Maternal smoking during pregnancy and offspring psychiatric disorder: a longitudinal birth cohort study.

BACKGROUND: There is evidence that prenatal stress and smoking during pregnancy both independently increase the risk of offspring psychopathology. Here we examine whether increased levels of self-reported stress is associated with increased smoking in a population of pregnant women, and whether prenatal smoking is associated with offspring psychiatric diagnoses independent of prenatal stress exposure. METHOD: Using a longitudinal birth cohort, we used ordered logistic regressions to examine associations between maternal stress and smoking during pregnancy. We then used logistic regression analyses to examine associations between prenatal smoking and later offspring psychiatric disorders. RESULTS: A dose-response relationship was found between maternally reported stress and smoking during pregnancy. Pregnant women reporting severe stress were more likely to smoke compared to both the moderate stress and no stress groups, and those reporting moderate stress were significantly more likely to smoke compared to the no stress group. Smoking more than 5 cigarettes daily during pregnancy increased the risk of offspring personality disorder (OR 3.08, 95% CI 1.60-5.94) as well as developing any Axis 1 psychiatric disorder, inclusive of mood, anxiety and psychotic disorders (OR 1.45, 95% CI 1.04-2.04). After adjusting for parental psychiatric history and maternal self-reported stress during pregnancy, associations between smoking more than 5 cigarettes daily when pregnancy and offspring personality (OR 2.58 95% CI 1.32-5.06) disorder remained. CONCLUSION: Exposure to cigarette smoking during gestation could impact a child's mental health. Smoking during pregnancy is a prime target for preventative interventions as unlike most other environmental risk factors, it is very amenable to change.

Childhood temperament and its association with adult psychiatric disorders in a prospective cohort study.

BACKGROUND: Childhood temperament and its component factors have previously been shown to be associated with depression and anxiety disorders in later life. Studies have also suggested possible links between childhood temperament and later psychosis. AIMS: To investigate the association between childhood temperament and its individual component factors, measured at age 5, and later psychiatric disorders. METHOD: Using a sample from a Finnish birth cohort (N = 1014), we used logistic regression models to examine associations between maternal reported childhood temperament at age 5, and later psychiatric diagnosis, ascertained through linkage with the Finnish Hospital Discharge Register (FHDR). RESULTS: Individuals with a childhood temperament rated as difficult at age 5 had almost 5-times the odds of developing a psychotic disorder in adulthood compared to those with a temperament rated as average by their mothers (OR = 4.91, 95% CI = 1.51-15.91). The individual temperament factors of approach withdrawal, adaptability and quality of mood were each independently associated with later psychotic disorder while the factors of regularity and threshold were associated with increased risk for mood disorders. CONCLUSIONS: This study reports association between early childhood temperament and risk for psychosis and suggests that early childhood temperament may be a good target for early intervention to reduce the risk of psychiatric disorders.

The role of prenatal stress as a pathway to personality disorder: longitudinal birth cohort study.

BACKGROUND: Many studies have reported associations between prenatal stress and the development of psychotic, anxiety and depressive disorders; however, to date no studies have investigated potential associations with personality disorders. AIMS: This study investigated potential associations between exposure to prenatal stress and personality disorder in offspring. METHOD: In a subsample (N = 3626) of a large Finnish birth cohort, we used logistic regression models to examine associations between self-reported maternal stress during pregnancy, collected monthly during antenatal clinic appointments, and personality disorder in offspring. Familial and outcome information were obtained by linking data from the Finnish Hospital Discharge Register and the Finnish Population Register. RESULTS: Compared with those unexposed, children exposed to any maternal stress during gestation had three times the odds of developing a personality disorder (odds ratio 2.76, 95% CI 1.59-4.80, P = 0.000). Those exposed to moderate stress had three times the odds (odds ratio 3.13, 95% CI 1.42-6.88, P = 0.005) and those exposed to severe stress had seven times the odds (odds ratio 7.06, 95% CI 2.10-23.81, P = 0.002) of developing a personality disorder. These associations remained after adjusting for parental psychiatric history, comorbid psychiatric diagnoses, prenatal smoking and antenatal depression. CONCLUSIONS: Exposure to stress during gestation increases the odds of personality disorder in offspring, independent of other psychiatric disorders. These results suggest the assessment of maternal stress and well-being during pregnancy may be useful in identifying those at greatest risk of developing personality disorder, and highlight the importance of prenatal care for good maternal mental health during pregnancy.

