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BACKGROUND AND PURPOSE The aim of this study was to define the prevalence of pre-eclampsia, gestational hypertension (HT), chronic HT, and gestational diabetes during pregnancy in a defined population of patients with saccular intracranial aneurysms (sIAs). METHODS We included all patients with sIA, first admitted to the Neurosurgery Department of Kuopio University Hospital from its defined catchment population between 1990 and 2015, who had given birth for the first time in 1990 or later. The patients' medical records were reviewed, and clinical data were linked with prescription drug usage, hospital diagnoses and causes of death, obtained from nationwide registries. The prevalences of pre-eclampsia, other hypertensive disorders and gestational diabetes in patients were compared with a matched control population (n = 324). In addition, the characteristics of sIA disease in patients with pre-eclampsia were compared to those of sIA patients without pre-eclampsia. RESULTS A total of 169 patients with sIA fulfilled the inclusion criteria. Of these, 22 (13%) had pre-eclampsia and 32 (19%) had other hypertensive disorders during pregnancy. In 324 matched controls who had given birth, the prevalence of pre-eclampsia was 5% (n = 15) and other hypertensive disorders were diagnosed in 10% (n = 34). There was no significant difference in prevalence of gestational diabetes (12% vs. 11%). Patients with sIA with pre-eclampsia more frequently had irregularly shaped aneurysms (p = 0·003). CONCLUSIONS Pre-eclampsia was significantly more frequent in patients with sIA than in their population controls. Irregularly shaped aneurysms were more frequent in sIA patients with pre-eclampsia. Further studies are required to determine whether history of pre-eclampsia may indicate an elevated risk for sIA formation or rupture.

Objective To characterize surgical treatment and outcomes of C1 fractures in a population-based setup. Methods Patients with C1 fracture treated at Kuopio University Hospital Neurosurgery were retrospectively identified from January 1996 to June 2017. C1 fractures were classified according to the AO Spine Upper Cervical and Gehweiler classification systems. Patients were divided into 4 groups based on their treatment: group 1 (underwent C1 surgery as a primary option), group 2 (underwent C1 surgery as a secondary option after initial nonoperative treatment), group 3 (underwent surgery involving the C1 level with main indication being a concomitant cervical spine fracture), and group 4 (C1 fracture treatment was nonoperative). Results We identified 47 patients with C1 fracture (mean age, 60.3 ± 18.2 years; 83.0% men; American Society of Anesthesiologists score, 2.3 ± 0.8). Concomitant cervical spine fractures were present in 89.4% of cases, most commonly in the C2 vertebra (75.4%). In group 2, 3 of 5 fractures changed from AO Spine type A to B in control imaging after nonoperative treatment, indicating fracture instability and requiring secondary surgery. Good C1 fracture alignment was achieved for 10 of 10 followed-up patients in groups 1 and 2, and for 10 of 11 followed-up patients in group 3. Residual neck pain and stiffness were present in all groups. Neurologic symptoms were rare and mild. Conclusions For unstable C1 fractures, surgery is safe treatment with good outcomes. Fractures initially determined as stable may require surgery if alignment is worsened in follow-up imaging. Magnetic resonance imaging is recommended to better detect unstable C1 fractures in diagnostic imaging.

Anxiety disorders are the most common mental disorders in children and youth. Effective screening methods are needed to identify children in need of treatment. The Screen for Child Anxiety Related Emotional Disorders (SCARED) questionnaire is a widely used tool to assess childhood anxiety. We aim toevaluate the psychometric properties of the SCARED questionnaire, test the SCARED factor structure, and evaluate the prevalence of anxiety symptoms in a community sample of Finnish elementary school children, based on both a child and parent report. The sample included all pupils (n = 1,165) in grades 2 through 6 (ages 8-13) in four elementary schools in the city of Turku, Finland. Children completed a Finnish translation of the SCARED questionnaire at school, with one parent report questionnaire per child completed at home. In total, 663 child-parent dyads (56.9%) completed the questionnaire. Internal consistency was high for both child and parent reports on all subscales (0.71-0.92), except for school avoidance (0.57 child, 0.63 parent report). Inter-rater reliability ranged from poor to fair across subscales (intraclass correlation 0.27-0.47). Self-reported anxiety scores were higher than the parent reported scores. Females had significantly higher total scores than males based on the child reports (p = 0.003), but not the parent reports. In the confirmatory factor analysis, hypothesized models did not have a good fit with the data, and modification was needed. The Finnish SCARED questionnaire has good internal consistency. Low child-parent agreement calls for the importance of including both child and parental reports in the assessment of anxiety symptoms.

Objective: We conducted an open-label cross-over study assessing the global effect of two high-frequency protocols of electric-field navigated repetitive transcranial magnetic stimulation (rTMS) targeted to functional facial motor cortex and comparing their efficacy and tolerability in patients with chronic facial pain. Outcome predictors were also assessed. Methods: We randomized twenty consecutive patients with chronic facial pain (post-traumatic trigeminal neuropathic pain, n=14; persistent idiopathic facial pain, n=4; secondary trigeminal neuralgia, n=2) to receive two distinct 5-day rTMS interventions (10Hz, 2400 pulses and 20Hz, 3600 pulses) separated by six weeks. The target area was assessed by mapping of lower face representation. The primary endpoint was the change in weekly mean of pain intensity (numeric rating scale, NRS) between the baseline and therapy week (1st week), and follow-up weeks (2nd and 3rd weeks) for each rTMS intervention. Response was defined using a combination scale including the patient’s global impression of change and continuance with maintenance treatment. Results: Overall, pain intensity NRS decreased from 7.4 at baseline to 5.9 ten weeks later, after the second rTMS intervention (p=0.009). The repetition of the treatment had a significant effect (F=4.983, p=0.043) indicating that the NRS scores are lower during the second four weeks period. Eight (40%) patients were responders, 4 (20%) exhibited a modest effect, 4 (20%) displayed no effect, and 4 (20%) experienced worsening of pain. High disability and high pain intensity (>7) predicted a better outcome (p=0.043 and p=0.045). Female gender, shorter duration of pain and low Beck Anxiety Inventory scores showed a trend towards a better outcome (p=0.052, 0.060 and 0.055, respectively). Conclusions: High-frequency rTMS targeted to face M1 alleviates treatment resistant chronic facial pain. Repeated treatment improves the analgesic effect. A protocol with higher frequency (above 10Hz), longer session duration (more than 20 minutes) and higher number of pulses (above 2400 pulses/session) did not improve the outcome. The results support early consideration of rTMS.

The purpose of this population-based case-control study was to evaluate analgesic use after subarachnoid hemorrhage (SAH) caused by rupture of a saccular intracranial aneurysm (sIA).The study consisted of 1187 patients alive 12 months after an sIA-SAH who were admitted to Kuopio University Hospital (KUH) between 1995 and 2014. Three controls, matched with age, sex, and birthplace, were included for each patient. Data on ruptured sIA cases admitted to KUH from a defined catchment population in Eastern Finland were obtained from the KUH intracranial aneurysm database. Analgesics were classified according to the Anatomical Therapeutic Chemical Classification system. Data on analgesic medication were retrieved from the Finnish national registry of prescribed medicines of the Social Insurance Institution of Finland.Among 1187 patients with sIA-SAH who were alive 12 months after admission, 83 (7.0%) commenced analgesics use within 12 months after the sIA-SAH versus 53 (1.5%) of the 3561 population controls. The results revealed significantly greater initiation rate of analgesic use among patients with sIA-SAH within a year after sIA-SAH as compared with that of matched population controls (odds ratio 5.0; 95% confidence interval 3.5-7.0; P0.001). Analgesic use commencement within 12 months of an sIA-SAH was independently associated with the presence of an intracerebral hematoma. Among patients, commencing analgesic use increased 11% when we compared a year before and a year after sIA-SAH.Our results indicate that patients with sIA-SAH had an increased risk for new pain after sIA-SAH as compared with that of matched control population.

