Modulation of startle and the startle-elicited P300 by the conditions of the cued continuous performance task in school-age boys.

OBJECTIVES: This study compares the modulation of the startle response by conditions requiring response preparation, production, and inhibition during a cued continuous performance task (CPT) in children to the results of previous studies in adults and evaluates the modulation of the startle-elicited P300 under the same conditions. The latter variable, reflecting the cognitive processing of the startling stimulus (SS), has not been studied under these conditions. METHODS: Normal boys completed a cued CPT in which the cue was the letter T, the go condition requiring a button press was an X following the T, and the no-go condition requiring response inhibition was a letter other than X following the T. SS were presented 450 ms following the letter of interest in each condition. The amplitudes of the startle-elicited P300 at Fz, Cz, and Pz and the startle blink were compared in the different CPT conditions. RESULTS: The startle blink, measured by orbicularis oculi electromyography, was not inhibited by the no-go CPT condition as is the case in adults. The vertical electro-oculogram was actually largest in the no-go condition. The startle-elicited P300 showed a central predominance and was significantly larger in the no-go condition and in the cue condition than in the go condition. CONCLUSIONS: The absence of inhibition of the startle response during the no-go condition probably reflects a relative inefficiency of prefrontal cortical mechanisms that mediate response inhibition in children compared to adults. The enhanced startle-elicited P300 in the no-go and cue conditions of the CPT reflects cognitive processing of the SS that has been influenced by response inhibition or its anticipation.

Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study.

BACKGROUND: This study tested the hypothesis that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining if first-degree relatives of COS probands have an increased risk for schizophrenia and schizotypal and paranoid personality disorders. METHODS: Relatives of COS probands (n = 148) were compared with relatives of attention-deficit/hyperactivity disorder (ADHD) (n = 368) and community control (n = 206) probands. Age-appropriate structured diagnostic interviews were used to assign DSM-III-R diagnoses to probands and their relatives. Family psychiatric history was elicited from multiple informants. Diagnoses of relatives were made blind to information about probands' diagnoses. Final consensus diagnoses, which integrated family history, direct interview information, and medical records, are reported in this article. RESULTS: There was an increased lifetime morbid risk for schizophrenia (4.95% +/- 2.16%) and schizotypal personality disorder (4.20% +/- 2.06%) in the parents of COS probands compared with parents of ADHD (0.45% +/- 0.45%, 0.91% +/- 0.63%) and community control (0%) probands. The parents of COS probands diagnosed as having schizophrenia had an early age of first onset of schizophrenia. Risk for avoidant personality disorder (9.41% +/- 3.17%) was increased in the parents of COS probands compared with parents of community controls (1.67% +/- 1.17%). CONCLUSIONS: The psychiatric disorders that do and do not aggregate in the parents of COS probands are remarkably similar to the disorders that do and do not aggregate in the parents of adults with schizophrenia in modern family studies. These findings provide compelling support for the hypothesis of etiological continuity between COS and AOS.

Prepulse inhibition of startle, intelligence and familial primary nocturnal enuresis.

UNLABELLED: Previous studies have shown a significant reduction of prepulse inhibition of startle in boys with primary nocturnal enuresis. Those enuretic boys who had higher IQs showed less prepulse inhibition. This study evaluates the association of prepulse inhibition and IQ in primary nocturnal enuresis in respect to family history of primary nocturnal enuresis. Prepulse inhibition of startle was studied in 83 boys with primary nocturnal enuresis and 57 non-enuretic boys using an interval of 120 ms between the onset of a 75 dB 1000 Hz tone and a 104 dB noise burst. Of the boys with primary nocturnal enuresis, 56 had a family history of primary nocturnal enuresis and 27 had no family history (no first-degree relative). Of the 57 non-enuretic boys, 42 also had no family history (no first-degree relative) of primary nocturnal enuresis, while 15 did have a positive family history. Associations between prepulse inhibition and IQ scores were compared among these four groups. Strong and significant associations between prepulse inhibition deficit and higher IQ scores in the enuretic group with familial primary nocturnal enuresis were unique in comparison to the other groups. CONCLUSIONS: The strong heritabilities of primary nocturnal enuresis, intelligence and prepulse inhibition suggest genetic mediation of the association of prepulse inhibition with intelligence in familial primary nocturnal enuresis.

