Maija Lindgren

The relationship between psychotic-like symptoms and neurocognitive performance in a general adolescent psychiatric sample

INTRODUCTION The current criteria for detecting a Clinical High-Risk (CHR) state for psychosis do not address cognitive impairment. A first step for identifying cognitive markers of psychosis risk would be to determine which aspects of neurocognitive performance are related with more severe psychotic-like symptoms. This study assessed cognitive impairment associated with prodromal symptoms in adolescents receiving public psychiatric treatment. METHODS 189 adolescents were recruited from consecutive new patients aged 15-18 attending mainly outpatient adolescent psychiatric units in Helsinki. They had been screened for prodromal symptoms using the Prodromal Questionnaire, and all screen-positives as well as a random sample of screen-negatives were interviewed using the Structured Interview for Prodromal Symptoms (SIPS) and underwent testing using a large, standardized neurocognitive test battery. The sample included 62 adolescents who met the CHR criteria (CHR) and 112 who did not (non-CHR). A healthy control sample (n=72) was also included to provide age- and gender-matched norms. RESULTS The CHR group performed worse on visuospatial tasks than the non-CHR group. Among CHR adolescents, negative symptoms were associated with slower processing speed and poorer performance on verbal tasks. Among non-CHR adolescents, positive symptoms were associated with poorer performance on visuospatial tasks, and negative symptoms with poorer performance on verbal tasks. CONCLUSION Clinical high-risk status is associated with impaired visuospatial task performance. However, both positive, psychotic-like symptoms and negative symptoms are associated with lower levels of neurocognitive functioning among adolescents in psychiatric treatment regardless of whether CHR criteria are met. Thus, even mild positive and negative symptoms may have clinical relevance in adolescents in psychiatric care. Adolescents with both psychotic-like symptoms and neurocognitive deficits constitute a group requiring special attention.

Predicting psychosis in a general adolescent psychiatric sample.

INTRODUCTION Current psychosis risk criteria have often been studied on a pre-selected population at specialized clinics. We investigated whether the Structured Interview for Prodromal Syndromes (SIPS) is a useful tool for psychosis risk screening among adolescents in general psychiatric care. METHODS 161 adolescents aged 15-18 with first admission to adolescent psychiatric services in Helsinki were interviewed with the SIPS to ascertain Clinical High-Risk (CHR) state. The participants were followed via the national hospital discharge register, patient files, and follow-up interviews. DSM-IV Axis I diagnoses were made at baseline and 12 months. Register follow-up spanned 2.8-8.9 years, and hospital care for a primary psychotic disorder and any psychiatric disorder were used as outcomes. RESULTS CHR criteria were met by 54 (33.5%) of the adolescents. Three conversions of psychosis as defined by SIPS emerged during follow-up, two of whom belonged to the CHR group. The positive predictive value of the CHR status was weak (1.9%) but its negative predictive value was 98.0%. Using the DSM-IV definition of psychosis, there were five conversions, three of which were in the CHR group. In regression analyses, hospital admissions for primary psychotic disorder were predicted by positive symptom intensity in the baseline SIPS. In addition, CHR status and SIPS positive and general symptoms predicted hospitalization for psychiatric disorder. DISCUSSION Psychosis incidence was low in our unselected sample of adolescent psychiatric patients. CHR status failed to predict SIPS or DSM-IV psychoses significantly at 12 months. However, in a longer follow-up, CHR did predict psychiatric hospitalization.

Low verbal ability predicts later violence in adolescent boys with serious conduct problems

Abstract Background: Delinquent adolescents are a known high-risk group for later criminality. Cognitive deficits correlate with adult criminality, and specific cognitive deficits might predict later criminality in the high-risk adolescents. Aims: This study aimed to explore the neuropsychological performance and predictors of adult criminal offending in adolescents with severe behavioural problems. Methods: Fifty-three adolescents (33 boys and 20 girls), aged 15–18 years, residing in a reform school due to serious conduct problems, were examined for neuropsychological profile and psychiatric symptoms. Results were compared with a same-age general population control sample, and used for predicting criminality 5 years after the baseline testing. Results: The reform school adolescents’ neuropsychological performance was weak on many tasks, and especially on the verbal domain. Five years after the baseline testing, half of the reform school adolescents had obtained a criminal record. Males were overrepresented in both any criminality (75% vs. 10%) and in violent crime (50% vs. 5%). When cognitive variables, psychiatric symptoms and background factors were used as predictors for later offending, low verbal intellectual ability turned out to be the most significant predictor of a criminal record and especially a record of violent crime. Conclusions: Neurocognitive deficits, especially in the verbal and attention domains, are common among delinquent adolescents. Among males, verbal deficits are the best predictors for later criminal offending and violence. Clinical implications: Assessing verbal abilities among adolescent population with conduct problems might prove useful as a screening method for inclusion in specific therapies for aggression management.

