The prevalence of vitamin D deficiency and associated factors in first-episode psychosis.

AIM: Vitamin D deficiency is prevalent in people with established psychotic disorders, but less is known about vitamin D levels in people with first-episode psychosis (FEP). This study aimed to determine the prevalence of vitamin D deficiency in people with FEP and identify the factors associated with vitamin D status. METHODS: This was a prospective cohort study nested within a randomized controlled trial, which included 37 young people with an FEP with minimal antipsychotic medication exposure. RESULTS: Twenty-four percent of participants were vitamin D deficient, and a further 30% were vitamin D insufficient. There was no association between vitamin D and demographic factors or clinical symptoms (positive, negative, general psychopathology and depressive symptoms) or cognition and functioning. However, vitamin D levels were associated with season of sampling. CONCLUSIONS: Considering the longer-term adverse effects associated with vitamin D deficiency, it is warranted to ensure this clinical population receives supplementation if indicated.

Risk of first-episode psychosis in migrants to the Republic of Ireland.

BACKGROUND: Migration is an established risk factor for developing a psychotic disorder in countries with a long history of migration. Less is known for countries with only a recent history of migration. This study aimed to determine the risk for developing a psychotic disorder in migrants to the Republic of Ireland. METHODS: We included all presentations of first-episode psychosis over 8.5 years to the DETECT Early Intervention for psychosis service in the Republic of Ireland (573 individuals aged 18-65, of whom 22% were first-generation migrants). Psychotic disorder diagnosis relied on SCID. The at-risk population was calculated using census data, and negative binomial regression was used to estimate incidence rate ratios. RESULTS: The annual crude incidence rate for a first-episode psychotic disorder in the total cohort was 25.62 per 100000 population at risk. Migrants from Africa had a nearly twofold increased risk for developing a psychotic disorder compared to those born in the Republic of Ireland (IRR = 1.83, 95% CI 1.11-3.02, p = 0.02). In contrast, migrants from certain Asian countries had a reduced risk, specifically those from China, India, Philippines, Pakistan, Malaysia, Bangladesh and Hong Kong (aIRR = 0.36, 95% CI 0.16-0.81, p = 0.01). CONCLUSIONS: Further research into the reasons for this inflated risk in specific migrant groups could produce insights into the aetiology of psychotic disorders. This information should also be used, alongside other data on environmental risk factors that can be determined from census data, to predict the incidence of psychotic disorders and thereby resource services appropriately.

High-risk sexual behaviours in young people experiencing a first episode of psychosis.

AIM: The sexual health of adults with schizophrenia is poorer than the general population; however, less is known about young people experiencing a first episode of psychosis (FEP). The aim of this study was to explore the high-risk sexual behaviours and sexual well-being indicators of a cohort of young people with FEP. METHODS: Data collected from young people (15-24 years) with FEP attending the EPPIC service in Melbourne and participating in a physical health intervention were analysed. Baseline trial data collected on sexual health and high-risk behaviours, psychiatric symptomology, functioning, and substance use are presented by gender. Associations between symptomology and functioning with sexual behaviour are explored. RESULTS: A total of 69 young people were included in this study; mean age was 19.6 years (SD±2.8), 53.6% were male, 59.6% identified as heterosexual, and 21.7% were currently in a relationship. Within the cohort, 78.3% had ever been sexually active. Of these, 44.2% consistently used a condom at last sex act and 35.7% used barrier contraception consistently, 22.5% had previously been pregnant, and 18.6% had tested positive for an STI. Finally, young people were more likely to have been sexually active if they were currently using substances. CONCLUSIONS: These findings suggest that high rates of high-risk sexual behaviour remain an issue for young people experiencing a first episode of psychosis. Promoting sexual well-being and communication skills between sexual partners should be targeted to ensure that high-risk sexual health outcomes are mitigated as early as possible.

Disrupted auditory N1, theta power and coherence suppression to willed speech in people with schizophrenia.