Prepulse inhibition of startle and the neurobiology of primary nocturnal enuresis.

BACKGROUND: Children with primary nocturnal enuresis (PNE) wet the bed during all stages of sleep and irrespective of state of arousal, suggesting that during sleep, when voluntary, i.e., cortical control, is not available, the signal from the distended bladder is not registered in the subcortical centers inhibiting micturition. Deficient prepulse inhibition (PPI) of startle has been reported in PNE. This study evaluates the association of this PPI deficit in PNE with comorbidity with attention-deficit hyperactivity disorder (ADHD) and with intelligence. METHODS: Prepulse modulation of startle was studied in 96 boys with PNE and 105 nonenuretic boys using intervals of 60, 120, and 4000 msec between the onset of a 75-dB 1000-Hz tone and a 104-dB noise burst. Thirty-one percent of the enuretic and 36% of the nonenuretic boys were diagnosed with ADHD. RESULTS: After adjustment for presence or absence of ADHD, lower or higher IQ, age, and unmodulated startle amplitude, there was a significant association between PNE and deficient PPI of startle following the 120-msec prepulse interval. Those enuretic boys who also were ADHD or had higher performance IQs (> or = 110) showed the greatest PPI deficit. CONCLUSIONS: A common deficiency of inhibitory signal processing in the brain stem may underlie both deficient PPI and the inability to inhibit micturition in PNE. Strong familiarity for PNE, ADHD, and intelligence suggests a possible genetic mediation of these effects.

Transmission of primary nocturnal enuresis and attention deficit hyperactivity disorder.

Primary nocturnal enuresis (PNE) is a prevalent disorder among children with a complex mode of inheritance. Family, twin, and linkage studies have provided evidence that genetic factors underlie the familiality of PNE. Linkage investigations support the hypothesis that PNE is heterogeneous, and the genetic heterogeneity may be reflected in co-morbid clinical conditions such as attention deficit hyperactivity disorder (ADHD). This study used a family study method and examined the transmission of PNE in relatives of PNE and control probands with and without ADHD, to determine if these disorders co-occur due to common genetic susceptibilities or other, i.e. non-genetic, reasons. This study concluded that the pattern of inheritance found is consistent with the independent transmission of PNE and ADHD.

Affective valence and arousal in ADHD and normal boys during a startle habituation experiment.

OBJECTIVE: To measure two dimensions of emotion (affective valence and arousal) in 29 boys with attention-deficit hyper-activity disorder (ADHD) and 32 normal boys. METHOD: After a startle habituation experiment during which these subjects heard 40 startling sounds while watching a silent interesting movie, they were asked 12 questions (categorized a priori into questions relating to affective valence and to arousal) about their emotional reactions to these putatively unpleasant and pleasurable stimuli. Responses were recorded for the two dimensions of emotion, using two cartoon strips in each of which five expressions of a cartoon character varied linearly from happy to unhappy (affective valence dimension) and calm to excited (arousal dimension). RESULTS: Factor analyses of the 12 responses revealed four factors in which the highest loadings were for affective valence to the startle responses, affective valence to the silent movie, arousal, and scary feelings. Relative to the normal group, the responses of the ADHD group were significantly biased toward pleasurable valence to the startling stimuli and to the silent movie, with a trend toward hypoarousal. Startle magnitude and habituation were similar in both groups. The normal tonic heart rate acceleration throughout the experimental session was not sustained in the ADHD group. CONCLUSIONS: The self-reports of affective valence biased in the direction of pleasure and away from displeasure and the trend toward hypoarousal suggest an emotional dysfunction in ADHD.

