The Addition of Fish Oil to Cognitive Behavioral Case Management for Youth Depression: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial.

BACKGROUND: Clinical trials suggest that long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) (fish oil) may reduce depressive symptoms in adults with major depressive disorder. Therefore, n-3 PUFAs may be a potential treatment for depression in youth. METHODS: Participants were 15- to-25 year-old individuals with major depressive disorder who sought care in one of three government-funded mental health services for young people in metropolitan Melbourne, Perth, or Sydney, Australia. Participants were randomly assigned in a double-blind, parallel-arm design to receive either fish oil (840 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid) or placebo capsules as adjunct to cognitive behavioral case management. All participants were offered 50-minute cognitive behavioral case management sessions every 2 weeks delivered by qualified therapists (treatment as usual) at the study sites during the intervention period. The primary outcome was change in the interviewer-rated Quick Inventory of Depressive Symptomatology, Adolescent Version, score at 12 weeks. Erythrocyte n-3 PUFA levels were assessed pre-post intervention. RESULTS: A total of 233 young people were randomized to the treatment arms: 115 participants to the n-3 PUFA group and 118 to the placebo group. Mean change from baseline in the Quick Inventory of Depressive Symptomatology score was -5.8 in the n-3 PUFA group and -5.6 in the placebo group (mean difference, 0.2; 95% CI, -1.1 to 1.5; p = .75). Erythrocyte PUFA levels were not associated with depression severity at any time point. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS: This placebo-controlled trial and biomarker analysis found no evidence to support the use of fish oil for treatment in young people with major depressive disorder.

Prevalence and Correlates of Tobacco Use in Young People Presenting to Australian Primary Mental Health Services.

INTRODUCTION: In Australian youth primary mental health settings it is unclear as to the rates and correlates of tobacco use at service entry. AIMS AND METHODS: We aimed to delineate the prevalence and correlates of recent tobacco use (eg, cigarettes, chewing tobacco, cigars, etc) in the past 3 months in young people at their first presentation to primary mental health services as a function of age. Cross-sectional self-report measures were collected using a tablet device from young people presenting to one of five Australian primary mental health (headspace) services. Logistic regression assessed correlates of past 3-month tobacco use in adolescents (12-17 years) and young adults (18-25 years). RESULTS: Regular (at least monthly) tobacco use in the past 3 months was found in 23.4% (n = 247, N = 1055) of the sample. Increasing age (odds ratio [OR] =1.47 per year; 95% confidence interval [CI]: 1.15 to 1.89), male sex (OR = 1.98; 95% CI: 1.02 to 3.83), being in a relationship (OR = 1.96; 95% CI: 1.01 to 3.82), and poorer functioning (OR = 0.95 per unit Social and Occupational Functioning Assessment Scale increase; 95% CI: 0.91 to 0.99) predicted regular tobacco use in adolescents, but not in young adults. Living in a regional location (OR = 2.10; 95% CI: 1.40 to 3.13) and not studying (OR = 0.47; 95% CI: 0.31 to 0.73) predicted tobacco use in young adults. Having a diagnosed mental illness other than depression and/or anxiety predicted tobacco use in both groups (adolescents OR = 2.49; 95% CI: 1.26 to 4.94; young adults OR = 1.80; 95% CI: 1.13 to 2.89). CONCLUSIONS: Nearly a quarter of young people with mental illness are using tobacco, supporting the need for early intervention approaches. Adapting treatment targets by age could improve the impact of interventions in adolescents versus young adults. Poor functioning and lack of engagement in education were associated with tobacco use in both age groups, respectively; however, more research is needed to determine the direction of these relationships. IMPLICATIONS: Young people with mental illness have a high prevalence of recent tobacco use and this is evident when they first present to youth primary mental health services. Youth-oriented mental health settings may provide a unique window for tobacco use prevention and early intervention to reduce smoking in people with mental illness, a priority population. Age-specific targeted approaches might be needed in adolescents and young adults.