The phenomenon of sensory self-suppression - also known as sensory attenuation - occurs when a person generates a perceptible stimulus (such as a sound) by performing an action (such as speaking). The sensorimotor control system is thought to actively predict and then suppress the vocal sound in the course of speaking, resulting in lowered cortical responsiveness when speaking than when passively listening to an identical sound. It has been hypothesized that auditory hallucinations in schizophrenia result from a reduction in self-suppression due to a disruption of predictive mechanisms required to anticipate and suppress a specific, self-generated sound. It has further been hypothesized that this suppression is evident primarily in theta band activity. Fifty-one people, half of whom had a diagnosis of schizophrenia, were asked to repeatedly utter a single syllable, which was played back to them concurrently over headphones while EEG was continuously recorded. In other conditions, recordings of the same spoken syllables were played back to participants while they passively listened, or were played back with their onsets preceded by a visual cue. All participants experienced these conditions with their voice artificially shifted in pitch and also with their unaltered voice. Suppression was measured using event-related potentials (N1 component), theta phase coherence and power. We found that suppression was generally reduced on all metrics in the patient sample, and when voice alteration was applied. We additionally observed reduced theta coherence and power in the patient sample across all conditions. Visual cueing affected theta coherence only. In aggregate, the results suggest that sensory self-suppression of theta power and coherence is disrupted in schizophrenia.

A single-blind, randomised controlled trial of a physical health nurse intervention to prevent weight gain and metabolic complications in first-episode psychosis: the Physical Health Assistance in Early Psychosis (PHAstER) study.

BACKGROUND: Factors that contribute to the early mortality observed in psychotic disorders, specifically obesity, smoking and sedentary behaviour, occur early in the disorder. AIMS: We aimed to determine whether the integration of a physical health nurse in the care of young people with first-episode psychosis could prevent clinically significant weight gain (≥7% body weight). Secondary outcomes included rates of smoking, metabolic syndrome and sedentary behaviour. METHOD: In this single-blind, randomised controlled trial, participants who had received under 4 weeks of antipsychotic medication were randomly allocated to either the intervention (addition of a physical health nurse to their care) or treatment as usual (TAU) for 12 weeks. RESULTS: Of the 77 participants, there were follow-up data for 86.8% (n = 33) of the intervention group and 82.1% (n = 32) of the TAU group. After 12 weeks, 27.3% of the intervention group experienced clinically significant weight gain compared with 34.4% of the TAU group (odds ratio 0.72, 95% CI 0.25-2.06, P = 0.54). After 6 months, 40.7% of the intervention group gained clinically significant weight compared with 44.1% of the TAU group (P = 0.79). There was no difference in mean change in weight between groups after 12 weeks (2.6 kg v. 2.9 kg, P = 0.87) or 6 months (3.6 kg v. 4.3 kg, P = 0.64). There were no differences in the rates of tobacco smoking cessation, prevalence of metabolic syndrome or physical activity levels. CONCLUSIONS: This intervention failed to prevent the metabolic complications that are highly prevalent in psychotic disorders in the short to medium term, indicating that more intensive interventions are required.

Proportion and characteristics of young people in a first-episode psychosis clinic who first attended an at-risk mental state service or other specialist youth mental health service.

BACKGROUND: Services for young people identified as having an 'at-risk mental state' (ARMS) aim to prevent transition to first-episode psychosis (FEP), in addition, early intervention services for other mental health disorders have also been developed. The aim of the current study was to determine the proportion of young people attending a specialist FEP service who had been referred via other early intervention clinics, including an ARMS clinic, and compare the characteristics to those who presented directly to the FEP service. METHODS: We included young people diagnosed with FEP who received treatment at Orygen between 01.01.2012 and 31.12.2016. We examined rates of direct entry to the First Episode Psychosis service and rates from other early intervention services, specifically ARMS, personality disorders, mood disorders and a primary care youth mental health service clinics. RESULTS: 1138 young people were diagnosed with a FEP, of whom 13.7% first attended an ARMS clinic and a further 7.6% attended other youth mental health services. Individuals who first presented to an ARMS clinic were more likely to be female, younger, and less likely to be migrants or use substances. Rates of both voluntary and involuntary hospital admissions were significantly reduced for young people who transitioned from the ARMS clinic, the personality disorder clinic or the primary care service compared to those who presented directly with FEP. CONCLUSIONS: A significant proportion of young people with FEP initially attended another specialist youth mental health service, and importantly, they had much lower rates of hospital admission at the time of transition to FEP.

