Individual placement and support for vocational recovery in first-episode psychosis: randomised controlled trial.

BACKGROUND: High unemployment is a hallmark of psychotic illness. Individual placement and support (IPS) may be effective at assisting the vocational recoveries of young people with first-episode psychosis (FEP).AimsTo examine the effectiveness of IPS at assisting young people with FEP to gain employment (Australian and Clinical Trials Registry ACTRN12608000094370). METHOD: Young people with FEP (n = 146) who were interested in vocational recovery were randomised using computer-generated random permuted blocks on a 1:1 ratio to: (a) 6 months of IPS in addition to treatment as usual (TAU) or (b) TAU alone. Assessments were conducted at baseline, 6 months (end of intervention), 12 months and 18 months post-baseline by research assistants who were masked to the treatment allocations. RESULTS: At the end of the intervention the IPS group had a significantly higher rate of having been employed (71.2%) than the TAU group (48.0%), odds ratio 3.40 (95% CI 1.17-9.91, z = 2.25, P = 0.025). However, this difference was not seen at 12- and 18-month follow-up points. There was no difference at any time point on educational outcomes. CONCLUSIONS: This is the largest trial to our knowledge on the effectiveness of IPS in FEP. The IPS group achieved a very high employment rate during the 6 months of the intervention. However, the advantage of IPS was not maintained in the long term. This seems to be related more to an unusually high rate of employment being achieved in the control group rather than a gross reduction in employment among the IPS group.Declaration of interestNone.

Ventricular volumes across stages of schizophrenia and other psychoses.

OBJECTIVE: Ventricular enlargement is common in established schizophrenia; however, data from ultra high-risk for psychosis and first-episode psychosis studies are inconclusive. This study aims to investigate ventricular volumes at different stages of psychosis. METHODS: Ventricular volumes were measured using a semi-automated and highly reliable method, for 89 established schizophrenia, 162 first-episode psychosis, 135 ultra high-risk for psychosis and 87 healthy controls using 1.5T magnetic resonance images. Clinical outcome diagnoses for ultra high-risk for psychosis were evaluated at long-term follow-up (mean: 7.5 years). RESULTS: Compared to controls, we identified significant ventricular enlargement of 36.2% in established schizophrenia ( p < 0.001). Ventricular enlargement was not significant in first-episode psychosis (6%) or ultra high-risk for psychosis (-3%). Examination across stages of schizophrenia-spectrum diagnoses subgroups revealed a significant linear trend ( p = 0.006; established schizophrenia = 36.2%, first-episode psychosis schizophrenia = 18.5%, first-episode psychosis schizophreniform = -4.2% and ultra high-risk for psychosis-schizophrenia converters = -18.5%). CONCLUSION: Ventricular enlargement is apparent in patients with established schizophrenia but is not a feature at the earliest stages of illness (ultra high-risk for psychosis and first-episode psychosis). Further research is needed to fully characterize the nature and timing of ventricular volume changes early in the course of illness and how these changes impact outcomes.

Effects of risperidone/paliperidone versus placebo on cognitive functioning over the first 6 months of treatment for psychotic disorder: secondary analysis of a triple-blind randomised clinical trial.

The drivers of cognitive change following first-episode psychosis remain poorly understood. Evidence regarding the role of antipsychotic medication is primarily based on naturalistic studies or clinical trials without a placebo arm, making it difficult to disentangle illness from medication effects. A secondary analysis of a randomised, triple-blind, placebo-controlled trial, where antipsychotic-naive patients with first-episode psychotic disorder were allocated to receive risperidone/paliperidone or matched placebo plus intensive psychosocial therapy for 6 months was conducted. A healthy control group was also recruited. A cognitive battery was administered at baseline and 6 months. Intention-to-treat analysis involved 76 patients (antipsychotic medication group: 37; 18.6Mage [2.9] years; 21 women; placebo group: 39; 18.3Mage [2.7]; 22 women); and 42 healthy controls (19.2Mage [3.0] years; 28 women). Cognitive performance predominantly remained stable (working memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. However, a significant group-by-time interaction was observed for immediate recall (p = 0.023), verbal learning (p = 0.024) and delayed recall (p = 0.005). The medication group declined whereas the placebo group improved on each measure (immediate recall: p = 0.024; ηp2 = 0.062; verbal learning: p = 0.015; ηp2 = 0.072 both medium effects; delayed recall: p = 0.001; ηp2 = 0.123 large effect). The rate of change for the placebo and healthy control groups was similar. Per protocol analysis (placebo n = 16, medication n = 11) produced similar findings. Risperidone/paliperidone may worsen verbal learning and memory in the early months of psychosis treatment. Replication of this finding and examination of various antipsychotic agents are needed in confirmatory trials. Antipsychotic effects should be considered in longitudinal studies of cognition in psychosis.Trial registration: Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au/ ; ACTRN12607000608460).

