Childhood dyspraxia predicts adult-onset nonaffective-psychosis-spectrum disorder.

Several neurological variables have been investigated as premorbid biomarkers of vulnerability for schizophrenia and other related disorders. The current study examined whether childhood dyspraxia predicted later adult nonaffective-psychosis-spectrum disorders. From a standardized neurological examination performed with children (aged 10-13) at genetic high risk of schizophrenia and controls, several measures of dyspraxia were used to create a scale composed of face/head dyspraxia, oral articulation, ideomotor dyspraxia (clumsiness), and dressing dyspraxia (n = 244). Multinomial logistic regression showed higher scores on the dyspraxia scale predict nonaffective-psychosis-spectrum disorders relative to other psychiatric disorders and no mental illness outcomes, even after controlling for genetic risk, χ2 (4, 244) = 18.61, p < .001. Findings that symptoms of dyspraxia in childhood (reflecting abnormalities spanning functionally distinct brain networks) specifically predict adult nonaffective-psychosis-spectrum disorders are consistent with a theory of abnormal connectivity, and they highlight a marked early-stage vulnerability in the pathophysiology of nonaffective-psychosis-spectrum disorders.

The association between p3 amplitude at age 11 and criminal offending at age 23.

Reduced P3 amplitude to targets is an information-processing deficit associated with adult antisocial behavior and may reflect dysfunction of the temporal-parietal junction. This study aims to examine whether this deficit precedes criminal offending. From a birth cohort of 1,795 children, 73 individuals who become criminal offenders at age 23 and 123 noncriminal individuals were assessed on P3 amplitude. The two groups did not differ on gender, ethnicity, and social adversity. P3 amplitude was measured over the temporal-parietal junction during a visual continuous performance task at age 11, together with antisocial behavior. Criminal convictions were assessed at age 23. Reduced P3 amplitude at age 11 was associated with increased antisocial behavior at age 11. Criminal offenders showed significantly reduced P3 amplitudes to target stimuli compared to controls. Findings remained significant after controlling for antisocial behavior and hyperactivity at age 11 and alcoholism at age 23. P3 deficits at age 11 are associated with adult crime at age 23, suggesting that reduced P3 may be an early neurobiological marker for cognitive and affective processes subserved by the temporal-parietal junction that place a child at risk for adult crime.

REM, not incubation, improves creativity by priming associative networks.

The hypothesized role of rapid eye movement (REM) sleep, which is rich in dreams, in the formation of new associations, has remained anecdotal. We examined the role of REM on creative problem solving, with the Remote Associates Test (RAT). Using a nap paradigm, we manipulated various conditions of prior exposure to elements of a creative problem. Compared with quiet rest and non-REM sleep, REM enhanced the formation of associative networks and the integration of unassociated information. Furthermore, these REM sleep benefits were not the result of an improved memory for the primed items. This study shows that compared with quiet rest and non-REM sleep, REM enhances the integration of unassociated information for creative problem solving, a process, we hypothesize, that is facilitated by cholinergic and noradrenergic neuromodulation during REM sleep.

A developmental increase in allostatic load from ages 3 to 11 years is associated with increased schizotypal personality at age 23 years.

Although allostatic load has been investigated in mood and anxiety disorders, no prior study has investigated developmental change in allostatic load as a precursor to schizotypal personality. This study employed a multilevel developmental framework to examine whether the development of increased allostatic load, as indicated by impaired sympathetic nervous system habituation from ages 3 to 11 years, predisposes to schizotypal personality at age 23 years. Electrodermal activity to six aversive tones was recorded in 995 subjects at age 3 years and again at 11 years. Habituation slopes at both ages were used to create groups who showed a developmental increase in habituation (decreased allostatic load), and those who showed a developmental decrease in habituation (increased allostatic load). Children who showed a developmental increase in allostatic load from ages 3 to 11 years had higher levels of schizotypal personality at 23 years. A breakdown of total schizotypy scores demonstrated specificity of findings to cognitive-perceptual features of schizotypy. Findings are the first to document a developmental abnormality in allostasis in relation to adult schizotypal personality. The relative failure to develop normal habituation to repeated stressors throughout childhood is hypothesized to result in an accumulation of allostatic load and consequently increased positive symptom schizotypy in adulthood.

