G. Paul Amminger

Age of onset of mental disorders: a review of recent literature.

Purpose of review The aim of this article is to review recent epidemiological research on age-of-onset of mental disorders, focusing on the WHO World Mental Health surveys. Recent findings Median and inter-quartile range (IQR; 25th–75th percentiles) of age-of-onset is much earlier for phobias (7–14, IQR 4–20) and impulse–control disorders (7–15; IQR 4–35) than other anxiety disorders (25–53, IQR 15–75), mood disorders (25–45, IQR 17–65), and substance disorders (18–29, IQR 16–43). Although less data exist for nonaffective psychosis, available evidence suggests that median age-of-onset is in the range late teens through early 20s. Roughly half of all lifetime mental disorders in most studies start by the mid-teens and three quarters by the mid-20s. Later onsets are mostly secondary conditions. Severe disorders are typically preceded by less severe disorders that are seldom brought to clinical attention. Summary First onset of mental disorders usually occur in childhood or adolescence, although treatment typically does not occur until a number of years later. Although interventions with early incipient disorders might help reduce severity-persistence of primary disorders and prevent secondary disorders, additional research is needed on appropriate treatments for early incipient cases and on long-term evaluation of the effects of early intervention on secondary prevention.

Pathways underlying neuroprogression in bipolar disorder: Focus on inflammation, oxidative stress and neurotrophic factors

There is now strong evidence of progressive neuropathological processes in bipolar disorder (BD). On this basis, the current understanding of the neurobiology of BD has shifted from an initial focus on monoamines, subsequently including evidence of changes in intracellular second messenger systems and more recently to, incorporating changes in inflammatory cytokines, corticosteroids, neurotrophins, mitochondrial energy generation, oxidative stress and neurogenesis into a more comprehensive model capable of explaining some of the clinical features of BD. These features include progressive shortening of the inter-episode interval with each recurrence, occurring in consort with reduced probability of treatment response as the illness progresses. To this end, emerging data shows that these biomarkers may differ between early and late stages of BD in parallel with stage-related structural and neurocognitive alterations. This understanding facilitates identification of rational therapeutic targets, and the development of novel treatment classes. Additionally, these pathways provide a cogent explanation for the efficacy of seemingly diverse therapies used in BD, that appear to share common effects on oxidative, inflammatory and neurotrophic pathways.

Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study

BACKGROUND There is increasing evidence that fatty acid deficiencies or imbalances may contribute to childhood neurodevelopmental disorders. METHODS We conducted a randomized, double-blind, placebo-controlled 6-week pilot trial investigating the effects of 1.5 g/d of omega-3 fatty acids (.84 g/d eicosapentaenoic acid, .7 g/d docosahexaenoic acid) supplementation in 13 children (aged 5 to 17 years) with autistic disorders accompanied by severe tantrums, aggression, or self-injurious behavior. The outcome measure was the Aberrant Behavior Checklist (ABC) at 6 weeks. RESULTS We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy, each with a large effect size. Repeated-measures ANOVA indicated a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity. No clinically relevant adverse effects were elicited in either group. CONCLUSIONS The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism.

Intervention in individuals at ultra high risk for psychosis : a review and future directions

OBJECTIVE Over the last 15 years, a focus on early intervention in psychotic disorders has emerged. Initially, the early psychosis movement focused on timely recognition and phase-specific treatment of first-episode psychosis. However, early psychosis researchers suspected that pushing the point of intervention even further back to the prodromal phase of psychotic disorders may result in even better outcomes. This article reviews intervention research in the ultra-high-risk phase of psychotic disorders. DATA SOURCES A literature search of intervention trials with ultra-high-risk cohorts published after 1980 was conducted on PubMed with the search terms prodrome and intervention. STUDY SELECTION All published intervention trials with ultra-high-risk cohorts. DATA SYNTHESIS The first generation of intervention trials indicated that both pharmacologic and psychological intervention strategies may be of value in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder. CONCLUSIONS Further controlled intervention trials with larger sample sizes are required in order to confirm and extend these findings. We argue that the clinical staging model provides a framework for the rationale and design of such studies, with simpler, safer, and more benign interventions being better candidates for first-line treatment, while more complex and potentially harmful treatments should be reserved for those cases in which response has failed to occur. Recent evidence indicates that neuroprotective agents, such as essential fatty acids, may be a suitable form of intervention for the ultra-high-risk phase of psychotic disorders, with a positive risk-benefit balance. Ethical aspects have become more salient given the recently observed declining transition rate in ultra-high-risk samples. We outline the key questions for the next generation of ultra-high-risk intervention trials.