Background To study the clinical condition of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients alive at 3 years after neurointensive care. Methods Of the 769 consecutive aSAH patients from a defined population (2005–2015), 269 (35%) were in poor condition on admission: 145 (54%) with H&H 4 and 124 (46%) with H&H 5. Their clinical lifelines were re-constructed from the Kuopio Intracranial Aneurysm Database and Finnish nationwide registries. Of the 269 patients, 155 (58%) were alive at 14 days, 125 (46%) at 12 months, and 120 (45%) at 3 years. Results The 120 H&H 4–5 patients alive at 3 years form the final study population. On admission, 73% had H&H 4 but only 27% H&H 5, 59% intracerebral hematoma (ICH; median 22 cm3), and 26% intraventricular blood clot (IVH). The outcome was favorable (mRS 0–1) in 45% (54 patients: ICH 44%; IVH clot 31%; shunt 46%), moderate (mRS 2–3) in 30% (36 patients: ICH 64%; IVH clot 19%; shunt 42%), and unfavorable (mRS 4–5) in 25% (30 patients: ICH 80%; IVH clot 23%; shunt 50%). A total of 46% carried a ventriculoperitoneal shunt. ICH volume was a significant predictor of mRS at 3 years. Conclusions Of poor-grade aSAH patients, 45% were alive at 3 years, even 27% of those extending to pain (H&H 5). Of the survivors, 75% were at least in moderate condition, while only 2.6% ended in hospice care. Consequently, we propose non-selected admission to neurointensive care (1) for a possibility of moderate outcome, and (2), in case of brain death, possibly improved organ donation rates.

Spinal cord stimulation (SCS) has proven to be a cost-effective treatment for failed back surgery syndrome (FBSS). However, the effect on patients' working capability remains unclear.To evaluate the impact of SCS on working capability and to identify the factors behind permanent disability in FBSS patients.The study group consisted of 198 working-age patients with SCS trialed or implanted for FBSS in a single center between 1996 and 2014. For each patient, 3 living controls, matched by age, gender, and birthplace, were otherwise randomly selected by the Population Register Center. The data on working ability were obtained from the Social Insurance Institution. Patients were divided into 3 groups: SCS trial only, SCS implanted permanently, and SCS implanted but later explanted.A rehabilitation subsidy was given to 68 patients and 8 controls for a mean of 5.2 (95% confidence interval [CI] 2.4-8.2) and 0.2 (95% CI 0.05-0.6) days per month (P .05). At the end of follow-up, 16 (37%), 13 (33%), 25 (22%), and 27 (5%) subjects were on disability pension (DP) in the SCS trial, SCS explanted, SCS permanent, and control groups. Patients in the SCS trial-only group were significantly more often on DP than were patients with permanent SCS (odds ratio 2.6; 95% CI 1.2-5.9; P = .02).Permanent SCS usage was associated with reduced sick leave and DP. Prospective study will be required to assess possible predictive value.

Background To analyze the organ donation action in population-based neurointensive care of acute aneurysmal subarachnoid hemorrhage (aSAH) and to seek factors that would improve the identification of potential organ donors (PODs) and increase the donor conversion rate (DCR) after aSAH. Methods The Kuopio Intracranial Aneurysm Database, prospective since 1995, includes all aSAH patients admitted to the Kuopio University Hospital (KUH) from its defined Eastern Finnish catchment population. We analyzed 769 consecutive acute aSAH patients from 2005 to 2015, including their data from the Finnish Transplantation Unit and the national clinical registries. We analyzed PODs vs. actual donors among the 145 (19%) aSAH patients who died within 14 days of admission. Finland had implemented the national presumed consent (opt-out) within the study period in the end of 2010. Results We retrospectively identified 83 (57%) PODs while only 49 (34%) had become actual donors (total DCR 59%); the causes for non-donorship were 15/34 (44%) refusals of consent, 18/34 (53%) medical contraindications for donation, and 1/34 (3%) failure of recognition. In 2005–2010, there were 11 refusals by near relatives with DCR 52% (29/56) and only three in 2011–2015 with DCR 74% (20/27). Severe condition on admission (Hunt and Hess grade IV or V) independently associated with the eventual POD status. Conclusions Nearly 20% of all aSAH patients acutely admitted to neurointensive care from a defined catchment population died within 14 days, almost half from cardiopulmonary causes at a median age of 69 years. Of all aSAH patients, 11% were considered as potential organ donors (PODs). Donor conversion rate (DCR) was increased from 52 to 74% after the national presumed consent (opt-out). Implicitly, DCR among aSAH patients could be increased by admitting them to the intensive care regardless of dismal prognosis for the survival, along a dedicated organ donation program for the catchment population.

Background Failed back surgery syndrome (FBSS) is a challenging condition that lacks a curative treatment. In selected patients, spinal cord stimulation (SCS) has provided a satisfactory outcome. Objective To evaluate the long-term outcome of SCS in FBSS, as measured by (1) the explantation rate, (2) complications, and (3) patient satisfaction with the global perceived effect (GPE). Methods We studied 224 consecutive FBSS patients who underwent an SCS trial with surgically implanted leads at our hospital between January 1996 and December 2014. The patients' satisfaction with the GPE of treatment was measured through a postal questionnaire at the end of follow-up. Results Based on a 1-wk trial, permanent SCS was implanted in 175 (78%) patients. Out of these patients, 153 (87%) reported satisfactory outcomes after 2 mo. During the mean follow-up of 6 yr, 34 (19%) of SCS devices were permanently explanted due to inadequate pain relief, and 11 (6%) were explanted for other reasons.Electrode revision due to inadequate pain relief was done for 22 patients. In total, 26 complications were reported due to: 7 deep infections, 11 hardware malfunctions, 1 subcutaneous hematoma, 4 instances of discomfort due to the pulse generator, and 3 electrode migrations.One hundred thirty patients (74%) continued with SCS until the end of follow-up. Of them, 61 (47%) returned the questionnaire, and 42 (69%) reported substantially improved or better GPE. Conclusion SCS can provide a good outcome in the treatment of FBSS. Patient selection could be further improved by developing novel predictive biomarkers.

Objective:To define the association of autosomal dominant polycystic kidney disease (ADPKD) with the characteristics of aneurysmal subarachnoid hemorrhage (aSAH) and unruptured intracranial aneurysm (IA) disease.Methods:We fused data from the Kuopio Intracranial Aneurysm database (n = 4,436 IA patients) and Finnish nationwide registries into a population-based series of 53 IA patients with ADPKD to compare the aneurysm- and patient-specific characteristics of IA disease in ADPKD and in the general IA population, and to identify risks for de novo IA formation.Results:In total, there were 33 patients with ADPKD with aSAH and 20 patients with ADPKD with unruptured IAs. The median size of ruptured IAs in ADPKD was significantly smaller than in the general population (6.00 vs 8.00 mm) and the proportion of small ruptured IAs was significantly higher (31% vs 18%). Median age at aSAH was 42.8 years, 10 years younger than in the general IA population. Multiple IAs were present in 45% of patients with ADPKD compared to 28% in the general IA population. Cumulative risk of de novo IA formation was 1.3% per patient-year (vs 0.2% in the general IA population). Hazard for de novo aneurysm formation was significantly elevated in patients with ADPKD (Cox regression hazard ratio 7.7, 95% confidence interval 2.8–20; p < 0.0005).Conclusions:Subarachnoid hemorrhage occurs at younger age and from smaller IAs in patients with ADPKD and risk for de novo IAs is higher than in the general Eastern Finnish population. ADPKD should be considered as an indicator for long-term angiographic follow-up in patients with diagnosed IAs.

Background Varying degrees of co‐occurrence of intracranial aneurysms ( IA ) and aortic aneurysms ( AA ) have been reported. We sought to compare the risk for AA in fusiform intracranial aneurysms ( fIA ) and saccular intracranial aneurysms ( sIA ) disease and evaluate possible genetic connection between the fIA disease and AA s. Additionally, the characteristics and aneurysms of the fIA and sIA patients were compared. Methods and Results The Kuopio Intracranial Aneurysm Database includes all 4253 sIA and 125 fIA patients from its Eastern Finnish catchment population, and 13 009 matched population controls and 18 455 first‐degree relatives to the IA patients were identified, and the Finnish national registers were used to identify the individuals with AA . A total of 33 fIA patients were studied using an exomic gene panel of 37 genes associated with AA s. Seventeen (14.4%) fIA patients and 48 (1.2%) sIA patients had a diagnosis of AA . Both fIA and sIA patients had AA s significantly more often than their controls (1.2% and 0.5%) or relatives (0.9% and 0.3%). In a competing risks Cox regression model, the presence of fIA was the strongest risk factor for AA (subdistribution hazard ratio 7.6, 95% CI 3.9–14.9, P COL 5A2 and 3 variants of unknown significance were identified in MYH 11 , COL 11A1 , and FBN 1 in 4 fIA patients. Conclusions The prevalence of AA s is increased slightly in sIA patients and significantly in fIA patients. fIA patients are older and have more comorbid diseases than sIA patients but this alone does not explain their clinically significant AA risk.