Emotional sensitivity in youth with borderline personality pathology.

If Borderline Personality Disorder (BPD) is characterized by an underlying emotional sensitivity, individuals with this disorder would be expected to demonstrate accurate identification of emotional expressions at earlier stages of expression (i.e., lower thresholds of facial expressivity across all emotional valences). Twenty-one outpatient youth (aged 15-24 years) meeting 3 or more DSM-IV BPD criteria and 20 community-derived participants (aged 15-24 years) with no history of psychiatric problems were tested on a measure of emotional sensitivity, the Face Morph Task. In this test faces morph from neutral to each of the six basic emotional expressions. The BPD group showed no evidence of heightened sensitivity to emotional facial expressions compared to the community control group (all P>0.05 and effect sizes ranging from 0 to 0.6). They require comparable levels of emotional expressivity in order to correctly identify emotions. Therefore, emotional sensitivity might not be apparent early in the course of BPD. Rather, it might develop later in the course of the disorder or be present only in severe BPD.

Relational memory in first episode psychosis: implications for progressive hippocampal dysfunction after illness onset.

OBJECTIVE: Verbal episodic memory deficits are prominent in schizophrenia and have also been found in first episode psychosis (FEP) and individuals at clinical risk of the disorder. The central role of the hippocampus in verbal memory processing and the consistent findings of hippocampal volume reductions in chronic patients have prompted the suggestion that impaired verbal memory performance may be a biomarker of schizophrenia. However, it is currently unclear as to when, during the early phase of psychosis, verbal memory performance becomes significantly impaired. The current study investigated verbal relational memory in FEP using a novel verbal paired associate task, and tested whether performance was dependent on phase of illness within FEP, where patients with a diagnosis of schizophrenia were considered to be in a more advanced stage than those with schizophreniform disorder. METHOD: Forty-seven currently psychotic FEP patients and 36 healthy non-psychiatric controls, aged 15-25 years old, completed a test comprising four trials of learning and cued recall of word pairs (denoted AB pairs), an interference phase comprising two trials with new second words (AC pairs), and finally cued recall for the original AB pairings. RESULTS: FEP patients performed similarly to controls on the relational memory task. There was no difference in performance between FEP patients who had a diagnosis of schizophrenia and those with a diagnosis of schizophreniform disorder. CONCLUSIONS: Verbal relational memory appears to be intact in FEP. This finding, along with chronic patient literature, suggests that decline in hippocampal and medial temporal lobe functioning occurs during later illness stages. Further research is needed to aid in the development of intervention strategies that may prevent decline in such cognitive domains at this crucial early stage of the illness.

Neuroprotective effects of ethyl-eicosapentaenoic acid in first episode psychosis: a longitudinal T2 relaxometry pilot study.

We used magnetic resonance imaging to examine the effect of ethyl-eicosapentaenoic acid (E-EPA) on hippocampal T(2) relaxation time in first episode psychosis patients at baseline and after 12 weeks of follow-up. There was an increase in T(2) in the placebo group but not in the E-EPA group, suggesting a neuroprotective effect of E-EPA treatment. In addition, the smaller the increase in T(2), the greater the improvement in negative symptoms.

Medial temporal lobe glutathione concentration in first episode psychosis: a 1H-MRS investigation.

Glutathione (GSH) is implicated in the pathophysiology of schizophrenia. Previous brain spectroscopy studies, however, have been inconsistent, and there is little data available from first episode psychosis patients. This study compared brain GSH in a first episode cohort (n=30) to controls (n=18), using magnetic resonance spectroscopy (MRS), examining a temporal lobe voxel. Short-echo (TE 30 ms) acquisition proton MRS was performed on a 3T clinical magnetic resonance scanner. Comparison of the first-episode and control groups' GSH concentrations revealed a significant main effect of group (F(1,46)=4.7, p=0.035), but no main effect of hemisphere (F(1,46)=2.3, p=0.137) or group-by-side interactions (F(1,46)=0.4, p=0.513). Medial temporal lobe GSH concentrations in the first episode group were 22% higher than those in the control group. This study provides further evidence of significant perturbations in brain GSH in first episode psychosis, and supports a broader involvement of GSH in the pathophysiology of schizophrenia.

