Early motor developmental milestones and schizophrenia: A systematic review and meta-analysis.

The neurodevelopmental hypothesis of schizophrenia proposes that impaired brain development is a cause of the illness. Early motor developmental milestones, such as learning to walk, are predictors of later schizophrenia but studies have not been systematically reviewed. The aim of the present systematic review and meta-analysis was to explore the association between early motor developmental milestones and the risk of adult schizophrenia. In addition, we updated a systematic review on motor function and risk of schizophrenia. The PubMed, PsycINFO and Scopus databases were searched for original research articles published up to July 2015. Motor milestones were measured between ages 0 and 13years. Random effect meta-analysis calculated effect estimates (Hedges' g) for the association between individual motor milestones and schizophrenia risk. An electronic database and selected articles reference list search identified 5990 articles after removing duplicates. Sixty-nine full text articles were assessed for eligibility of which six were included in the review. Five studies provided sufficient data for meta-analyses. The following motor milestones were significantly associated with adult schizophrenia risk: walking unsupported (g=0.46; 95% CI 0.27-0.64; p<0.001), standing unsupported (g=0.28; 0.16-0.40; p<0.001) and sitting unsupported (g=0.18; 0.05-0.31; p=0.007). Results for the milestones 'holding head up' and 'grabbing object' were not statistically significant. Delayed walking, sitting and standing unsupported were associated with adult onset schizophrenia. The findings emphasise the importance of timely achievement of these motor milestones in childhood and can contribute to the identification of individuals at risk of psychosis.

A comparison of the cumulative incidence and early risk factors for psychotic disorder in young adults in the Northern Finland Birth Cohorts 1966 and 1986.

AIMS: Few studies have compared time trends for the incidence of psychosis. To date, the results have been inconsistent, showing a decline, an increase or no significant change. As far as we know, no studies explored changes in prevalence of early risk factors. The aim of this study was to investigate differences in early risk factors and cumulative incidences of psychosis by type of psychosis in two comparable birth cohorts. METHODS: The Northern Finland Birth cohorts (NFBCs) 1966 (N = 12 058) and 1986 (N = 9432) are prospective general population-based cohorts with the children followed since mother's mid-pregnancy. The data for psychoses, i.e. schizophrenia (narrow, spectrum), bipolar disorder with psychotic features, major depressive episode with psychotic features, brief psychosis and other psychoses (ICD 8-10) were collected from nationwide registers including both inpatients and outpatients. The data on early risk factors including sex and place of birth of the offspring, parental age and psychosis, maternal education at birth were prospectively collected from the population registers. The follow-up reached until the age of 27 years. RESULTS: An increase in the cumulative incidence of all psychoses was seen (1.01% in NFBC 1966 v. 1.90% in NFBC 1986; p < 0.001), which was due to an increase in diagnosed affective and other psychoses. Earlier onset of cases and relatively more psychoses in women were observed in the NFBC 1986. Changes in prevalence of potential early risk factors were identified, but only parental psychosis was a significant predictor in both cohorts (hazard ratios ≥3.0; 95% CI 1.86-4.88). The difference in psychosis incidence was not dependent on changes in prevalence of studied early risk factors. CONCLUSIONS: Surprisingly, increase in the cumulative incidence of psychosis and also changes in the types of psychoses were found between two birth cohorts 20 years apart. The observed differences could be due to real changes in incidence or they can be attributable to changes in diagnostic practices, or to early psychosis detection and treatment.

Interaction between parental psychosis and early motor development and the risk of schizophrenia in a general population birth cohort.

BACKGROUND: Delayed motor development in infancy and family history of psychosis are both associated with increased risk of schizophrenia, but their interaction is largely unstudied. AIM: To investigate the association of the age of achieving motor milestones and parental psychosis and their interaction in respect to risk of schizophrenia. METHODS: We used data from the general population-based prospective Northern Finland Birth Cohort 1966 (n=10,283). Developmental information of the cohort members was gathered during regular visits to Finnish child welfare clinics. Several registers were used to determine the diagnosis of schizophrenia among the cohort members and psychosis among the parents. Altogether 152 (1.5%) individuals had schizophrenia by the age of 46 years, with 23 (15.1%) of them having a parent with psychosis. Cox regression analysis was used in analyses. RESULTS: Parental psychosis was associated (P<0.05) with later achievement of holding the head up, grabbing an object, and walking without support. In the parental psychosis group, the risk for schizophrenia was increased if holding the head up (hazard ratio [HR]: 2.46; degrees of freedom [df]=1; 95% confidence interval [95% CI]: 1.07-5.66) and touching the thumb with the index finger (HR: 1.84; df=1; 95% CI: 1.11-3.06) was later. In the group without parental psychosis, a delay in the following milestones increased the risk of schizophrenia: standing without support and walking without support. Parental psychosis had an interaction with delayed touching thumb with index finger (HR: 1.87; df=1; 95% CI: 1.08-3.25) when risk of schizophrenia was investigated. CONCLUSIONS: Parental psychosis was associated with achieving motor milestones later in infancy, particularly the milestones that appear early in a child's life. Parental psychosis and touching the thumb with the index finger had a significant interaction on risk of schizophrenia. Genetic risk for psychosis may interact with delayed development to raise future risk of schizophrenia, or delayed development may be a marker of other risk processes that interact with genetic liability to cause later schizophrenia.