The association between vitamin D and symptom domains in psychotic disorders: A systematic review.

BACKGROUND: Vitamin D deficiency is prevalent among people with psychosis and may play a role in the aetiology of psychotic disorders. However, its impact on clinical symptom severity has not been independently reviewed. METHODS: We conducted a systematic search of randomized trials and observational studies that assessed the relationship between vitamin D and symptom domains (positive and negative psychotic symptoms, total and general psychopathology, cognitive and depressive) in people with a psychotic disorder. RESULTS: 1040 articles were identified, of which 29 were eligible for inclusion: 26 observational studies and 3 randomized trials. Five studies included people with First-Episode Psychosis (FEP) and 24 included people with enduring psychosis. Most observational studies found that vitamin D was inversely associated with negative symptoms (57%; 13/23), positively associated with cognitive performance (63%; 5/8), and bore no association with positive symptoms (68%; 15/22), total psychopathology (64%; 7/11), general psychopathology (57%; 4/7) or depressive symptoms (64%; 9/14). Randomized controlled trials indicated that vitamin D supplementation improved cognitive performance (100%; 1/1) and, in some cases, reduced total psychopathology (50%; 1/2), general psychopathology (50%; 1/2) and negative symptoms (30%; 1/3), but had no effect on positive (100%; 3/3) or depressive (100%; 3/3) symptoms. Some positive associations were attenuated when controlled for potential confounders. CONCLUSION: Low vitamin D was found to be inversely associated with more severe clinical symptoms in some, but not all symptom domains in people with psychosis. These preliminary findings warrant further exploration, particularly in regard to cognitive performance and negative symptoms.

The associations between migrant status and ethnicity and the identification of individuals at ultra-high risk for psychosis and transition to psychosis: a systematic review.

PURPOSE: Migrant and ethnic minority populations exhibit a higher incidence of psychotic disorders. The Ultra-High Risk for psychosis (UHR) paradigm provides an opportunity to explore the stage at which such factors influence the development of psychosis. In this systematic review, we collate and appraise the literature on the association between ethnicity and migrant status and the rate of identification of individuals at UHR, as well as their rate of transition to psychosis. METHODS: We conducted a systematic review in the Ovid Medline, PsychINFO, Pubmed, CINAHL and EMBASE databases according to PRISMA guidelines. We included studies written in English that included an UHR cohort, provided a measure of ethnicity or migrant status, and examined the incidence, rate, or risk of UHR identification or transition to psychosis. RESULTS: Of 2182 unique articles identified, seven fulfilled the criteria. One study found overrepresentation of UHR individuals from black ethnic groups, while another found underrepresentation. Two studies found increased rates of transition among certain ethnic groups and a further two found no association. Regarding migrant status, one study found that first-generation migrants were underrepresented in an UHR sample. Lastly, a lower transition rate in migrant populations was identified in one study, while two found no association. CONCLUSION: Rates of UHR identification and transition according to ethnic and migrant status were inconsistent and insufficient to conclusively explain higher incidences of psychotic disorders among these groups. We discuss the clinical implications and avenues for future research, which is required to clarify the nature of the associations.

Symptomatic, functional and service utilization outcomes of migrants with a first episode of psychosis.