Inequalities in Access to Mental Health Treatment by Australian Youths During the COVID-19 Pandemic.

OBJECTIVE: The authors aimed to evaluate changes in use of government-subsidized primary mental health services, through the Medicare Benefits Schedule (MBS), by young people during the first year of the COVID-19 pandemic in Australia and whether changes were associated with age, sex, socioeconomic status, and residence in particular geographical areas. METHODS: Interrupted time-series analyses were conducted by using quarterly mental health MBS service data (all young people ages 12-25 years, 2015-2020) for individual Statistical Area Level 3 areas across Australia. The data captured >22.4 million service records. Meta-analysis and meta-regression models estimated the pandemic interruption effect at the national level and delineated factors influencing these estimates. RESULTS: Compared with expected prepandemic trends, a 6.2% (95% CI=5.3%-7.2%) increase was noted for all young people in use of MBS mental health services in 2020. Substantial differences were found between age and sex subgroups, with a higher increase among females and young people ages 18-25. A decreasing trend was observed for males ages 18-25 (3.5% reduction, 95% CI=2.5%-4.5%). The interruption effect was strongly associated with socioeconomic status. Service uptake increased in areas of high socioeconomic status, with smaller or limited uptake in areas of low socioeconomic status. CONCLUSIONS: During 2020, young people's use of primary mental health services increased overall. However, increases were inequitably distributed and relatively low, compared with increases in population-level mental health burden. Policy makers should address barriers to primary care access for young people, particularly for young males and those from socioeconomically disadvantaged backgrounds.

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.

Pineal morphology of the clinical high-risk state for psychosis and different psychotic disorders.

BACKGROUND: Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders. METHODS: This magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups. RESULTS: Pineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups. CONCLUSION: These results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis.

Keyworker mediated enhancement of physical health in patients with first episode psychosis: A feasibility/acceptability study.

AIM: Early intervention for people experiencing first episode psychosis is a priority, and keyworkers are vital to such services. However, keyworkers' roles in addressing first episode psychosis patients' physical health are under researched. This study addresses this knowledge gap by evaluating a keyworker-mediated intervention promoting physical health among first episode psychosis patients. METHODS: The study was informed by the Medical Research Council's Framework for Complex Interventions to Improve Health. First episode psychosis participants were recruited from three Irish mental health services. The intervention was evaluated in terms of its feasibility/acceptability. RESULTS: Feasibility outcomes were mixed (recruitment rate = 24/68 [35.3%]; retention rate = 18/24 [75%]). The baseline sample was predominantly male (M:F ratio = 13:6; Med age = 25 y; IQR = 23-42 y). Common health issues among participants included overweightness/obesity (n = 11) and substance use (smoking/alcohol consumption [n = 19]). Participants' initial health priorities included exercising more (n = 10), improving diet (n = 6), weight loss (n = 7) and using various health/healthcare services. The intervention's acceptability was evidenced by the appreciation participants had for physical health keyworkers' support, as well as the healthy lifestyle, which the intervention promoted. Acceptability was somewhat compromised by a low-recruitment rate, variable linkages between keyworkers and general practitioners (GPs) and COVID-19 restrictions. CONCLUSIONS: Physical health-oriented keyworker interventions for first episode psychosis patients show promise and further evaluation of such initiatives is warranted. Future interventions should be mindful of participant recruitment challenges, strategies to enhance relationships between keyworkers and GPs, and if necessary, they should mitigate COVID-19 restrictions' impacts on care.

Validation of a brief tool to assess and monitor suicidal ideation: The Youth Suicide Ideation Screen (YSIS-3).

