Kirsi Suominen

DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder.

Disrupted in schizophrenia 1 (DISC1) has been associated with risk of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, autism and Asperger syndrome, but apart from in the original translocation family, true causal variants have yet to be confirmed. Here we report a harmonized association study for DISC1 in European cohorts of schizophrenia and bipolar disorder. We identify regions of significant association, demonstrate allele frequency heterogeneity and provide preliminary evidence for modifying interplay between variants. Whereas no associations survived permutation analysis in the combined data set, significant corrected associations were observed for bipolar disorder at rs1538979 in the Finnish cohorts (uncorrected P=0.00020; corrected P=0.016; odds ratio=2.73±95% confidence interval (CI) 1.42–5.27) and at rs821577 in the London cohort (uncorrected P=0.00070; corrected P=0.040; odds ratio=1.64±95% CI 1.23–2.19). The rs821577 single nucleotide polymorphism (SNP) showed evidence for increased risk within the combined European cohorts (odds ratio=1.27±95% CI 1.07–1.51), even though significant corrected association was not detected (uncorrected P=0.0058; corrected P=0.28). After conditioning the European data set on the two risk alleles, reanalysis revealed a third significant SNP association (uncorrected P=0.00050; corrected P=0.025). This SNP showed evidence for interplay, either increasing or decreasing risk, dependent upon the presence or absence of rs1538979 or rs821577. These findings provide further support for the role of DISC1 in psychiatric illness and demonstrate the presence of locus heterogeneity, with the effect that clinically relevant genetic variants may go undetected by standard analysis of combined cohorts.

Determinants and Outcomes of Serious Attempted Suicide: A Nationwide Study in Finland, 1996–2003

Suicide is among the 10 leading causes of death. Attempted suicide is 10-40 times more frequent than completed suicide and is the strongest single predictor of subsequent suicide. The current study population included all persons in Finland who were hospitalized with a diagnosis of attempted suicide between 1996 and 2003 (N = 18,199). Information on background variables and mortality was obtained by register linkage. The risk of repeated attempted suicide was 30% and the risk of suicide was 10%. The risks of repeated attempted suicide, completed suicide, and death from any cause were high immediately after discharge from the hospital. Analysis of competing causes of death revealed that while alcohol-related disorder was not associated with suicide, it markedly increased the risk of other violent death: The subdistribution hazards rate (SHR) was 2.61 (95% confidence interval (CI): 2.12, 3.21). Schizophrenia-related disorders (SHR = 1.87, 95% CI: 1.57, 2.21) and mood disorders (SHR = 1.72, 95% CI: 1.47, 2.01) were associated with the risk of suicide. The risks of suicide and all-cause mortality were extremely high immediately after hospitalization for attempted suicide.

Breakdown of Long-Range Temporal Correlations in Theta Oscillations in Patients with Major Depressive Disorder

Neuroimaging has revealed robust large-scale patterns of high neuronal activity in the human brain in the classical eyes-closed wakeful rest condition, pointing to the presence of a baseline of sustained endogenous processing in the absence of stimulus-driven neuronal activity. This baseline state has been shown to differ in major depressive disorder. More recently, several studies have documented that despite having a complex temporal structure, baseline oscillatory activity is characterized by persistent autocorrelations for tens of seconds that are highly replicable within and across subjects. The functional significance of these long-range temporal correlations has remained unknown. We recorded neuromagnetic activity in patients with a major depressive disorder and in healthy control subjects during eyes-closed wakeful rest and quantified the long-range temporal correlations in the amplitude fluctuations of different frequency bands. We found that temporal correlations in the theta-frequency band (3-7 Hz) were almost absent in the 5-100 s time range in the patients but prominent in the control subjects. The magnitude of temporal correlations over the left temporocentral region predicted the severity of depression in the patients. These data indicate that long-range temporal correlations in theta oscillations are a salient characteristic of the healthy human brain and may have diagnostic potential in psychiatric disorders. We propose a link between the abnormal temporal structure of theta oscillations in the depressive patients and the systems-level impairments of limbic-cortical networks that have been identified in recent anatomical and functional studies of patients with major depressive disorder.