BACKGROUND: Certain migrant groups have been identified as being at increased risk of developing a psychotic disorder, but there is limited research on the outcomes for migrants who develop a first episode of psychosis (FEP). We investigated symptomatic outcomes (remission and relapse rates), functional outcomes (occupational status and relationships) and service utilization (hospital admission and engagement). METHODS: Young people, aged between 15 and 24, who presented with FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) at Orygen between 01.01.11 and 31.12.16 were included. Place of birth was recorded at the time of presentation. To determine remission, symptoms were scored at three-month intervals using the short-form Scale for the Assessment of Positive Symptoms. RESULTS: A total of 1220 young people presented with FEP over the six-year period (mean age = 19.6 ± 2.8). Of these, 58.1% were male and 24.0% were first-generation migrants. While there was no difference in overall rates of admission after presentation, migrants were more likely to have an involuntary admission after presentation (31.4% vs. 24.6%, aHR = 1.54, 95% CI [1.19, 2.01]) and this risk was greatest for African migrants (HR = 1.98, 95% C.I. [1.37, 2.86]. The rates of remission and relapse were similar in migrants and those born in Australia and there was no difference in functional outcomes, such as employment rates at follow-up. DISCUSSION: The outcomes for migrants who experience FEP appear to be largely similar to those for the Australian-born population. Our finding that a greater rate of involuntary admission for migrants at presentation supports existing literature and needs further exploration to improve clinical care.

The association between migrant status and transition in an ultra-high risk for psychosis population.

PURPOSE: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. METHODS: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. RESULTS: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51). CONCLUSIONS: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.

Risk of psychotic disorders in migrants to Australia.

BACKGROUND: Certain migrant groups are at an increased risk of psychotic disorders compared to the native-born population; however, research to date has mainly been conducted in Europe. Less is known about whether migrants to other countries, with different histories and patterns of migration, such as Australia, are at an increased risk for developing a psychotic disorder. We tested this for first-generation migrants in Melbourne, Victoria. METHODS: This study included all young people aged 15-24 years, residing in a geographically-defined catchment area of north western Melbourne who presented with a first episode of psychosis (FEP) to the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1 January 2011 and 31 December 2016. Data pertaining to the at-risk population were obtained from the Australian 2011 Census and incidence rate ratios were calculated and adjusted for age, sex and social deprivation. RESULTS: In total, 1220 young people presented with an FEP during the 6-year study period, of whom 24.5% were first-generation migrants. We found an increased risk for developing psychotic disorder in migrants from the following regions: Central and West Africa (adjusted incidence rate ratio [aIRR] = 3.53, 95% CI 1.58-7.92), Southern and Eastern Africa (aIRR = 3.06, 95% CI 1.99-4.70) and North Africa (aIRR = 5.03, 95% CI 3.26-7.76). Migrants from maritime South East Asia (aIRR = 0.39, 95% CI 0.23-0.65), China (aIRR = 0.25, 95% CI 0.13-0.48) and Southern Asia (aIRR = 0.44, 95% CI 0.26-0.76) had a decreased risk for developing a psychotic disorder. CONCLUSION: This clear health inequality needs to be addressed by sufficient funding and accessible mental health services for more vulnerable groups. Further research is needed to determine why migrants have an increased risk for developing psychotic disorders.

Outcomes for migrants with a first episode of psychosis: A systematic review.

Migrants are at a greater risk of developing a psychotic disorder, but knowledge about their outcomes has not yet been collated. We reviewed the literature concerning outcomes (symptomatic, functional, morbidity and mortality and service utilisation) for migrants with first-episode psychosis. Medline, EMBASE and PsycINFO were systematically searched for studies whose population included first- or second-generation migrants with first-episode psychosis, where outcome measures were examined after a minimum follow-up period of 6 months. Fourteen of the 1554 articles identified in the search fulfilled the inclusion criteria. Remission and disengagement rates in migrants were equal or greater than those in non-migrants. Migrants experienced more negative and fewer positive symptoms at follow-up. Functioning scores varied, with studies reporting lower, equivalent or higher functioning at follow-up for migrants. Migrants were less likely to die by suicide compared to native-born individuals affected by first-episode psychosis. Most included studies showed greater rates of involuntary hospitalisation among migrant populations but there were mixed findings regarding number of hospitalisations. Level of insight at follow-up and occupational outcomes for migrants was not found to be different than for non-migrants. No studies were identified which examined relapse rates or physical health outcomes. Migrants affected by psychotic disorders have been shown to be more likely to achieve remission, and often experience higher rates of involuntary admission and disengagement. For all other outcomes, migrants have largely similar outcomes to native-born populations.