A prospective study of smoking in young women and risk of later psychiatric hospitalization.

BACKGROUND: It is not known whether smoking is a risk factor for mental disorders. AIMS: To investigate the prospective associations between cigarette smoking in pregnant women and a range of psychiatric hospital diagnoses. METHOD: Using data from the Copenhagen Perinatal Cohort, we followed a cohort of 7926 young women from 1959-61 to 2007, linking data on cigarette smoking with psychiatric admission diagnoses obtained from the Danish Psychiatric Central Register. The women were interviewed by a physician in 1959-61 when data was obtained on smoking and other health related variables. With adjustment for age, social class and psychopharmacological treatment at baseline, the effects of smoking on the risk of (hierarchically ordered) major categories of mental disorders were examined. RESULTS: Significant positive associations were observed between number of cigarettes smoked and schizophrenia spectrum disorder, substance use-related disorder, a broad category of other non-psychotic disorders, and any psychiatric registration. For affective spectrum disorders, there was a significant, but non-linear association. CONCLUSION: Number of cigarettes smoked in young adulthood significantly predicted a range of psychiatric admission diagnoses and, for most diagnostic categories, evidence of a dose-response relationship was observed.

Reduced electrodermal fear conditioning from ages 3 to 8 years is associated with aggressive behavior at age 8 years.

BACKGROUND: Poor fear conditioning characterizes adult psychopathy and criminality, but it is not known whether it is related to aggressive/antisocial behavior in early childhood. METHODS: Using a differential, partial reinforcement conditioning paradigm, electrodermal activity was recorded from 200 male and female children at ages 3, 4, 5, 6, and 8 years. Antisocial/aggressive and hyperactive-inattentive measures were collected at age 8. RESULTS: Poor electrodermal fear conditioning from ages 3 to 8 years was associated with aggressive behavior at age 8 in both males and females. CONCLUSIONS: Results indicate that the relationship between poor fear conditioning and aggression occurs early in childhood. Enhanced electrodermal fear conditioning may protect children against future aggressive/violent behavior. Abnormal amygdala functioning, as indirectly assessed by fear conditioning, may be one of the factors influencing the development of childhood aggression.

The development of skin conductance fear conditioning in children from ages 3 to 8 years.

Although fear conditioning is an important psychological construct implicated in behavioral and emotional problems, little is known about how it develops in early childhood. Using a differential, partial reinforcement conditioning paradigm, this longitudinal study assessed skin conductance conditioned responses in 200 children at ages 3, 4, 5, 6, and 8 years. Results demonstrated that in both boys and girls: (1) fear conditioning increased across age, particularly from ages 5 to 6 years, (2) the three components of skin conductance fear conditioning that reflect different degrees of automatic and controlled cognitive processes exhibited different developmental profiles, and (3) individual differences in arousal, orienting, and the unconditioned response were associated with individual differences in conditioning, with the influence of orienting increasing at later ages. This first longitudinal study of the development of skin conductance fear conditioning in children both demonstrates that children as young as age 3 years evidence fear conditioning in a difficult acquisition paradigm, and that different sub-components of skin conductance conditioning have different developmental trajectories.

Premorbid IQ and adult schizophrenia spectrum disorder: verbal Performance subtests.

The present prospective high-risk study examined associations between childhood scores on five Wechsler Intelligence Scale for Children (WISC) subtests (vocabulary, similarities, block design, object assembly, and mazes) and later development of schizophrenia spectrum disorders (SSD). The sample comprised 244 high-risk or control children who were administered the WISC subtests at age 10 to 13 years in 1972. Adult psychiatric data were gathered from psychiatric interviews in 1992-93 and from the Danish Psychiatric Central Register in 2007. Thirty-two participants had developed SSD, 79 other psychiatric disorders (OPD), and 133 had no diagnosis (ND). The SSD group obtained lower scores than the ND group on all subtests and IQs, but when adjusted for sex and parental social status only significantly lower scores on similarities, object assembly, mazes, and total IQ. Compared with the ND group, the OPD group obtained significantly lower scores on similarities, vocabulary, verbal IQ, and total IQ. The only significant difference between the SSD and OPD groups was on object assembly (OPD performed at the level of ND). The results suggest a premorbid deficit in general intelligence in individuals who later develop SSD. The results for the OPD group support recent studies demonstrating that premorbid IQ deficits may characterize a wide range of psychiatric disorders.