Level of suicidal intent predicts overall mortality and suicide after attempted suicide: a 12-year follow-up study

BackgroundThe aim of this study was to comprehensively examine clinical risk factors, including suicide intent and hopelessness, for suicide and risk of death from all causes after attempted suicide over a 12-year follow-up period.MethodsA systematic sample of 224 patients from consecutive cases of attempted suicide referred to health care in four Finnish cities between 1 January and 31 July 1990 was interviewed.ResultsAfter 12 years of follow-up 22% of these patients had died, 8% by committing suicide. The only statistically significant risk factor for eventual suicide was high scores on Becks Suicidal Intention Scale. Male gender, older age, physical illness or disability and high scores on Becks Suicidal Intention Scale predicted death overall.ConclusionsFollowing attempted suicide, high intention to kill oneself is a significant risk factor for both death from all causes and suicide.

The Mood Disorder Questionnaire improves recognition of bipolar disorder in psychiatric care

BackgroundWe investigated our translation of The Mood Disorder Questionnaire (MDQ) as a screening instrument for bipolar disorder in a psychiatric setting in Finland.MethodsIn a pilot study for the Jorvi Bipolar Study (JoBS), 109 consecutive non-schizophrenic psychiatric out- and inpatients in Espoo, Finland, were screened for bipolar disorder using the Finnish translation of the MDQ, and 38 of them diagnostically interviewed with the SCID.ResultsForty subjects (37%) were positive in the MDQ screen. In the SCID interview, twenty patients were found to suffer from bipolar disorder, of whom seven (70%) of ten patients with bipolar I but only two (20%) of ten with bipolar II disorder had been previously clinically correctly diagnosed. The translated MDQ was found internally consistent (alpha 0.79) and a feasible screening tool.ConclusionsBipolar disorder, particularly type II, remains commonly unrecognized in psychiatric settings. The Mood Disorder Questionnaire is a feasible screen for bipolar disorder, which could well be integrated into psychiatric routine practice.

Differences in incidence of suicide attempts during phases of bipolar I and II disorders.

BACKGROUND Differences in the incidence of suicide attempts during various phases of bipolar disorder (BD), or the relative importance of static versus time-varying risk factors for overall risk for suicide attempts, are unknown. METHODS We investigated the incidence of suicide attempts in different phases of BD as a part of the Jorvi Bipolar Study (JoBS), a naturalistic, prospective, 18-month study representing psychiatric in- and outpatients with DSM-IV BD in three Finnish cities. Life charts were used to classify time spent in follow-up in the different phases of illness among the 81 BD I and 95 BD II patients. RESULTS Compared to the other phases of the illness, the incidence of suicide attempts was 37-fold higher [95% confidence interval (CI) for relative risk (RR): 11.8-120.3] during combined mixed and depressive mixed states, and 18-fold higher (95% CI: 6.5-50.8) during major depressive phases. In Coxs proportional hazards regression models, combined mixed (mixed or depressive mixed) or major depressive phases and prior suicide attempts independently predicted suicide attempts. No other factor significantly modified the risks related to these time-varying risk factors; their population-attributable fraction was 86%. CONCLUSIONS The incidence of suicide attempts varies remarkably between illness phases, with mixed and depressive phases involving the highest risk by time. Time spent in high-risk illness phases is likely the major determinant of overall risk for suicide attempts among BD patients. Studies of suicidal behavior should investigate the role of both static and time-varying risk factors in overall risk; clinically, management of mixed and depressive phases may be crucial in reducing risk.

Differences in outcome of DSM-IV bipolar I and II disorders.

OBJECTIVES To investigate whether the course of bipolar disorder (BD) type II is more depressive than that of BD I, and, if so, to explore the underlying factors that cause this difference. METHODS In a prospective, naturalistic study of 191 secondary care psychiatric in- and outpatients diagnosed in an acute phase of BD I or II, 160 patients (85.1%) were followed for 18 months. Using a life chart, the exact timing of symptom states in follow-up was examined. Differences between BD I (n = 75) and II (n = 85) in duration of index phase and episode, time to full remission and recurrence, and time in any mood episode were investigated. RESULTS Patients with BD II spent a higher proportion of time ill (47.5% versus 37.7%; p = 0.02) and in depressive symptom states (58.0% versus 41.7%; p = 0.003) than BD I patients. This was a result of the higher proportion (61.7% versus 48.6%; p = 0.03) and mean number (1.69 versus 1.11; p = 0.006) of depressive illness phases in BD II, rather than of differences in the duration of depressive phases. Type of index phase strongly predicted the outcome. In linear regression models, both BD II and type of index phase predicted more time spent in depressive symptom states. CONCLUSIONS In medium-term follow-up, BD II patients spend about 40% more time in depressive symptom states than BD I patients because a higher proportion of BD II patients have depressive phases and the frequency of these is higher. Differences in type of index phase may markedly confound differences in outcome between BD I and II.

