Prodromal stage of psychosis may be an aim of prevention first episode psychosis. In late-onset psychosis it’s low described.

The aim of this investigation is to describe prodromal phase of late-onset psychosis and their connection with psychopathology.

74 women with late-onset psychosis (age 64,3±6,7) - late-onset schizophrenia (LOS) (n=49, age 63±8,4), schizoaffective disorder (n=17, age 62,4±6,5), late onset delusion disorder (LoDD) (n=8, age 76,6±4,3) underwent clinical assessment (SOPS, PANSS, HAMD-17), cognitive examination (MMSE, MoCA), structured interviewing on life-time pathology. Spearman’s rho statistics was used.

LOP patients have low prodromal symptoms according to the SOPS score. In LOS patients middle score of SOPS is 18±8,5, in schizoaffective patients middle score of SOPS is 12,3±6,8, and for LoDD SOPS is 13,4 ±4,6. Prodromal disturbances are represented mainly by fragmentary paranoid ideas, thoughts of unusual content, acoasms and affective fluctuations. In LOS patients SOPS negative subscale correlate with HAMD (r=0,384, p<0,05), desorganisation subscale correlate with PANSS common psychopathology subscale (r=0,32, p<0,05) and total PANSS (r=0,28, p<0,05), generous subscale and common SOPS correlate with HAMD (r=0,29, r=0,3, p<0,05). For patients with schizoaffective disorder there is no correlations, and in patients with LoDD SOPS desorganisation subscale negative correlate with PANSS negative subscale (r=-0,71, p<0,05).

In patients with late psychoses, the severity of disorders in the prodromal period is minimal. However, prodromal features are associated with the psychopathology.

No significant relationships.

Cerebral glutamate and gamma-aminobutyric acid (GABA) levels might predict clinical outcome in individuals at ultrahigh risk (UHR) for psychosis but have previously primarily been investigated in smaller cohorts. We aimed to study whether baseline levels of glutamate and GABA in anterior cingulate cortex (ACC) and glutamate in thalamus could predict remission status and whether baseline metabolites differed in the remission versus the nonremission group. We also investigated the relationship between baseline metabolite levels and severity of clinical symptoms, functional outcome, and cognitive deficits at follow-up.

About 124 UHR individuals were recruited at baseline. In this, 74 UHR individuals were clinically and cognitively assessed after 12 months, while remission status was available for 81 (25 remission/56 nonremission). Glutamate and GABA levels were assessed at baseline using 3 T proton magnetic resonance spectroscopy. Psychopathology, symptom severity, and remission were assessed with the Comprehensive Assessment of At-Risk Mental States and Clinical Global Impression and functional outcome with the Social and Occupational Functioning Assessment Scale. Cognitive function was estimated with the Cambridge Neuropsychological Test Automated Battery.

There were no differences between baseline glutamate and GABA levels in subjects in the nonremission group compared with the remission group, and baseline metabolites could not predict remission status. However, higher baseline levels of GABA in ACC were associated with clinical global improvement (r = −0.34, N = 51, p = 0.01) in an explorative analysis.

The variety in findings across studies suggests a probable multifactorial influence on clinical outcome in UHR individuals. Future studies should combine multimodal approaches to attempt prediction of long-term outcome.

While recent research points to the potential benefits of clinical intervention before the first episode of psychosis, the logistical feasibility of this is unclear.

To assess the feasibility of providing a clinical service for people with prodromal symptoms in an inner city area where engagement with mental health services is generally poor.

Following a period of liaison with local agencies to promote the service, referrals were assessed and managed in a primary care setting. Activity of the service was audited over 30 months.

People with prodromal symptoms were referred by a range of community agencies and seen at their local primary care physician practice. Over 30 months, 180 clients were referred; 58 (32.2%) met criteria for an at risk mental state, most of whom (67.2%) had attenuated psychotic symptoms. Almost 30% were excluded due to current or previous psychotic illness, of which two-thirds were in the first episode of psychosis. The socio-demographic composition of the 'at risk' group reflected that of the local population, with an over-representation of clients from an ethnic minority. Over 90% of suitable clients remained engaged with the service after 1 year.

It is feasible to provide a clinical service for people with prodromal symptoms in a deprived inner city area with a large ethnic minority population.

This study explores psychopathological aspects of acute and transient psychotic disorders (ATPD), a diagnostic category introduced with ICD-10, to elucidate its relationship with schizophrenia and schizoaffective psychoses.

