Dysthymia in male adolescents is associated with increased risk of later hospitalization for psychotic disorders: a historical-prospective cohort study

Aim: Retrospective studies indicate that patients with psychotic disorders and schizophrenia often suffer from depressive symptoms before the onset of psychosis. In a historical‐prospective design, we studied the association between dysthymia in adolescence and later hospitalization for psychotic disorders and schizophrenia. Methods: The Israeli Draft Board screens the entire, unselected population of 16–17 years old male adolescents for psychiatric disorders. These adolescents were followed for hospitalization for psychotic disorders and schizophrenia using the Israeli National Psychiatric Hospitalization Case Registry. Of 275 705 male adolescents screened, 1267 (0.5%) were hospitalized for psychotic disorders (International Classification of Diseases [ICD]‐10 20.0–29.9), and 757 (0.3%) were hospitalized for schizophrenia (ICD‐10 20.0–20.9) over the next 1–10 years. Results: Of 275 705 male adolescents screened, 513 (0.2%) were diagnosed as suffering from dysthymia by the Draft Board. Of these adolescents, 10/513 (2.0%) were later hospitalized for psychotic disorders (including schizophrenia, HR = 3.967, 95%CI (confidence intervals): 2.129–7.390), and 4/513 (0.8%) were later hospitalized for schizophrenia (HR = 2.664, 95%CI: 0.997–7.116). Conclusions: In this population‐based cohort of male adolescents, dysthymia was associated with increased risk for future psychotic disorders. Dysthymia in some adolescents might be a prodromal symptom, while in others it might be a risk factor for later psychosis. Clinicians assessing dysthymic adolescents should be aware that these symptoms might be part of the prodrome.     

The CCC2000 Birth Cohort Study of Register-Based Family History of Mental Disorders and Psychotic Experiences in Offspring

Psychotic experiences (PE) in individuals of the general population are hypothesized to mark the early expression of the pathology underlying psychosis. This notion of PE as an intermediate phenotype is based on the premise that PE share genetic liability with psychosis. We examined whether PE in childhood was predicted by a family history of mental disorder with psychosis rather than a family history of nonpsychotic mental disorder and whether this association differed by severity of PE. The study examined data on 1632 children from a general population birth cohort assessed at age 11–12 years by use of a semistructured interview covering 22 psychotic symptoms. The Danish national registers were linked to describe the complete family history of hospital-based psychiatric diagnoses. Uni- and multivariable logistic regressions were used to test whether a family history of any mental disorder with psychosis, or of nonpsychotic mental disorder, vs no diagnoses was associated with increased risk of PE in offspring (hierarchical exposure variable). The occurrence of PE in offspring was significantly associated with a history of psychosis among the first-degree relatives (adjusted relative risk [RR] = 3.29, 95% CI: 1.82–5.93). The risk increased for combined hallucinations and delusions (adjusted RR = 5.90, 95% CI: 2.64–13.16). A history of nonpsychotic mental disorders in first-degree relatives did not contribute to the risk of PE in offspring nor did any mental disorder among second-degree relatives. Our findings support the notion of PE as a vulnerability marker of transdiagnostic psychosis. The effect of psychosis in first-degree relatives may operate through shared genetic and environmental factors.Key words: psychosis, schizophrenia, epidemiology, family liability, general population, psychiatric family history     

Hospital Admission With Infection During Childhood and Risk for Psychotic Illness—A Population-based Cohort Study