Long-term Follow-up of a Group at Ultra High Risk (“Prodromal”) for Psychosis: The PACE 400 Study

IMPORTANCE The ultra high-risk (UHR) criteria were introduced to prospectively identify patients at high risk of psychotic disorder. Although the short-term outcome of UHR patients has been well researched, the long-term outcome is not known. OBJECTIVE To assess the rate and baseline predictors of transition to psychotic disorder in UHR patients up to 15 years after study entry. DESIGN Follow-up study of a cohort of UHR patients recruited to participate in research studies between 1993 and 2006. SETTING The Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service for UHR patients in Melbourne, Australia. PARTICIPANTS Four hundred sixteen UHR patients previously seen at the PACE clinic. MAIN OUTCOMES AND MEASURES Transition to psychotic disorder, as measured using the Comprehensive Assessment of At-Risk Mental States, Brief Psychiatric Rating Scale/Comprehensive Assessment of Symptoms and History, or state public mental health records. RESULTS During the time to follow-up (2.4-14.9 years after presentation), 114 of the 416 participants were known to have developed a psychotic disorder. The highest risk for transition was within the first 2 years of entry into the service, but individuals continued to be at risk up to 10 years after initial referral. The overall rate of transition was estimated to be 34.9% over a 10-year period (95% CI, 28.7%-40.6%). Factors associated with transition included year of entry into the clinic, duration of symptoms before clinic entry, baseline functioning, negative symptoms, and disorders of thought content. CONCLUSIONS AND RELEVANCE The UHR patients are at long-term risk for psychotic disorder, with the highest risk in the first 2 years. Services should aim to follow up patients for at least this period, with the possibility to return for care after this time. Individuals with a long duration of symptoms and poor functioning at the time of referral may need closer monitoring. Interventions to improve functioning and detect help-seeking UHR patients earlier also may be indicated.

Age of onset and timing of treatment for mental and substance use disorders: implications for preventive intervention strategies and models of care.

Purpose of review To provide an update of the recent studies on the age of onset of the major mental illnesses, with a special focus on the prospects for prevention and early intervention. Recent findings The studies reviewed here confirm previous reports on the age of onset of the major mental disorders. While the behaviour disorders, and certain anxiety disorders, emerge during childhood, most of the high prevalence disorders (anxiety, mood and substance use) emerge during adolescence and early adulthood, as do the psychotic disorders. Early age of onset has been shown to be associated with a longer duration of untreated illness and poorer clinical and functional outcomes. Summary Although the onset of most mental disorders usually occurs during the first three decades of life, effective treatment is typically not initiated until a number of years later. Although there is increasing evidence to suggest that intervention during the early stages of a disorder may help reduce the severity and/or the persistence of the initial or primary disorder and prevent secondary disorders, additional research is needed into appropriate treatment for early stage cases as well as the long-term effects of early intervention, and to appropriate service design for those in the early stages of a mental illness. This will mean not only the strengthening and re-engineering of existing systems but also, crucially, the construction of new streams of care for young people in transition to adulthood.

Nutritional medicine as mainstream in psychiatry

Psychiatry is at an important juncture, with the current pharmacologically focused model having achieved modest benefits in addressing the burden of poor mental health worldwide. Although the determinants of mental health are complex, the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and gastroenterology. Evidence is steadily growing for the relation between dietary quality (and potential nutritional deficiencies) and mental health, and for the select use of nutrient-based supplements to address deficiencies, or as monotherapies or augmentation therapies. We present a viewpoint from an international collaboration of academics (members of the International Society for Nutritional Psychiatry Research), in which we provide a context and overview of the current evidence in this emerging field of research, and discuss the future direction. We advocate recognition of diet and nutrition as central determinants of both physical and mental health.