Physical health assistance in early recovery of psychosis: Study protocol for a randomized controlled trial.

AIM: Young people with psychotic disorders have poorer physical health compared to their healthy peers, a state compounded by the metabolic side-effects of antipsychotic medications. To address this, Orygen Youth Health has introduced physical health services including exercise physiologists and dieticians. These services are typically coordinated by the case manager and doctor. It is not yet known whether a treating team member dedicated to physical health will improve engagement, adherence and outcomes with these services. Hence, the protocol is presented here for a trial to evaluate the effect of including a physical health nurse in the care of young people with first-episode psychosis. METHODS: This will be a single-blind randomized controlled trial that includes 15- to 24-year-olds with first-episode psychosis who have just commenced (within 30 days) antipsychotic medication. The primary outcome will be the event of clinically significant weight gain (≥7% body weight). Participants will be assigned either a physical health nurse in their treating team (in addition to the case manager and doctor) for a 12-week period, or treatment as usual (case manager and doctor). Research assessments will be conducted at baseline, 12 and 26 weeks. Activity trackers worn by participants for the study's duration will measure sleep and physical activity. CONCLUSION: The present study will determine whether a physical health nurse will facilitate participants in attending and engaging in physical health interventions and whether this will be associated with physical health improvements or the prevention of worsening physical health.

Attenuation of visual evoked responses to hand and saccade-initiated flashes.

Sensory attenuation refers to reduced brain responses to self-initiated sensations relative to those produced by the external world. It is a low-level process that may be linked to higher-level cognitive tasks such as reality monitoring. The phenomenon is often explained by prediction error mechanisms of universal applicability to sensory modality; however, it is most widely reported for auditory stimuli resulting from self-initiated hand movements. The present series of event-related potential (ERP) experiments explored the generalizability of sensory attenuation to the visual domain by exposing participants to flashes initiated by either their own button press or volitional saccade and comparing these conditions to identical, computer-initiated stimuli. The key results showed that the largest reduction of anterior visual N1 amplitude occurred for saccade-initiated flashes, while button press-initiated flashes evoked an intermediary response between the saccade-initiated and externally initiated conditions. This indicates that sensory attenuation occurs for visual stimuli and suggests that the degree of electrophysiological attenuation may relate to the causal likelihood of pairings between the type of motor action and the modality of its sensory response.

Sensory attenuation of self-initiated sounds maps onto habitual associations between motor action and sound.

Sensory attenuation refers to reduced brain responses to self-initiated sensations relative to those produced by the external world, a distinction that is vital for dynamic motor control and our sense of agency. Typically, willed vocalizations elicit larger N1 reduction of the auditory evoked potential compared to indirectly evoked sounds, such as tones generated by button-presses, which is attributed to the prediction and cancellation of incoming signals enabled by speech motor commands. However, physical confounds exist, including different stimuli and the increased motor artefact associated with mouth vs. finger movements. The present study investigated N1 attenuation to physically identical sounds evoked by hand, eye, and mouth-initiated movements. Twenty-eight healthy participants had their electroencephalogram (EEG) recorded as they blew into a microphone, pressed a button, or moved their eye to generate a pure tone. We found that N1 and P2 response was most reduced in the blow initiation condition, and that both blow and button-press but not saccade initiated tones elicited significantly reduced N1 and P2 amplitude compared to external initiation. This indicates that the eliciting motor action markedly influences ERP response to auditory stimuli. Given that saccades are never associated with sounds, finger movements sometimes are, and mouth movements often are, the pattern of results suggests that N1 attenuation to self-initiated sounds may depend on existing associations between the initiating action and resultant sensation.

Attenuation of auditory evoked potentials for hand and eye-initiated sounds.