The Vitamins in Psychosis Study: A Randomized, Double-Blind, Placebo-Controlled Trial of the Effects of Vitamins B12, B6, and Folic Acid on Symptoms and Neurocognition in First-Episode Psychosis.

BACKGROUND: Elevated homocysteine is observed in schizophrenia and associated with illness severity. The aim of this study was to determine whether vitamins B12, B6, and folic acid lower homocysteine and improve symptomatology and neurocognition in first-episode psychosis. Whether baseline homocysteine, genetic variation, sex, and diagnosis interact with B-vitamin treatment on outcomes was also examined. METHODS: A randomized, double-blind, placebo-controlled trial was used. A total of 120 patients with first-episode psychosis were randomized to an adjunctive B-vitamin supplement (containing folic acid [5 mg], B12 [0.4 mg], and B6 [50 mg]) or placebo, taken once daily for 12 weeks. Coprimary outcomes were change in total symptomatology (Positive and Negative Syndrome Scale) and composite neurocognition. Secondary outcomes included additional measures of symptoms, neurocognition, functioning, tolerability, and safety. RESULTS: B-vitamin supplementation reduced homocysteine levels (p = .003, effect size = -0.65). B-vitamin supplementation had no significant effects on Positive and Negative Syndrome Scale total (p = .749) or composite neurocognition (p = .785). There were no significant group differences in secondary symptom domains. A significant group difference in the attention/vigilance domain (p = .024, effect size = 0.49) showed that the B-vitamin group remained stable and the placebo group declined in performance. In addition, 14% of the sample had elevated baseline homocysteine levels, which was associated with greater improvements in one measure of attention/vigilance following B-vitamin supplementation. Being female and having affective psychosis was associated with improved neurocognition in select domains following B-vitamin supplementation. Genetic variation did not influence B-vitamin treatment response. CONCLUSIONS: While 12-week B-vitamin supplementation might not improve overall psychopathology and global neurocognition, it may have specific neuroprotective properties in attention/vigilance, particularly in patients with elevated homocysteine levels, patients with affective psychosis, and female patients. Results support a personalized medicine approach to vitamin supplementation in first-episode psychosis.

A 1H-MRS investigation of the medial temporal lobe in antipsychotic-naïve and early-treated first episode psychosis.

Schizophrenia is associated with significant brain abnormalities, including changes in brain metabolites as measured by proton magnetic resonance spectroscopy (MRS). What remains unclear is the extent to which these changes are a consequence of the emergence of psychotic disorders or the result of treatment with antipsychotic medication. We assessed 34 patients with first episode psychosis (15 antipsychotic naïve) and 19 age- and gender-matched controls using short-echo MRS in the medial temporal lobe bilaterally. Overall, there were no differences in any metabolite, regardless of treatment status. However, when the analysis was limited to patients with a diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, significant elevations of creatine/phosphocreatine (Cr/PCr) and myo-inositol (mI) were found in the treated group. These data indicate a relative absence of temporal lobe metabolic abnormalities in first episode psychosis, but suggest that some treatment-related changes in mI might be apparent in patients with schizophrenia-spectrum diagnoses. Seemingly illness-related Cr/PCr elevations were also specific to the diagnosis of schizophrenia-spectrum disorder and seem worthy of future study.

The topical niacin sensitivity test: an inter- and intra-rater reliability study in healthy controls.

Topical application of nicotinic acid results in erythema, and in some cases oedema of the skin, supporting a strong relationship between niacin sensitivity and prostaglandin D2. The aim of this study was to examine the inter-rater and intra-rater reliability of a 12-min niacin sensitivity test in healthy adults. Three raters assessed the skin reaction of 12 volunteers, over 3-min intervals across four niacin concentrations (0.1, 0.01, 0.001, and 0.0001), and over six sessions. Inter-rater reliability estimates ranged from 0.85 to 0.97 for the total niacin sensitivity score. Similar inter-rater reliability estimates were found for niacin sensitivity ratings by concentration and time. Intra-rater reliability estimates ranged from 0.63 to 0.93 for the total niacin sensitivity score. These data indicate that the 12-min topical niacin sensitivity test has excellent reliability.