A growing body of literature suggests that exposure to infections, particularly maternal infections, during pregnancy confers risk for later development of psychotic disorder. Though brain development proceeds throughout childhood and adolescence, the influence of infections during these ages on subsequent psychosis risk is insufficiently examined. The aim of this study was to investigate the potential association between infections during childhood and nonaffective psychoses in a large population-based birth cohort with follow up long enough to include peak incidence of nonaffective psychosis. We included all individuals born in Sweden between 1973 and 1985, (N = 1172879), with follow up on first time inpatient care with nonaffective psychosis from age 14 years until 2006, (N = 4638). Following adjustment for differences in sex, socioeconomic status, family history of psychosis, and hospital admissions involving noninfectious, nonpsychiatric care, we observed a small but statistically significant association between hospital admissions for infections, in general, throughout childhood (0–13 years) and a later diagnosis of nonaffective psychosis, hazard ratio (HR) = 1.10 (95% CI 1.03–1.18), and this association seemed to be driven by bacterial infection, HR = 1.23 (95% CI 1.08–1.40). Bacterial infections and central nervous system infections during preadolescence (10–13 years) conferred the strongest risk, HR 1.57 (95% CI 1.21–2.05) and HR 1.96 (95% CI 1.05–3.62), respectively. Although preadolescence appeared to be a vulnerable age period, and bacterial infection the most severe in relation to psychosis development, the present findings can also indicate an increased susceptibility to hospital admission for infections among children who will later develop nonaffective psychosis due to social or familial/genetic factors.Key words: psychosis, prenatal, schizophrenia, epidemiology, cohort study     

Do premorbid impairments predict emergent ‘prodromal’ symptoms in young relatives at risk for schizophrenia?

Aims: Individuals at risk for developing schizophrenia (SZ) in the future frequently exhibit subtle behavioural and neurobiological abnormalities in their childhood. A better understanding of the role of these abnormalities in predicting later onset of ‘prodromal’ symptoms or psychosis may help in early identification of SZ. Methods: In an ongoing prospective follow‐up study of young genetically at‐risk relatives of patients with SZ, we studied the prevalence of problems in premorbid social adjustment and childhood psychopathology and examined their relationship with the presence and progression of ‘prodromal’ symptoms of SZ. Results: Growth curve analyses showed that ‘prodromal’ symptoms, as measured by the Scale of ‘Prodromal’ Symptoms, increased during follow‐up. Premorbid maladjustment and childhood behavioural disturbances were cross‐sectionally correlated broadly with ‘prodromal’ symptomatology scores. Longitudinal analyses revealed that behavioural disturbances, but not childhood maladjustment at baseline, significantly predicted increases in ‘prodromal’ symptomatology during the 2‐year study period. Conclusion: Premorbid behavioural disturbance and maladjustment may predict the later emergence of ‘prodromal’ symptoms. ‘Prodromal’ symptoms in young at‐risk relatives may define a subgroup worthy of follow‐up into the age of risk for psychosis in order to cost‐effectively characterize the predictors of psychotic symptoms and SZ.     

Interplay Between Childhood Physical Abuse and Familial Risk in the Onset of Psychotic Disorders

Background: Childhood abuse is considered one of the main environmental risk factors for the development of psychotic symptoms and disorders. However, this association could be due to genetic factors influencing exposure to such risky environments or increasing sensitivity to the detrimental impact of abuse. Therefore, using a large epidemiological case-control sample, we explored the interplay between a specific form of childhood abuse and family psychiatric history (a proxy for genetic risk) in the onset of psychosis. Methods: Data were available on 172 first presentation psychosis cases and 246 geographically matched controls from the Aetiology and Ethnicity of Schizophrenia and Other Psychoses study. Information on childhood abuse was obtained retrospectively using the Childhood Experience of Care and Abuse Questionnaire and occurrence of psychotic and affective disorders in first degree relatives with the Family Interview for Genetic Studies. Results: Parental psychosis was more common among psychosis cases than unaffected controls (adjusted OR = 5.96, 95% CI: 2.09–17.01, P = .001). Parental psychosis was also associated with physical abuse from mothers in both cases (OR = 3.64, 95% CI: 1.06–12.51, P = .040) and controls (OR = 10.93, 95% CI: 1.03–115.90, P = .047), indicative of a gene-environment correlation. Nevertheless, adjusting for parental psychosis did not measurably impact on the abuse-psychosis association (adjusted OR = 3.31, 95% CI: 1.22–8.95, P = .018). No interactions were found between familial liability and maternal physical abuse in determining psychosis caseness. Conclusions: This study found no evidence that familial risk accounts for associations between childhood physical abuse and psychotic disorder nor that it substantially increases the odds of psychosis among individuals reporting abuse.Key words: family history, gene-environment correlation, gene-environment interaction, liability, schizophrenia, trauma     

