Kaksisuuntaisen mielialahäiriön tunnistus, muu psykiatrinen sairastavuus ja ennuste psykiatrisessa erikoissairaanhoidossa

This study is part of an ongoing collaborative bipolar research project, the Jorvi Bipolar Study (JoBS). The JoBS is run by the Department of Mental Health and Alcohol Research of the National Public Health Institute, Helsinki, and the Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital (HUCH), Espoo, Finland. It is a prospective, naturalistic cohort study of secondary level care psychiatric in- and outpatients with a new episode of bipolar disorder (BD). The second report also included 269 major depressive disorder (MDD) patients from the Vantaa Depression Study (VDS). The VDS was carried out in collaboration with the Department of Psychiatry of the Peijas Medical Care District. Using the Mood Disorder Questionnaire (MDQ), all in- and outpatients at the Department of Psychiatry at Jorvi Hospital who currently had a possible new phase of DSM-IV BD were sought. Altogether, 1630 psychiatric patients were screened, and 490 were interviewed using a semistructured interview (SCID-I/P). The patients included in the cohort (n=191) had at intake a current phase of BD. The patients were evaluated at intake and at 6- and 18-month interviews. Based on this study, BD is poorly recognized even in psychiatric settings. Of the BD patients with acute worsening of illness, 39% had never been correctly diagnosed. The classic presentations of BD with hospitalizations, manic episodes, and psychotic symptoms lead clinicians to correct diagnosis of BD I in psychiatric care. Time of follow-up elapsed in psychiatric care, but none of the clinical features, seemed to explain correct diagnosis of BD II, suggesting reliance on cross- sectional presentation of illness. Even though BD II was clearly less often correctly diagnosed than BD I, few other differences between the two types of BD were detected. BD I and II patients appeared to differ little in terms of clinical picture or comorbidity, and the prevalence of psychiatric comorbidity was strongly related to the current illness phase in both types. At the same time, the difference in outcome was clear. BD II patients spent about 40% more time depressed than BD I patients. Patterns of psychiatric comorbidity of BD and MDD differed somewhat qualitatively. Overall, MDD patients were likely to have more anxiety disorders and cluster A personality disorders, and bipolar patients to have more cluster B personality disorders. The adverse consequences of missing or delayed diagnosis are potentially serious. Thus, these findings strongly support the value of screening for BD in psychiatric settings, especially among the major depressive patients. Nevertheless, the diagnosis must be based on a clinical interview and follow-up of mood. Comorbidity, present in 59% of bipolar patients in a current phase, needs concomitant evaluation, follow-up, and treatment. To improve outcome in BD, treatment of bipolar depression is a major challenge for clinicians.Tämä tutkimus on osa Kansanterveyslaitoksen ja Helsingin ja Uudenmaan sairaanhoitopiirin Jorvin sairaalan psykiatrian tulosyksikön kaksisuuntaisen mielialahäiriön seurantatutkimusta (Jorvi Bipolar Study), jossa seurataan 191 ajankohtaisesta (DSM-IV) mielialajaksosta kärsivää psykiatrisen erikoissairaanhoidon avohoito- ja sairaalapotilasta. Tutkimusta varten seulottiin Jorvin psykiatrisessa erikoissairaanhoidossa 1630 potilasta, joista 490 haastateltiin puolistrukturoidulla haastattelumenetelmällä SCID-I/P. Tutkimuksessa mukana olevat potilaat (n=191) täyttivät tutkimuksen alussa ajankohtaisen mielialavaiheen kriteerit. Potilaiden tila kartoitettiin sisäänottovaiheen lisäksi 6kk ja 18kk haastatteluissa. Verrattaessa kaksisuuntaisen mielialahäiriön tyyppi I ja II komorbiditeettia vakavasta masennuksesta kärsivien komorbiditeettiin vertailuryhmänä käytettiin 269 vakavaa unipolaarista masennusjaksoa sairastavaa potilasta Vantaa Depression Studysta. Tutkimuksessa todettiin, että kaksisuuntainen mielialahäiriö oli erittäin huonosti tunnistettu psykiatrisessa erikoissairaanhoidossa: niistä kaksisuuntaista mielialahäiriötä sairastavista potilaista, jotka tarvitsivat akuutisti hoitoa, 39% ei ollut koskaan saanut oikeaa kliinistä diagnoosia. Erityisesti tyyppi II häiriötä sairastavat potilaat ja naiset olivat huonommin tunnistettuja. Tunnistaminen näytti tapahtuvan perustuen ajankohtaisesti ilmeneviin ns. klassisiin eli maanisiin tai psykoottisiin oireisiin erityisesti sairaalahoitoa vaativissa jaksoissa. Näyttää että mielialahäiriö diagnosoitiin perustuen ajankohtaiseen oirekuvaan, unohtaen pitkittäisanamneesin merkitys. Vaikka tyyppi II mielialahäiriö oli selvästi huonommin tunnistettu kuin tyyppi I, häiriöt erosivat vain muutamassa muussa kliinisessä piirteessä. Komorbiditeetti eli muu psykiatrinen sairastaminen oli yhtä yleistä. Tyyppi II häiriössä ennuste oli huonompi: potilaat viettivät noin 40% enemmän aikaa masentuneena kuin tyyppi I sairastavat. Komorbiditeetti oli vakavassa unipolaarisessa masennuksessa ja kaksisuuntaisessa mielialahäiriössä laadullisesti jonkin verran erilaista. Ajankohtaisesti jokin akseli I häiriö oli yleisempi vakavassa masennuksessa kuin kaksisuuntaisessa mielialahäiriössä (69.1% vs. 57.1%) ja ero johtui erityisesti ahdistuneisuushäiriöistä. Viivästyneen tai puuttuvan diagnoosin seuraukset voivat olla vakavia niin yksilölle kuin yhteiskunnalle. Tämän vuoksi tutkimuksen tulosten perusteella on suositeltavaa seuloa kaksisuuntaista mielialahäiriötä erityisesti vakavasti masentuneiden potilaiden joukossa. Kliinisen diagnoosin täytyy kuitenkin aina perustua perusteelliseen kliiniseen haastatteluun ja seurantaan, jossa huomioidaan pitkäaikainen sairauden kulku. Myös muiden psykiatristen sairauksien esiintyminen kaksisuuntaisessa mielialahäiriössä on yleistä ja huonontaa entisestään sairauden kulkua. Sen vuoksi se vaatii erillistä arviointia, seurantaa ja hoitoa. Masennusoireiden hoito on erityisen keskeinen haaste, jotta kaksisuuntaisen mielialahäiriön ennustetta saataisiin parannettua

