japanese version, including Verbal Memory, Working Memory, Motor Speed, Verbal Fluency, Attention/Processing Speed, and Executive Function. We also assessed global functional outcome using the modified Global Assessment of Functioning (mGAF) scale both at baseline and after the follow-up period. Thirty-four UHR-NP individuals (34/47, 72%) and 29 FEP individuals (29/36, 81%) completed assessment of neurocognitive function at baseline and functional outcome at follow up. In the UHR-NP group, Attention/Processing Speed was significantly associated with the mGAF score at follow up. In the FEP group, Executive Function was significantly associated with the average mGAF score during follow up. Attention/Processing Speed and Executive Function at baseline may predict global functional outcome of early psychosis. These neurocognitive tests are easy to incorporate in clinical settings and, if replicated in independent samples, may be included in routine clinical assessments for prediction of functional outcome in early psychosis.

The associations between quality of life and clinical symptoms in individuals with an at-risk mental state and first-episode psychosis

Quality of life (QOL) is strongly associated with severity of clinical symptoms and is often compromised in patients with chronic or first-episode psychosis (FEP). However, it remains unclear whether baseline QOL in individuals with an at-risk mental state (ARMS) for psychosis is higher or lower than that in patients with FEP, or what specific clinical symptoms relate to a decreased QOL in individuals with ARMS and FEP. The World Health Organization's WHOQOL-BREF, an instrument assessing QOL, was administered to 104 individuals with ARMS and 53 with FEP. Clinical symptoms were assessed by the Positive and Negative Syndrome Scale and the Beck Depression Inventory-II. We compared the four domain scores of the WHOQOL-BREF between the two groups, and calculated Pearson correlations between each WHOQOL-BREF domain score and the clinical symptoms and compared these correlations between the groups. We observed significant correlations between poor QOL and severity of depressive symptoms in both the FEP and ARMS group. No between-group differences were found in any correlation coefficients between WHOQOL-BREF domains and clinical symptoms. Thus, depressive symptoms should be investigated as a key factor relating to poor QOL in both individuals with ARMS and those with FEP.

Tobacco smoking and its association with cognition in first episode psychosis patients

Available evidence suggests that nicotine may enhance cognitive functioning. Moreover, it has been suggested that the high prevalence of smoking in people with schizophrenia is in part due to self-medication behaviour to alleviate cognitive deficits. We assessed the association between tobacco smoking and cognitive functioning in a large population of first episode psychosis (FEP) patients (n=304) and healthy controls (n=156). Smokers were not tobacco deprived, or were minimally deprived (≤2h). Verbal memory, visual memory, working memory, processing speed, executive function, motor dexterity and attention were assessed. The smoking prevalence among the FEP group was 57% (n=174). The age at which patients began smoking cigarettes regularly was 16.2years (SD=3.1), an average of 12years before experiencing the first frank symptoms of psychosis (age of onset=28.8; SD=9.3). The number of cigarettes smoked per day was 19.6 (SD=9.4), significantly more than healthy controls [11.0 (SD=7.6); p<0.001]. ANCOVA analysis did not show any significant difference between smokers and non-smokers in in the performance of any of the cognitive tasks in the FEP group or in the healthy control group, independent of gender, age, education or premorbid IQ. This suggests chronic exposure to nicotine through cigarette smoking is not associated with cognitive functioning in first-episode psychosis. These findings do not support the nicotine self-medication hypothesis as a contributor to the high prevalence of smoking among individuals suffering from serious mental illness.

SA88. Hippocampal Subfield Volumes in First-Episode Psychosis: Association With Glucose Metabolism

Abstract Background: It is well documented that the hippocampal volume is reduced in schizophrenia. Latest studies suggest that the reduction is more robust in certain hippocampal subfields in patients with chronic schizophrenia. It remains unclear whether these differences are already present during first-episode of psychosis.Furthermore, the clinical correlates of these brain abnormalities have remained elusive. Since impaired glucose tolerance has known detrimental effect on the central nervous system, we tested if glucose metabolism could underlie the changes seen in the hippocampus. Methods: We recruited 58 first-episode psychosis (FEP) patients and 54 matched randomly selected general population controls. Patient sample included both non-affective and affective psychoses (DSM-IV). Hippocampal subfield volumes were measured using a novel segmentation protocol in FreeSurfer6. A general linear model was used to test for group differences in hippocampal subfield volumes. All tests were corrected for age, sex, body mass index, and total intracranial volume, and test within the FEP group were also corrected for antipsychotic medication. After excluding subjects with diabetes, we tested associations between fasting glucose (<6.2 mmol/l), insulin, HOMA-index, clinical symptoms, and the subfield volumes. Results: We found that several hippocampal subfields (ROI) were significantly smaller in FEP than in controls (ROI × Group P = .010, Partial η2 .039). In FEP patients particularly molecular layer (P = .001, left β = −38.95, right β = −27.81), subiculum (P = .028, left β = −19.71, right β = −13.35), CA1 (P = .016, left β = −29.73, right β = −28.58) and presubiculum (P = .004, left β = −14.01, right β = −13.92) were smaller than in the controls.Blood fasting glucose-dependent group interaction was found between FEP and control group (Group × Glucose P = .038). Glucose correlated positively with hippocampal volumes in the controls but not in the FEP. In FEP group, fasting glucose levels correlated negatively with volumes in right subiculum (P = .033, β = −25.13), left presubiculum (P = .004, β = −29.31) and right presubiculum (P = .038, β = −21.04). Cognitive tests or symptom severity were not associated with the hippocampal subfield volumes. Conclusion: We showed that hippocampal subregions are differently affected already in the first episode of psychosis. We found that several hippocampal subfields were differently associated with blood glucose levels in FEP and control group. The findings do not provide evidence for causal relationships but suggest that hippocampal subregions are differently involved in the regulation of glucose metabolism in FEP and control group. The results suggest FEP patients are susceptible to the negative effects of impaired glucose metabolism.