Untreated psychotic illness in the survivors of violent suicide attempts

Background: Recent studies suggest that violence is more common in the first episode of psychosis than after treatment. Aim: To estimate the proportion of survivors of violent suicide attempts during psychotic illness who had not previously received treatment with antipsychotic medication. Methods: An audit of the medical records of patients admitted to an inner city trauma centre after having survived a jump of more than 3 m or a self‐inflicted gunshot wound or stab wound to a vital body part. Results: There were 88 survivors of violent suicide attempts. Thirty‐seven of those had a psychotic illness, including 33 with a schizophrenia‐spectrum psychosis. Of the 37, 18 (48.6%, 95% confidence interval (CI) 32.3–65.0%) had never received treatment for psychosis. Conclusion: As first episode psychosis is less common than previously treated psychosis, there appears to be a higher risk of violent suicide attempts during the first episode of psychosis than later in the illness.     

Childhood growth and future development of psychotic disorder among Helsinki high-risk children

BACKGROUND: The Helsinki High-Risk (HR) Study is a follow-up study of offspring (born between 1960 and 1964) of all females treated for schizophrenia spectrum disorders in mental hospitals in Helsinki before 1975, and controls. AIM: To compare childhood growth among HR and control children, and to determine if any patterns in childhood growth predict later development of psychotic disorders within the HR group. METHODS: We accessed growth information from childhood health cards, which we obtained for 114 HR and 53 control offspring. The growth of HR children was compared with that of control children. Within the HR group, we investigated whether any association existed between childhood growth patterns and morbidity from psychotic disorders using logistic regression models. RESULTS: The HR girls were shorter than controls at birth (p=0.030), but this disparity vanished by age 7. In contrast, HR boys were only slightly shorter at birth than controls, but the height difference increased with age, being statistically significant at 10 years (p=0.020). Among HR children, the combination of being in the lowest tertile for ponderal index at birth but in the highest tertile for BMI at 7 years predicted later development of schizophrenia (OR 22.8, 95% CI 2.0, >100, p=0.040). CONCLUSIONS: Catch-up growth increases the risk of schizophrenia among offspring of mothers with psychotic disorder. Whether this is an independent risk factor or merely a reflection of some other risk factors needs further research.     

Predictors of psychosis remission in psychotic disorders that co-occur with substance use

OBJECTIVE: To examine rates and predictors of psychosis remission at 1-year follow-up for emergency admissions diagnosed with primary psychotic disorders and substance-induced psychoses. METHOD: A total of 319 patients with comorbid psychosis and substance use, representing 83% of the original referred sample, were rediagnosed at 1 year postintake employing a research diagnostic assessment. Remission of psychosis was defined as the absence of positive and negative symptoms for at least 6 months. Likelihood ratio chi-square tests and multivariate logistic regression were the main means of analysis. RESULTS: Of those with a baseline diagnosis of primary psychotic disorder, 50% were in remission at 1 year postintake, while of those with a baseline diagnosis of substance-induced psychosis, 77% were in remission at this time point. Lower Positive and Negative Syndrome Scale (PANSS) symptom levels at baseline, better premorbid functioning, greater insight into psychosis, and a shorter duration of untreated psychosis predicted remission at 1 year in both diagnostic groups. No interaction effects of baseline predictors and diagnosis type were observed. A stepwise multivariate logistic regression holding baseline diagnosis constant revealed the duration of untreated psychosis (odds ratio [OR] = 0.97; 95% confidence interval [CI] = 0.95, 0.997), total PANSS score (OR = 0.98; 95% CI = 0.97, 0.987), Premorbid Adjustment Scale score (OR = 0.13; 95% CI = 0.02, 0.88), and Scale to Assess Unawareness of Mental Disorders unawareness score (OR = 0.84; 95% CI = 0.71, 0.993) as key predictors of psychosis remission. CONCLUSIONS: The association of better premorbid adjustment, a shorter duration of untreated psychosis, better insight into psychotic symptoms, and lower severity of psychotic symptoms with improved clinical outcome, reported previously in studies of schizophrenia, generalizes to psychosis remission in psychotic disorders that are substance induced.     