Background and Purpose- At acute phase and neurointensive care, patients with aneurysmal subarachnoid hemorrhage (aSAH) may become agitated or delirious. We found no previous studies on psychotic disorders or antipsychotic drug (APD) use by long-term aSAH survivors. We defined the APD use and its risk factors among 12-month survivors of aSAH in an Eastern Finnish population-based cohort with long-term follow-up. Methods- We analyzed APD use in 1144 consecutive patients with aSAH alive at 12 months of the Kuopio intracranial aneurysm patient and family database and their age, sex, and birth municipality matched controls (3:1; n=3432) from 1995 to 2013 and median follow-up of 9 years. Using the Finish nationwide health registries, we obtained drug purchase and hospital discharge data. Results- In total, 140 (12%) of the 1144 patients started APD use first time after aSAH (index date), in contrast to 145 (4%) of the 3432 matched population controls. The cumulative rate of starting APD was 6% at 1 year and 9% at 5 years, in contrast to 1% and 2% in the controls, respectively. The rates at 1 and 5 years were only 1% and 2% in the 489 patients with a good condition (modified Rankin Scale score, 0 or 1 at 12 months; no shunt, intracerebral hemorrhage, or intraventricular hemorrhage). Instead, the highest rate of APD use, 23% at 5 years was among the 192 patients shunted for hydrocephalus after aSAH. Eighty-eight (63%) of the 140 aSAH patients with APD use had also concomitant antidepressant or antiepileptic drug use. Conclusions- The 12-month survivors of aSAH were significantly more likely to be started on APD after aSAH than their matched population controls. These patients often used antidepressant and antiepileptic drugs concomitantly. The use of APDs strongly correlated with signs of brain injury after aSAH, with low use if no signs of significant brain injury were present.

Background and Purpose— Shunt dependent hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH) is a common sequela that may lead to poor neurological outcome and predisposes to various interventions, admissions, and complications. We reviewed post-aSAH shunt dependency in a population-based sample and tested the feasibility of a clinical risk score to identify subgroups of aSAH patients with increasing risk of shunting for hydrocephalus. Methods— A total of 1533 aSAH patients from the population-based Eastern Finland Saccular Intracranial Aneurysm Database (Kuopio, Finland) were used in a recursive partitioning analysis to identify risk factors for shunting after aSAH. The risk model was built and internally validated in random split cohorts. External validation was conducted on 946 aSAH patients from the Southwestern Tertiary Aneurysm Registry (Dallas, TX) and tested using receiver-operating characteristic curves. Results— Of all patients alive ≥14 days, 17.7% required permanent cerebrospinal fluid diversion. The recursive partitioning analysis defined 6 groups with successively increased risk for shunting. These groups also successively risk stratified functional outcome at 12 months, shunt complications, and time-to-shunt rates. The area under the curve–receiver-operating characteristic curve for the exploratory sample and internal validation sample was 0.82 and 0.78, respectively, with an external validation of 0.68. Conclusions— Shunt dependency after aSAH is associated with higher morbidity and mortality, and prediction modeling of shunt dependency is feasible with clinically useful yields. It is important to identify and understand the factors that increase risk for shunting and to eliminate or mitigate the reversible factors. The aSAH-PARAS Consortium (Aneurysmal Subarachnoid Hemorrhage Patients’ Risk Assessment for Shunting) has been initiated to pool the collective insights and resources to address key questions in post-aSAH shunt dependency to inform future aSAH treatment guidelines.

Background and Purpose— To elucidate the predictors of antidepressant use after subarachnoid hemorrhage from saccular intracranial aneurysm (sIA-SAH) in a population-based cohort with matched controls. Methods— The Kuopio sIA database includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland, with 3 matched controls for each patient. The use of all prescribed medicines has been fused from the Finnish national registry of prescribed medicines. In the present study, 2 or more purchases of antidepressant medication indicated antidepressant use. The risk factors of the antidepressant use were analyzed in 940 patients alive 12 months after sIA-SAH, and the classification tree analysis was used to create a predicting model for antidepressant use after sIA-SAH. Results— The 940 12-month survivors of sIA-SAH had significantly more antidepressant use (odds ratio, 2.6; 95% confidence interval, 2.2–3.1) than their 2676 matched controls (29% versus 14%). Classification tree analysis, based on independent risk factors, was used for the best prediction model of antidepressant use after sIA-SAH. Modified Rankin Scale until 12 months was the most potent predictor, followed by condition (Hunt and Hess Scale) and age on admission for sIA-SAH. Conclusions— The sIA-SAH survivors use significantly more often antidepressants, indicative of depression, than their matched population controls. Even with a seemingly good recovery (modified Rankin Scale score, 0) at 12 months after sIA-SAH, there is a significant risk of depression requiring antidepressant medication.

Background and Purpose— Formation of new (de novo) aneurysms in patients carrying saccular intracranial aneurysm (sIA) disease has been published, but data from population-based cohorts are scarce. Methods— Kuopio sIA database ( http://www.uef.fi/ns ) contains all unruptured and ruptured sIA patients admitted to Kuopio University Hospital from its Eastern Finnish catchment population. We studied the incidence and risk factors for de novo sIA formation in 1419 sIA patients with ≥5 years of angiographic follow-up, a total follow-up of 18 526 patient-years. Results— There were 42 patients with a total of 56 de novo sIAs, diagnosed in a median of 11.7 years after the first sIA diagnosis. The cumulative incidence of de novo sIAs was 0.23% per patient-year and that of subarachnoid hemorrhage from a ruptured de novo sIA 0.05% per patient-year. The risk of de novo sIA discovery per patient-year increased with younger age at the first sIA diagnosis: 2.2% in the patients aged Conclusions— Patients aged < 40 years at the first sIA diagnosis are in a significant risk of developing de novo sIAs, and they should be scheduled for long-term angiographic follow-up. Smoking increases the risk of de novo sIA formation, suggesting long-term follow-up for smokers. Antismoking efforts are highly recommended for sIA patients.

AIM: There are few population-based studies on bullying behaviour among preschool children. The aims of the study were to investigate the prevalence of bullying behaviour among four-year-old children, as reported by their parents, the prevalence of types of bullying behaviour and the associations between bullying behaviour and psychosocial factors. METHODS: This study was based on a population-based study sample of 931 children who attended their check-up at a child health clinic at four years of age. Parents completed the questionnaire about their child's bullying behaviour and risk factors during the check-up. RESULTS: Bullying behaviour, especially being both a bully and a victim, was a common phenomenon among four-year-old children. Being a bully or both a bully and victim were most strongly associated with conduct problems, while being a victim was associated with somatic symptoms and peer problems. CONCLUSION: Bullying behaviour was frequently found in preschool children and associated with a wide range of other problems, which indicate that routine checking of bullying behaviour should be included in child health clinic check-ups. Bullying prevention programmes are usually targeted at school-aged children, but this study highlights the importance of focusing already on preschool children. This article is protected by copyright. All rights reserved. Language: en

Recent studies have shown an increasing incidence of attention-deficit/hyperactivity disorder (ADHD) among children diagnosed in specialized services. This study aims to describe children with ADHD in Finnish specialized healthcare by reporting the demographic characteristics, time trends in diagnosis, psychiatric comorbidity, and the validity of register-based diagnoses. All the singletons born in Finland between 1991 and 2005 and diagnosed with ADHD by 2011 were identified and their psychiatric comorbidity data was obtained from the Finnish Hospital Discharge Register (FHDR). Parents of 69 patients were interviewed via telephone for a diagnostic validation. A total of 10,409 children were identified with ADHD, with a male: female ratio of 5.3:1 and a psychiatric comorbidity rate of 76.7 %. Of the validation sample 88 % met the diagnostic criteria of ADHD for DSM-IV. There is an increasing trend of ADHD diagnosis among both males and females. Psychiatric comorbidity is common and includes a wide range of disorders among children with ADHD. There was an increase of ADHD diagnoses especially among boys. More attention is needed to detect ADHD among girls in health services. Diagnoses in the FHDR show diagnostic validity and their sociodemographic patterns are in line with previous studies.