BACKGROUND: . Suicidal ideation is common in young people. Assessment and monitoring can help to understand its dynamic nature and inform treatment planning. AIMS: . The aims were to evaluate psychometric properties of a brief screening tool - the Youth Suicide Ideation Screen-3 item (YSIS-3) and determine its correlation with the Suicidal Ideation Question-Junior (SIQ-JR) and measures of depressive and anxiety symptoms a. METHOD: . Cronbach's alpha (α) was used to evaluate internal consistency of the YSIS-3 in 1107 young people. Convergent validity was evaluated using network analysis based on individual item polychoric correlations. Structural equation modelling was used to understand latent constructs; pearson product moment correlations to validate the integrity of the underlying construct. and two-way mixed Intraclass Correlation Coefficient to examine longitudinal stability and Cohen's d to assess sensitivity to change. RESULTS: . The YSIS-3 was found to have internal consistency, convergent validity and criteria validity almost identical to the 15-item SIQ-JR. There was a high correlation (0.91) between the latent factor underpinning YSIS-3 and SIQ-JR. The YSIS-3 was more sensitive to change among those presenting with suicidal ideation at baseline. CONCLUSIONS: . The YSIS-3 is a valid measure for the assessment and monitoring of suicidal ideation, and is sensitive to change. This brief measure can contribute to regular monitoring of the presence and nature of suicidal ideation, which when included in comprehensive assessment, will inform the clinical management of those at risk of suicide.

Omega-3 fatty acids and neurocognitive ability in young people at ultra-high risk for psychosis.

BACKGROUND: Neurocognitive impairments are core early features of psychosis and are observed in those at ultra-high risk (UHR) for psychosis. The aim of the present study was to explore whether neurocognition is associated with polyunsaturated fatty acids (PUFAs), as has been observed in other clinical populations. METHOD: Erythrocyte levels of total omega-3-and omega-6 PUFAs the omega-3/omega-6 ratio, were measured in 265 UHR individuals. Six domains of neurocognition as well a Composite Score, were assessed using the Brief Assessment of Cognition in Schizophrenia. Pearson's correlations were used to assess the relationship between PUFAs and neurocognition. All analyses were controlled for tobacco smoking. RESULTS: Verbal Fluency correlated positively with eicosapentaenoic acid (P = .024) and alpha-linolenic acid (P = .01), and negatively with docosahexanoic acid (P = .007) and Working Memory positively correlated with omega-3/omega-6 ratio (P = .007). CONCLUSIONS: The current results provide support for a relationship between Verbal Fluency and omega-3 PUFAs in UHR. Further investigation is required to elucidate whether these biomarkers are useful as risk markers or in understanding the biological underpinning of neurocognitive impairment in this population.

Comparison of erythrocyte omega-3 index, fatty acids and molecular phospholipid species in people at ultra-high risk of developing psychosis and healthy people.

People classified as ultra-high risk (UHR) of developing psychosis have reduced cellular membrane omega-3 and omega-6 polyunsaturated fatty acids (PUFA). We aimed to compare omega-3 index, fatty acids and molecular phospholipid species from erythrocytes of people with UHR (n = 285) with age-matched healthy controls (n = 120) assessed by mass spectrometry. Lower proportions of PUFA were observed in the UHR group compared to healthy controls; specifically, eicosapentaenoic acid (EPA) was 29.3% lower, docosahexaenoic acid (DHA) was 27.2% lower, arachidonic acid (AA) was 15.8% lower and the omega-3 index was 26.9% lower. The AA to EPA ratio was higher in the UHR group compared to the healthy group. Smoking status had no significant effect on PUFA levels in healthy or the UHR groups. BMI was associated with PUFA levels in the UHR group only and the statistical model only explains 2% of the variance of the PUFA levels. The proportion of nervonic acid was 64.4% higher in the UHR group compared to healthy controls. At a lipid class level, the UHR group had 16% higher concentrations of sphingomyelin (SM) and 46% lower concentrations phosphatidylethanolamine (PE) compared to healthy group. Of the 49 individual molecular phospholipids, twenty-seven phospholipid species were lower in the UHR group. In conclusion, there are clear differences in the proportions of erythrocyte fatty acids and phospholipids between UHR and healthy controls and UHR had higher concentrations of SM and lower concentrations of PE. These differences may represent a promising prodromal risk biomarker in the UHR population to aid clinical diagnosis.