Neuropsychological Test Performance to Enhance Identification of Subjects at Clinical High Risk for Psychosis and to Be Most Promising for Predictive Algorithms for Conversion to Psychosis: A Meta-Analysis.

To compare neuropsychological performance in people at clinical high risk for psychosis (CHR), healthy controls (HCs), or subjects with first-episode psychosis (FEP). Systematic PubMed/MEDLINE search through January 2014, without language restrictions, using search terms prodrome OR clinical high-risk OR ultra-high risk AND cognition OR individual test names. Studies reporting neuropsychological data in CHR versus a HC or FEP groups or comparing CHR subjects who converted to psychosis (CHR-P) with CHR subjects who did not convert to psychosis (CHR-NP). Two authors independently extracted and compared neurocognitive test data. A meta-analysis was performed on 60 neuropsychological tests from 9 domains in 32 studies with 21 nonoverlapping samples (CHR = 1,684 patients, HC = 986, FEP = 405). Compared to HCs, people with CHR performed significantly worse in 7 of 9 domains (Hedges g effect size [95% confidence limit] = -0.17 [-0.30, -0.04] [attention/vigilance] to -0.42 [-0.64, -0.20] [verbal learning, speed of processing] and -0.43 [-0.68, -0.18] [social cognition]), except reasoning/problem solving and working memory (which separated in longitudinal studies). California Verbal Learning Test (-0.65 [-0.84, -0.46]) and Digit Symbol Test (-0.63 [-0.86, -0.40]) separated groups the most. Compared to FEP subjects, people with CHR performed significantly better in 5 of 6 domains (from 0.29 [0.03, 0.56] [speed of processing] to 0.39 [0.17, 0.62] [attention/vigilance, verbal learning] and -0.40 [0.18, 0.64] [working memory]), except reasoning/problem solving. CHR-P and CHR-NP performed significantly worse than HC (except visual learning, working memory in CHR-NP). Compared to CHR-NP, CHR-P performed significantly worse in 6 of 8 domains (from -0.24 [-0.44, -0.03] [attention/vigilance] to -0.49 [-0.76, -0.22] [verbal learning] and -0.54 [-0.80, -0.27] [visual learning]), without differences in reasoning/problem solving and working memory. Three individual tests (Rey-Osterrieth Complex Figure Test, Verbal Fluency Test/Controlled Oral Word Association Test, and California Verbal Learning Test) discriminated the best between CHR-P and CHR-NP (-0.49 [-0.82, -0.16], -0.45 [-0.86, -0.03], and -0.40 [-0.80, -0.00], respectively). CHR has mild to moderate globally distributed neuropsychological performance deficits that lie between FEP and HCs. Neuropsychological performance deficits are greater in CHR-P than in CHR-NP, but they overlap, reducing their current utility for risk stratification.

Cytokines, cortisol and IGF-1 in first episode psychosis and ultra high risk males. Evidence for TNF-α, IFN-γ, ΤNF-β, IL-4 deviation.

The aim of the study was to determine circulating cytokines, cortisol and Insulin-like Growth Factor (IGF)-1, known for their involvement in inflammation, in male patients with First Episode Psychosis (FEP) and subjects at Ultra High Risk (UHR) for Psychosis. The FEP group presented increased pro-inflammatory cytokines (TNF-α, IFN-γ, ΤNF-β) as well as increased anti-inflammatory cytokine (IL-4) compared with Healthy Controls (HC). The UHR group showed increased IL-4 against HC. In contrast, none of the groups did show deviation from normality in either cortisol or IGF-1 levels. These preliminary findings support the cytokines' role in the inflammatory hypothesis in psychosis.