Background It is not yet definitively known whether dynamic features of head circumference growth are associated with autism. To address this issue, we carried out a nested matched case-control study using data from national well baby clinics in Finland; autism cases were identified from the Finnish Hospital and Outpatient Discharge Registry. Methods A nonparametric Bayesian method was used to construct growth velocity trajectories between birth and 2 years of age in autism cases and matched control subjects ( n = 468 in main analyses, 1:1 matched control subjects). Estimates of odds ratios for autism risk in relation to the growth velocities were obtained using conditional logistic regression. Results Growth velocity of head circumference at 3 months of age, adjusting for gestational age at birth and maternal age, is significantly associated with autism ( p = .014); the finding was observed in subjects with comorbid intellectual disability (ID) ( p = .025) but not in those without ID ( p = .15). Height growth velocity among subjects with autism and without ID is significantly associated with autism at 6 months ( p = .007), and weight growth velocity at 18 months without ID ( p = .02) and 24 months without ID ( p = .042) and with ID ( p = .037). Conclusions Acceleration in head circumference growth is associated with autism with comorbid ID at 3 months but not subsequently. This association is unrelated to acceleration in height and weight, which are not strongly associated with autism until after 6 months.

Animal models and epidemiologic studies suggest that prenatal maternal infection, and sexually transmitted infection (STI) in particular, is associated with an increased risk of schizophrenia in the offspring. However, findings from prior research studies on common infections, including herpes simplex virus type 2 (HSV-2) and Chlamydia trachomatis (C. trachomatis) have been inconsistent. To investigate these associations, we conducted a case-control study nested in the population-based Finnish Prenatal Study of Schizophrenia. Using linked national registries, 963 cases with schizophrenia (ICD-10 F20) or schizoaffective disorder (ICD-10 F25), and 963 matched controls were identified from among all persons born between 1983 and 1998 in Finland. HSV-2 IgG antibody levels were quantified in archived maternal serum samples drawn during pregnancy. Mothers of 16.4% of cases versus 12.6% of controls were HSV-2 seropositive. Mean levels of maternal HSV-2 IgG were marginally higher among cases than controls (index values of 0.98 versus 0.86; p=0.06). The unadjusted odds ratio (OR) of maternal HSV-2 IgG seropositivity was 1.33 (95% confidence interval (CI)=1.03-1.72, p=0.03). Following adjustment for covariates, the relationship was attenuated (OR=1.22, CI=0.93-1.60; p=0.14). In an exploratory analysis of another STI, C. trachomatis antibodies were measured in a subsample of 207 case-control pairs drawn from the cohort. The proportions of subjects that were seropositive and the mean levels of C. trachomatis antibodies were similar for cases and controls. This study does not support a strong association of HSV-2 or C. trachomatis IgG antibodies in maternal serum during early to mid-gestation with the development of schizophrenia in the offspring.

Background Saccular intracranial aneurysm (sIA) growth during follow-up is associated with high risk for subsequent rupture. Finnish patients have been suggested to have higher risk for subarachnoid hemorrhage, but follow-up studies of sIA growth in the Finnish population are scarce. Objective To identify the strongest risk factors for sIA growth in Eastern Finnish population by studying 205 patients with 350 unruptured sIAs with angiographic follow-up imaging. Methods In this population-based cohort study, we included unruptured sIA patients from the Kuopio University Hospital Intracranial Aneurysm Patient and Family database with at least 6 mo of angiographic follow-up after the diagnosis of sIAs. Angiograms were re-evaluated to detect aneurysms with growth of at least 1.0 mm. Cox regression analysis with patient- and aneurysm-related risk factors was used to calculate hazard ratios with 95% confidence intervals for growth. In addition, we tested the diagnostic value of previously introduced PHASES score for the prediction of sIA growth in Eastern Finnish population. Results Of the 350 unruptured aneurysms, 36 (10.3%) showed growth during median follow-up of 1.7 yr and total follow-up of 790 yr. In the multivariate Cox regression analysis, sIA size and location in the middle cerebral artery were significant risk factors for sIA growth. In receiver operator characteristic curves, both PHASES score and sIA size had relatively low areas under the curve. Conclusion Our study indicates that aneurysm size is the strongest risk factor for aneurysm growth in Eastern Finnish population. Further studies are required to identify new risk factors for aneurysm growth.

We describe the epidemiology of crime between ages 15 and 30 in a population-based sample. We received police register data for 5405 males and females, representing the children born in Finland in 1981. We classified crimes into drug, violent, property, traffic, drunk driving, and sexual crimes, excluding minor traffic offenses. Of males, 60% and of females, 25% were registered for offending. For males, prevalence peaked in late adolescence, while for females, there was no peak age. Offending frequency remained stable for male offenders but was lower among adolescent female offenders. All crime types overlapped each other. Crime accumulated: 1% committed 34% of male and 56% of female offenses. In conclusion, the adolescent peak in offending reflects peaking prevalence among males, not females, nor frequency of offending among offenders. The crime problem is focused on two key groups: late adolescent males and the few males and females in whom crime concentrates.

Aim The aim of this study was to describe the characteristics and incidence rates of diagnosed tic disorders in the Finnish Hospital Discharge Register, including changing incidence rates between 1991 and 2010. We also aimed to validate the diagnoses of Tourette's syndrome recorded in the register. Methods Children born between January 1, 1991 and December 31, 2010, who were diagnosed with tic disorders, were identified from the Finnish Hospital Discharge Register (n = 3003). We studied the validity of the Tourette's syndrome diagnoses by reviewing the medical charts of 88 children born since 1997 and carrying out telephone interviews with 55 of their guardians. Results The incidence rates of all diagnosed tic disorders increased during the study period. A comorbid diagnosis of hyperkinetic disorder diagnosis was recorded in 28.2% of the children with Tourette's syndrome, and the validity of the register-based Tourette's syndrome diagnosis was approximately 95%. Conclusion This is the first nationwide study to demonstrate the increasing incidence of all register-based tic disorder diagnoses. The validity of the Tourette's syndrome diagnoses in the Finnish Hospital Discharge Register was good, and the data provided are suitable for use in further register-based studies of tic disorders.

This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical biopsy.Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain.[18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-β levels contralateral (r = 0.86, P 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003).[18F]Flutemetamol detects brain amyloid-β in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-β pathology, both in patients with possible NPH and among the wider population.

Objective: To elucidate the epilepsy-associated causes of death and subsequent excess long-term mortality among 12-month survivors of subarachnoid hemorrhage from saccular intracranial aneurysm (SIA-SAH). Methods: The Kuopio SIA Database (kuopioneurosurgery.fi) includes all SIA-SAH patients admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland. The study cohort consists of 779 patients, admitted from 1995 to 2007, who were alive at 12 months after SIA-SAH. Their use of reimbursable antiepileptic drugs and the causes of death (ICD-10) were fused from the Finnish national registries from 1994 to 2014. Results: The 779 12-month survivors were followed up until death (n = 197) or December 31, 2014, a median of 12.0 years after SIA-SAH. Epilepsy had been diagnosed in 121 (15%) patients after SIA-SAH, and 34/121 (28%) had died at the end of follow-up, with epilepsy as the immediate cause of death in 7/34 (21%). In the 779 patients alive at 12 months after SIA-SAH, epilepsy was an independent risk factor for mortality (hazard ratio 1.8, 95% confidence interval 1.1–3.0). Conclusions: Comorbid epilepsy in 12-month survivors of SIA-SAH is associated with increased risk of death in long-term follow-up. Survivors of SIA-SAH require long-term dedicated follow-up, including identification and effective treatment of comorbid epilepsy to prevent avoidable deaths., published version, peerReviewed

This article presents an overview of the Finnish Prenatal Study of Autism and Autism Spectrum Disorders (FIPS-A), a new study designed to examine the relationship between prenatal serologic factors, mediating and moderating developmental antecedents, and risk of autism spectrum disorders (ASD). The FIPS-A is based on register linkages between births from 1987 to 2005 ascertained from the Finnish Medical Birth Register (FMBR) and other national registers on treatment for this group of disorders. All subjects were members of the Finnish Maternity Cohort (FMC), which consists of virtually all births in Finland from 1983 to the present, and which includes archived maternal serum samples. This study also capitalizes on other registry information, such as systematically collected data on pregnancy, prenatal and neonatal complications and manual data collection from well-child clinics providing developmental data from birth to the age of 7 years. In this paper, we describe the methods used in the FIPS-A study, including a description of the national registers, available data and case ascertainment procedures. Finally, we discuss implications of the data for future work on uncovering putative aetiologies of ASD and key strengths and limitations of the design.

