Long duration of untreated psychosis (DUP) predicts poor short- and long-term outcome in schizophrenia. It may also be a marker of resilience and associate with lower doses or shorter periods of using antipsychotic medication which may or may not be correlated with the association between DUP and outcome.

To study the association between DUP and the use of antipsychotic medication in long-term follow-up.

To find out whether the delayed treatment in first-episode psychosis associates with using less antipsychotic medication during the course of illness

In the prospective Northern Finland 1966 Birth Cohort length of DUP and information on lifetime use of antipsychotic medication for 60 individuals with schizophrenia was assessed from medical records from the first episode until age 34 years. Association between length of DUP and cumulative dose-years of antipsychotics was analysed using linear regression analysis. Logarithmic transformations of DUP and dose years were used.

Mean DUP was 227 days (SD 359) and mean of cumulative dose years was 2.41 (SD 1.29). Symptoms measured using PANSS ranged from 30 to 122, mean 53 (SD 21). Duration of untreated psychosis did not associate with the use of antipsychotic medication (beta = −0.124, p = 0.343).

There was no evidence of an association between DUP and the use of antipsychotic medication. Although long DUP has long-term association with poor outcome, it does not have an association with the use of antipsychotic medication based on the population-based long-term follow-up.

We analyzed longitudinal course of illness in schizophrenia until age 43 years, and its correlates to antipsychotic medication and cognition.

Northern Finland 1966 Birth Cohort Study has been followed serially since mid-pregnancy. Structural and functional MRI, cognitive, and clinical examinations were performed at ages 34 (73 schizophrenic psychoses, 104 controls) and 43 (63 schizophrenic psychoses, 192 controls); 40 cases and 75 controls participated in both surveys. Psychiatric outcomes have been ascertained through data linkage to a national case registers, hospital charts and clinical evaluations.

Prognosis of schizophrenia is heterogeneous: minority of individuals experience recovery, some achieve remission, but many are on disability pension, and excess mortality (especially suicides) is common. Long duration of untreated psychosis, early age of illness onset and presence of suicidal ideation associated with poorer long-term outcome. Both cases and non-psychotic controls show a small decline in verbal learning and memory, but the difference in decline is not significantly more pronounced in cases. Higher doses of antipsychotics at age 43-years associated to lower education and poorer clinical and functional outcomes, and high cumulative life-time use of antipsychotics associated to decrease of verbal learning and memory in 9-year follow-up.

Based on this naturalistic sample, midlife progression of schizophrenia may follow a variety of different trajectories. Poor clinical course is common but not necessary outcome. Compared to controls, more pronounced cognitive decline was not seen in schizophrenia cases. However, high doses of antipsychotics may relate to a decrease of verbal learning and memory.

Although neuroimaging studies suggest brain regional abnormalities in depressive disorders, it remains unclear whether abnormalities are present at illness onset or reflect disease progression.

We hypothesized that cerebral variations were present in adolescents with subthreshold depression known to be at high risk for later full-blown depression.

We examined brain structural and diffusion-weighted magnetic resonance images of adolescents with subthreshold depression.

The participants were extracted from the European IMAGEN study cohort of healthy adolescents recruited at age 14. Subthreshold depression was defined as a distinct period of abnormally depressed or irritable mood, or loss of interest, plus two or more depressive symptoms but without diagnosis of Major Depressive Episode. Comparisons were performed between adolescents meeting these criteria and control adolescents within the T1-weighted imaging modality (118 and 475 adolescents respectively) using voxel-based morphometry and the diffusion tensor imaging modality (89 ad 422 adolescents respectively) using tract-based spatial statistics. Whole brain analyses were performed with a statistical threshold set to p< 0.05 corrected for multiple comparisons.

Compared with controls, adolescents with subthreshold depression had smaller gray matter volume in caudate nuclei, medial frontal and cingulate cortices; smaller white matter volume in anterior limb of internal capsules, left forceps minor and right cingulum; and lower fractional anisotropy and higher radial diffusivity in the genu of corpus callosum.

The findings suggest that adolescents with subthreshold depression have volumetric and microstructural gray and white matter changes in the emotion regulation frontal-striatal-limbic network.

Midlife progression of schizophrenia shows evidence of longitudinal brain volume decrease and heterogeneous outcomes.

We analyzed the relation between brain volume changes, lifetime antipsychotic medication and clinical outcomes.