Relationship between allostatic load and clinical outcomes in youth at ultra-high risk for psychosis in the NEURAPRO study.

Individuals at ultra-high risk (UHR) for psychosis have an elevated risk of developing psychosis and other psychiatric outcomes. Risk biomarkers can assist in delineating individual risk and allow better prediction of longer-term outcomes. The aim of the present study was to examine if allostatic load (AL), a multisystem index of neuroendocrine, cardiovascular, immune and metabolic dysregulation, is associated with clinical outcomes in youth at UHR for psychosis. AL was measured in 106 participants of the NEURAPRO study (n = 70 female, n = 36 male; mean age 17.21, SD 2.37), a multicentre randomized-controlled trial of long-chain omega-3 polyunsaturated fatty acids versus placebo in people at UHR for psychosis. Psychiatric symptoms and social and occupational functioning were assessed at baseline and 6 and 12 months after study intake. Multivariate linear and logistic regression models were used to test the relationship between AL and clinical outcomes. High AL at baseline was associated with poor social and occupational functioning at 6 months (ß = -0.224, p = 0.025) and with more severe manic symptoms at 6 months (ß = 0.207, p = 0.026), taking into account relevant covariates including age and smoking status. No significant associations were observed at the 12-month follow-up assessment or with any other clinical outcome measures. Our data provide initial evidence for a link between AL and impaired functioning in individuals at UHR for psychosis. Further studies are needed to evaluate AL as a potential predictor of early treatment response.

Relationship Between Polyunsaturated Fatty Acids and Psychopathology in the NEURAPRO Clinical Trial.

Background: Deficiencies in membrane polyunsaturated fatty acids (PUFA) such as omega-3 (n-3) fatty acids are thought to contribute to the pathophysiological processes underlying psychotic disorders. Emerging evidence suggests that the levels of PUFA are related to clinical symptoms but significant heterogeneity exists between studies. Here, we investigated associations of membrane PUFA with clinical symptoms and functioning in a large sample of individuals at ultra-high risk (UHR) for psychosis. Methods: A total of 285 participants of the NEURAPRO clinical trial were investigated for erythrocyte PUFA levels, including the n-3 index, n-6/n-3 PUFA ratio, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Severity of general psychopathology [Brief Psychiatric Rating Scale (BPRS)], psychotic symptoms (BPRS psychosis subscale), negative symptoms [Scale for the Assessment of Negative Symptoms (SANS)], manic symptoms [Young Mania Rating Scale (YMRS)], depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS)], and functioning [Social and Occupational Functioning Scale (SOFAS), Global Functioning Social (GF-S) and Role (GF-R) scales] were assessed concurrently. Partial correlation taking into account the effects of gender, age, and smoking was used to examine the relationship between PUFAs and symptoms severity. Results: The n-3 index negatively correlated with the severity of general psychopathology, psychotic symptoms, depressive symptoms, and manic symptoms. The n-6/n-3 PUFA ratio positively correlated with severity of psychotic and depressive symptoms. The n-3 PUFA DHA negatively correlated with the severity of general psychopathology, positive, manic, and depressive symptoms. EPA negatively correlated with manic symptoms. Nervonic acid, an n-9 monounsaturated fatty acid, positively correlated with general psychopathology, positive and negative symptoms, depressive symptoms, and manic symptoms. The long-chain saturated fatty acid tetracosanoic acid positively correlated with general psychopathology, positive, manic, and depressive symptoms. Conclusions: Partially consistent with a previous study, psychotic symptoms, depressive symptoms, and symptoms of mania were associated with several classes of FAs in the present study. These findings support the relevance of membrane fatty acids for the onset of psychotic symptoms and indicate that FAs should be further evaluated as biomarkers in the UHR for psychosis group. Clinical Trial Registration: ANZCTR, identifier: 12608000475347.