Reasons for referral and findings of clinical neuropsychological assessment in youth with mental illness: A clinical file audit.

Study aims were to 1) determine the characteristics and reasons for referral for Clinical Neuropsychological Assessment (CNA) and 2) characterize the findings and recommendations contained in the CNA reports, of clients attending a youth mental health service. File audit of all CNA reports (N = 140) of youth attending a mental health service. Cognitive performances on neuropsychological tests that were administered to >50% of clients were examined. Referral reasons, findings, and recommendations for future treatment were coded and described from neuropsychological files. Age of clients referred for CNA ranged from 13-29, the majority were male (62.5%), referred primarily from the early psychosis clinic (63.2%), and had a mean number of 3.5 presenting problems. Cognitive performances ranged from extremely low to very superior. Mean number of reasons for referral was 2, with treatment recommendation (55%) and diagnostic clarification (50.7%) being the most common. Mean number of findings from CNA was 5.8; most commonly, a diagnosis of clinically meaningful cognitive impairment (85%), followed by a recommendations for additional services/investigations (77.1%). CNA provides diagnostic clarification and treatment recommendations for youth receiving mental health treatment. Future studies should examine the cost-effectiveness, implementation, and objective impact of CNA in clinical practice.

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

AIMS: Memory 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). METHODS: Morning blood sampling and tests of attention, working memory and verbal memory occurred at baseline and 12-week follow-up. RESULTS: FEP 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. CONCLUSIONS: These 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.

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.

Cognitive decline following psychosis onset: data from the PACE clinic.

BACKGROUND: The origin of cognitive impairments in psychotic disorders is still unclear. Although some deficits are apparent prior to the onset of frank illness, it is unknown if they progress. AIMS: To investigate whether cognitive function declined over the transition to psychosis in a group of ultra-high risk individuals. METHOD: Participants consisted of two groups: controls (n=17) and individuals at ultra-high risk for development of psychosis (n=16). Seven of the latter group later developed psychosis. Neuropsychological testing was conducted at baseline and again after at least a 12-month interval. RESULTS: Both the Visual Reproduction sub-test of the Wechsler Memory Scale-Revised and Trail-Making Test B showed a decline over the follow-up period that was specific to the group who became psychotic. In addition, both high-risk groups showed a decline in digit span performance. No other task showed significant change over time. CONCLUSIONS: These preliminary data suggest that as psychosis develops there may be a specific decline in visual memory and attentional set-shifting, reflecting impairments in efficient organisation of visual stimuli. This may be caused by either the illness itself or treatment with antipsychotic medication.

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.

Adjunctive Taurine in First-Episode Psychosis: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study.

OBJECTIVE: Taurine is an inhibitory neuromodulatory amino acid in the central nervous system that activates the GABA- and glycine-insensitive chloride channel and inhibits the N-methyl-D-aspartate receptor. It also functions as a neuroprotective agent and has a role in neural development and neurogenesis. The aim of this study was to determine the efficacy of adjunctive taurine in improving symptomatology and cognition among patients with a DSM-IV first-episode psychotic disorder. METHODS: 121 patients with first-episode psychosis, aged 18-25 years, attending early intervention services consented to participate in this randomized, double-blind, placebo-controlled trial conducted from January 2007 to May 2009. Patients taking low-dose antipsychotic medication were randomly assigned to receive once-daily taurine 4 g or placebo for 12 weeks. The coprimary outcomes were change in symptomatology (measured by the Brief Psychiatric Rating Scale [BPRS] total score) and change in cognition (measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] Consensus Cognitive Battery composite score) at 12 weeks. Secondary outcomes included tolerability and safety and additional clinical and functioning measures. RESULTS: 86 participants (n = 47 taurine; n = 39 placebo) were included in the final analysis. Taurine significantly improved symptomatology measured by the BPRS total score (95% CI, 1.8-8.5; P = .004) and psychotic subscale (95% CI, 0.1-1.5; P = .026) compared to placebo. Additionally, improvements were observed in the Calgary Depression Scale for Schizophrenia (95% CI, 0.1-3.0; P = .047) and Global Assessment of Functioning (95% CI, 0.3-8.8; P = .04) scores. There was no group difference in composite cognitive score (95% CI, -1.7 to 1.0; P = .582). A significant group difference was found on one safety and tolerability item (psychic item 2, asthenia/lassitude/increased fatigability) of the Udvalg for Kliniske Undersogelser, with the taurine group showing a more favorable outcome (P = .006). CONCLUSIONS: Adjunctive taurine did not improve cognition, but it appears to improve psychopathology in patients with first-episode psychosis. The use of taurine warrants further investigation in larger randomized studies, particularly early in the course of psychosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00420823.