Is It Possible to Predict the Future in First-Episode Psychosis?

The outcome of first-episode psychosis (FEP) is highly variable, ranging from early sustained recovery to antipsychotic treatment resistance from the onset of illness. For clinicians, a possibility to predict patient outcomes would be highly valuable for the selection of antipsychotic treatment and in tailoring psychosocial treatments and psychoeducation. This selective review summarizes current knowledge of prognostic markers in FEP. We sought potential outcome predictors from clinical and sociodemographic factors, cognition, brain imaging, genetics, and blood-based biomarkers, and we considered different outcomes, like remission, recovery, physical comorbidities, and suicide risk. Based on the review, it is currently possible to predict the future for FEP patients to some extent. Some clinical features—like the longer duration of untreated psychosis (DUP), poor premorbid adjustment, the insidious mode of onset, the greater severity of negative symptoms, comorbid substance use disorders (SUDs), a history of suicide attempts and suicidal ideation and having non-affective psychosis—are associated with a worse outcome. Of the social and demographic factors, male gender, social disadvantage, neighborhood deprivation, dysfunctional family environment, and ethnicity may be relevant. Treatment non-adherence is a substantial risk factor for relapse, but a small minority of patients with acute onset of FEP and early remission may benefit from antipsychotic discontinuation. Cognitive functioning is associated with functional outcomes. Brain imaging currently has limited utility as an outcome predictor, but this may change with methodological advancements. Polygenic risk scores (PRSs) might be useful as one component of a predictive tool, and pharmacogenetic testing is already available and valuable for patients who have problems in treatment response or with side effects. Most blood-based biomarkers need further validation. None of the currently available predictive markers has adequate sensitivity or specificity used alone. However, personalized treatment of FEP will need predictive tools. We discuss some methodologies, such as machine learning (ML), and tools that could lead to the improved prediction and clinical utility of different prognostic markers in FEP. Combination of different markers in ML models with a user friendly interface, or novel findings from e.g., molecular genetics or neuroimaging, may result in computer-assisted clinical applications in the near future

Mortality in people with psychotic disorders in Finland : A population-based 13-year follow-up study