Staging in bipolar disorder: from theoretical framework to clinical utility.

Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage-specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage-specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at-risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative-type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper are to: a) explore the current level of evidence supporting the descriptive staging of the syndromal pattern of bipolar disorder; b) describe preliminary attempts at validation; c) make recommendations for the direction of further studies; and d) provide a distillation of the potential clinical implications of staging in bipolar disorder within a broader transdiagnostic framework.

Effects of omega-3 PUFA on immune markers in adolescent individuals at ultra-high risk for psychosis - Results of the randomized controlled Vienna omega-3 study.

Alterations of immune function have been reported in ultra-high risk (UHR) for psychosis patients causing expectations in terms of predictive meaningfulness and benefits of anti-inflammatory agents. According to a RCT in UHR-patients supplementation of omega-3 polyunsaturated fatty acids (PUFA) was effective in reducing transition to psychosis risk and to improve symptomatology. Based on preclinical findings, we now investigated state marker properties of and the influence of PUFA on immune markers in a RCT (clinical trials.gov Identifier: NCT00396643). In a longitudinal design we measured plasma levels of the pro-inflammatory interleukin 6 (IL-6), the soluble alpha (Tac) subunit of the interleukin 2 receptor (sIL-2r), and the circulating soluble form of the intercellular adhesion molecule one (sICAM-1), in 79 help-seeking UHR individuals (13-25years of age). Using linear mixed model (LMM) analysis, we investigated the effects of 12weeks supplementation of either 1.2g/d PUFA (n=38) or Placebo (n=41). At baseline, inflammatory markers were not altered in patients who later suffered transition to psychosis within one year (n=12; 11 PUFA-group, 1 PL-group). IL-6 was weakly inverse associated with omega-6 PUFA, and highly increased in nicotine users. In univariate tests of the LMM omega-3 PUFA caused a significant increase of sICAM-1 (p=0.022). PUFA did not significantly influence IL-6 or sIL-2r. The enhancement of sICAM-1 in the PUFA condition is suggestive for supportive effects on vascular immune response and immediate Th1 helper cell mediated immune answer, which was found disturbed in manifest schizophrenia, e.g. by facilitating the leukocyte adhesion and migration across the endothelium.

Responding to challenges for people with psychotic illness: Updated evidence from the Survey of High Impact Psychosis.

OBJECTIVE: The objective is to summarise recent findings from the 2010 Australian Survey of High Impact Psychosis (SHIP) and examine their implications for future policy and planning to improve mental health, physical health and other circumstances of people with a psychotic disorder. METHODS: Survey of High Impact Psychosis collected nationally representative data on 1825 people with psychotic illness. Over 60 papers have been published covering key challenges reported by participants: financial problems, loneliness and social isolation, unemployment, poor physical health, uncontrolled symptoms of mental illness, and lack of stable, suitable housing. Findings are summarised under the rubric of participant-ranked top challenges. RESULTS: The main income source for the majority (85%) of participants was a government benefit. Only one-third was employed, and the most appropriate employment services for this group were under-utilised. High rates of loneliness and social isolation impacted mental and physical health. The rate of cardiometabolic disease was well above the general population rate, and associated risk factors were present from a very young age. Childhood abuse (30.6%), adult violent victimisation (16.4%) and alcohol and substance abuse/dependence (lifetime rates of 50.5% and 54.5%, respectively) complicated the clinical profile. Treatment with medication was suboptimal, with physical health conditions undertreated, a high rate of psychotropic polypharmacy and underutilisation of clozapine in chronic persistent psychotic illness. Only 38.6% received evidence-based psychosocial therapies. In the previous year, 27.4% had changed housing and 12.8% had been homeless, on average for 155 days. CONCLUSION: Money, social engagement and employment are the most important challenges for people with psychotic illness, as well as good physical and mental health. An integrated approach to recovery is needed to optimise service delivery and augment evidence-based clinical practice with measures to improve physical health and social circumstances. Meeting these challenges has the potential to reduce costs to government and society, as well as promote recovery.