Psychotic members (n= 41) and non-psychotic controls (n=75) of the Northern Finland 1966 Birth Cohort were invited for a MRI brain scan and clinical and cognitive assessment at the age of 34 years (mean 10 years after onset of illness). A follow-up was 9 years later at age 43.

Clinical outcomes were heterogeneous and generally poor: 10% were recovered. The mean annual whole brain volume reduction was 0.69% in schizophrenia and 0.49 % in controls, especially in temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were generally not associated with volume reduction. However, decline in social and occupational function was associated with supramarginal gyrus reduction and was independent from antipsychotics exposure. Larger amount of antipsychotics over the follow-up associated significantly with larger brain volume loss. Higher doses of lifetime antipsychotic medication were associated to larger decrease of verbal learning change in a 9-year follow-up.

Brain volume and verbal learning reduction occurs in schizophrenia long after the onset of illness. Antipsychotics may contribute to these reductions. We do not know the real effectiveness and benefits/risks of antipsychotic drugs in schizophrenia from longitudinal and lifespan view. New data does not change current care guidelines but may expand clinical decision making into lower doses, even medication discontinuation in selected groups, and biopsychosocial care.

Long duration of untreated psychosis (DUP) has been associated to brain morphological changes in schizophrenia in cross sectional analyses. It is unclear DUP relates to brain volume change over time.

Our aim was to analyze the association between length of DUP and total brain volume change in schizophrenia in a general population based sample.

All members of the Northern Finland 1966 Birth Cohort (NFBC1966) known to have had psychotic illness were invited for a field study at the age 34-years (in average 10 year after onset of psychosis) and follow up nine years later at the age 43-years. DUP was assessed from medical records. The total brain volume scan interval change and the DUP information were available for 32 subjects with DSM III R schizophrenia. We analysed the correlation between length of DUP and the mean annual whole brain reduction, adjusted for age of illness onset and sex.

The mean annual whole brain volume reduction was 0.66%. The reduction was 0.76% among those with shortest DUP, 0.58% among those with median DUP, and 0.63% among those with longest DUP. There was no statistically significant correlation between DUP and annual brain volume change when adjusted for onset age and/or sex.

We did not find an association between long DUP and brain volume decrease in schizophrenia in 9 years follow up. Although long DUP has been associated with differences in brain volume in cross sectional analyses, the significance of DUP on brain morphology in long term is unclear.

Duration of untreated psychosis (DUP) is one of the few potentially modifiable predictors of outcome in schizophrenia. The long DUP and its relation to poor short-term outcome of schizophrenia has been studied in meta-analyses, but the conclusions remain unclear regarding the long-term effects of DUP.

To study the association between DUP and long-term outcome in a meta-analysis.

A systematic literature search of studies on DUP and long-term outcome in schizophrenia was performed using seven electronic databases. Studies were included if the follow-up was at least two years, the majority of subjects had a diagnosis of schizophrenia and DUP was studied with at least one of the following outcome categories: positive, negative, general and total symptoms, need of treatment, social functioning, employment, global outcome, quality of life and remission. Random effect methods were used to pool the effects of original studies.

2636 unique publications were identified of which 37 met our pre-defined selection criteria. Long DUP correlated with more severe positive (number of studies n=16; r=0.17), negative (n=17; r=0.14), general (n=4; r=0.29) and total symptoms (n=7; r=0.14) and with poor social functioning (n=13; r=0.13), poor global outcome (n=15; r=0.22) and less likely remission (n=16; r=0.14). The association between long DUP and decreased need of treatment was close to statistical significance (n=12; r=0.12). Employment (n=5) and quality of life (n=5) were not associated with DUP.

Severe symptoms and decreased functionality does not seem to increase the need of treatment or decrease the quality of life or employment.

Employment is important from the point of view of social inclusion and quality of life in individuals with schizophrenia.

To explore employment status in individuals with schizophrenia.

To examine register based employment and disability pension in average 20 years after onset of schizophrenia and compare those to population controls.

Individuals in the Northern Finland Birth Cohort 1966 (NFBC 1966; n=10277) were linked with the registers of Care Register of Health Care, Social Insurance Institution and Finnish Centre for Pensions. Individuals were considered as having schizophrenia, if they had diagnosis until the end of 2006. The sample included 161 individuals with schizophrenia (1.6% of all NFBC 1966 members). Good occupational outcome was defined as working at least 50% of the days during the two-year follow-up (2010 – 2011, age 44-45 years) and not being on disability pension, and poor occupational outcome as being on disability pension.