Early insulin resistance predicts weight gain and waist circumference increase in first-episode psychosis--A one year follow-up study.

First-episode psychosis (FEP) is associated with weight gain during the first year of treatment, and risk of abdominal obesity is particularly increased. To identify early risk markers of weight gain and abdominal obesity, we investigated baseline metabolic differences in 60 FEP patients and 27 controls, and longitudinal changes during the first year of treatment in patients. Compared to controls at baseline, patients had higher low-density lipoprotein, triglyceride and apolipoprotein B levels, and lower levels of high-density lipoprotein and apolipoprotein A-I but no difference in body mass index or waist circumference. At 12-month follow-up, 60.6% of patients were overweight or obese and 58.8% had abdominal obesity. No significant increase during follow-up was seen in markers of glucose and lipid metabolism or blood pressure, but increase in C-reactive protein between baseline and 12-month follow-up was statistically significant. Weight increase was predicted by baseline insulin resistance and olanzapine use, while increase in waist circumference was predicted by baseline insulin resistance only. In conclusion, insulin resistance may be an early marker of increased vulnerability to weight gain and abdominal obesity in young adults with FEP. Olanzapine should be avoided as a first-line treatment in FEP due to the substantial weight increase it causes. In addition, the increase in the prevalence of overweight and abdominal obesity was accompanied by the emergence of low-grade systemic inflammation.

Predicting psychosis and psychiatric hospital care among adolescent psychiatric patients with the Prodromal Questionnaire

The Prodromal Questionnaire (PQ) identifies psychiatric help-seekers in need of clinical interviews to diagnose psychosis risk. However, some providers use the PQ alone to identify risk. Therefore, we tested its predictive utility among 731 adolescent psychiatric help-seekers, with a 3-9-year register-based follow-up. Nine latent factors corresponded well with postulated subscales. Depersonalization predicted later hospitalization with a psychosis diagnosis (HR 1.6 per SD increase), and Role Functioning predicted any psychiatric hospitalization (HR 1.3). Published cut-off scores were poor predictors of psychosis; endorsement rates were very high for most symptoms. Therefore, we do not recommend using the PQ without second-stage clinical interviews.

Suicidality, self-harm and psychotic-like symptoms in a general adolescent psychiatric sample

We investigated the associations between clinical high‐risk for psychosis (CHR), psychotic‐like symptoms and suicidality among adolescent psychiatric patients.

Toxoplasma gondii infection and common mental disorders in the Finnish general population

OBJECTIVE We investigated whether T. gondii seropositivity is associated with 12-month depressive, anxiety and alcohol use disorders and current depressive symptoms and whether inflammation, measured by C-reactive protein (CRP) level, explains these associations. METHOD Health 2000 study (BRIF8901), conducted in years 2000-2001, is based on a nationally representative sample of Finns aged 30 and above, with 7112 participants and 88.6% response rate. DSM-IV depressive, anxiety and alcohol use disorders were assessed with the Composite International Diagnostic Interview and depressive symptoms with the Beck Depressive Inventory (BDI-21). We used logistic regression to investigate the association of T. gondii seropositivity with mental disorders and linear regression with BDI-21 scores. RESULTS T. gondii seroprevalence was significantly associated with 12-month generalized anxiety disorder but not with other anxiety, depressive or alcohol use disorders. T. gondii seropositivity was associated with higher BDI-21 scores (beta 0.56, 95% CI 0.12-1.00, P = 0.013) and with having a comorbid depressive and anxiety disorder (OR 1.86, 95% CI 1.16-2.97, P = 0.010). Higher CRP levels were associated with these outcomes and with T. gondii seropositivity, but adjusting for CRP did not change the effect of T. gondii seropositivity. LIMITATIONS Cross-sectional study design with no information on the timing of T. gondii infection. CONCLUSION T. gondii seropositivity is associated with generalized anxiety disorder, depressive symptoms and comorbid depressive and anxiety disorders, which is not mediated by inflammation.

Community-oriented family-based intervention superior to standard treatment in improving depression, hopelessness and functioning among adolescents with any psychosis-risk symptoms

The aim of the present study was to compare change in functioning, affective symptoms and level of psychosis-risk symptoms in symptomatic adolescents who were treated either in an early intervention programme based on a need-adapted Family- and Community-orientated integrative Treatment Model (FCTM) or in standard adolescent psychiatric treatment (Treatment As Usual, TAU). 28 pairs were matched by length of follow-up, gender, age, and baseline functioning. At one year after the start of treatment, the matched groups were compared on change in functioning (GAF-M), five psychosis-risk dimensions of the Structured Interview for Psychosis-Risk Syndromes (SIPS), and self-reported anxiety, depression, and hopelessness symptoms (BAI, BDI-II, BHS). FCTM was more effective in improving functioning (20% vs. 6% improvement on GAF-M), as well as self-reported depression (53% vs. 14% improvement on BDI-II) and hopelessness (41% vs. 3% improvement on BHS). However, for psychosis-risk symptoms and anxiety symptoms, effectiveness differences between treatment models did not reach statistical significance. To conclude, in the present study, we found greater improvement in functioning and self-reported depression and hopelessness among adolescents who received a need-adapted Family- and Community-orientated integrative Treatment than among those who were treated in standard adolescent psychiatry.