We recruited all consecutive inpatients fulfilling the ICD-10 criteria of ATPD (F23) during a 5-year period as well as control groups with “positive” schizophrenia (PS) and bipolar schizoaffective disorder (BSAD) matched for gender and age at index episode. For the evaluation of psychopathological parameters during index episode a standardized symptom list was used. Prepsychotic (prodromal) symptoms were also assessed.

During the prepsychotic period few differences between the groups were detected. The most important difference between ATPD and the other two other psychotic disorders regarding phenomenology of the full-blown episodes was a higher frequency of “rapidly changing delusional topics”, “rapidly changing mood” and anxiety in ATPD.

ATPD show a characteristic psychopathological picture consistent with earlier concepts such as cycloid psychoses and bouffée délirante. Nevertheless, psychopathology alone is not enough to establish ATPD as an independent nosological entity.

Prevention of psychosis has become a major objective of modern clinical psychiatry. An increasing number of new services have been established in Europe and in the world. The OASIS team has become an established model where clinical practice and research are fully integrated in the field of preventative interventions in psychosis.

Comprehensive analysis of different clinical and service measures describing the 2001–2011 implementation of the OASIS team.

Over the last decade, the OASIS team has received a total of 1102 referrals, mostly young males from ethnic minorities. After the assessment, 35% were diagnosed with an At Risk Mental State (ARMS) while 32% were already psychotic. Within the ARMS, 70% met the inclusion criteria for the attenuated psychotic symptoms subgroup, 1% met the inclusion criteria for the genetic deterioration syndrome, 9% met inclusion criteria for a brief and self-limited intermittent psychotic episode and the others met inclusion criteria for more than one subgroup. Most of them had at least one comorbid diagnosis, mainly relating to anxiety and depressive domains. The majority of the OASIS clients received cognitive behavioural therapy alone or in combination with antidepressants/antipsychotics. Over the 2-year follow-up time, 44 subjects (15.2%) developed a frank psychotic episode.

The OASIS service represents one of the largest and most established prodromal services in the world. The burden of research evidence and the translational impact produced on the clinical practice support the OASIS as a model for the development of similar services.

Rapid diagnosis of dementia is essential to ensure optimum patient care. This study used real-world data to quantify the dementia diagnostic pathway in Australia.

A real-world, cross-sectional survey of physicians and patients.

Clinical practice.

Primary care or specialist physicians managing patients with cognitive impairment (CI).

Descriptive analyses focused on key events in the diagnostic pathway. Regression modeling compared the duration between first consultation and formal diagnosis with various factors.

Data for 600 patients were provided by 60 physicians. Mean time from initial symptoms to first consultation was 6.1 ± 4.4 months; 20% of patients had moderate or severe CI at first consultation. Mean time from first consultation to formal diagnosis was 4.0 ± 7.4 months (1.2 ± 3.6 months if not referred to a secondary physician, and 5.3 ± 8.3 months if referred). Time from first consultation to diagnosis was significantly associated with CI severity at first consultation; time was shorter with more severe CI. There was no association of disease severity and referral to a secondary physician; 69.5% of patients were referred, the majority (57.1%) to a geriatrician. The highest proportion of patients were diagnosed by geriatricians (47.4%). Some form of test or scale was used to aid diagnosis in 98.8% of patients.

A substantial number of Australians experience cognitive decline and behavioral changes some time before consulting a physician or being diagnosed with dementia. Increasing public awareness of the importance of early diagnosis is essential to improve the proportion of patients receiving comprehensive support prior to disease progression.

In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate.

In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers.

Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring.

ARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people.

Oxidative stress has been documented in chronic schizophrenia and in the first episode of psychosis, but there are very little data on oxidative stress prior to the disease onset.

This work aimed to compare serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in young individuals at ultra-high risk (UHR) of developing psychosis with a comparison healthy control group (HC).

Thirteen UHR subjects and 29 age- and sex-matched healthy controls (HC) were enrolled in this study. Clinical assessment included the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and the Global Assessment of Functioning (GAF) scale. Activities of SOD and GPx were measured in serum by the spectrophotometric method using enzyme-linked immunosorbent assay kits.

After adjusting for age and years of education, there was a significant lower activity of SOD and lower GPX activity in the UHR group compared to the healthy control group (rate ratio [RR]=0.330, 95% CI 0.187; 0.584, p<0.001 and RR=0.509, 95% CI 0.323; 0.803, p=0.004, respectively). There were also positive correlations between GAF functioning scores and GPx and SOD activities.