Investigation of orbitofrontal sulcogyral pattern in chronic schizophrenia.

Abnormalities of orbitofrontal cortex (OFC) pattern type distribution have been associated with schizophrenia-spectrum disorders. We investigated OFC pattern type in a large sample of chronic schizophrenia patients and healthy controls. We found an increased frequency of Type II but no difference in Type I or III folding pattern in the schizophrenia group in comparison to controls. Further large studies are required to investigate the diagnostic specificity of altered OFC pattern type and to confirm the distribution of pattern type in the normal population.

The impact of neuropsychological functioning and coping style on perceived stress in individuals with first-episode psychosis and healthy controls.

Stress is implicated in the development and course of psychotic illness, but the factors that influence stress levels are not well understood. The aim of this study was to examine the impact of neuropsychological functioning and coping styles on perceived stress in people with first-episode psychosis (FEP) and healthy controls (HC). Thirty-four minimally treated FEP patients from the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, and 26 HC participants from a similar demographic area participated in the study. Participants completed a comprehensive neuropsychological test battery as well as the Coping Inventory for Stressful Situations (task-, emotion- and avoidance-focussed coping styles) and Perceived Stress Scale (PSS). Linear regressions were used to determine the contribution of neuropsychological functioning and coping style to perceived stress in the two groups. In the FEP group, higher levels of emotion-focussed and lower levels of task-focussed coping were associated with elevated stress. Higher premorbid IQ and working memory were also associated with higher subjective stress. In the HC group, higher levels of emotion-focussed coping, and contrary to the FEP group, lower premorbid IQ, working memory and executive functioning, were associated with increased stress. Lower intellectual functioning may provide some protection against perceived stress in FEP.

The effects of click and tone-burst stimulus parameters on the vestibular evoked myogenic potential (VEMP).

Vestibular evoked myogenic potentials (VEMP) are short latency electromyograms (EMG) evoked by high-level acoustic stimuli and recorded from surface electrodes over the tonically contracted sternocleidomastoid (SCM) muscle and are presumed to originate in the saccule. The present experiments examined the effects of click and tone-burst level and stimulus frequency on the latency, amplitude, and threshold of the VEMP in subjects with normal hearing sensitivity and no history of vestibular disease. VEMPs were recorded in all subjects using 100 dB nHL click stimuli. Most subjects had VEMPs present at 500, 750, and 1000 Hz, and few subjects had VEMPs present at 2000 Hz. The response amplitude of the VEMP increased with click and tone-burst level, whereas VEMP latency was not influenced by the stimulus level. The largest tone-burst-evoked VEMPs and lowest thresholds were obtained at 500 and 750 Hz. VEMP latency was independent of stimulus frequency when tone-burst duration was held constant.

Vascular endothelial growth factor and brain-derived neurotrophic factor in quetiapine treated first-episode psychosis.

Objective. It has been suggested that atypical antipsychotics confer their effects via brain-derived neurotrophic factor (BDNF). We investigated the effect of quetiapine on serum levels of BDNF and vascular endothelial growth factor (VEGF) in drug-naive first-episode psychosis subjects. Methods. Fifteen patients drawn from a larger study received quetiapine treatment for twelve weeks. Baseline levels of serum BDNF and VEGF were compared to age- and sex-matched healthy controls and to levels following treatment. Linear regression analyses were performed to determine the relationship of BDNF and VEGF levels with outcome measures at baseline and week 12. Results. The mean serum BDNF level was significantly higher at week 12 compared to baseline and correlated with reductions in Brief Psychiatric Rating Scale (BPRS) and general psychopathology scores. Changes in serum VEGF levels also correlated significantly with a reduction in BPRS scores, a significant improvement in PANNS positive symptoms scores, and displayed a positive relationship with changes in BDNF levels. Conclusions. Our findings suggest that BDNF and VEGF are potential biomarkers for gauging improvement of psychotic symptoms. This suggests a novel neurotrophic-based mechanism of the drug effects of quetiapine on psychosis. This is the first report of VEGF perturbation in psychosis.