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

AIM: We investigated the associations between clinical high-risk for psychosis (CHR), psychotic-like symptoms and suicidality among adolescent psychiatric patients. METHODS: The sample consisted of 54 CHR and 107 non-CHR psychiatric patients aged 15-18 in Helsinki, Finland, who were assessed at the beginning of their psychiatric treatment with the Structured Interview for Prodromal Syndromes (SIPS). Current suicidality was measured with the Beck Depression Inventory (item 9), while lifetime suicidality was evaluated from all available data, including patient files. The participants were followed for 2.8-8.9 years via the national hospital discharge register, with the follow-up outcome being intentional self-harm. Data on suicides were also gathered from the Causes of Death statistics. RESULTS: Only 30.5% of the adolescents had no suicidal ideation at the beginning of their treatment. CHR risk state and SIPS-assessed delusions, suspiciousness, and hallucinations were associated with higher current suicidality. Of the 154 adolescents with register follow-up, there were five (3.2%) with intentional self-harm resulting in hospital treatment, all female. CHR status was not associated with self-harm. Current suicidality, familial risk of psychosis, and SIPS decreased expression of emotions were associated with self-harm during follow-up. In a Cox regression analysis model among girls, only decreased expression of emotions remained a significant predictor of intentional self-harm. Baseline suicidality measures were not associated with transitions to psychosis. CONCLUSIONS: CHR status was associated with higher current suicidality but did not predict follow-up intentional self-harm in treatment-seeking adolescents. Decreased expression of emotions may indicate higher risk of intentional self-harm in adolescent treatment-seeking girls.

Evaluation of verbal list learning as a predictor of psychosis.

AIM: We explored whether cognitive performance, and verbal learning in particular, predicts psychosis or psychiatric hospitalizations among unselected first-admission adolescent patients in general psychiatric care. METHODS: Up to 152 adolescents aged 15-18 were interviewed with the SIPS, tested with a cognitive test battery in the beginning of their psychiatric treatment, and followed for a maximum of 9 years (median 4.5 years). RESULTS: The composite factors of processing speed, verbal performance and visuospatial performance did not predict psychosis (n = 7) or all-cause psychiatric hospitalizations (n = 26) beyond psychosis risk symptoms. However, those who developed psychosis performed worse on California Verbal Learning Test (CVLT) compared to other adolescents. Lower scores of CVLT immediate recall predicted psychosis (P = .003, HR = 1.13 per CVLT point decrease). However, when general verbal ability was adjusted for, CVLT did not reach significance. CONCLUSIONS: Impaired verbal list learning may predict psychosis also among adolescent psychiatric patients not preselected for psychosis risk suspicion.

Psychotherapy effectiveness for major depression: a randomized trial in a Finnish community.

BACKGROUND: The purpose of this study is to assess the relative effectiveness of Interpersonal Psychotherapy (IPT), Psychoeducative Group Therapy (PeGT), and treatment as usual (TAU) for patients with Major Depressive Disorder (MDD) in municipal psychiatric secondary care in one Finnish region. METHODS: All adult patients (N = 1515) with MDD symptoms referred to secondary care in 2004-2006 were screened. Eligible, consenting patients were assigned randomly to 10-week IPT (N = 46), PeGT (N = 42), or TAU (N = 46) treatment arms. Antidepressant pharmacotherapy among study participants was evaluated. The Hamilton Depression Rating scale (HAM-D) was the primary outcome measure. Assessment occurred at 1, 5, 3, 6, and 12 months. Actual amount of therapists' labor was also evaluated. All statistical analyses were performed with R software. RESULTS: All three treatment cells showed marked improvement at 12-month follow-up. At 3 months, 42 % in IPT, 61 % in PeGT, and 42 % in TAU showed a mean ≥50 % in HAM-D improvement; after 12 months, these values were 61 %, 76 %, and 68 %. Concomitant medication and limited sample size minimized between-treatment differences. Statistically significant differences emerged only between PeGT and TAU favoring PeGT. Secondary outcome measures (CGI-s and SOFAS) showed parallel results. CONCLUSION: All three treatments notably benefited highly comorbid MDD patients in a public sector secondary care unit. TRIAL REGISTRATION: ClinicalTrials.gov NCT02314767 (09.12.2014).

