Jan K. Buitelaar

Stress during pregnancy is associated with developmental outcome in infancy

BACKGROUNDnAnimal studies show that prenatal maternal stress may be related to cognitive impairments in offspring. Therefore, we examined whether psychological and endocrinologic measures of stress during human pregnancy predicted developmental outcome of the infant at 3 and 8 months.nnnMETHODnSelf-report data about daily hassles and pregnancy-specific anxiety and salivary cortisol levels were collected in 170 nulliparous women in early, mid- and late pregnancy in a prospective design, in which healthy infants born at term were followed up after birth.nnnRESULTSnHigh levels of pregnancy-specific anxiety in mid-pregnancy predicted lower mental and motor developmental scores at 8 months (p < .05). High amounts of daily hassles in early pregnancy were associated with lower mental developmental scores at 8 months (p < .05). Early morning values of cortisol in late pregnancy were negatively related to both mental and motor development at 3 months (p < .05 and p < .005, respectively) and motor development at 8 months (p < .01). On average a decline of 8 points on the mental and motor development scale was found. All results were adjusted for a large number of covariates.nnnCONCLUSIONnStress during pregnancy appears to be one of the determinants of delay in motor and mental development in infants of 8 months of age and may be a risk factor for later developmental problems. Further systematic follow-up of the present sample is needed to determine whether these delays are transient, persistent or even progressive.

Prenatal stress and risk for psychopathology: specific effects or induction of general susceptibility?

This review focuses on prenatal stress as a risk factor for psychopathology. Evidence from animal studies is summarized, and the relevance of prenatal stress models in animals for human studies is discussed. In the offspring of prenatally stressed animals, overactivity and impaired negative feedback regulation of the hypothalamic-pituitary-adrenal axis are consistent findings and may reflect a pathophysiological mechanism involved in the development of psychopathology. Reduced activity of the opioid GABA/benzodiazepine, serotonin, and dopamine systems and increased activity of the sympathico-adrenal system have been found as well. These alterations have been linked to a diverse spectrum of psychopathology. Therefore, the evidence supports the view that exposure to prenatal stress may result in a general susceptibility to psychopathology, rather than exerting a direct effect on a specific form of psychopathology.

Magnetic resonance imaging of boys with attention-deficit/hyperactivity disorder and their unaffected siblings

OBJECTIVEnTo study the influence of increased familial risk for attention-deficit/hyperactivity disorder (ADHD) on brain morphology.nnnMETHODnVolumetric cerebral measures based on whole brain magnetic resonance imaging scans from 30 boys with ADHD, 30 of their unaffected siblings, and 30 matched controls were compared.nnnRESULTSnBoth subjects with ADHD and their unaffected siblings displayed reductions in right prefrontal gray matter and left occipital gray and white matter of up to 9.1% (p < 0.05). Right cerebellar volume was reduced by 4.9% in subjects with ADHD (p = 0.026) but not in their unaffected siblings (p = 0.308). A 4.0% reduction in intracranial volume was found in subjects with ADHD (p = 0.031), while a trend was observed in their unaffected siblings (p = 0.068).nnnCONCLUSIONSnThe volumetric reductions in cortical gray and white matter in subjects with ADHD are also present in their unaffected siblings, suggesting that they are related to an increased familial risk for the disorder. In contrast, the cerebellum is unaffected in siblings, suggesting that the reduction in volume observed in subjects with ADHD may be more directly related to the pathophysiology of this disorder.

Psychological measures of prenatal stress as predictors of infant temperament

OBJECTIVEnTo examine, in a prospective study, whether maternal stress during pregnancy is related to infant temperament.nnnMETHODnSelf-report data on various aspects of prenatal stress were collected from nulliparous women in early pregnancy. Infant temperament was measured at 3 and 8 months by direct observation and by parent report.nnnRESULTSnComplete data were available for 170 term-born infants. Pregnancy-specific anxiety explained 3.3% of the variance of attention regulation at 3 months. Perceived stress and pregnancy anxiety taken together explained 5% of the variance of attention regulation at 8 months. Perceived stress accounted for 8.2% of the variance of difficult behavior of the 3-month-old infant. All results were adjusted for covariates.nnnCONCLUSIONSnIncreased maternal prenatal stress seems to be associated with temperamental variation of young infants and may be a risk factor for psychopathology later in life.

Prenatal stress and cognitive development and temperament in infants

Studies in rodents and nonhuman primates indicate that maternal stress during pregnancy can influence the developing fetus, resulting in delay of motor and cognitive development and impaired adaptation to stressful situations. These effects may be mediated by the hypothalamic-pituitary-adrenal (HPA) axis. We examined whether stress during pregnancy predicted developmental outcome of human infants in a prospective design. Self-report data about daily hassles and pregnancy-specific anxiety and salivary cortisol levels were collected in nulliparous pregnant women. Dependent measures were scores on the Bayley Scales of Infant Development and on temperamental questionnaires at 3 and 8 months. Pregnancy-specific anxiety in mid pregnancy predicted lower mental and motor developmental scores at 8 months. Early morning values of cortisol in late pregnancy were negatively related to both mental and motor development at 3 months and motor development at 8 months. Pregnancy-specific anxiety explained 7% of the variance of test-affectivity and goal-directedness at 8 months. Increased maternal stress during pregnancy seems to be one of the determinants of temperamental variation and delay of development of infants and may be a risk factor for developing psychopathology later in life.