Our results suggest that oxidative imbalances could be present prior to the onset of full-blown psychosis, including in at-risk stages. Future studies should replicate and expand these results.

Although cognitive deficits in patients with schizophrenia are rooted early in development, the impact of psychosis on the course of cognitive functioning remains unclear. In this study a nested case-control design was used to examine the relationship between emerging psychosis and the course of cognition in individuals ascertained as clinical high-risk (CHR) who developed psychosis during the study (CHR + T).

Fifteen CHR + T subjects were administered a neurocognitive battery at baseline and post-psychosis onset (8.04 months, s.d. = 10.26). CHR + T subjects were matched on a case-by-case basis on age, gender, and time to retest with a group of healthy comparison subjects (CNTL, n = 15) and two groups of CHR subjects that did not transition: (1) subjects matched on medication treatment (i.e. antipsychotics and antidepressants) at both baseline and retesting (Meds-matched CHR + NT, n = 15); (2) subjects unmedicated at both assessments (Meds-free CHR + NT, n = 15).

At baseline, CHR + T subjects showed large global neurocognitive and intellectual impairments, along with specific impairments in processing speed, verbal memory, sustained attention, and executive function. These impairments persisted after psychosis onset and did not further deteriorate. In contrast, CHR + NT subjects demonstrated stable mild to no impairments in neurocognitive and intellectual performance, independent of medication treatment.

Cognition appears to be impaired prior to the emergence of psychotic symptoms, with no further deterioration associated with the onset of psychosis. Cognitive deficits represent trait risk markers, as opposed to state markers of disease status and may therefore serve as possible predictors of schizophrenia prior to the onset of the full illness.

The clinical condition of dementia is now recognized as a diagnosis that can only be applied too late in the disease process to be useful for therapeutic approaches centring on disease modification. As a result, in recent years increasing attention has been given to mild cognitive impairment (MCI) and the diagnosis of prodromal dementia. This paper reviews the evidence for the clinical presentation of prodromal dementia with Lewy bodies (DLB).

A Medline search was carried out to identify articles with original data on the prodromal presentation of DLB.

In MCI cohorts that progress to dementia, the proportion diagnosed with DLB is similar to that reported in dementia cohorts. Prodromal DLB may present as any MCI subtype, although visuospatial and executive domains may be most commonly affected. Rapid eye movement (REM) sleep behaviour disorder (RBD), autonomic symptoms, hyposmia, hallucinations and motor symptoms seem to be more common in prodromal DLB than in prodromal Alzheimer's disease (AD). Some of these symptoms can precede the diagnosis of DLB by several years. There has been little research into the use of biomarkers in prodromal DLB, although in RBD cohorts, clinical and imaging biomarkers have been associated with the development of DLB.

The evidence available suggests that prodromal DLB may be differentiated from other dementia prodromes in most cases. Further research is needed to confirm this, and to assess the utility of biomarkers such as 123I-FP-CIT and 123I-MIBG imaging.

The past two decades have seen exponential clinical and research interest in help-seeking individuals presenting with potentially prodromal symptoms for psychosis. However, the epidemiological validity of this paradigm has been neglected, limiting future advancements in the field.

We undertook a critical review of core epidemiological issues underlying the clinical high-risk (HR) state for psychosis and which model of prodromal intervention is best suited for mental health.

The HR state for psychosis model needs refining, to bring together population-based findings of high levels of psychotic experiences (PEs) and clinical expression of risk. Traditionally, outcome has been attributed to ‘HR criteria’ alone rather than taking into account sampling strategies. Furthermore, the exclusive focus on variably defined ‘transition’ obscures true variation in the slow and non-linear progression across stages of psychopathology. Finally, the outcome from HR states is variable, indicating that the underlying paradigm of ‘schizophrenia light progressing to schizophrenia’ is inadequate.

In the general population, mixed and non-specific expression of psychosis, depression, anxiety and subthreshold mania is common and mostly transitory. When combined with distress, it may be considered as the first, diagnostically neutral stage of potentially more severe psychopathology, which only later may acquire a degree of diagnostic specificity and possible relative resistance to treatment. Therefore, rather than creating silos of per-disorder ultra-HR syndromes, an early intervention focus on the broad syndrome of early mental distress, requiring phase-specific interventions, may be more profitable.

Increased sensitivity and exposure to stress are associated with psychotic symptoms in schizophrenia and its risk states, but little is known about the co-evolution of stress sensitivity and exposure with positive and other symptoms in a clinical high-risk (CHR) cohort.