[Pitfalls in psychopharmacological drug use]. / Psyykenlääkkeiden käytön sudenkuopat.

Psychiatric drug therapy is based on diagnoses and controlled examinations Psychiatric illnesses or disorders are, however, heterogenous conditions in their nature and treatment response. It is not possible to know beforehand whether a drug is beneficial or actually harmful for an individual patient. In practice, the use of psychopharmacological drugs is actually experimental, and success will require critical monitoring of the response, flexibility and good pharmacotherapeutic rapport. The pitfall in the use of all psychopharmacological drugs is cessation of effective treatment and, on the other hand, unnecessary medication that sometimes involves even dangerous adverse effects.

[Hoarding]. / Keräilypakko.

Hoarding is a mental disorder having its onset at young age and often worsening with age, manifested as a need of storing up goods to an extent that significantly hampers everyday life. In the light of conducted studies, at least 1 to 2% of the adult population suffers from hoarding. Upon increased compulsive hoarding with aging, problems arise especially for those living alone. Hoarding differs from obsessive-compulsive disorder in its course and treatment response. Treatment of hoarding disorder is based on methods applied in cognitive behavior therapy.

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.

Sudden death of father or sibling in early childhood increases risk for psychotic disorder.

OBJECTIVE: To determine if exposure to a severe, acute stressor during early development is associated with an increased incidence of schizophrenia and bipolar disorder compared to exposure to a chronic stressor. DESIGN: We identified all those born in Helsinki between 1960 and 1990 whose father or sibling died between their conception and 5-years-of-age through linking two national registers: the Finnish Population Register and the Cause of Death Register. The reason for the death was also extracted from the Cause of Death Register. A third register, the Finnish Hospital Discharge Register, was used to determine psychiatric outcomes in adulthood. SAMPLE: 11,855 individuals whose father or sibling had died before they were 5-years-old. In total, 129 individuals had an ICD 8, 9 or 10 diagnosis of schizophrenia and 165 had a diagnosis of bipolar disorder. 6136 individuals had a father or sibling who died from a sudden, external cause (e.g. accident or suicide) and 5719 individuals had father or sibling who died from a non-external, illness-associated cause. RESULTS: Sudden loss of a father or sibling led to a significantly greater risk of developing bipolar disorder or schizophrenia in adulthood compared to loss of a father or sibling from illness. These associations are independent of sex, parental history of psychiatric illness, age at exposure to loss and age at follow-up. CONCLUSION: Our findings are in keeping with accumulating evidence which indicates that exposure to stress during early development can increase the risk of psychotic illness among those exposed.

Genetic risk for schizophrenia, obstetric complications, and adolescent school outcome: evidence for gene-environment interaction.

Low birth weight (LBW) and hypoxia are among the environmental factors most reliably associated with schizophrenia; however, the nature of this relationship is unclear and both gene-environment interaction and gene-environment covariation models have been proposed as explanations. High-risk (HR) designs that explore whether obstetric complications differentially predict outcomes in offspring at low risk (LR) vs HR for schizophrenia, while accounting for differences in rates of maternal risk factors, may shed light on this question. This study used prospectively obtained data to examine relationships between LBW and hypoxia on school outcome at age 15-16 years in a Finnish sample of 1070 offspring at LR for schizophrenia and 373 offspring at HR for schizophrenia, based on parental psychiatric history. Controlling for offspring sex, maternal smoking, social support, parity, age, and number of prenatal care visits, HR offspring performed worse than LR offspring across academic, nonacademic, and physical education domains. LBW predicted poorer academic and physical education performance in HR offspring, but not in LR offspring, and this association was similar for offspring of fathers vs mothers with schizophrenia. Hypoxia predicted poorer physical education score across risk groups. Rates of LBW and hypoxia were similar for LR and HR offspring and for offspring of fathers vs mothers with schizophrenia. Results support the hypothesis that genetic susceptibility to schizophrenia confers augmented vulnerability of the developing brain to the effects of obstetric complications, possibly via epigenetic mechanisms.