Background Secondary hypertension is a serious form of hypertension, involving 5% to 10% of all hypertension patients. Hypertension is a risk factor of the saccular intracranial aneurysm (sIA) disease and subarachnoid hemorrhage from ruptured sIA (aSAH), but the impact of secondary hypertension on sIA disease is poorly known. In a defined Eastern Finnish sIA population we studied the prevalence of secondary hypertension and its impact on sIA disease phenotype. Methods We included 2704 consecutive sIA patients first admitted to Kuopio University Hospital from 1995 to 2014. Their clinical data from Kuopio Intracranial Aneurysm patient and Family Database was fused with prescription drug usage data, hospital diagnoses and causes of death, retrieved from nationwide registries. Medical records of hypertensive sIA patients were reviewed to confirm or exclude secondary hypertension. Prevalence of secondary hypertension and associated diagnoses were calculated. Logistic regression was used to identify clinical characteristics of sIA disease that associated with secondary hypertension. Results We identified 2029 (75%) sIA patients with hypertension and 208 (10%) of them had secondary hypertension. Most frequent conditions associated with secondary hypertension were kidney and renovascular diseases (45%), sleep apnea (27%) and hypothyroidism (19%); 46 (22%) of the 208 patients had more than one such condition. In multivariate logistic regression analyses of 1561 aSAH patients, secondary hypertension significantly associated with the number of sIAs (p = 0.003; OR 1.32; 95% CI 1.10-1.58) and male gender (p = 0.034; OR 1.59; 95% CI 1.04-2.43). Conclusions Secodary hypertension was relatively common (10%) among hypertensive sIA patients. Secondary causes for hypertension should be taken into account in hypertensive sIA patients, especially in aSAH patients with multiple intracranial aneurysms. Further research is indicated to evaluate the impact of secondary hypertension on the long-term rupture risk of unruptured sIA carriers and long-term outcome after aSAH.

To determine whether an internet-based and telephone-assisted parent training intervention, which used whole population screening and which comprehensively targeted symptomatic 4-year-old children, was effective 24 months after the start of treatment. No long-term follow-up studies using a randomized controlled trial (RCT) existed on this subject.Of the 4,656 children 4 years old who were screened in Southwest Finland, 730 met the criteria for high-level disruptive behavioral problems, and 464 parents agreed to be randomized to the 11-week Strongest Families Smart Website (SFSW) intervention (n = 232) or an educational control (EC) (n = 232). After 24 months, 163 SFSW parents (70%) and 165 EC parents (71%) were still participating.When we compared the results at baseline and 24 months, the primary outcome of the Child Behavior Checklist (CBCL) externalizing score showed significantly higher improvements in the SFSW group (effect size 0.22; p 0.001). This group also showed greater improvements in the secondary outcomes: the CBCL total and internalizing scales, 5 of the 7 CBCL symptom domains, 3 of the 5 DSM subscores, and self-reported parenting skills. Fewer SFSW children (17.5%) than EC children (28.0%) had been referred to child mental health services between baseline and 24 months (odds ratio = 1.8; 95% confidence interval = 1.1-3.1).The SFSW internet-based and telephone-assisted parental training program was effective 24 months after initiation, underlining the value of identifying children at risk in the community early and providing evidence-based parent training for a large number of families.STRONGEST FAMILIES FINLAND CANADA: Family-based Prevention and Treatment Program of Early Childhood Disruptive Behavior (Fin-Can). http://www.clinicaltrials.gov; NCT01750996.

The aim of this study was to describe the PROD‐screen, an instrument for screening prodromal symptoms indicating risk for psychotic conversion in the near future. PROD‐screen consists of 29 questions assessing performance and symptoms. Clinical construct validity was tested by comparing scores from the unselected general population (GP, n = 64) with those of general psychiatric patients from a community mental health centre (CMHC, n = 107). The concordant validity of PROD‐screen for prodromal symptoms of psychosis was assessed in a large epidemiologically mixed sample of research subjects (n = 132) by comparing PROD‐screen scores with the prodromal diagnosis made by Structured Interview for Prodromal Symptoms as a gold standard. Using the cut‐off point of 2/12 specific symptoms, PROD‐screen gave correct classification of prodromal status in 77% of cases, distinguishing prodromal from non‐prodromal subjects with reasonable sensitivity (80%) and specificity (75%) in the epidemiologically mixed sample. According to subsample analysis PROD‐screen functions well with first‐degree relatives of schizophrenic patients and probably also with general population samples, but not with psychiatric outpatients. In conclusion, PROD‐screen is a useful tool for screening prodromal symptoms of psychosis and selecting subjects for more extensive research interviews. Copyright © 2003 Whurr Publishers Ltd.

Objectives : To examine in detail the activation of the primary (SI) and secondary (SII) somatosensory cortex in CLN5, the Finnish variant of late infantile neuronal ceroid lipofuscinoses (NCL). Methods : Somatory evoked magnetic fields were recorded with a 122-channel planar gradiometer in response to median nerve stimulation in 5 CLN5 patients (aged 8.8–16.7 years) and in 10 healthy age-matched controls. Results : The first two responses from contralateral SI, N20m and P35m, were 6–20 times stronger in the patients than in the controls. The morphology of the subsequent deflections from SI was abnormal in the patients: a prominent N45m was detected, while the normally present P60m deflection was missing. In 4 patients the contra- and in two patients the ipsilateral SII responses were also enlarged. Furthermore, the SII activation was detected at shorter latency in patients than in controls. Conclusions : At SI, CLN5 is associated with a selective enhancement of the early cortical responses. We propose that the enlargement of N20m most likely reflects increased synchronous input from thalamus, whereas the altered morphology of the following responses may reflect defective interneuronal inhibition at the cortex. The enlargement of SII responses shows that the imbalance between excitation and inhibition in CLN5 extends outside the primary somatosensory areas.

Bipolar disorders (BPD) are chronic mental illnesses, the development of which involves genetic factors and environmental influences.The aim of this paper is to provide an overall description of the Finnish Prenatal Study of Bipolar Disorders (FIPS-B), including the study design, national registers and linkage of the registers.FIPS-B is a population-based prenatal epidemiological study of BPD with a nested case-control study design using several national registers. The registers used are: the Finnish Medical Birth Register (FMBR), the Finnish Hospital Discharge Register (FHDR), the Population Central Register and the Finnish Maternity Cohort (FMC), which are linked using the unique personal identity code (PIC). FIPS-B includes all children born from January 1, 1983 to December 31, 1998 and diagnosed with BPD in Finland by December 31, 2008.The total number of cases included in the FIPS-B is 1887. The age at first diagnosis ranged from 4 to 25 years. Half (50.4%) of the cases utilized only outpatient services, 12.7% only inpatient services and the rest (36.9%) utilized both services. Offspring of mothers with the lowest educational level had an increased odds of BPD (OR = 1.46, 95% CI 1.13-1.88). The cumulative incidence of BPD in the population aged 25 years or younger was 11.6/10,000 in 2008.FIPS-B has all the strengths of a register-based prenatal epidemiological study, along with the availability of maternal biomarkers, enabling it to examine several prenatal, perinatal and familial risk factors for BPD.