Reduction of auditory event-related potentials (ERPs) to self-initiated sounds has been considered evidence for a predictive model in which copies of motor commands suppress sensory representations of incoming stimuli. However, in studies which involve arbitrary auditory stimuli evoked by sensory-unspecific motor actions, learned associations may underlie ERP differences. Here, in a new paradigm, eye motor output generated auditory sensory input, a naïve action-sensation contingency. We measured the electroencephalogram (EEG) of 40 participants exposed to pure tones, which they produced with either a button-press or volitional saccade. We found that button-press-initiated stimuli evoked reduced amplitude compared to externally initiated stimuli for both the N1 and P2 ERP components, whereas saccade-initiated stimuli evoked intermediate attenuation at N1 and no reduction at P2. These results indicate that the motor-to-sensory mapping involved in speech production may be partly generalized to other contingencies, and that learned associations also contribute to the N1 attenuation effect.

Self-initiated actions result in suppressed auditory but amplified visual evoked components in healthy participants.

Self-suppression refers to the phenomenon that sensations initiated by our own movements are typically less salient, and elicit an attenuated neural response, compared to sensations resulting from changes in the external world. Evidence for self-suppression is provided by previous ERP studies in the auditory modality, which have found that healthy participants typically exhibit a reduced auditory N1 component when auditory stimuli are self-initiated as opposed to externally initiated. However, the literature investigating self-suppression in the visual modality is sparse, with mixed findings and experimental protocols. An EEG study was conducted to expand our understanding of self-suppression across different sensory modalities. Healthy participants experienced either an auditory (tone) or visual (pattern-reversal) stimulus following a willed button press (self-initiated), a random interval (externally initiated, unpredictable onset), or a visual countdown (externally initiated, predictable onset-to match the intrinsic predictability of self-initiated stimuli), while EEG was continuously recorded. Reduced N1 amplitudes for self- versus externally initiated tones indicated that self-suppression occurred in the auditory domain. In contrast, the visual N145 component was amplified for self- versus externally initiated pattern reversals. Externally initiated conditions did not differ as a function of their predictability. These findings highlight a difference in sensory processing of self-initiated stimuli across modalities, and may have implications for clinical disorders that are ostensibly associated with abnormal self-suppression.

Cortical Suppression to Delayed Self-Initiated Auditory Stimuli in Schizotypy: Neurophysiological Evidence for a Continuum of Psychosis.

Schizophrenia patients have been shown to exhibit subnormal levels of electrophysiological suppression to self-initiated, button press elicited sounds. These self-suppression deficits have been shown to improve following the imposition of a subsecond delay between the button press and the evoked sound. The current study aimed to investigate whether nonclinical individuals who scored highly on the personality dimension of schizotypy would exhibit similar patterns of self-suppression abnormalities to those exhibited in schizophrenia. Thirty-nine nonclinical individuals scoring above the median (High Schizotypy) and 41 individuals scoring below the median (Low Schizotypy) on the Schizotypal Personality Questionnaire (SPQ) underwent electroencephalographic recording. The amplitude of the N1-component was calculated while participants (1) listened to tones initiated by a willed button press and played back with varying delay periods between the button press and the tone (Active conditions) and (2) passively listened to a series of tones (Listen condition). N1-suppression was calculated by subtracting the amplitude of the N1-component of the auditory evoked potential in the Active condition from that of the Listen condition, while controlling for the activity evoked by the button press per se. The Low Schizotypy group exhibited significantly higher levels of N1-suppression to undelayed tones compared to the High Schizotypy group. Furthermore, while N1-suppression was found to decrease linearly with increasing delays between the button press and the tone in the Low Schizotypy group, this was not the case in the High Schizotypy group. The findings of this study suggest that nonclinical, highly schizotypal individuals exhibit subnormal levels of N1-suppression to undelayed self-initiated tones and an abnormal pattern of N1-suppression to delayed self-initiated tones. To the extent that these results are similar to those previously reported in patients with schizophrenia, these findings provide support for the existence of a neurophysiological "continuum of psychosis".