Autonomic, electroencephalographic, and myogenic activity accompanying startle and its habituation during mid-childhood.

This study investigated (a) possible associations of the large individual variation in startle, with accompanying autonomic, central nervous system, and myogenic activities in a habituation paradigm; and (b) the patterns of habituation of these variables. Startle blinks to 40 noise bursts, heart rate, alpha activity, and orbicularis oculi electromyographic (EMG) activity preceding and following each startle response were measured in 40 normal 7-11-year-old boys. Startle amplitude and its habituation were independent of association with either initial values or successive changes in the autonomic, alpha, and EMG activities; whereas startle habituated, pre- and poststartle myogenic, alpha, and cardiac activities failed to habituate. Tonic cardiac activity was facilitated, suggesting sensitization of state, as proposed in the dual-process theory of habituation.

Habituation of P300 and reflex motor (startle blink) responses to repetitive startling stimuli in children.

Positive EEG deflections with the latency and scalp distribution of the P300 accompany startle in response to loud auditory stimuli in a non-task context. The purpose of this investigation is to determine if habituation would have effects on the P300 similar to those on the startle blink. Thirty-four normal 7 to 11-year-old boys from a startle habituation study had EEG recordings of sufficient quality to provide data for the current study. Startle was measured both as orbicularis oculi EMG and vertical EOG and P300 was recorded at Pz in response to 40,104 dB bursts of white noise presented at 23-s intervals. Both the startle response and the P300 habituated toward asymptotic levels after the first 28 trials, suggesting that both startle and the subsequent cognitive evaluation of the startling stimulus, reflected in the P300 response, are modulated by a common neurophysiological mechanism extrinsic to the direct startle pathway. A modest significant correlation between the P300 and the vertical EOG peak latencies for the initial trials suggests that the cognitive evaluation of the startling stimulus may also include evaluation of the reflex response to that stimulus. Analyses of the within-subject associations between startle and P300 initial amplitudes and rates of habituation showed that these parameters varied independently within the individual subject, suggesting that the P300 is not a component of the startle response. Rather, it reflects an evaluation of the startling stimulus, decreasing in amplitude as the surprising value of the startling stimulus decreases with habituation.

The clinical presentation of childhood-onset schizophrenia.

This review describes the symptomatic presentation of schizophrenia with onset in childhood. Phenomenologic data from an original sample of 35 children with onset before the age of 12, from the University of California, Los Angeles (UCLA) Childhood-Onset Schizophrenia Research Program, are presented and compared with similar data from two other major studies. Similarities and differences between childhood-onset and adult-onset forms of the disorder are discussed, with special emphasis on gender ratio and mode of onset. Among the 35 children in the UCLA study, 80 percent presented with auditory hallucinations, 74 percent with flat or inappropriate affect, 63 percent with delusions, 40 percent with formal thought disorder, and 37 percent with visual hallucinations. In the vast majority of cases onset was insidious. The mean age at onset of general psychiatric symptoms was estimated to be 4.6 years, the mean age at onset of psychotic symptoms was 6.9 years, and the mean age at diagnosis was 9.5 years. The phenomenology of the UCLA sample is compared with two other major studies of childhood-onset schizophrenia. The relative frequency of core symptoms, with the exception of thought disorder, was strikingly similar across the three studies, as was the mode of onset. The groups were also similar in age at diagnosis, gender ratio, and IQ. Limited comparisons with studies of first-onset schizophrenia in adults suggest basic similarities between schizophrenia with onset in childhood and adulthood. The qualitative nature of the symptoms reported is similar to that seen in adult cases with the expected developmental variations, for example, delusions are less complex in children and reflect childhood themes. Limited data from a cross-sectional assessment using DSM-III criteria indicate that the relative frequency of core symptoms may also be similar to that seen in adult cases. In contrast to previous reports, this review suggests that the high male to female ratio seen in childhood-onset cases represents a continuum with young adult cases, and gender ratio does not truly distinguish childhood-onset from (young) adult-onset forms of the disorder. Schizophrenia with onset before adolescence does seem to differ from later-onset cases in the very high rates of insidious as opposed to acute onset. The insidious onset may also help explain the clinical observation that in some children psychotic symptoms, particularly those of long duration, can be relatively ego-syntonic.