Association of cytomegalovirus and Epstein-Barr virus with cognitive functioning and risk of dementia in the general population: 11-year follow-up study

BACKGROUND Earlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. Few studies have investigated the association of cytomegalovirus and Epstein-Barr virus with cognitive decline longitudinally. Our aim was to examine whether cytomegalovirus and Epstein-Barr virus are associated with cognitive decline in adults. METHOD The study sample is from the Finnish Health 2000 Survey (BRIF8901, n = 7112), which is representative of the Finnish adult population. The sample was followed up after 11 years in the Health 2011 Survey. In addition, persons with dementia were identified from healthcare registers. RESULTS In the Finnish population aged 30 and over, the seroprevalence of cytomegalovirus was estimated to be 84% and the seroprevalence of Epstein-Barr virus 98%. Seropositivity of the viruses and antibody levels were mostly not associated with cognitive performance. In the middle-aged adult group, cytomegalovirus serointensity was associated with impaired performance in verbal learning. However, the association disappeared when corrected for multiple testing. No interactions between infection and time or between the two infections were significant when corrected for multiple testing. Seropositivity did not predict dementia diagnosis. CONCLUSIONS The results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level.

F166. LOW-GRADE INFLAMMATION IN FIRST-EPISODE PSYCHOSIS IS DETERMINED BY WAIST CIRCUMFERENCE INCREASE

Abstract Background There is evidence of low-grade inflammation in psychosis, as measured by the high-sensitivity C-reactive protein (hs-CRP). Significant weight gain is common during the first months of antipsychotic treatment. In the general population, overweight and obesity often lead to systemic low-grade inflammation. Lifestyle factors, such as smoking, can contribute to the pro-inflammatory changes. The metabolic changes in people with first-episode psychosis (FEP) taking place after the onset of psychosis can be especially harmful as these individuals are typically young and without major somatic illnesses. We aimed to study how the low-grade inflammation, measured by hs-CRP, develops in FEP and to clarify the effect of waist circumference increase in the inflammation. Methods The Helsinki Early Psychosis Study recruited FEP patients (age 18 to 40 years) attaining their first treatment for psychosis from the catchment area of the Helsinki University Hospital. We recruited 95 FEP patients and 62 controls. The inclusion criterion for the study was receiving a score of at least 4 in Unusual thought content or Hallucinations in the Brief Psychiatric Rating Scale - Extended (BPRS-E). Diagnoses of psychotic disorders according to the DSM-IV criteria were later verified using the Structured Diagnostic Interview for DSM-IV and reviewing all medical records. Substance-induced psychotic disorders and psychotic disorders due to a general medical condition were excluded. We measured the changes in hs-CRP, weight, waist circumference, glucose metabolism and lipids at baseline and at follow-ups of 2 and 12 months. We used linear mixed effects models to analyze the relationship between hs-CRP and waist circumference. In the model, we included a random intercept for each patient and, as fixed effects, we entered sex, time (days from baseline measurement), waist circumference and antipsychotic use at each assessment point, and baseline cigarette smoking. Results At baseline, FEP patients (mean age 26.1 years) had higher insulin resistance, total and LDL cholesterol, apolipoprotein B and triglyceride levels than controls. However, baseline weight and waist circumference, hs-CRP, fasting glucose and HDL cholesterol were similar between patients and controls. A robust change in anthropometric measures and inflammation was evident among patients by 12 months. Hs-CRP was significantly higher in patients at 12-month follow up than at baseline (baseline hs-CRP 0.67 mg/l, IQR 0.33–2.54; 12-month 1.73 mg/l, IQR 0.49–4.21; Wilcoxon signed-rank p = 0.007). When at the baseline the prevalence of overweight or obesity was 30% (28/94) in patients with FEP, by 12 months the prevalence was 59% (35/59) (McNemar′s test p < 0.001). The proportion of patients gaining ≥ 7 % of baseline weight was 68 % (40/59). The median weight gain among patients was 9.6 kg (IQR 1.5–13.6 kg), and the waist circumference increase 6.0 cm (IQR 2.0–13.0 cm). In the mixed effects model waist circumference (p < 0.0001) and sex (p = 0.014) were significantly associated with hs-CRP level. Discussion We detected a significant elevation in hs-CRP in people with FEP during the first treatment year. The rise in hs-CRP was determined by waist circumference increase. Patients with FEP are in a marked risk of developing abdominal obesity and subsequent low-grade inflammation during the first year of treatment. Prevention of the early metabolic changes in first-episode psychosis is important, as abdominal obesity and inflammation are associated with increased risk of cardiovascular events and mortality.