Objectives: We conducted a population based study aiming at finding predictors of mortality in psychotic disorders and evaluating the extent to which sociodemographic, lifestyle and health-related factors explain the excess mortality. Methods: In a nationally representative sample of Finns aged 30-70 years (n = 5642), psychotic disorders were diagnosed using structured interviews and medical records in 2000-2001. Information on mortality and causes of death was obtained of those who died by the end of year 2013. Cox proportional hazards models were used to investigate the mortality risk. Results: No people with affective psychoses (n = 36) died during the follow-up, thus the analysis was restricted to non-affective psychotic disorders (NAP) (n = 106). Adjusting for age and sex, NAP was statistically significantly associated with all-cause mortality (hazard ratio (HR) 2.99, 95% CI 2.03-441) and natural-cause mortality (HR 2.81, 95% CI 1.85-4.28). After adjusting for sociodemographic factors, health status, inflammation and smoking, the HR dropped to 2.11 (95%CI 1.10-4.05) for all-cause and to 1.98 (95% CI 0.94-4.16) for natural-cause mortality. Within the NAP group, antipsychotic use at baseline was associated with reduced HR for natural-cause mortality (HR 0.25, 95% CI 0.07-0.96), and smoking with increased HR (HR 3.54, 95% CI 1.07-11.69). Conclusions: The elevated mortality risk in people with NAP is only partly explained by socioeconomic factors, lifestyle, cardio-metabolic comorbidities and inflammation. Smoking cessation should be prioritized in treatment of psychotic disorders. More research is needed on the quality of treatment of somatic diseases in people with psychotic disorders. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Is It Possible to Predict the Future in First-Episode Psychosis?

The outcome of first-episode psychosis (FEP) is highly variable, ranging from early sustained recovery to antipsychotic treatment resistance from the onset of illness. For clinicians, a possibility to predict patient outcomes would be highly valuable for the selection of antipsychotic treatment and in tailoring psychosocial treatments and psychoeducation. This selective review summarizes current knowledge of prognostic markers in FEP. We sought potential outcome predictors from clinical and sociodemographic factors, cognition, brain imaging, genetics, and blood-based biomarkers, and we considered different outcomes, like remission, recovery, physical comorbidities, and suicide risk. Based on the review, it is currently possible to predict the future for FEP patients to some extent. Some clinical features-like the longer duration of untreated psychosis (DUP), poor premorbid adjustment, the insidious mode of onset, the greater severity of negative symptoms, comorbid substance use disorders (SUDs), a history of suicide attempts and suicidal ideation and having non-affective psychosis-are associated with a worse outcome. Of the social and demographic factors, male gender, social disadvantage, neighborhood deprivation, dysfunctional family environment, and ethnicity may be relevant. Treatment non-adherence is a substantial risk factor for relapse, but a small minority of patients with acute onset of FEP and early remission may benefit from antipsychotic discontinuation. Cognitive functioning is associated with functional outcomes. Brain imaging currently has limited utility as an outcome predictor, but this may change with methodological advancements. Polygenic risk scores (PRSs) might be useful as one component of a predictive tool, and pharmacogenetic testing is already available and valuable for patients who have problems in treatment response or with side effects. Most blood-based biomarkers need further validation. None of the currently available predictive markers has adequate sensitivity or specificity used alone. However, personalized treatment of FEP will need predictive tools. We discuss some methodologies, such as machine learning (ML), and tools that could lead to the improved prediction and clinical utility of different prognosticmarkers in FEP. Combination of differentmarkers inMLmodels with a user friendly interface, or novel findings from e.g., molecular genetics or neuroimaging, may result in computer-assisted clinical applications in the near future.Peer reviewe

Childhood adversities and clinical symptomatology in first-episode psychosis

In addition to severe traumatic experiences, milder, more common childhood adversities reflecting psychosocial burden may also be common in people with psychotic disorders and have an effect on symptomatology and functioning. We explored eleven negative childhood experiences and their influence on clinical symptoms among young adults with first-episode psychosis (FEP, n = 75) and matched population controls (n = 51). Individuals with FEP reported more adversities than controls. Specifically serious conflicts within the family, bullying at school, maternal mental health problems, and one's own and parents' serious illness during childhood were experienced by the patients more often than by controls. In the FEP group, the severity of adversity was associated with increased anxiety, manic, and obsessive-compulsive symptoms, but not with the severity of positive psychotic symptoms. Adversity produced a more pronounced effect on symptoms in male patients than in female patients. To conclude, in line with earlier studies of more chronic psychosis, a majority of the participants with FEP reported exposure to childhood adversities, with the FEP group reporting more adversities than controls. High levels of mood and anxiety symptoms in patients with FEP may be related to cumulative exposure to childhood adversities. This should be taken into account in the treatment for FEP.Peer reviewe

Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response

The effects of gut microbiota on the central nervous system, along its possible role in mental disorders, have received increasing attention. Here we investigated differences in fecal microbiota between 28 patients with first-episode psychosis (FEP) and 16 healthy matched controls and explored whether such differences were associated with response after up to 12 months of treatment. Numbers of Lactobacillus group bacteria were elevated in FEP-patients and significantly correlated with severity along different symptom domains. A subgroup of FEP patients with the strongest microbiota differences also showed poorer response after up to 12 months of treatment. The present findings support the involvement of microbiota alterations in psychotic illness and may provide the basis for exploring the benefit of their modulation on treatment response and remission. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Low-grade inflammation in first-episode psychosis is determined by increased waist circumference