The relationship between risk of hospitalization for schizophrenia, SES, and cognitive functioning

Although most studies find low socioeconomic status (SES) to be associated with prevalence of schizophrenia, incidence studies do not generally support this, and some even report an inverse association. The objective of the current historical prospective study was to examine the relationship between SES, cognitive functioning, and risk of hospitalization for schizophrenia in a population-based sample of Israeli adolescents. Subjects were 811 487 adolescents, assessed by the Israeli military draft board for socio-demographic factors and cognitive functioning. Data on later hospitalization for schizophrenia were obtained from a population-based hospitalization registry. Findings indicated that when simply examining SES and schizophrenia, lower SES was associated with greater risk of hospitalization for schizophrenia (Hazard Ratio [HR] = 1.193, 95% CI = 1.091-1.303). When dividing the cohort into low, average, and high cognitive functioning, SES did not influence the risk for schizophrenia among individuals with high and average cognitive functioning, whereas among individuals with low cognitive functioning, high SES was found to slightly increase the risk for schizophrenia (HR = 1.21, 95% CI = 1.03-1.42). One possible explanation for this finding might be that among individuals from low socioeconomic backgrounds, low IQ may reflect decreased opportunities related to SES, whereas among individuals from high SES backgrounds, low IQ might reflect risk for later psychopathology.     

Do urbanicity and familial liability coparticipate in causing psychosis?

OBJECTIVE: The urban environment and familial liability are risk factors for psychotic illness, but it is not known whether a biological synergism exists between these two proxy causes. METHOD: The amount of biological synergism between familial liability (defined as a family history of delusions and/or hallucinations necessitating psychiatric treatment) and a five-level rating of population density of place of residence was estimated from the additive statistical interaction in a general population risk set of 5,550 individuals. RESULTS: Both the level of urbanicity (adjusted summary odds ratio=1.57, 95% CI=1.30-1.89) and familial liability (adjusted odds ratio=4.59, 95% CI=2.41-8.74) increased the risk for psychotic disorder, independently of each other. However, the effect of urbanicity on the additive scale was much larger for individuals with evidence of familial liability (risk difference=2.58%) than in those without familial liability (risk difference=0.40%). An estimated 60%-70% of the individuals exposed to both urbanicity and familial liability had developed psychotic disorder because of the synergistic action of the two proxy causes. CONCLUSIONS: Given that familial clustering of psychosis is thought to reflect the effect of shared genes, the findings support a mechanism of gene-environment interaction in the causation of psychosis.     

Sex differences in symptoms of psychosis in a non-selected,general population sample

BACKGROUND: Little is known about sex differences in psychosis beyond the borders of clinical disorder. METHODS: A general population sample of 7,076 subjects was assessed using the Composite International Diagnostic Interview, in order to explore sex differences in the prevalence of any positive and negative symptoms of psychosis, and to examine to what degree any differences could be explained by differences in level of affective symptoms. RESULTS: Male sex was associated with higher prevalence of negative symptoms (OR = 1.6, 95% CI = 1.0, 2.5), independent of differences in affective symptoms and presence of DSM-III-R psychotic disorder. Women had higher rates of positive psychotic experiences (OR = 0.8, 95% CI = 0.7, 0.9), but this difference disappeared after adjustment for depressive symptoms (adjusted OR = 1.2, 95% CI = 0.9, 1.5). CONCLUSION: The sex differences in psychopathology that are seen in schizophrenia are expressed beyond the clinical phenotype, suggesting sex-dependent continuous and normal variation of several psychosis dimensions. The higher rates of positive psychotic experiences seen in women may be secondary to differences in the rate of affective symptoms.     

Generalized and specific neurocognitive deficits in prodromal schizophrenia.