Emotion Recognition in Individuals at Clinical High-Risk for Schizophrenia

Problems in the perception of emotional material, in particular deficits in the recognition of negative stimuli, have been demonstrated in schizophrenia including in first-episode samples. However, it is largely unknown if emotion recognition impairment is present in people with subthreshold psychotic symptoms. Here, we examined the capacity to recognize facially expressed emotion and affective prosody in 79 individuals at ultra high-risk for psychosis, 30 clinically stable individuals with first-episode schizophrenia assessed as outpatients during the early recovery phase of illness, and 30 unaffected healthy control subjects. We compared (1) scores for a combined fear-sadness aggregate index across face and voice modalities, (2) summary scores of specific emotions across modalities, and (3) scores for specific emotions for each sensory modality. Findings supported deficits in recognition of fear and sadness across both modalities for the clinical groups (the ultra high-risk and first-episode group) as compared with the healthy controls. Furthermore, planned contrasts indicated that compared with the healthy control subjects, both clinical groups had a significant deficit for fear and sadness recognition in faces and for anger recognition in voices. Specific impairments in emotion recognition may be apparent in people at clinical high-risk for schizophrenia before the full expression of psychotic illness. The results suggest a trait deficit and an involvement of the amygdala in the pathology of ultra high-risk states.

Ethyl-Eicosapentaenoic Acid in First-Episode Psychosis. A 1H-MRS Study

Ethyl-eicosapentaenoic acid (E-EPA) is an omega-3 fatty acid that has been used in a range of neuropsychiatric conditions with some benefits. However, its mechanism of action is unknown. Here, we investigate its effects on in vivo brain metabolism in first-episode psychosis (FEP). Proton magnetic resonance spectroscopy at 3 T was performed in the temporal lobes of 24 FEP patients before and after 12 weeks of treatment in the context of a larger double-blind, placebo-controlled E-EPA augmentation study. Treatment group effects for glutathione (F1,12=6.1, p=0.03), and a hemisphere-by-group interaction for glutamine/glutamate (F1,20=4.4, p=0.049) were found. Glutathione increased bilaterally and glutamate/glutamine increased in the left hemisphere following E-EPA administration. Improvement in negative symptoms correlated with metabolic brain changes, particularly glutathione (r=−0.57). These results suggest that E-EPA augmentation alters glutathione availability and modulates the glutamine/glutamate cycle in early psychosis, with some of the metabolic brain changes being correlated with negative symptom improvement. Larger confirmatory studies of these postulated metabolic brain effects of E-EPA are warranted.

Outcome in early-onset schizophrenia revisited: Findings from the Early Psychosis Prevention and Intervention Centre long-term follow-up study

OBJECTIVE To compare the long-term outcome in individuals with early-onset (before age 18) and adult-onset schizophrenia spectrum disorder who were initially diagnosed and treated in the same clinical center. METHOD A prospective follow-up study of 723 consecutive first-episode psychosis patients (age range 14 to 30 years) on average 7.4 years after initial presentation to an early psychosis service, the Early Psychosis Prevention and Intervention Centre in Melbourne, Australia. The outcome measures included the Brief Psychiatric Rating Scale, the Schedule for the Assessment of Negative Symptoms, the Beck Depression Inventory, the Global Assessment of Functioning Scale, the Social and Occupational Functioning Assessment Scale, and the Quality of Life Scale. RESULTS Follow-up interviews were conducted on 66.9% (484/723) individuals, of whom 75.6% (366/484) received a schizophrenia spectrum disorder diagnosis at baseline. Early-onset schizophrenia spectrum disorder was observed in 11.2% (41/366). At follow-up, individuals with early-onset reported significantly fewer positive symptoms and were characterised by significantly superior functioning on measures assessing global functioning, social-occupational functioning, and community functioning than individuals with adult-onset. The early-onset group also achieved significantly better vocational outcomes and had a more favourable course of illness with fewer psychotic episodes over the last two years prior to follow-up. Finally, when investigated as a continuous variable, younger age at onset significantly correlated with better symptomatic and functional outcomes. CONCLUSIONS These results question the assumption that early-onset schizophrenia typically has a poor outcome. Early detection and specialised treatment for the first psychotic episode appear to be more effective at improving long-term functional outcomes in people with early-onset schizophrenia as in those with adult-onset schizophrenia. This possibility and the reasons for it need further investigation.