At the follow-up, 63% of the individuals with schizophrenia had poor and 6% had good outcome. Corresponding figures for population controls without schizophrenia were 4% and 69% (p<0.001). In the congress, we will report also results regarding early biological and psychosocial risk factors of employment status.

Employment rate at midlife in individuals with schizophrenia is low. Better ways of occupational rehabilitation are needed to support employment in individuals with schizophrenia.

Resilience is the capacity of individuals to resist mental disorders despite exposure to stress. Little is known about its neural underpinnings. The putative variation of white-matter microstructure with resilience in adolescence, a critical period for brain maturation and onset of high-prevalence mental disorders, has not been assessed by diffusion tensor imaging (DTI). Lower fractional anisotropy (FA) though, has been reported in the corpus callosum (CC), the brain's largest white-matter structure, in psychiatric and stress-related conditions. We hypothesized that higher FA in the CC would characterize stress-resilient adolescents.

Three groups of adolescents recruited from the community were compared: resilient with low risk of mental disorder despite high exposure to lifetime stress (n = 55), at-risk of mental disorder exposed to the same level of stress (n = 68), and controls (n = 123). Personality was assessed by the NEO-Five Factor Inventory (NEO-FFI). Voxelwise statistics of DTI values in CC were obtained using tract-based spatial statistics. Regional projections were identified by probabilistic tractography.

Higher FA values were detected in the anterior CC of resilient compared to both non-resilient and control adolescents. FA values varied according to resilience capacity. Seed regional changes in anterior CC projected onto anterior cingulate and frontal cortex. Neuroticism and three other NEO-FFI factor scores differentiated non-resilient participants from the other two groups.

High FA was detected in resilient adolescents in an anterior CC region projecting to frontal areas subserving cognitive resources. Psychiatric risk was associated with personality characteristics. Resilience in adolescence may be related to white-matter microstructure.

We compared heart rate dynamics during surgical levels of propofol and sevoflurane anaesthesia in a highly standardized setting.

We recorded electrocardiography from 24 anaesthetized healthy male subjects. In the first parallel part of the study, the subjects were anaesthetized either with sevoflurane (n = 8) or propofol (n = 8) targeted to match 1.0, 1.5 and 2.0 minimal alveolar concentration/effective concentration 50. In the second part, a separate group (n = 8) underwent four different anaesthetic regimens targeted to bispectral index 40: sevoflurane alone, sevoflurane + 70% nitrous oxide, propofol alone and propofol + 70% nitrous oxide. The electrocardiography data were analysed using conventional time and frequency domain methods, and the approximate entropy method, which estimates the complexity of the data.

The induction of anaesthesia was followed by an overall reduction of heart rate variability, evident in all frequency bands in the spectral analysis, and also in the time domain measures. Approximate entropy decreased at 1 effective concentration 50 with propofol and at 2 minimal alveolar concentration with sevoflurane. In the second part of the study, the time domain variables and high-frequency spectral power were all similarly reduced by sevoflurane and propofol anaesthesia, with and without nitrous oxide. Approximate entropy tended to decrease during propofol anaesthesia.

Hypnotic levels of sevoflurane and propofol anaesthesia suppressed the heart rate variability measured using conventional analysis methods. Deeper surgical levels of anaesthesia also reduce the complexity of heart rate variability.

Trends and availability of the methods used for suicide in Finland were analysed in order to base proposals for prevention of access to methods.

Finnish suicides from 1947 to 1990 were analysed by sex, age, time period and suicide method using confidence intervals for rates, χ2 test for trends and suicide risks for different medicines.

Suicide rate by parathion, a highly lethal pesticide and commonly used for suicide in the 1950s, decreased after its availability was restricted, but this was offset by an increased rate by other methods. Since 1982, the suicide risk for antidepressants and neuroleptics increased coincident with their availability, although that for barbiturates remained stable but high despite a reduction in availability. Suicide risk for antidepressants other than tricyclics decreased despite increased availability.

Restriction of a method reduces its use for suicide, but other methods tend to replace it. Restrictive measures should focus on some specific situations. Antidepressants other than tricyclics are recommended for the treatment of suicidal depressive patients.