P2RX7 gene is associated consistently with mood disorders and predicts clinical outcome in three clinical cohorts

We investigated the effect of nine candidate genes on risk for mood disorders, hypothesizing that predisposing gene variants not only elevate the risk for mood disorders but also result in clinically significant differences in the clinical course of mood disorders. We genotyped 178 DSM‐IV bipolar I and II and 272 major depressive disorder patients from three independent clinical cohorts carefully diagnosed with semistructured interviews and prospectively followed up with life charts for a median of 60 (range 6–83) months. Healthy control subjects (n = 1322) were obtained from the population‐based national Health 2000 Study. We analyzed 62 genotyped variants within the selected genes (BDNF, NTRK2, SLC6A4, TPH2, P2RX7, DAOA, COMT, DISC1, and MAOA) against the presence of mood disorder, and in post‐hoc analyses, specifically against bipolar disorder or major depressive disorder. Estimates for time ill were based on life charts. The P2RX7 gene variants rs208294 and rs2230912 significantly elevated the risk for a familial mood disorder (OR = 1.35, P = 0.0013, permuted P = 0.06, and OR = 1.44, P = 0.0031, permuted P = 0.17, respectively). The results were consistent in all three cohorts. The same risk alleles predicted more time ill in all cohorts (OR 1.3, 95% CI 1.1–1.6, P = 0.0069 and OR 1.7, 95% CI 1.3–2.3, P = 0.0002 with rs208294 and rs2230912, respectively), so that homozygous carriers spent 12 and 24% more time ill. P2RX7 and its risk alleles predisposed to mood disorders consistently in three independent clinical cohorts. The same risk alleles resulted in clinically significant differences in outcome of patients with major depressive and bipolar disorder.

Substance use and male gender as risk factors for deaths and suicide: A 5-year follow-up study after deliberate self-harm

The aim of this study was to determine the mortality by suicide and other causes of death in a cohort of suicide attempters and identify predictive factors, including contact to healthcare after the attempt. All consecutive 1198 deliberate self-harm patients treated in hospital emergency rooms in Helsinki during a 12-month period were identified. Data were gathered on healthcare contacts preceding and following the index attempt, and cause-specific mortality over a 5- year period. By the end of the 5-year follow-up period, 171 (14%) of the patients had died. A total of 57 (5 %) had committed suicide. The age- and sex-adjusted risk for suicide among deliberate self-harm patients was 40-fold, and for death overall tenfold, compared to general population during the 5-year follow-up period. Risk factors for subsequent suicide were a diagnosis of substance use disorder, male gender and previous suicide attempts. A diagnosis of substance use disorder and male gender predicted death. Furthermore, male gender and substance use disorders had a strong interaction for both classes of death. The findings of this study suggest that deliberate self-harm patients have a high risk for both suicide and other causes of death. Male gender and substance use disorders are significant risk factors for both later suicide and other causes of death. Male suicide attempters with substance use disorders have remarkably high total and suicide mortality.

General hospital suicides—a psychological autopsy study in finland

Although both severe medical disorders and mental disorders are established risk factors for suicide, it is not known if patients who commit suicide in general hospitals differ from others. This study investigated current mental disorders and other clinical characteristics among general hospital suicide victims and compared them with other suicide victims in an unselected nationwide population. Drawing on data from a psychological autopsy study of all suicides (N = 1397) in Finland during one year, all suicides committed by patients in a general hospital setting were identified. Retrospective DSM-III-R consensus diagnoses were assigned and general hospital suicide victims were compared with other suicide completers in terms of clinical characteristics. Twenty-six general hospital suicide victims, 1.9% of all suicides, were identified. Subjects who completed suicide during general hospital treatment were older and used more violent suicide methods than other suicide victims. One or more diagnoses of psychiatric (Axis I) disorders were assigned for 88% of the general hospital suicide victims. Overall, the most prevalent disorder was major depression, which was more common among the general hospital suicide victims, even when age was controlled for. The findings of this study suggest that most people who commit suicide during a spell of general hospital treatment suffer from current mental disorder, as do suicide victims in general. The recognition and treatment of major depression in particular should be improved in order to prevent suicide in general hospitals.