A combined cross-sectional and longitudinal design was used to examine the associations over time of stress sensitivity and exposure (i.e. life events) with ‘prodromal’ symptoms in a cohort of 65 CHR patients assessed quarterly for up to 4 years, and at baseline in 24 healthy controls similar in age and gender.

Impaired stress tolerance was greater in patients, in whom it was associated over time with positive and negative symptoms, in addition to depression, anxiety and poor function. By contrast, life events were comparable in patients and controls, and bore no association with symptoms. In this treated cohort, there was a trajectory of improvement in stress tolerance, symptoms and function over time.

Impaired stress tolerance was associated with a wide range of ‘prodromal’ symptoms, consistent with it being a core feature of the psychosis risk state. Self-reported life events were not relevant as a correlate of clinical status. As in other treated CHR cohorts, most patients improved over time across symptom domains.

Deficits in automatic sensory discrimination, as indexed by a reduction in the mismatch negativity (MMN) and P3a event-related potential amplitudes, are well documented in chronic schizophrenia. However, MMN and P3a have not been sufficiently studied early in the course of psychotic illness. The present study aimed to investigate MMN, P3a and reorienting negativity (RON) across the course of schizophrenia.

MMN, P3a, and RON were assessed in 118 subjects across four groups: (1) individuals at risk for psychosis (n=26); (2) recent-onset patients (n=31); (3) chronic patients (n=33); and (4) normal controls (n=28) using a duration-deviant auditory oddball paradigm.

Frontocentral deficits in MMN and P3a were present in all patient groups. The at-risk group's MMN and P3a amplitudes were intermediate to those of the control and recent-onset groups. The recent-onset and chronic patients, but not the at-risk subjects, showed significant RON amplitude reductions, relative to the control group. Associations between MMN, P3a, RON and psychosocial functioning were present in the chronic patients. In the at-risk subjects, P3a and RON deficits were significantly associated with higher levels of negative symptoms.

Abnormalities in the automatic processes of sensory discrimination, orienting and reorienting of attention are evident in the early phases of schizophrenia and raise the possibility of progressive worsening across stages of the illness. The finding that MMN and P3a, but not RON, were reduced before psychosis onset supports the continued examination of these components as potential early biomarkers of schizophrenia.

Identifying prodromal features that predate the onset of bipolar disorder (BD) may enable the prevention of BD and aid early intervention. This review addresses two key questions: Is there a bipolar prodrome? And, if there is, what are its characteristic features?

A comprehensive search of databases (PubMed, Medline, EMBASE and PsycINFO) supplemented by hand searches was used to identify studies of symptoms preceding the onset of BD.

Fifty-nine studies were identified, of which 14 met inclusion criteria. Symptoms can predate the onset of BD by months to years and can be categorized as attenuated forms of BD symptoms, general symptoms common to a range of mental disorders, and personality traits, particularly cyclothymia. Two studies provided sufficient data to enable sensitivity and specificity to be calculated. Specificity of several of the features was high (>90%) but sensitivity was generally low (all <60%). We propose a model based on the findings in the studies reviewed to illustrate the potential trajectory to BD and the points at which it may be possible to intervene.

Clinical features preceding the onset of BD can be identified. However, conclusions about whether there is a distinct prodrome to BD are restricted by the limitations of current evidence. The high specificity of some features suggests they may be useful in clinical practice. Large-scale longitudinal studies are needed to validate these features and characterize their specificity and sensitivity in independent samples.

Cognitive impairment is considered to be a core characteristic of schizophrenia. The relationship between psychosis and cognitive deterioration, however, remains unclear. This longitudinal study investigated the neuropsychological functioning of patients before and after their first psychotic episode. Cognitive functioning of participants who later developed a psychosis was compared to that of people at ultra-high risk (UHR) for psychosis who did not develop psychosis at follow-up and healthy controls.

Participants were 41 persons at UHR for psychosis (the UHR group), of whom 17 developed psychosis between the first and second assessment. Seventeen healthy controls were included in the study. Cognitive performance was assessed at intake (T0) and again after 18 months (T1). The areas of cognitive functioning assessed include verbal memory and learning, visuospatial working memory, executive function, sustained attention and motor speed.

The transition group did not perform significantly worse at the second assessment than at the first on any of the outcome measures. The UHR group performed better on a verbal learning and memory test at T1 compared to T0. At T0, the control group scored significantly better than the UHR group and the transition group on the verbal learning and memory test and the verbal fluency test.

The results indicate that no cognitive deterioration occurs during the first psychotic episode. Problems in verbal memory may be present before the first episode of psychosis.