Association between prenatal exposure to bacterial infection and risk of schizophrenia.

Recent research suggests that prenatal exposure to nonviral infection may be associated with increased risk of schizophrenia, and we hypothesized an association between maternal bacterial infection during pregnancy and elevated offspring risk of schizophrenia. Data on maternal infections from the Copenhagen Perinatal Cohort were linked with the Danish National Psychiatric Register. Offspring cases of narrowly defined schizophrenia (International Classification of Diseases, Eighth Revision [ICD-8]) and more broadly defined schizophrenia (ICD-8 and ICD-10) were identified before the ages of 32-34 and 45-47 years, respectively. The effect of prenatal exposure to bacterial infections was adjusted for prenatal exposure to analgesics and parental social status. In a risk set of 7941 individuals, 85 cases (1.1%) of ICD-8 schizophrenia were identified by the age of 32-34 years and 153 cases (1.9%) of more broadly defined schizophrenia by the age of 45-47 years. First-trimester exposure conferred an elevated risk of ICD-8 schizophrenia (odds ratio 2.53; 95% confidence interval [CI] 1.07-5.96) and also of broadly defined schizophrenia (odds ratio 2.14; 95% CI 1.06-4.31). Second-trimester exposure also conferred a significantly elevated risk of schizophrenia but only in unadjusted analyses. These findings suggest a relationship between maternal bacterial infection in pregnancy and offspring risk of schizophrenia, and this effect was somewhat stronger for ICD-8 schizophrenia with earlier onset. Post hoc analyses showed that upper respiratory tract and gonococcal infections were associated with elevated risk of the disease. An association between risk of schizophrenia and prenatal exposure to bacterial infections might be mediated through transplacental passage of maternally produced cytokines in response to bacterial infections.

Suicide and mental illness in parents and risk of suicide in offspring: a birth cohort study.

BACKGROUND: A family history of completed suicide and psychiatric illness has been identified as risk factors for suicide. AIMS: To examine the risk of offspring suicide in relation to parental history of suicide and other parental risk factors. METHOD: The study population consisted of 7,177 adult offspring born 1959-1961 and their parents from the Copenhagen Perinatal Cohort. Cohort members and their parents who had committed suicide were identified in the Danish Causes of Death Registry (follow-up until December 31, 2005), while information on psychiatric hospitalisation history was obtained from the Danish Psychiatric Central Research Register. RESULTS: Forty-eight cohort members, 77 mothers and 133 fathers had committed suicide during the follow-up. Independent of parental psychiatric illness and social status, parental suicide significantly increased suicide risk in offspring (hazard ratio 4.40 with 95% CI 1.81-10.69). A stronger effect of parental suicide was observed in offspring without a history of psychiatric hospitalisation. CONCLUSION: Parental history of suicide is a risk factor for suicide in offspring, but primarily in offspring without psychiatric hospitalisation.

Early temperamental and psychophysiological precursors of adult psychopathic personality.

Emerging research on psychopathy in children and adolescents raises the question of whether indicators, such as temperament or psychophysiology, exist very early in life in those with a psychopathic-like personality in adulthood. This study tests the hypothesis that individuals who are more psychopathic in adulthood would be less fearful and inhibited and more stimulation seeking/sociable at age 3 and that they would also show reduced age 3 skin-conductance (SC) responsivity. In a community sample of 335 3-year-olds, behavioral measures of temperament were taken and electrodermal activity was recorded in response to both orienting and aversive tones. R. D. Hare's (1985) Self-Report Psychopathy scale (SRP-II) was administered at follow-up at age 28. Individuals scoring higher on the measure were significantly less fearful and inhibited, were more sociable, and displayed longer SC half-recovery times to aversive stimuli compared with controls at age 3. Contrary to predictions, they also showed increased autonomic arousal and SC orienting. Findings appear to be the first to suggest that a prospective link may exist between temperament and psychophysiology in very young children and psychopathic personality in adulthood.