Hypothalamic-pituitary-adrenal axis and autonomic nervous system activity in disruptive children and matched controls.

OBJECTIVESnTo investigate whether a pattern of lower autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis activity is found in children with disruptive behavior disorders (DBD) under nonstressful and stressful conditions, and whether such a pattern would correspond with their feelings of control and negative emotionality.nnnMETHODnThe effects of stress were studied by comparing cortisol response, heart rate (HR), skin conductance level (SCL), and subjective feelings of 26 children with DBD and 26 matched normal controls. An additional 12 normal control children were studied in a nonstress control condition.nnnRESULTSnBaseline HR and SCL but not cortisol were lower in the DBD group. Stress significantly affected cortisol, HR, SCL, and negative moods, although children with DBD showed a weaker HPA stress response and the difference between the groups was greater under stress.nnnCONCLUSIONSnChildren with DBD are characterized by lower ANS activity and HPA axis responsivity, but higher levels of emotional arousal. It is possible that in children with DBD the HPA axis and ANS, on the one hand, and their emotional arousal, on the other, are less well coordinated. It is speculated that this could be due to differences in genetic makeup or to stressful conditions during pre- or postnatal life.

Theory of mind and emotion-recognition functioning in autistic spectrum disorders and in psychiatric control and normal children

The hypothesis was tested that weak theory of mind (ToM) and/or emotion recognition (ER) abilities are specific to subjects with autism. Differences in ToM and ER performance were examined between autistic (n = 20), pervasive developmental disorder-not otherwise specified (PDD-NOS) (n = 20), psychiatric control (n = 20), and normal children (n = 20). The clinical groups were matched person-to-person on age and verbal IQ. We used tasks for the matching and the context recognition of emotional expressions, and a set of first- and second-order ToM tasks. Autistic and PDD-NOS children could not be significantly differentiated from each other, nor could they be differentiated from the psychiatric controls with a diagnosis of ADHD (n = 9). The psychiatric controls with conduct disorder or dysthymia performed about as well as normal children. The variance in second-order ToM performance contributed most to differences between diagnostic groups.

Inhibition in children with attention-deficit/hyperactivity disorder: a psychophysiological study of the stop task.

BACKGROUNDnThe purpose of the study was to investigate and identify abnormal brain activity, as revealed by event-related potentials (ERPs) concurring with deficient inhibitory control in children with attention-deficit/hyperactivity disorder (ADHD).nnnMETHODSnPerformance and ERPs from 16 children with ADHD and 16 control subjects were compared in the stop-signal paradigm.nnnRESULTSnThe ADHD children showed a lower inhibition percentage and their (estimated) response time to the stop signal was disproportionally longer compared to the slowing of reaction times to primary-task stimuli. In normal control subjects, fronto-central positivity (100-400 msec) after the onset of the stop-signal was larger in case of successful inhibition, relative to failed inhibition; this was less so in ADHD children. A late positive wave (500-700 msec), maximal at Oz on failed inhibition trials, and possibly related to error-detection, was smaller in ADHD children.nnnCONCLUSIONSnThese results point to abnormalities in brain processes involved in motor inhibition and error-detection in ADHD children.

Event-related potentials and performance of attention-deficit hyperactivity disorder: Children and normal controls in auditory and visual selective attention tasks

Attention-deficit hyperactivity disorder (ADHD) children and normal controls (7-13 yrs old) performed an auditory and visual selective attention task. Subjects were instructed to respond to the infrequent (10%) stimuli in the relevant channel. Processing negativity (PN) and several other ERP peaks were scored at the midline electrodes. In the auditory task, controls had more correct detections (hits), less false alarms, larger P3b amplitudes to nontarget stimuli (but not to hits), a larger central PN and larger early frontal positivity (100-250 ms) to target stimuli than ADHD subjects. In the visual modality, controls had more correct detections, less false alarms, larger P3b amplitudes to nontarget stimuli (but not to hits), and larger frontal P3(1) amplitudes to infrequent than to frequent stimuli. It was hypothesized that in ADHD children in both the auditory and the visual task, there is a deficit in the activation of the P3b process. Incorrect triggering of the P3b process might be caused by disturbances in other aspects of the attention process, preceding the P3b.

Prediction of Clinical Response to Methylphenidate in Children with Attention-Deficit Hyperactivity Disorder

OBJECTIVEnTo examine the pattern of individual responses to to methylphenidate (MPH) in children with attention-deficit hyperactivity disorder and to examine factors that predict drug response.nnnMETHODnIndividual drug response was defined on the basis of changes on the Abbreviated Conners Rating Scales completed by parents and teachers. These scales were the main outcome measures in a double-blind, placebo-controlled trial of MPH. Response prediction was examined in stepwise discriminant analyses, in which baseline variables and the response to a single, 10-mg dose of MPH were entered.nnnRESULTSnPredictors of a strong MPH response were a high IQ, considerable inattentiveness, young age, low severity of disorder, and low rates of anxiety. A positive response to a single dose of MPH significantly improved the prediction of less stringently defined levels of MPH response.nnnCONCLUSIONnOnly strong levels of response could be predicted by baseline characteristics. Severity of disorder based on clinical judgment and improvement after a single dose of MPH are found to be important contributors to response prediction.