Evidence for shared susceptibility to epilepsy and psychosis: a population-based family study.

BACKGROUND: There is emerging evidence of an etiological overlap between a range of neurodevelopmental disorders, including schizophrenia and epilepsy. Here we investigate shared familial vulnerability to psychotic illness and epilepsy in a family-based study. METHODS: The study population consisted of parents and their children born in Helsinki between 1947 and 1990. The Finnish Hospital Discharge Register was used to determine psychiatric and neurological outcomes in adulthood for all offspring. Parental history of psychosis and epilepsy was determined by linking the Hospital Discharge Register and the Finnish Population Register. RESULTS: Our total sample comprised 9653 families and 23,404 offspring. Individuals with epilepsy had a 5.5-fold increase in the risk of having a broadly defined psychotic disorder, an almost 8.5-fold increase in the risk of having schizophrenia, and a 6.3-fold increase in the risk of having bipolar disorder. There was strong evidence of clustering of the association between epilepsy and psychosis within families. Individuals with a parental history of epilepsy had a 2-fold increase in the risk of developing psychosis, compared with individuals without a parental history of epilepsy. Individuals with a parental history of psychosis had, reciprocally, a 2.7-fold increase in the risk of having a diagnosis of generalized epilepsy, compared with individuals without a parental history of psychosis. Post hoc analyses showed that these associations were not driven by the comorbidity of epilepsy and psychosis in the parents. CONCLUSIONS: These findings support recent evidence of overlapping etiological factors between epilepsy and schizophrenia, especially recent evidence of a genetic overlap between these disorders.

The genetic and environmental determinants of the association between brain abnormalities and schizophrenia: the schizophrenia twins and relatives consortium.

BACKGROUND: Structural brain abnormalities are consistently found in schizophrenia (Sz) and have been associated with the familial risk for the disorder. We aim to define the relative contributions of genetic and nongenetic factors to the association between structural brain abnormalities and Sz in a uniquely powered cohort (Schizophrenia Twins and Relatives consortium). METHODS: An international multicenter magnetic resonance imaging collaboration was set up to pool magnetic resonance imaging scans from twin pairs in Utrecht (The Netherlands), Helsinki (Finland), London (United Kingdom), and Jena (Germany). A sample of 684 subjects took part, consisting of monozygotic twins (n = 410, with 51 patients from concordant and 52 from discordant pairs) and dizygotic twins (n = 274, with 39 patients from discordant pairs). The additive genetic, common, and unique environmental contributions to the association between brain volumes and risk for Sz were estimated by structural equation modeling. RESULTS: The heritabilities of most brain volumes were significant and ranged between 52% (temporal cortical gray matter) and 76% (cerebrum). Heritability of cerebral gray matter did not reach significance (34%). Significant phenotypic correlations were found between Sz and reduced volumes of the cerebrum (-.22 [-.30/-.14]) and white matter (-.17 [-.25/-.09]) and increased volume of the third ventricle (.18 [.08/.28]). These were predominantly due to overlapping genetic effects (77%, 94%, and 83%, respectively). CONCLUSIONS: Some of the genes that transmit the risk for Sz also influence cerebral (white matter) volume.

Phospholipids and insulin resistance in psychosis: a lipidomics study of twin pairs discordant for schizophrenia.

BACKGROUND: Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission. METHODS: Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 ± 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples. RESULTS: In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed. CONCLUSIONS: Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins.

Prodromal psychosis screening in adolescent psychiatry clinics.

BACKGROUND: Research has identified a syndrome conferring ultra-high risk (UHR) for psychosis, although UHR interviews require intensive staff training, time and patient burden. Previously, we developed the Prodromal Questionnaire (PQ) to screen more efficiently for UHR syndromes. AIMS: This study examined the concurrent validity of the PQ against UHR status and preliminary predictive validity for later psychotic disorder. METHOD: We assessed a consecutive patient sample of 408 adolescents who presented to psychiatry clinics in Helsinki, Finland, seeking mental health treatment, including 80 participants who completed the Structured Interview for Prodromal Syndromes (SIPS). RESULTS: A cut-off score of 18 or more positive symptoms on the PQ predicted UHR diagnoses on the SIPS with 82% sensitivity and 49% specificity. Three of 14 (21%) participants with high PQ scores and SIPS UHR diagnoses developed full psychotic disorders within 1 year. CONCLUSIONS: Using the PQ and SIPS together can be an efficient two-stage screening process for prodromal psychosis in mental health clinics.