BACKGROUND: Neurocognitive deficits are considered to be central to the pathophysiology of schizophrenia, and the neurodevelopmental model suggests that such deficits precede full-blown psychosis. The present study examined performance on a broad neuropsychological battery of young subjects considered to be at clinical high risk for schizophrenia, who were subsequently followed to determine clinical outcome. METHODS: Subjects were 38 clinical high-risk patients (58% male patients; mean age = 16.5) and 39 sex- and age-matched healthy control subjects. At baseline, all high-risk patients had attenuated (subpsychotic) schizophrenialike positive symptoms. Clinical follow-up data of at least 6 months duration was available on 33 patients, of whom 12 developed nonaffective psychotic disorders. RESULTS: At baseline, clinical high-risk patients had significantly impaired global cognitive performance relative to control subjects and to estimates of their own prior intellectual functioning. Measures of verbal memory and executive functioning/working memory showed significantly greater impairments; visuospatial functioning was relatively spared. Prodromal patients who later developed psychosis had significantly lower verbal memory scores at baseline compared with patients who remained nonpsychotic. CONCLUSIONS: Verbal memory deficits may be an important risk marker for the development of schizophrenia-spectrum psychotic disorders, possibly indicating the presence of a prefrontal-hippocampal neurodevelopmental abnormality. Generalized neurocognitive impairment may be a nonspecific vulnerability marker.     

Childhood abuse as a risk factor for psychotic experiences

OBJECTIVE: To examine the hypothesis that individuals from the general population who report childhood abuse are at increased risk of developing positive psychotic symptoms. METHOD: Data were derived from a general population sample of 4045 subjects aged 18-64 years. First ever onset of positive psychotic symptoms at 2-year follow-up were assessed using the Composite International Diagnostic Interview and additional clinical interviews if necessary. Childhood abuse was assessed at baseline. RESULTS: Baseline reported childhood abuse predicted development of positive psychotic symptoms associated with need for care [odds ratio (OR) = 11.5, 95% CI 2.6-51.6]. This association remained after adjustment for demographic variables, reported risk factors and presence of any lifetime psychiatric diagnosis at baseline (OR = 7.3, 95% CI 1.1-49.0). CONCLUSION: The results suggest that early childhood trauma increases the risk for positive psychotic symptoms. This finding fits well with recent models that suggest that early adversities may lead to psychological and biological changes that increase psychosis vulnerability.     

Investigating the association between neurocognition and psychosis in bipolar disorder: further evidence for the overlap with schizophrenia

Objectives: In schizophrenia, a distinction is made between psychosis with developmental and cognitive impairment on the one hand and psychosis without developmental impairment and positive symptoms on the other. In this study, we investigated whether this model can be extended to bipolar disorder by testing the hypothesis that neurocognitive functioning is inversely related to positive psychotic symptoms in bipolar disorder. Methods: Neurocognitive functioning and psychopathology were assessed in (i) 76 patients with bipolar disorder, (ii) 39 of their healthy first‐degree relatives, and (iii) 61 healthy controls. Cognitive performance of bipolar patients and their first‐degree relatives was investigated, taking into account the possible moderating effect of the level of expression of psychosis in patients and relatives. Results: Bipolar patients showed impaired cognitive performance on multiple cognitive domains, whereas performance of their relatives was comparable to that of controls. A history of psychotic symptoms in patients was suggestive of less likelihood of cognitive alterations in relatives, and the presence of subclinical psychotic symptoms within the group of relatives predicted better cognitive performance. Conclusions: The finding of similar psychosis‐cognition associations in bipolar disorder as implied by the two pathways leading to nonaffective psychotic disorders suggests that this model might be extended to the continuum spanning affective and nonaffective psychosis. This is in line with the idea of a partially overlapping vulnerability to bipolar disorder and schizophrenia and provides an explanation for the apparent differences in cognitive alterations in those at risk for the two disorders.     

Theory of mind impairment: a distinct trait‐marker for schizophrenia spectrum disorders and bipolar disorder?

Objective: The aim of this study was to critically review the literature in order to determine if Theory of Mind (ToM) impairment can be considered a trait‐marker for schizophrenia spectrum disorders and bipolar disorder (BD). Method: After a thorough literature search, we reviewed the empirical studies investigating ToM impairments in remitted schizophrenia patients, first episode patients, subjects at high‐risk (HR) for psychosis and first‐degree relatives of schizophrenia patients. Studies investigating ToM impairment in other schizophrenia spectrum conditions, affective psychosis and BD were also reviewed. Results: ToM abnormalities exist at onset and continue throughout the course of schizophrenia, persist into remission, and while less severe, are apparent in HR populations. Mentalizing impairments are also observed in other forms of psychotic illness and BD. Conclusion: Mentalizing impairment in schizophrenia spectrum disorders and BD might reflect underlying general cognitive deficits and residual symptom expression, rather than representing a specific trait‐marker.     