Early weaning and hospitalization with alcohol-related diagnoses in adult life.

OBJECTIVE: This study attempted to determine whether lack of breast-feeding or a short duration of breast-feeding during infancy is associated with an elevated risk of hospitalization with alcohol-related diagnoses in adult life. METHOD: The study was a prospective longitudinal birth cohort design conducted in a sample of 6,562 men and women, all of whom were born in Copenhagen, Denmark, between October 1959 and December 1961. The sample was divided into two categories based on duration of breast-feeding, as assessed by a physician interview with mothers at a 1-year examination. Psychiatric hospitalizations with alcohol-related diagnoses according to ICD-8 or ICD-10 were identified in the Danish Psychiatric Central Register in 1999. Nine potential confounders were included as covariates: gender of the cohort member, maternal age, parental social status, maternal prenatal smoking, unwanted pregnancy, maternal and paternal psychiatric hospitalization with alcohol-related diagnosis, and maternal and paternal psychiatric hospitalization with other diagnosis. RESULTS: Alcohol-related diagnoses were more frequent in men, but the results were comparable for men and women. The adjusted predictive effect of early weaning was 1.47. Elevated relative risks were also associated with maternal smoking during pregnancy (1.52) and unwanted pregnancy status (1.59). Other independent predictors were male gender, maternal psychiatric hospitalization with alcohol-related diagnosis, and low parental social status. CONCLUSIONS: Independent of a number of other risk factors for alcoholism, a significant association between early weaning and elevated risk of hospitalization with alcohol-related diagnoses was observed.

Premorbid childhood ocular alignment abnormalities and adult schizophrenia-spectrum disorder.

This study examined the relation between childhood ocular alignment deficits and adult psychiatric outcomes among children at high-risk for schizophrenia and controls. A sample of 265 Danish children was administered a standardized eye exam assessing strabismus and related ocular alignment deficits. All children whose mothers or fathers had a psychiatric diagnosis of schizophrenia comprised the first group (N=90). Children who had at least one parent with a diagnosis other than schizophrenia comprised the first matched control group (N=93). The second control group consisted of children with no parental diagnoses (N=82). In 1992, adult psychiatric outcome data were obtained for 242 of the original subjects. It was found that children who later developed a schizophrenia-spectrum disorder had significantly higher eye exam scale and strabismus scale scores compared to children who developed other non-psychotic psychopathology and children who did not develop a mental illness. The mean rank for children in the high-risk group (offspring of parents with schizophrenia) on the eye scale and the strabismus scale was greater than the mean rank for children in the matched control groups (both offspring of parents with other non-psychotic disorder and no mental illness), although the results failed to reach statistical significance. Results from this study suggest a premorbid relation between ocular deficits and schizophrenia-spectrum disorders in childhood prior to onset of psychopathology in adulthood. Strabismus may serve as a premorbid marker for spectrum disorders and may have implications for the understanding of early aberrant neurological development related to later schizophrenia-spectrum disorders.

Premorbid neurocognitive functioning in schizophrenia spectrum disorder.