Efficiency of working memory encoding in twins discordant for schizophrenia.

It has been proposed that patients with schizophrenia and some of their relatives suffer from reduced neurocognitive efficiency, increasing their sensitivity to experimental task demands. The present study evaluated such a possibility during performance of a working memory task by schizophrenia patients and their co-twins along with a healthy control sample. Electrophysiological data were obtained from sets of nine twin pairs (monozygotic and dizygotic pairs collapsed) discordant for a diagnosis of schizophrenia and from nine matched healthy control twin pairs, during administration of a variable-load spatial working memory task. Event-related potentials (ERPs) were measured immediately after memory set onset and during a delay period. For correctly performed trials, slow-wave ERP activity measured during the late stimulus encoding and delay periods exhibited a significant Diagnostic Group-by-Memory Load interaction, with schizophrenia patients showing a differentially strong load effect. Patients' co-twins displayed an intermediate level of load sensitivity while healthy controls showed no significant load effect. These results support an inefficiency model of neurocognitive dysfunction in schizophrenia, a pattern that appears to be related to the pathogenesis and inheritance of the disorder. Furthermore, this inefficiency appeared during the late stimulus encoding stage of working memory functioning, possibly reflecting disruptions in stimulus representation consolidation.

Lack of association between neuropsychological performance and level of psychosis-proneness in an adolescent psychiatric sample.

Studies of the prodromal stage of schizophrenia show that the late prepsychotic phase is associated with mild neuropsychological deficits that parallel those of schizophrenia. However, it is still unclear whether this association is present across the whole range of symptoms of psychosis-proneness, or specific to the extreme groups. In this study, the linear associations between dimensions of psychosis-proneness (as measured by the 92-item Prodromal Questionnaire) and performance on 20 neuropsychological measures were assessed in a group of 71 nonpsychotic adolescent psychiatric patients. A structure of positive, negative and disorganized prodromal symptom dimensions was found, replicating earlier findings. No symptom dimension was significantly associated with neuropsychological performance, even when corrected for nonspecific psychological distress. These findings suggest that the association between symptoms and neuropsychological performance is specific to high levels of symptoms or to the truly prodromal subpopulation. The results also highlight the importance of simultaneous assessment of affective state.

[Male aspect towards good aging]. / Miesnäkökulma hyvään ikääntymiseen.

Columnist "Kirsti" of Helsingin Sanomat newspaper divided middle age into three stages: early middle age (35-45 years), mid-middle age (45-55) and late middle age (55-65). Similarly, those at 65-75 are living juvenile old age, those at 75-85 midlife old age and those over 85, senescent old age. Classification of these ages according to the years of life does, however, not correspond with personal feelings. The intrinsic relation to life and death may provide a better definition of the stages of life. At the middle age we become aware of the limitation of life and begin to count the remaining years.

Abnormally high EEG alpha synchrony during working memory maintenance in twins discordant for schizophrenia.

BACKGROUND: The present analyses aimed to test the prediction that schizophrenia patients and their non-schizophrenic co-twins would display reduced efficiency of the neurocognitive mechanisms subserving active maintenance of spatial information in working memory. METHODS: Upper alpha frequency band EEG event-related desynchronization and synchronization (ERD/ERS) were calculated as percent changes in power relative to an inter-trial baseline across 4 memory loads in a spatial delayed-response task. RESULTS: During the delay, the diagnostic groups showed equivalent ERD/ERS activity over posterior scalp regions at the lowest memory load; however, as memory load increased, patients, and to an intermediate degree, their non-schizophrenic co-twins (monozygotic and dizygotic pairs collapsed together), showed significantly greater increases in ERD/ERS amplitude as compared with controls. CONCLUSIONS: These findings demonstrate abnormally increased ERD/ERS amplitudes with increasing memory load in patients with schizophrenia and their co-twins, consistent with inefficiency of the neurocognitive mechanisms supporting active maintenance of information across a delay.