Background : Estimations about the lifetime risk of suicide in schizophrenia vary between 4 and 10%. At present, there does not exist a suicide risk scale developed particularly for schizophrenic patients. The aims of the present study were to: (1) develop a clinically useful semi-structured scale for the estimation of short-term suicide risk among schizophrenic patients, and (2) to carry out an initial validation of the scale. Methods : A 25-item Schizophrenia Suicide Risk Scale (SSRS) was constructed on the base of the literature. The SSRS scores of 69 living schizophrenic patients (LS group) were compared with the scores of 69 schizophrenic suicides (SS group) whose data had been collected previously from The Finnish nationwide and representative psychological autopsy study. Internal consistency of the SSRS was evaluated with Cronbach alpha. The most important SSRS items predicting suicide were identified with a logistic regression analysis. Sensitivity, specificity, positive predictive value, and negative predictive value of the SSRS in predicting suicide with various cut-off scores were calculated. Results : In the final logistic regression model, the following SSRS items significantly predicted suicide: suicide plans communicated to someone during the past 3 months; one or more previous suicide attempts; loss of professional skills demanding job; depression observed during an interview; and suicide plans communicated during an interview. With high cut-off scores the specificity of the SSRS became satisfactory, but the sensitivity dropped below 32%. Internal consistency of the anamnestic history of the SSRS was low, which suggests that anamnestic risk factors for suicide in schizophrenia are multifactorial. Internal consistency of the interview-based items was high, and present state risk factors seemed to consist of two separate factors, depression–anxiety and irritability. Conclusions : The SSRS may be clinically useful in identifying schizophrenic patients with a particularly high risk for suicide. However, the SSRS seems not to be a practical screening instrument for suicide risk in schizophrenia, and it is probably impossible to construct a suicide risk scale with both high sensitivity and high specificity in this disorder.

Northern epilepsy syndrome (NES, EPMR, progressive epilepsy with mental retardation, CLN8), an inherited childhood-onset epilepsy with mental retardation, has been recently characterized to belong to the family of neuronal ceroid lipofuscinoses (NCLs). In this study, four patients (ages 26-44 years) with NES and eight healthy controls underwent magnetic resonance imaging (MRI) and electrophysiological evaluation with somatosensory evoked magnetic field (SEF) studies. The findings in NES were compared with the known findings in juvenile NCL (JNCL, CLN3) and Finnish variant late infantile NCL (vLINCLFIN, CLN5) that manifest around the same age as NES. Also postmortem MRI was performed on one brain. On the MRIs, slight to moderate cerebellar atrophy was seen in all patients, whereas only two patients had slightly enlarged cerebral sulci. None of the MRIs demonstrated signal intensity abnormalities that are commonly seen in JNCL and vLINCLFIN and are considered to reflect the Wallerian degeneration after neuronal death. Generally SEFs in NES were within normal limits, indicating that the disease had not impaired the function of the neurons on the somatosensory pathway. In conclusion, MRI imaging and SEF findings suggest that the cerebral neuronal death and dysfunction in NES are minimal compared with JNCL and vLINCLFIN.

Background Oppositional Defiant Disorder (ODD) is characterized by angry and noncompliant behaviour. It is the most common disruptive behaviour disorder (DBD), with prevalence estimates of 6-9% for preschoolers and is closely linked to several long-term difficulties, including disorders of conduct, mood, anxiety, impulse-control, and substance abuse. ODD in children is related to parental depression, family dysfunction, and impairments in parental work performance. Children displaying early DBDs exhibit more symptoms of greater severity, more frequent offences, and commit more serious crimes later in life. The goal of the Strongest Families™ Finland Canada (SFFC) Smart Website intervention research program is to develop and evaluate an affordable, accessible, effective secondary prevention parent training program for disruptive behaviour in preschoolers to prevent the negative sequelae of ODD. Strongest Families is an 11-session program with two booster sessions that focuses on teaching skills to: strengthen parent–child relationships; reinforce positive behaviour; reduce conflict; manage daily transitions; plan for potentially problematic situations; promote emotional regulation and pro-social behaviour and decrease antisocial behaviour. Methods/design This protocol paper describes an ongoing population-based randomized controlled trial (RCT) of high-risk 4 year-olds attending well-child clinics in Turku, Finland and environs to examine the effectiveness of the Strongest Families Smart Website intervention compared to an Education Control condition. Randomization consists of a 1:1 ratio for intervention versus the education group, stratified by the child’s sex. The participants randomized to the intervention group receive access to the Strongest Families Smart Website and weekly telephone coaching sessions. The participants randomized to the Education Control condition receive access to a static website with parenting tips. Children are followed using parental and daycare teacher measures at 6 and 12 months after randomization. Discussion The Strongest Families Smart Website intervention is hypothesized to improve parenting skills, reduce child disruptive behaviour, reduce parental distress and improve family functioning. These results will likely inform subsequent investigations, public policy, and early treatment of childhood disruptive behaviour problems. Trial registration ClinicalTrials.gov # NCT01750996

There is a large gap worldwide in the provision of evidence-based early treatment of children with disruptive behavioral problems.To determine whether an Internet-assisted intervention using whole-population screening that targets the most symptomatic 4-year-old children is effective at 6 and 12 months after the start of treatment.This 2-parallel-group randomized clinical trial was performed from October 1, 2011, through November 30, 2013, at a primary health care clinic in Southwest Finland. Data analysis was performed from August 6, 2015, to December 11, 2015. Of a screened population of 4656 children, 730 met the screening criteria indicating a high level of disruptive behavioral problems. A total of 464 parents of 4-year-old children were randomized into the Strongest Families Smart Website (SFSW) intervention group (n = 232) or an education control (EC) group (n = 232).The SFSW intervention, an 11-session Internet-assisted parent training program that included weekly telephone coaching.Child Behavior Checklist version for preschool children (CBCL/1.5-5) externalizing scale (primary outcome), other CBCL/1.5-5 scales and subscores, Parenting Scale, Inventory of Callous-Unemotional Traits, and the 21-item Depression, Anxiety, and Stress Scale. All data were analyzed by intention to treat and per protocol. The assessments were made before randomization and 6 and 12 months after randomization.Of the children randomized, 287 (61.9%) were male and 79 (17.1%) lived in other than a family with 2 biological parents. At 12-month follow-up, improvement in the SFSW intervention group was significantly greater compared with the control group on the following measures: CBCL/1.5-5 externalizing scale (effect size, 0.34; P .001), internalizing scale (effect size, 0.35; P .001), and total scores (effect size, 0.37; P .001); 5 of 7 syndrome scales, including aggression (effect size, 0.36; P .001), sleep (effect size, 0.24; P = .002), withdrawal (effect size, 0.25; P = .005), anxiety (effect size, 0.26; P = .003), and emotional problems (effect size, 0.31; P = .001); Inventory of Callous-Unemotional Traits callousness scores (effect size, 0.19; P = .03); and self-reported parenting skills (effect size, 0.53; P .001).The study reveals the effectiveness and feasibility of an Internet-assisted parent training intervention offered for parents of preschool children with disruptive behavioral problems screened from the whole population. The strategy of population-based screening of children at an early age to offering parent training using digital technology and telephone coaching is a promising public health strategy for providing early intervention for a variety of child mental health problems.clinicaltrials.gov Identifier: NCT01750996.

AimRisk of psychosis is defined by the presence of positive psychotic-like symptoms, by subtle self-perceived cognitive and perceptual deficiencies, or by decreased functioning with familial risk of psychosis. We studied the associations of psychiatric outpatients' self-reported functioning and interpersonal relationships with vulnerability to and risk of psychosis.MethodsA total of 790 young patients attending psychiatric outpatient care completed the PROD screen [Heinimaa M, Salokangas RKR, Ristkari T, Plathin M, Huttunen J, Ilonen T, et al. PROD-screen – a screen for prodromal symptoms of psychosis. Int J Meth Psychiatr Res 2003;12:92–04.], including questions on functioning, interpersonal relationships and subtle specific (psychotic-like) and non-specific symptoms. Vulnerability to psychosis was assessed employing the patient's written descriptions of specific symptoms. Of the patients vulnerable to psychosis, those at current risk of psychosis were assessed using the Bonn Scale for Assessment of Basic Symptoms [Schultze-Lutter F, Klosterkötter J. Bonn scale for assessment of basic symptoms – prediction list, BSABS-P. Cologne: University of Cologne; 2002] and the Structured Interview for Positive symptoms [Miller TJ, McGlashan TH, Rosen JL, Somjee L, Markovich PJ, Stein K, et al. Prospective diagnosis of the initial prodrome for schizophrenia based on the structured interview for prodromal syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiatry 2002;159:863–65.].ResultsIn all, 219 patients vulnerable to and 55 patients at current risk of psychosis were identified. Vulnerability to psychosis was associated with all items of functioning and interpersonal relationships. Current risk of psychosis, however, was associated only with the subjectively reported negative attitude of others. Negative attitude of others was also associated with feelings of reference at both vulnerability and risk levels.ConclusionThe subjective experience of negative attitude of others towards oneself may be an early indicator of psychotic development.