Stepwise expansion of evidence-based care is needed for mental health reform.

Mortality from mental illnesses is increasing and, because they frequently occur early in the life cycle, they are the largest source of disability and reduced economic productivity of all non-communicable diseases. Successful mental health reform can reduce the mortality, morbidity, growing welfare costs and losses in economic productivity caused by mental illness. The government has largely adopted the recommendations of the National Mental Health Commission focusing on early intervention and stepwise care and will implement a reform plan that involves devolving commissioning of federally funded mental health services to primary health networks, along with a greater emphasis on e-mental health. Stepwise expanded investment in and structural support (data collection, evaluation, model fidelity, workforce training) for evidence-based care that rectifies high levels of undertreatment are essential for these reforms to succeed. However, the reforms are currently constrained by a cost-containment policy framework that envisages no additional funding. The early intervention reform aim requires financing for the next stage of development of Australia's youth mental health system, rather than redirecting funds from existing evidence-based programs. People with complex, enduring mental disorders need more comprehensive care. In the context of the National Disability Insurance Scheme, there is a risk that these already seriously underserved patients may paradoxically receive a reduction in coverage. E-health has a key role to play at all stages of illness but must be integrated in a complementary way, rather than as a barrier to access. Research and evaluation are the keys to cost-effective, sustainable reform.

A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis.

Schizophrenia risk has often been conceptualized using a model which requires two hits in order to generate the clinical phenotype-the first as an early priming in a genetically predisposed individual and the second a likely environmental insult. The aim of this paper was to review the literature and reformulate this binary risk-vulnerability model. We sourced the data for this narrative review from the electronic database PUBMED. Our search terms were not limited by language or date of publication. The development of schizophrenia may be driven by genetic vulnerability interacting with multiple vulnerability factors including lowered prenatal vitamin D exposure, viral infections, smoking intelligence quotient, social cognition cannabis use, social defeat, nutrition and childhood trauma. It is likely that these genetic risks, environmental risks and vulnerability factors are cumulative and interactive with each other and with critical periods of neurodevelopmental vulnerability. The development of schizophrenia is likely to be more complex and nuanced than the binary two hit model originally proposed nearly thirty years ago. Risk appears influenced by a more complex process involving genetic risk interfacing with multiple potentially interacting hits and vulnerability factors occurring at key periods of neurodevelopmental activity, which culminate in the expression of disease state. These risks are common across a number of neuropsychiatric and medical disorders, which might inform common preventive and intervention strategies across non-communicable disorders.

Relationship between Erythrocyte Fatty Acid Composition and Psychopathology in the Vienna Omega-3 Study.

This study investigated the relationship between erythrocyte membrane fatty acid (FA) levels and the severity of symptoms of individuals at ultra-high risk (UHR) for psychosis. Subjects of the present study consisted of 80 neuroleptic-naïve UHR patients. Partial correlation coefficients were calculated between baseline erythrocyte membrane FA levels, measured by gas chromatography, and scores on the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning Scale, and Montgomery-Asberg Depression Rating Scale (MADRS) after controlling for age, sex, smoking and cannabis use. Subjects were divided into three groups according to the predominance of positive or negative symptoms based on PANSS subscale scores; membrane FA levels in the three groups were then compared. More severe negative symptoms measured by PANSS were negatively correlated with two saturated FAs (myristic and margaric acids), one ω-9 monounsaturated FA (MUFA; nervonic acid), and one ω-3 polyunsaturated FA (PUFA; docosapentaenoic acid), and were positively correlated with two ω-9 MUFAs (eicosenoic and erucic acids) and two ω-6 PUFAs (γ-linolenic and docosadienoic acids). More severe positive symptoms measured by PANSS were correlated only with nervonic acid. No associations were observed between FAs and MADRS scores. In subjects with predominant negative symptoms, the sum of the ω-9 MUFAs and the ω-6:ω-3 FA ratio were both significantly higher than in those with predominant positive symptoms, whereas the sum of ω-3 PUFAs was significantly lower. In conclusion, abnormalities in FA metabolism may contribute to the neurobiology of psychopathology in UHR individuals. In particular, membrane FA alterations may play a role in negative symptoms, which are primary psychopathological manifestations of schizophrenia-related disability.