Obstetric complications and transition to psychosis in an "ultra" high risk sample

OBJECTIVE: An association between birth and pregnancy complications and the later development of schizophrenia has been described for decades and obstetric complications (OCs) have been proposed as a vulnerability marker for psychosis in line with the neurodevelopmental hypothesis of psychotic disorders. Previous studies of OCs have focused on established schizophrenia. In this study, the association between OCs and the development of psychotic disorder was studied in a group of 74 young people identified as being at very high risk for the first onset of psychosis. METHOD: The "ultra" high risk (UHR) cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-eight per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of OCs experienced by the UHR cohort was assessed at intake. RESULTS: Obstetric complications were not associated with the later development of psychosis in the UHR group included in this study. CONCLUSIONS: This study does not support a role for OCs as a risk factor for the later development of psychosis; however, we cannot conclude that they should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study suggest that it may be premature to dismiss OCs as a risk factor for the development of psychosis and further research is urged in this area.     

Intervention to improve level of overall functioning and mental condition of adolescents at high risk of developing first-episode psychosis in Finland

Aim: Being at high risk of developing psychosis has been suggested to be a result of a combination of acute life stressors and trait‐like vulnerability to psychosis. Reducing levels of stress could support overall functioning and mental condition in those at risk. Methods: The Jorvi Early Psychosis Recognition and Intervention (JERI) project at Helsinki University Central Hospital, Jorvi Hospital, Finland, is an early intervention team for adolescents at risk of developing first‐episode psychosis. The project is based on the idea of multiprofessional, community, home, family and network‐oriented, stress‐reducing, overall functioning‐supporting, low‐threshold care. The JERI team meets multiprofessionally with adolescents in their natural surroundings, for example, at school or at home, together with their parents, network and community co‐worker, who has originally contacted the JERI team because of unclear mental health problems. Subjects were assessed with the PROD‐prodromal screen to identify those at risk of developing first‐episode psychosis. Results: Statistically significant difference between baseline and follow‐up measures was found in at risk subjects (n = 28) in scales of overall functioning (P = 0.000), depression (P = 0.001), anxiety (P = 0.001), quality of life (QOL) and pre‐psychotic symptoms. Conclusions: JERI‐type intervention may improve level of overall functioning and support mental condition in adolescents at risk of developing first‐episode psychosis, even though further study with larger numbers of subjects, with a control group and with a longer follow‐up time, is needed.     

Association Between Childhood Green Space,Genetic Liability,and the Incidence of Schizophrenia

Childhood exposure to green space has previously been associated with lower risk of developing schizophrenia later in life. It is unclear whether this association is mediated by genetic liability or whether the 2 risk factors work additively. Here, we investigate possible gene–environment associations with the hazard ratio (HR) of schizophrenia by combining (1) an estimate of childhood exposure to residential-level green space based on the normalized difference vegetation index (NDVI) from Landsat satellite images, with (2) genetic liability estimates based on polygenic risk scores for 19 746 genotyped individuals from the Danish iPSYCH sample. We used information from the Danish registers of health, residential address, and socioeconomic status to adjust HR estimates for established confounders, ie, parents’ socioeconomic status, and family history of mental illness. The adjusted HRs show that growing up surrounded by the highest compared to the lowest decile of NDVI was associated with a 0.52-fold (95% confidence interval [CI]: 0.40 to 0.66) lower schizophrenia risk, and children with the highest polygenic risk score had a 1.24-fold (95% CI: 1.18 to 1.30) higher schizophrenia risk. We found that NDVI explained 1.45% (95% CI: 1.07 to 1.90) of the variance on the liability scale, while polygenic risk score for schizophrenia explained 1.01% (95% CI: 0.77 to 1.46). Together they explained 2.40% (95% CI: 1.99 to 3.07) with no indication of a gene–environment interaction (P = .29). Our results suggest that risk of schizophrenia is associated additively with green space exposure and genetic liability, and provide no support for an environment-gene interaction between NDVI and schizophrenia.