Infant motor development is associated with adult cognitive categorisation in a longitudinal birth cohort study.

BACKGROUND: The relationship between the age of reaching infant developmental milestones and later intellectual function within the normal population remains unresolved. We hypothesised that the age of learning to stand in infancy would be associated with adult executive function and that the association would be apparent throughout the range of abilities, rather than confined to extremes. METHODS: The Northern Finland 1966 Birth Cohort is based upon 12,058 live-born children in a geographic and temporally defined population. Information on age at learning to stand without support was obtained at one year. At age 33-35 a random sample of 104 subjects underwent a neuropsychological test battery including tests of executive function (cognitive categorisation), visuo-spatial memory, verbal learning and visual object learning. We investigated associations between developmental data and adult neuropsychological test scores. RESULTS: There was a significant linear relationship between age of learning to stand and adult categorisation: the earlier the attainment of the milestone, the better was the categorisation. No such relationships were observed between infant neurodevelopment and adult cognition in other neuropsychological domains. CONCLUSION: Even within the normal range of development, early development in the gross motor domain is associated with better adult executive function (in tests of categorisation). Investigation of the determinants and sequelae of normal neural development will facilitate research into a variety of neurodevelopmental disorders.

Infant motor development and adult cognitive functions in schizophrenia.

BACKGROUND: Childhood neuromotor dysfunction is a risk factor for schizophrenia, a disorder in which cognitive deficits are prominent. The relationship between early neurodevelopment and adult cognition in schizophrenia remains unclear. METHODS: We examined the associations between infant motor development and adult cognitive functions in schizophrenia (n = 61) and the general population (n = 104) in a sample drawn from the The Northern Finland 1966 Birth Cohort. Data on ages of learning to stand and walk with or without support were obtained at age 12 months by health visitor assessment. Neurocognitive measures at age 33-35 included executive function, verbal and visual episodic memory, and visuo-spatial working memory. RESULTS: The schizophrenia group achieved neuromotor milestones later and performed significantly worse than the control group on all measures of cognition. In pooled analyses there were associations between infant motor development and adult cognition in the domains of executive function, verbal learning and visuospatial working memory, but not in visual object learning. The pattern of associations between development and cognition was similar in schizophrenia and the general population. CONCLUSIONS: These findings are consistent with the hypothesis that in schizophrenia mild infant motor developmental delay and adult cognitive deficits (at least in some domains) are age dependent manifestations of the same underlying neural process. Thus, they may be better considered as part of a single longitudinal syndrome.

Early developmental milestones in adult schizophrenia and other psychoses. A 31-year follow-up of the Northern Finland 1966 Birth Cohort.

Delayed childhood development may precede adult psychoses. We tested this hypothesis in a large, general population birth cohort (n=12058) followed to age 31 years. The ages at which individuals learned to stand, walk, speak, and became potty-trained (bowel control) and dry (bladder control), were recorded at a 1-year examination. Psychiatric outcome was ascertained through linkage to a national hospital discharge register. Cumulative incidence of DSM-III-R schizophrenia, other psychoses and non-psychotic disorders were stratified according to the timing of milestones and compared within the cohort using internal standardization. 100 cases of DSM-III-R schizophrenia, 55 other psychoses, and 315 non-psychotic disorders were identified. The ages at learning to stand, walk and become potty-trained were each related to subsequent incidence of schizophrenia and other psychoses. Compared with the whole cohort, earlier milestones reduced, and later milestones increased, the risk in a linear manner. These developmental effects were not seen for non-psychotic outcomes. The findings support hypotheses regarding psychosis as having a developmental dimension with precursors apparent in early life.

Postnatal developmental pattern of thyrotrophin releasing hormone-degrading activity in rat plasma, hypothalamus and liver: role of tri-iodothyronine.