Network-Level Dysconnectivity in Drug-Na\xefve First-Episode Psychosis: Dissociating Transdiagnostic and Diagnosis-Specific Alterations

The neuroimaging literature provides compelling evidence for functional dysconnectivity in people with psychosis. However, it is likely that at least some of the observed alterations represent secondary effects of illness chronicity and/or antipsychotic medication. In addition, the extent to which these alterations are specific to psychosis or represent a transdiagnostic feature of psychiatric illness remains unclear. The aim of this study was therefore to examine the diagnostic specificity of functional dysconnectivity in drug-naïve first-episode psychosis (FEP). We used resting-state functional magnetic resonance imaging and functional connectivity analysis to estimate network-level connectivity in 50 patients with FEP, 50 patients with major depressive disorder (MDD), 50 patients with post-traumatic stress disorder (PTSD), and 122 healthy controls (HCs). The FEP, MDD, and PTSD groups showed reductions in intranetwork connectivity of the default mode network relative to the HC group (p<0.05 corrected); therefore, intranetwork alterations were expressed across the three diagnostic groups. In addition, the FEP group showed heightened internetwork connectivity between the default mode network, particularly the anterior cingulate cortex, and the central executive network relative to the MDD, PTSD, and HC groups (p<0.05 corrected); therefore, internetwork alterations were specific to the FEP. These findings suggest that network-level alterations are present in individuals with a first episode of psychosis who have not been exposed to antipsychotic medication. In addition, they suggest a dissociation between aberrant internetwork connectivity as a distinctive feature of psychosis and aberrant intranetwork connectivity as a transdiagnostic feature of psychiatric illness.

Differences in Facial Emotion Recognition between First Episode Psychosis, Borderline Personality Disorder and Healthy Controls.

BackgroundFacial emotion recognition (FER) is essential to guide social functioning and behaviour for interpersonal communication. FER may be altered in severe mental illness such as in psychosis and in borderline personality disorder patients. However, it is unclear if these FER alterations are specifically related to psychosis. Awareness of FER alterations may be useful in clinical settings to improve treatment strategies. The aim of our study was to examine FER in patients with severe mental disorder and their relation with psychotic symptomatology.Materials and MethodsSocio-demographic and clinical variables were collected. Alterations on emotion recognition were assessed in 3 groups: patients with first episode psychosis (FEP) (n = 64), borderline personality patients (BPD) (n = 37) and healthy controls (n = 137), using the Degraded Facial Affect Recognition Task. The Positive and Negative Syndrome Scale, Structured Interview for Schizotypy Revised and Community Assessment of Psychic Experiences scales were used to assess positive psychotic symptoms. WAIS III subtests were used to assess IQ.ResultsKruskal-Wallis analysis showed a significant difference between groups on the FER of neutral faces score between FEP, BPD patients and controls and between FEP patients and controls in angry face recognition. No significant differences were found between groups in the fear or happy conditions. There was a significant difference between groups in the attribution of negative emotion to happy faces. BPD and FEP groups had a much higher tendency to recognize happy faces as negatives. There was no association with the different symptom domains in either group.ConclusionsFEP and BPD patients have problems in recognizing neutral faces more frequently than controls. Moreover, patients tend to over-report negative emotions in recognition of happy faces. Although no relation between psychotic symptoms and FER alterations was found, these deficits could contribute to a patient’s misinterpretations in daily life.

Association between serum levels of bioavailable vitamin D and negative symptoms in first-episode psychosis

Total vitamin D levels had been commonly reported to be lowered in patients with chronic psychotic illnesses in countries from the higher latitudes. However, studies on patients with first episode psychosis (FEP) are limited. In this study we investigated serum concentrations of total and bioavailable vitamin D levels in FEP patients compared to healthy controls and the association between symptom severity and vitamin D components. A total of 31 FEP patients and 31 healthy controls were recruited from Institute of Mental Health, Singapore. FEP patients were identified using Structured Clinical Interview for DSM-IV Axis I disorders (SCID-1) and severity symptoms were assessed using the positive and negative syndrome scale (PANSS). Sera from participants were analyzed for total vitamin D, vitamin D-binding protein (DBP) and bioavailable vitamin D. Linear regressions were performed to examine the associations between serum total and bioavailable vitamin D and the PANSS subscales. Current study noted a significantly lower bioavailable vitamin D was in the FEP group and an association between bioavailable vitamin D and negative symptoms in FEP patients in a population with a consistent supply of sun exposure throughout the year.

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.

Increased superior frontal gyrus activation during working memory processing in psychosis: Significant relation to cumulative antipsychotic medication and to negative symptoms

ObjectivesImpairment in working memory (WM) is a core symptom in schizophrenia. However, little is known about how clinical features influence functional brain activity specific to WM processing during the development of first-episode psychosis (FEP) to schizophrenia (SZ). We compared functional WM-specific brain activity in FEP and SZ patients, including the effects of the duration of illness, psychopathological factors and antipsychotic medication. MethodsCross-sectional study of male FEP (n=22) and SZ (n=20) patients performing an n-back task when undergoing functional magnetic resonance imaging (fMRI). Clinical features were collected by semi-structured interviews and medical records. ResultsThe SZ group performed significantly worse than the FEP group in the 2-back condition. The SZ group also showed significantly higher activation in the left superior frontal gyrus in the 2-back versus 0-back condition (2-back>0-back). This frontal activation correlated positively with negative symptoms and with cumulative antipsychotic medication during the year before the fMRI examination. There were no significant correlations between activation and duration of illness. ConclusionThere was greater frontal neural activation in SZ than in FEP. This indicated differences in WM processing, and was significantly related to cumulative antipsychotic exposure and negative symptoms, but not to the duration of illness.