A prospective study based on the U.S. National Collaborative Perinatal Project and using the Wechsler Intelligence Scale for Children (WISC) found lower test scores for the Coding subtest in preschizophrenic children than in their unaffected siblings. Using data on cognitive functioning in adolescence, the aim of the present prospective study was to examine whether low scores on Coding is associated with the risk of developing schizophrenia spectrum disorders. The 12 subtests of the WISC were administered to 311 children and adolescents with a mean age of 15.1 years (range: 8 to 20 years), and the diagnostic assessment (DSM-IIIR) was conducted by senior clinicians 25 years later. The group with schizophrenia spectrum disorder consisted of 84 individuals, and this group obtained significantly lower scores on Coding than nonschizophrenic controls. This difference could not be explained by differences in WISC IQ. Logistic regression analysis controlling for age at examination, gender, and social status yielded a significant, but relatively weak, association between low Coding test score and risk of schizophrenia spectrum disorder. For each unit increase in the Coding raw score, the adjusted odds ratio was 0.97 (95% CI 0.94-1.00) (p = .022), and the risk of schizophrenia spectrum disorder decreased by 3% (95% CI 6 to 0%). The Coding deficit on the WISC may indicate deficits in perceptual motor speed or in working memory processing speed in young individuals who later develop schizophrenia, schizotypal personality disorder, or other disorders within the schizophrenia spectrum.

Childhood pegboard task predicts adult-onset psychosis-spectrum disorder among a genetic high-risk sample.

Motor abnormalities have been established as a core aspect of psychosis-spectrum disorders, with numerous studies identifying deficits prior to clinical symptom presentation. Additional research is needed to pinpoint standardized motor assessments associated with psychosis-spectrum disorders prior to illness onset to enhance prediction and understanding of etiology. With a long history of findings among people with diagnosable psychosis-spectrum disorders, but little research conducted during the premorbid phase, pegboard tasks are a viable and understudied measure of premorbid for psychosis motor functioning. In the current study, examining data from the Copenhagen Perinatal Cohort, the Simultaneous Pegs Test was performed with children (n=244, aged 10-13) at genetic high risk for psychosis (n=94) and controls (n=150). Findings suggest that children who eventually developed a psychosis-spectrum disorder (n=33) were less likely to successfully complete the task within time limit relative to controls (χ2(2, N=244)=6.94, p=0.03, ϕ=0.17). Additionally, children who eventually developed a psychosis-spectrum disorder took significantly longer to complete the task relative to controls (χ2(2, N=244)=7.06, p=0.03, ϕ=0.17). As pegboard performance is thought to tap both diffuse and specific brain networks, findings suggest that pegboard tests may be useful premorbid measures of motor functioning among those on a trajectory towards a psychosis-spectrum disorder.

Childhood cognitive measures as predictors of alcohol use and problems by mid-adulthood in a non-Western cohort.

This study examined the relationship between childhood cognitive functioning and academic achievement and subsequent alcohol use and problems in a non-Western setting. We examined longitudinal data from a birth cohort sample (N = 1,795) who were assessed at age 11 years on cognitive measures and then approximately 25 years later on lifetime alcohol use and alcohol use disorder symptom count. The sample was from Mauritius (eastern Africa), which allowed us to examine these relationships in a non-Western society with a different social structure than is typical of prior cognitive studies on primarily White samples in Western societies. Poorer performance on the Trail Making Test B-A in childhood predicted being a lifetime drinker, even after covarying for gender, childhood psychosocial adversity, and Muslim religion. Lower academic achievement and verbal IQ, but not performance IQ, were predictive of subsequent alcohol problems after including demographic covariates; the relationship between verbal IQ and alcohol problems was stronger in females than males. A nonlinear relationship emerged for Trails, suggesting that only more extreme impairment on this measure was indicative of later alcohol problems. Results of this study provide evidence that verbal deficits and poor academic performance exist in a general cohort sample by age 11 years (when 99% were nondrinkers) for those who go on to develop alcohol problems. (PsycINFO Database Record

Premorbid multivariate prediction of adult psychosis-spectrum disorder: A high-risk prospective investigation.

Premorbid prediction of psychosis-spectrum disorders has implications for both understanding etiology and clinical identification. The current study used a longitudinal high-risk for psychosis design that included children of parents with schizophrenia as well as two groups of controls (children whose parents had no mental illness, and children with at least one parent with a non-psychotic psychiatric diagnosis). Premorbid neurological factors and an indication of social function, as measured when participants were 10-13years of age, were combined to predict psychosis-spectrum disorders in adulthood. Through a combination of childhood predictors, the model correctly classified 82% (27 of 33) of the participants who eventually developed a psychosis-spectrum outcome in adulthood. With replication, multivariate premorbid prediction, including genetic risk, social, and neurological variables, could potentially be a useful complementary approach to identifying individuals at risk for developing psychosis-spectrum disorders.