Youth depression alleviation: the Fish Oil Youth Depression Study (YoDA-F): A randomized, double-blind, placebo-controlled treatment trial.

AIM: US authorities have recommended 'black-box' warnings for antidepressants because of the increased risk of suicidality for individuals up to age 25. There is thus a clinical and ethical imperative to provide effective treatment for youth depression with an acceptable risk-benefit balance. Long-chain omega-3 polyunsaturated fatty acids (PUFAs) play an important role in a range of physiological processes in living organisms. Supplementation with omega-3 PUFAs has been shown to have a range of beneficial effects on both physical and mental health, and results of previous trials suggest that omega-3 PUFAs may be a safe and effective treatment for depression. However, conclusions from these trials have been limited by their relatively small sample sizes. METHODS: This trial will test the effectiveness of a 12-week parallel group, double-blind, randomized, placebo-controlled trial of 1.4 g day(-1) omega-3 PUFAs in help seeking 15- to 25-year-olds (N = 400) presenting with major depressive disorder. The primary hypothesis is that young people will show greater improvement of depressive symptoms after 12 weeks of treatment with omega-3 PUFAs plus cognitive behavioural case management compared with treatment with placebo plus cognitive behavioural case management. CONCLUSION: Because of using a large sample, results from this study will provide the strongest evidence to date to inform the use of omega-3 PUFAs as first-line therapy in young people presenting with major depressive disorder. The study also heralds an important step towards indicated prevention of persistent depression, which may reduce the burden, stigmatization, disability and economic consequences of this disorder.

Preventing mental illness: closing the evidence-practice gap through workforce and services planning.

BACKGROUND: Mental illness is prevalent across the globe and affects multiple aspects of life. Despite advances in treatment, there is little evidence that prevalence rates of mental illness are falling. While the prevention of cardiovascular disease and cancers are common in the policy dialogue and in service delivery, the prevention of mental illness remains a neglected area. There is accumulating evidence that mental illness is at least partially preventable, with increasing recognition that its antecedents are often found in infancy, childhood, adolescence and youth, creating multiple opportunities into young adulthood for prevention. Developing valid and reproducible methods for translating the evidence base in mental illness prevention into actionable policy recommendations is a crucial step in taking the prevention agenda forward. METHOD: Building on an aetiological model of adult mental illness that emphasizes the importance of intervening during infancy, childhood, adolescence and youth, we adapted a workforce and service planning framework, originally applied to diabetes care, to the analysis of the workforce and service structures required for best-practice prevention of mental illness. RESULTS: The resulting framework consists of 6 steps that include identifying priority risk factors, profiling the population in terms of these risk factors to identify at-risk groups, matching these at-risk groups to best-practice interventions, translation of these interventions to competencies, translation of competencies to workforce and service estimates, and finally, exploring the policy implications of these workforce and services estimates. The framework outlines the specific tasks involved in translating the evidence-base in prevention, to clearly actionable workforce, service delivery and funding recommendations. CONCLUSIONS: The framework describes the means to deliver mental illness prevention that the literature indicates is achievable, and is the basis of an ongoing project to model the workforce and service structures required for mental illness prevention.