The phenomenology of schizophrenia occurring in childhood.

Thirty-five children, aged 4 to 13 (X = 9.54), meeting strict DSM-III criteria for schizophrenia, are described. The subjects were diagnosed using a new semistructured interview. All were in the normal range of intelligence (mean IQ = 94) and free of neurological disorders. Characteristic auditory hallucinations were present in 80% and delusions in 63% of the sample. The mean age of onset of psychotic symptoms was 6.9 years. Premorbid histories of attention deficit, conduct disturbance and/or developmental abnormalities were common. The nature and content of psychotic symptoms varied with developmental stage. The phenomenological presentation of the sample was similar to previous studies of young schizophrenic children.

Behavioral disturbance in mentally retarded children in TMR and EMR classrooms.

The frequency with which disruptive behavior actually takes place in ongoing classroom settings was examined. Disruptive behavior of 646 subjects in TMR and EMR classrooms was observed over a 4-day period. Although mean disruptive behavior occurred at relatively low levels, considerable variability was evident with some differences observed in the nature of disruptive behavior between TMR and EMR subjects. This variability was further examined within a subsample of "high" and "low" disrupters.

DSM-III in the clinical practice of child psychiatry.

The clinical usefulness of DSM-III was assessed by examining its inclusiveness, its correspondence to DSM-II, and difficulties encountered in its use in evaluations of 108 children. DSM-III covered adequately a wide range of diagnostic entities, showed relatively good correspondence to DSM-II with some exceptions, and presented relatively few major difficulties in a child psychiatry clinic setting. DSM-III seems likely to be accepted and used by a majority of practicing child psychiatrists.

Mental illness and mental retardation: cause or coincidence?

A sample of 93 patients admitted to an inpatient psychiatric unit for emotionally disturbed, developmentally disabled adolescents was studied in an attempt to clarify the relationship between intellectual functioning and psychoses occurring in the developmental period. The severity and duration of the psychosis, the presence of hallucinations, and the degree of isolation of the child from his or her environment appear to be important factors influencing the occurrence of decreased psychometric test scores in the individuals studied.

A comparison of DSM-II and DSM-III in the diagnosis of childhood psychiatric disorders. I. Agreement with expected diagnosis.

This study was conducted to compare DSM-II and DSM-III in the diagnosis of childhood and adolescent psychiatric disorders. Twenty psychiatrist-raters completed standardized diagnostic questionnaires for 24 actual case histories. This report, the first of four, presents the rater agreement with the "expected diagnosis," ie, the diagnosis that we considered most appropriate for each case. The average rater agreement with the expected diagnosis was less than 50%. It was highest in cases of mental retardation, psychosis, hyperactivity, and conduct disorder. In only five cases did the most common diagnosis of the raters differ from the expected diagnosis. Analyses of these cases and those we selected to present specific diagnostic problems to the raters have produced suggestions to improve the reliability of DSM-III.

A comparison of DSM-II and DSM-III in the diagnosis of childhood psychiatric disorders. II. Interrater agreement.

A case-history format was utilized to compare interrater agreement on childhood and adolescent psychiatric disorders, using DSM-II and DSM-III. The average interrater agreement was 57% for DSM-II and 54% for axis I (clinical psychiatric syndrome) of DSM-III. There was high agreement in both systems on cases of psychosis, conduct disorder, hyperactivity, and mental retardation, with DSM-III appearing slightly better. There was noteworthy interrater disagreement in both systems for "anxiety" disorders, complex cases, and in the subtyping of depression. Overall, the reliability of DSM-III appears to be good and is comparable with that of DSM-II and other classification systems of childhood psychiatric disorders.