Psychosis is associated with low-grade inflammation as measured by high-sensitivity C-reactive protein (hs-CRP), a risk factor for cardiovascular events and mortality in the general population. We investigated the relationship between hs-CRP and anthropometric and metabolic changes in first-episode psychosis (FEP) during the first treatment year. We recruited 95 FEP patients and 62 controls, and measured longitudinal changes in hs-CRP, weight, waist circumference, insulin resistance, and lipids. We used linear mixed models to analyze the longitudinal relationship between hs-CRP and clinical, anthropometric and metabolic measures. At baseline, patients with FEP had higher levels of insulin resistance, total and low-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Baseline weight, waist circumference, hs-CRP, fasting glucose, and high-density lipoprotein cholesterol were similar between patients and controls. Marked increases in anthropometric measures and hs-CRP were observed in FEP during the 12-month follow-up. However, glucose and lipid parameters did not change significantly. In the mixed models, waist circumference and female sex were significant predictors of hs-CRP levels in FEP. Prevention of the early development of abdominal obesity in FEP is crucial, as abdominal obesity is accompanied by chronic low-grade inflammation, which increases further the cardiovascular risk in this vulnerable population.Peer reviewe

State and trait hopelessness in a prospective five-year study of patients with depressive disorders

Background: Hopelessness is a common experience of patients with depressive disorders (DD) and an important predictor of suicidal behaviour. However, stability and factors explaining state and trait variation of hopelessness in patients with DD over time are poorly known. Methods: Patients with DD (n = 406) from the Vantaa Depression Study and the Vantaa Primary Care Depression Study filled in the Beck Hopelessness Scale (BHS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Perceived Social Support Scale-Revised (PSSS-R), and Eysenck Personality Inventory-Q (EPI-Q) at baseline, at six and eighteen months, and at five years. We conducted a multilevel linear regression analyses predicting BHS with these covariates. Results: During the five-year follow-up half of the variance in BHS was attributable to between-patient variance (50.6%, CI = 41.2-61.5%), and the rest arose from within-patient variance and measurement errors. BDI and BAI explained 5.6% of within-patient and 28.4% of between-patient variance of BHS. High Neuroticism and low Extraversion explained 2.6% of the between-patient variance of BHS. PSSS-R explained 5% of between-patient variance and 1.7% of within-patient variance of BHS. Limitations: No treatment effects were controlled. Conclusions: Hopelessness varies markedly over time both within and between patients with depression; it is both state-and trait-related. Concurrent depressive and anxiety symptoms and low social support explain both state and trait variance, whereas high Neuroticism and low Extraversion explain only trait variance of hopelessness. These variations influence the utility of hopelessness as an indicator of suicide risk.Peer reviewe

Personality disorders and suicide attempts in unipolar and bipolar mood disorders

Background: Comorbid personality disorders may predispose patients with mood disorders to suicide attempts (SAs), but factors mediating this effect are not well known. Methods: Altogether 597 patients from three prospective cohort studies (Vantaa Depression Study, Jorvi Bipolar Study, and Vantaa Primary Care Depression Study) were interviewed at baseline, at 18 months, and in VDS and PC-VDS at 5 years. Personality disorders (PDs) at baseline, number of previous SAs, life-charted time spent in major depressive episodes (MDEs), and precise timing of SAs during follow-up were determined and investigated. Results: Overall, 219 (36.7%) patients had a total of 718 lifetime SAs; 88 (14.7%) patients had 242 SAs during the prospective follow-up. Having any PD diagnosis increased the SA rate, both lifetime and prospectively evaluated, by 90% and 102%, respectively. All PD clusters increased the rate of new SAs, although cluster C PDs more than the others. After adjusting for time spent in MDEs, only cluster C further increased the SA rate (by 52%). Mediation analyses of PD effects on prospectively ascertained SAs indicated significant mediated effects through time at risk in MDEs, but also some direct effects. Limitations: Findings generalizable only to patients with mood disorders. Conclusions: Among mood disorder patients, comorbid PDs increase the risk of SAs to approximately two-fold. The excess risk is mostly due to patients with comorbid PDs spending more time in depressive episodes than those without. Consequently, risk appears highest for PDs that most predispose to chronicity and recurrences. However, also direct risk-modifying effects of PDs exist. (C) 2015 Elsevier B.V. All rights reserved.Peer reviewe