Thyrotrophin releasing hormone-degrading activity (TRH-DA) is present in plasma, hypothalamus, pituitary gland, liver and kidney of adults of several species. Each of these tissues contains more than one TRH-degrading enzyme but only one, pyroglutamate aminopeptidase, isolated from the blood, is a TRH-specific enzyme. The aim of this study was to describe the developmental pattern of TRH-DA in the plasma, hypothalamus and liver and the role of tri-iodothyronine (T3) in the development of TRH-DA in the rat. Based on the hypothesis that thyroid hormones stimulate plasma TRH-DA in adult rats, degradation of TRH was studied in hypo- or hyperthyroid rats induced by 6-n-propyl-2-thiouracil or T3 respectively. Tritiated TRH was incubated with plasma and homogenates of hypothalamus or liver. After separation of degradation products by thin-layer chromatography, the amount of degraded [3H]TRH (pmol/50 microliters plasma or homogenate) was taken as a comparative index of TRH-DA. Plasma TRH-DA was not detectable before day 9 while hypothalamic and hepatic TRH-DA was already active at birth. Furthermore, the maturation pattern of total TRH-DA was different in plasma compared with other tissues and T3 appeared to play a significant role in its development. The absence of plasma TRH-DA in the neonatal period, its special thyroid-dependent developmental pattern and the presence of a specific TRH-degrading enzyme in adult blood suggest a physiological regulatory role for this activity.

Maternal, fetal and aminiotic fluid ACTH, cortisol and prolactin in association with medical beta-adrenergic stimulation.

In view of observations indicating accelerated fetal pulmonary maturation after tocolytic therapy with beta-adrenergic agonists, this study was undertaken to determine whether the phenomenon is related to enhanced maternal or fetal ACTH, cortisol or prolactin secretion. The concentrations of ACTH, cortisol and prolactin in maternal venous blood, umbilical arterial and venous blood, and amniotic fluid were similar after short-term maternal intravenous infusion of isoxsuprine, fenoterol or isotonic saline, and they did not increase in the maternal venous blood during these treatments or during long-term treatment with intravenous ritodrine. These results suggest that the accelerated fetal pulmonary maturation induced by beta-adrenergic stimulation is not mediated by ACTH, cortisol or prolactin.

The effect of segmental epidural analgesia on maternal prolactin during labour.

Maternal plasma prolactin (PRL) concentrations were determined during the course of induced labours in 18 normal parturients. Every second mother was given segmental epidural analgesia for pain relief during the first stage of labour and the remaining parturients served as controls. The maternal PRL level declined during labour in both groups, which contrasts with the increased output seen in nonpregnant patients subjected to stress. The lowest levels were reached during the first stage of labour. The reduction in PRL levels was statistically significant in the control group but not in the epidural group of patients.

Maternal, fetal and neonatal effects of beta-adrenergic stimulation in connection with cesarean section.

To investigate the combined metabolic effects of beta-mimetic therapy and general anesthesia on maternal and fetal/neonatal metabolism, 14 patients were treated with isotonic saline, 11 with intravenous fenoterol (3 microgram/min) and 9 with intravenous isoxsuprine (150 microgram/min) for 30 minutes prior to cesarean section. The maternal heart rate and blood pressure as well as the maternal and fetal acid-base balance were followed. The neonatal glucose level was monitored for 36 hours after delivery. The heart rate and the diastolic and systolic blood pressure values increased during the operation in each group, without any marked differences between the groups. At delivery, the mean maternal BD (base-deficit) value was higher in the fenoterol patients than in the control patients, indicating a trend towards metabolic acidosis. The other values of acid-base balance in the maternal and umbilical arterial and venous blood did not reveal any differences between the groups. The neonatal glucose level at 2 hours after delivery was higher in the fenoterol group than in the control group. The other values recorded during 36 hours revealed no differences between the groups. Beta-mimetic treatment preceding general anesthesia in cesarean section does not have unfavorable effects on the mother, the fetus or the newborn. Such therapy thus does not seem contraindicated when uterine contractions should be rapidly suppressed in cases of fetal distress before operation.

Airborne and surface residues of parathion and its conversion products in a treated plum orchard environment.

Airborne pesticide residues were collected both within and downwind from a parathion-treated plum orchard by high volume sampling through XAD-4 macroreticular resin. Levels of paraoxon in excess of 100 ng/m3 were found in orchard air, along with parathion, during the early days of two 21-day sampling studies. Paraoxon:parathion ratios in the orchard air were relatively constant, averaging ca. 0.5 for days 1 to 21 following treatment. Likely sources of airborne paraoxon include vaporization and dislodgement from soil and leaf surfaces, and chemical conversion of parathion in the air. Support for the latter came from observation of an increased paraoxon:parathion ration in air samples collected downwind from the orchard. Atmospheric conversion of parathion to paraoxon, accelerated by sunlight, was indicated by both field and laboratory studies. Overall dissipation of parathion from the orchard air, soil, and leaf tissue proceeded to a considerable extent through breakdown to paraozon under the dry climatic conditions of these studies. Eventual conversion to the relatively stable breakdown product, p-nitrophenol, was indicated from analysis of air in the orchard vicinity.