We studied prevalence of depressive symptoms in primary care (PrC) and in psychiatric outpatient care (PsC), and how psychotic and manic symptoms are associated with current depressive symptoms. Altogether 563 patients attending PrC and 163 patients attending PsC filled in a questionnaire including the Depression Scale (DEPS), the Mood Disorder Questionnaire (MDQ) and questions on psychotic symptoms from the Composite International Diagnostic Interview (CIDI). Patients with depressive symptoms (DEPS score8) were interviewed by phone using the same checklist 6 months after baseline examination. From the PrC sample, 19.5% and from the PsC sample 73.0% were DEPS positive. In the PrC but not in the PsC sample, patients' background associated strongly with occurrence of depressive symptoms. Both at baseline and at follow-up, depressive symptoms correlated significantly with psychotic and manic symptoms. In multivariate analyses, when the effects of background, health and functioning were taken into account, baseline depressive symptoms associated significantly with lifetime psychotic symptoms. Depressive symptoms at follow-up associated significantly with psychotic symptoms during the follow-up period. In the PrC sample, this association was significant even when the effect of baseline depressive symptoms was controlled. About one-fifth of patients attending primary care and about three-quarters of patients attending psychiatric outpatient patient care suffer from depressive symptoms. Vulnerability to psychosis, indicated by occurrence of psychotic symptoms, increases the risk of and slower recovery from depressive symptoms in the patients attending primary care. Therefore, vulnerability to psychosis should be evaluated when treatment intervention for patients with depressive symptoms is planned.

Background First degree relatives (FDR) of patients with schizophrenia have higher risk of developing schizophrenia than the general population. Previous positron emission tomography (PET) studies have shown that striatal presynaptic dopamine synthesis capacity is increased in schizophrenia. We investigated whether this same phenomenon is shared by individuals with increased genetic risk for schizophrenia. Methods We used 6-[18F]-fluorodopa (FDOPA) PET imaging to measure striatal dopamine synthesis capacity. We studied 17 nonpsychotic subjects with an FDR with schizophrenia. This group was compared to 17 healthy subjects with no FDRs with schizophrenia. Results A conventional region of interest (ROI)-analysis indicated that FDOPA uptake (Ki) in the caudate-putamen was statistically significantly higher in the FDR group than in the control group. A voxel-level analysis confirmed these results. Conclusions These results suggest that the changes of striatal presynaptic dopamine synthesis seen previously in neuroleptic-naive schizophrenic patients is also present in FDRs of patients with schizophrenia. These findings have implications for the early detection of psychosis as well as for pharmacological interventions in individuals at risk for psychosis.

Background It is well established that quality of life (QOL) and functioning ability are impaired in psychosis, especially schizophrenia. Little is known about QOL and functioning in subjects vulnerable to psychosis (VTP). Method Three samples of nonpsychotic subjects (first-degree relatives of psychotic or severely ill patients, treatment-seeking patients, and a random community sample, in all 133 subjects) were assessed by the Structured Interview for Prodromal Symptoms and their vulnerability to psychosis was defined by severity of lifetime psychotic-like positive symptoms (nonsymptomatic, symptomatic, VTP). Quality of life was assessed by the Heinrichs' Quality of Life Scale and the Global Assessment of Functioning Ability (GAF) was used to measure functioning. Variance of QOL and GAF was explained by vulnerability status and psychiatric symptoms. Results Quality of life and functioning ability decreased linearly as positive symptom intensity increased and was lowest in the VTP subjects when background factors were controlled for. In multivariate analysis, negative symptoms predicted low QOL/GAF scores in addition to vulnerability status that was based on positive symptoms. Conclusion Vulnerability to psychosis is associated with decreased QOL and impaired functioning ability. Although current diagnostic evaluation of patients at high risk of psychosis relies heavily on the occurrence of positive symptoms, negative symptoms seem to be strongly associated with QOL and functioning ability in VTP subjects. This should be taken into account when assessing putatively vulnerable patients and planning treatment interventions for them.

The dopamine hypothesis of schizophrenia postulates that a dysfunctional dopaminergic system is a major pathophysiological mechanism in the disease. Most studies have focused on striatal dopamine D2 receptors, but a disturbed link between dopamine D1 and D2 receptors has also been proposed. Schizophrenia is highly heritable, and recent evidence suggests that alterations in the dopaminergic system confer susceptibility for schizophrenia instead of being solely related to the to overt expression of the disease. To explore the impact of genetic vulnerability for schizophrenia on the balance of striatal dopamine D1 and D2 receptors, we studied monozygotic (MZ) and dizygotic (DZ) unaffected co-twins from twin pairs discordant for schizophrenia as well as healthy control twins using positron emission tomography (PET). Both [ 11 C]SCH 23390 and [ 11 C]raclopride were used to quantitate D1 and D2 receptor binding, respectively, in the same individuals during the same day. The association between D1 and D2 receptor binding was analyzed using conventional region of interests as well as voxel-wise D1/D2 ratio maps. All levels of analyses failed to show any differences in D1/D2 ratio between the unaffected MZ or DZ co-twins and control twins. We noted rostrocaudally declining and dorsoventrally increasing gradients in D1/D2 ratio in the striatum, with no differences between groups in these gradients. In this sample, we did not find evidence for an association between increased genetic risk for schizophrenia and altered D1/D2 receptor balance in the striatum.

Context Schizophrenia has a heritability of about 80%, but the detailed molecular genetic basis of the disorder has remained elusive. Relative hyperfunction of the subcortical dopamine system has been previously suggested to be one of the key pathophysiologic mechanisms in schizophrenic psychosis. Objective To examine the contributions of genetic vulnerability for schizophrenia to the dopamine system in the human brain. Design Population-based twin cohort study. Setting Finland. Participants Six monozygotic and 5 dizygotic unaffected co-twins of patients with schizophrenia were ascertained, along with 4 monozygotic and 3 dizygotic healthy control twins with no family history of psychotic disorders. Main Outcome Measures Striatal dopamine D 2 receptor availability estimated with positron emission tomographic imaging and carbon 11 ( 11 C)–labeled raclopride, and performance on neuropsychological tests sensitive to frontal lobe functioning and to schizophrenia vulnerability. Results Unaffected monozygotic co-twins had increased caudate D 2 density compared with unaffected dizygotic co-twins and healthy control twins. Higher D 2 receptor binding in caudate was associated with a poor performance on cognitive tasks related to schizophrenia vulnerability in the whole sample. Conclusions The caudate dopamine D 2 receptor up-regulation is related to genetic risk for schizophrenia. Higher dopamine D 2 receptor density in caudate is also associated with poorer performance on cognitive tasks involving corticostriatal pathways. This finding suggests that caudate dopamine dysregulation is also a trait phenomenon related to psychosis vulnerability. This pattern of results provides a theoretical rationale for early pharmacologic intervention approaches using dopamine D 2 receptor blocking drugs.

The psychopathology that manifests during the prodromal phase of first-episode psychosis is varied. Little is known about the clinical diagnoses of subjects with so-called prodromal or psychotic-like symptoms.Samples of psychotic patients, first-degree relatives (FDRs) of psychotic, or severely ill patients, treatment-seeking patients, and a random community sample (in all 157 subjects) were assessed by the Structured Interview for Prodromal Symptoms (SIPS) and the SCID-I. Vulnerability to psychosis (VTP) was defined by severity of positive symptoms reported in the SIPS interview and associated with lifetime SCID-I diagnoses.The number of lifetime diagnoses received increased linearly as the SIPS symptoms approached more psychotic-like phenomena. All VTP subjects received on average 2.5, and currently prodromal subjects 2.9 lifetime SCID-I diagnoses, while the corresponding figure for non-VTP subjects was 0.7 (p0.0001). Mood disorders and comorbid anxiety disorders were particularly common.Vulnerability to psychosis seems to be associated with a high number of lifetime Axis-I diagnoses. Occurrence of anxiety disorders is remarkable, and most VTP subjects can be diagnosed with a lifetime mood disorder. VTP subjects require careful assessment of mood and anxiety symptoms and adequate treatment for their multiple disorders.