Effects of environmental enrichment at ages 3-5 years on schizotypal personality and antisocial behavior at ages 17 and 23 years.

OBJECTIVE: Methods to prevent two major mental disorders, schizophrenia and conduct disorder, have been elusive. This study assessed the effects of an early nutritional, educational, and physical exercise enrichment program on adult outcome for schizotypal personality, conduct disorder, and criminal behavior. METHOD: Eighty-three children were assigned to an experimental enrichment program from ages 3 to 5 years and matched on temperament, nutritional, cognitive, autonomic, and demographic variables with 355 children who experienced usual community conditions (control group). Both self-report and objective measures of schizotypal personality and antisocial behavior were obtained when the subjects were ages 17 and 23 years. RESULTS: Subjects who participated in the enrichment program at ages 3-5 years had lower scores for schizotypal personality and antisocial behavior at age 17 years and for criminal behavior at age 23 years, compared with the control subjects. The beneficial effects of the intervention were greater for children who showed signs of malnutrition at age 3 years, particularly with respect to outcomes for schizotypy at ages 17 and 23 and for antisocial behavior at age 17. CONCLUSIONS: The results are consistent with an increasing body of knowledge that implicates an enriched, stimulating environment in beneficial psychological and behavioral outcomes. These findings have potential implications for the prevention of schizophrenia and criminal behavior.

Malnutrition at age 3 years and externalizing behavior problems at ages 8, 11, and 17 years.

OBJECTIVE: Poor nutrition is thought to predispose to externalizing behavior problems, but to date there appear to have been no prospective longitudinal studies testing this hypothesis. This study assessed whether 1) poor nutrition at age 3 years predisposes to antisocial behavior at ages 8, 11, and 17 years, 2) such relationships are independent of psychosocial adversity, and 3) IQ mediates the relationship between nutrition and externalizing behavior problems. METHOD: The participants were drawn from a birth cohort (N=1,795) in whom signs of malnutrition were assessed at age 3 years, cognitive measures were assessed at ages 3 and 11 years, and antisocial, aggressive, and hyperactive behavior was assessed at ages 8, 11, and 17 years. RESULTS: In relation to comparison subjects (N=1,206), the children with malnutrition signs at age 3 years (N=353) were more aggressive or hyperactive at age 8 years, had more externalizing problems at age 11, and had greater conduct disorder and excessive motor activity at age 17. The results were independent of psychosocial adversity and were not moderated by gender. There was a dose-response relationship between degree of malnutrition and degree of externalizing behavior at ages 8 and 17. Low IQ mediated the link between malnutrition and externalizing behavior at ages 8 and 11. CONCLUSIONS: These results indicate that malnutrition predisposes to neurocognitive deficits, which in turn predispose to persistent externalizing behavior problems throughout childhood and adolescence. The findings suggest that reducing early malnutrition may help reduce later antisocial and aggressive behavior.

Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

OBJECTIVE: Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code 295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug treatment during pregnancy. RESULTS: In a risk set of 7,866 individuals, 84 cases of schizophrenia were found (1.1% prevalence). Logistic multiple regression analysis identified the following independent risk factors: maternal hypertension (odds ratio=1.69 [95% CI=1.02-2.80]), diuretic treatment in the third trimester (odds ratio=2.55 [95% CI=1.21-5.37]), and maternal schizophrenia (odds ratio=11.12 [95% CI=4.60-29.91]). Prenatal exposure to both hypertension and diuretic treatment in the third trimester conferred a 4.01-fold (95% CI=1.41-11.40) elevated risk. CONCLUSIONS: Children of mothers with hypertension in pregnancy plus diuretic treatment in the third trimester were at significantly increased risk of developing schizophrenia. In pregnancies complicated by hypertension, diuretics may interfere with aspects of fetal neurodevelopment and thus increase the vulnerability of offspring to the development of schizophrenia later in life.