Substance abuse seems to be common among those with early signs of evolving psychosis. This article seeks to determine the prevalence of substance abuse and substance use disorders (SUDs) and the association of abuse and SUD with vulnerability psychosis among a sample of first-degree relatives of schizophrenic patients (n = 70), help-seekers (n = 29), and control subjects (n = 34). The Structured Interview for Prodromal Symptoms (SIPS) 1.0 was used to define the vulnerability status and the Structured Clinical Interview for DSM-IV Axis I to diagnose the subjects. Data on various other measures, including premorbid adjustment, personality disorder symptoms, psychological distress, and abuse of substances, were collected. Those who were identified as vulnerable to psychosis reported significantly more lifetime alcohol abuse and had more commonly an SUD than controls. Substance use disorder, as well as alcohol and drug abuse, correlated significantly with personality disorder symptoms and current positive SIPS score and both types of abuse also with disorganization SIPS score. The odds ratio for having an SUD among those vulnerable to psychosis was 6.33 (95% confidence interval, 1.77-22.73). Early psychosis and substance abuse frequently occur together.

Formation and rupture of saccular intracranial aneurysms (sIAs) may have different pathobiologies in patients with younger age at first diagnosis of sIA disease.To study the phenotype of sIA disease and formation of new (de novo) sIAs in patients below 40 yr.A population-based cohort study was conducted in 613 young (40 yr) sIA patients with first diagnosis between 1980 and 2014 and total angiographic follow-up of 3768 yr.Of the 613 sIA patients40 yr, 508 had aneurysmal subarachnoid hemorrhage (sIA-SAH) and 105 unruptured sIA(s) at first sIA diagnosis. Hypertension was 2 times less common among40 than40-yr-old patients (unruptured and ruptured). Smoking was very prevalent in40-yr-old patients (33% in SAH, 68% unruptured). SAH patients40 yr more often had family history of sIA, and lower PHASES scores (age omitted, P .001). Ruptured sIAs were small (7 mm) in 33% of 39 to 30 yr patients, in 44% of 29 to 20 yr patients, and 57% of19 yr patients. Their shape was irregular in 90%, 94%, and 95%, respectively. Smoking history (hazard ratio [HR] 2.8, 95% confidence interval [CI] 1.2-7.0), family history for sIAs (HR 3.1, 95% CI 1.3-7.7), and age at presentation (HR .91 per year, 95% CI .85-.98) were risk factors for de novo sIA formation, diagnosed in 4% even after 20 yr (median 11.8 yr).Smoking and family history are risk factors for sIA formation and aneurysmal SAH at young age. Young aneurysmal SAH patients had lower PHASES scores and often rupture from a small sIA, suggesting need for more aggressive management.

Objective: The aim was to elucidate the incidence and risk factors of epilepsy after subarachnoid hemorrhage (SAH) from saccular intracranial aneurysm (sIA) in a population-based cohort. Methods: The Kuopio sIA Database (www.uef.fi/ns) includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland. The use of prescribed medicines, including reimbursable antiepileptic drugs, has been entered from the Finnish national registries. The cumulative incidence and independent risk factors of epilepsy and death were analyzed in 876 patients with sIA-SAH admitted from 1995 to 2007. The competing risks analysis was used to correctly estimate the probability of epilepsy, because epilepsy and death after sIA-SAH may share risk factors. Results: The follow-up ended at death (n = 200) or December 31, 2008; median follow-up time was 76 months. Epilepsy was diagnosed in 113 patients in a median of 8 months after sIA-SAH. Cumulative incidence of epilepsy after sIA-SAH was 8% at 1 year and 12% at 5 years. Thirty-three percent of patients with intracerebral hemorrhage (ICH) >15 cm 3 developed epilepsy. In the 876 patients with sIA-SAH, the independent risk factors for epilepsy were ICH >15 cm 3 , Hunt and Hess grade III–V, and acute seizures. Conclusions: Cumulative incidence of epilepsy is 12% at 5 years. Epilepsy and 12-month mortality after sIA-SAH share poor Hunt and Hess grading as an independent risk factor. Epilepsy in the 2-week survivors of sIA-SAH is predicted by signs of primary injury in the brain tissue, most notably ICH.

Background: Spinal cord stimulation (SCS) relieves pain by delivering doses of electric current to the dorsal column of the spinal cord and has been found to be most effective in the treatment of neuropathic pain. Psychological distress is a significant risk factor for the development of chronic pain and has been found to affect the outcome of SCS. Childhood trauma is a risk factor for chronic pain, but has not previously been studied in SCS patients. Objectives: The objective of this prospective registry-based study was to investigate the prevalence of 5 domains of childhood trauma (emotional neglect, emotional abuse, physical neglect, physical abuse, and sexual abuse) and their relationship with the outcome of spinal cord stimulation on patients suffering from treatment-resistant chronic pain. Methods: SCS patients treated at Kuopio University Hospital between 1/1/2015 and 12/31/2016 were sent a survey in the mail, the Trauma and Distress Scale, assessing childhood trauma (n = 43). Neuropathic pain, disability, anxiety, and depression were measured in the patients pre-surgery and at 6 and 12 months post-surgery. The patients who provided their name on the questionnaire (n = 22) and had suffered from 3 or more domains of trauma were grouped as the high-trauma group (n = 13) and the rest as the low-trauma group (n = 9). Results: The questionnaire was completed by 40 patients (93%). At least 1 domain of trauma was experienced by 35 (88%) patients, and at least 2 by 24 (60%). The low-trauma group displayed a statistically significant decrease in the mean PainDETECT score from 21.5 before SCS to 16.5 at 12 months post-surgery (Wilk’s lambda = 0.297, F(2,9) = 10.6, P = 0.004), contrary to the hightrauma group (Wilk’s lambda = 0.904, F(2,6) = 0.3, P = 0.739). Limitations: Only 22 of the 40 patients provided their name on the questionnaire, which decreased the sample size on follow-up. Conclusion: This was the first study to investigate childhood trauma in SCS patients. Patients who had experienced high amounts of childhood trauma did not experience any relief from neuropathic pain 12 months’ post-SCS, contrary to the low-trauma group. Childhood trauma might be a factor worth screening in the preoperative evaluation and aftercare of SCS candidates. Key words: Spinal cord stimulation, the Trauma and Distress Scale, chronic pain, childhood trauma, childhood abuse, childhood neglect, chronic back pain, back pain, psychological distress, neuropathic pain

Background The prevalence of intracranial aneurysms (IAs) has been proposed to be elevated in the patients with neurofibromatosis type 1 (NF1). Our aims were to determine the prevalence of NF1 in a large Finnish population based cohort of IA patients and, on the other hand, the occurrences of subarachnoid haemorrhage and unruptured intracranial aneurysms in a nationwide population-based cohort of NF1 patients and its matched ten-fold control cohort. Methods The Kuopio IA Database (www.kuopioneurosurgery.fi) includes all ruptured and unruptured IA cases admitted to the Kuopio University Hospital (KUH) from its defined Eastern Finnish catchment population since 1980. In this registry-based study, we cross-linked the Kuopio IA database with the Finnish national registry covering all hospital diagnoses. The NF1 diagnoses of the 4543 patients with either saccular of fusiform IA were identified from 1969 to 2015 and verified from patient records. Our second approach was to analyze the occurrence of aneurysmal subarachnoid haemorrhage (aSAH) and unruptured IAs in a nationwide population-based database of 1410 NF1 patients and its ten-fold matched control cohort (n = 14030) using national registry of hospital diagnoses between 1987 and 2014. Results One NF1 patient was identified among the 4543 IA patients. Three verified IA cases (one unruptured IA and two aSAH cases) were identified in the cohort of 1410 NF1 patients, with similar occurrences in the control cohort. Conclusions We found no evidence in our population-based cohorts to support the conception that NF1 is associated with IAs. Our results indicate that the incidence of aSAH is not elevated in patients with NF1. Further studies are required to confirm that there is no association between NF1 and unruptured IAs, published version, peerReviewed