Thought disorder in childhood schizophrenia: replication and update of concept

OBJECTIVES: To examine whether measures of thought disorder differentiated schizophrenic from normal children and to examine the relationship of these measures with developmental and cognitive factors. METHOD: The speech samples of 88 schizophrenic and 190 normal children, aged 9 to 13 years, were coded with the Kiddie Formal Thought Disorder Rating Scale and Halliday and Hassan's analysis of cohesion. RESULTS: Above and beyond differences in mental age, gender, and neuroleptic status, the patients had significantly more formal thought disorder (FTD) and cohesive deficits than the normal children matched by mental age. The younger schizophrenic and normal children had significantly more thought disorder than the older children with these diagnoses. Combined FTD and cohesion scores correctly identified 76% of schizophrenic and 88% of normal children with little variability across mental age. The thought disorder measures generated 2 independent components: FTD and cohesion. CONCLUSIONS: Thought disorder measures that include both FTD and cohesion provide a quantitative diagnostic tool of childhood-onset schizophrenia.     

Neuropsychological deficits in adolescent-onset schizophrenia compared with attention deficit hyperactivity disorder.

OBJECTIVE: Impaired neuropsychological performance involving abstraction-flexibility, memory, motor function, and attention has frequently been reported in schizophrenia as well as in attention deficit hyperactivity disorder (ADHD). This study represents an attempt to compare groups of adolescents with schizophrenia and ADHD on a comprehensive neuropsychological test battery. Such a comparison affords the opportunity to ascertain differences in the degree, profile, and specificity of impairments. METHOD: The performance of 19 adolescents with schizophrenia, 20 adolescents with ADHD, and 30 normal adolescents on a broad battery of cognitive tests was compared. RESULTS: The schizophrenic group showed the most pronounced deficits on tests of abstraction, visual memory, and motor function in comparison with the subjects with ADHD, while the ADHD subjects had the most pronounced deficits on measures of attention, verbal memory, and learning. CONCLUSIONS: The subjects with schizophrenia appeared to have a more general pattern of brain dysfunction, whereas the impairment of the ADHD subjects seemed to be relatively specific to tests associated with frontal lobe function.     

Childhood schizophrenia: responsiveness to questions during conversation

OBJECTIVES: This study characterized further the communicative deficits associated with childhood-onset schizophrenia. It examined the use of speech functions that involve responses to Yes/No and Wh- questions in children with schizophrenia and normal children during conversation. It also ascertained the relationship of these speech functions with cognition and thought disorder. METHOD: Speech function variables, formal thought disorder, and cohesion were coded in 32 schizophrenic and 34 normal children, aged 5.6 to 12.4 years, from speech samples elicited with the Story Game. RESULTS: The schizophrenic children were significantly more impaired in the use of speech functions than the normal children. Other than the association of a subset of the speech functions with distractibility and loose associations, the speech function measures were unrelated to cognitive and thought disorder measures. CONCLUSIONS: Speech function analysis detects communication deficits not captured by thought disorder measures in children with schizophrenia.     

Social competence and positive and negative symptoms: a longitudinal study of children and adolescents at risk for schizophrenia and affective disorder

OBJECTIVE: The authors longitudinally examined social competence and positive and negative symptoms in children at risk for schizophrenia, children at risk for affective disorder, and matched normal subjects. METHOD: The subjects were offspring of parents with schizophrenia or affective disorder and normal comparison subjects matched on age, sex, and socioeconomic status. Ratings of social competence (Premorbid Adjustment Scale), affective flattening and poverty of speech (Scale for the Assessment of Negative Symptoms), and positive formal thought disorder (Scale for the Assessment of Positive Symptoms) were based on videotaped psychiatric interviews conducted in childhood (N = 144), early adolescence (N = 127), and adolescence (N = 106). RESULTS: In childhood, there were no significant group differences. In early adolescence, the subjects at risk for schizophrenia had poorer social competence than those at risk for affective disorder and the normal subjects. In early adolescence, the subjects at risk for schizophrenia also had greater positive thought disorder than those at risk for affective disorder but did not differ significantly from the normal subjects; there were no differences in negative symptoms. In adolescence, the subjects at risk for schizophrenia had poorer social competence and greater positive and negative symptoms than the adolescents at risk for affective disorder and the normal subjects. CONCLUSIONS: During early adolescence and adolescence, poor social competence may be more characteristic of children at risk for schizophrenia than those at risk for affective disorder. Higher levels of positive and negative symptoms may also be specific to subjects at risk for schizophrenia, but only during adolescence.     

The P50 auditory event-evoked potential in adult attention-deficit disorder: comparison with schizophrenia.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and schizophrenia are both conceptualized as disorders of attention. Failure to inhibit the P50 auditory event-evoked response, extensively studied in schizophrenia, could also occur in ADHD patients, if these two illnesses have common underlying neurobiological substrates. METHODS: This study examined the inhibition of the P50 auditory event-evoked potential in 16 unmedicated adults with ADHD, 16 schizophrenic outpatients, and 16 normal control subjects. Auditory stimuli were presented in a paired stimulus, conditioning-testing paradigm. RESULTS: The amplitude of initial or conditioning P50 response did not differ between the three groups; however, significant effects of psychiatric diagnosis on the amplitude of the test response and the ratio of the test to the conditioning response amplitudes were observed. Schizophrenic patients' P50 ratios and test amplitudes were higher than both the ADHD and normal groups. CONCLUSIONS: Adults with ADHD do not have the inhibitory deficit seen in patients with schizophrenia, suggesting that the mechanism of attentional disturbance in the two illnesses may be fundamentally different.     

Attentional and neurocognitive characteristics of high-risk offspring of parents with schizophrenia compared with DSM-IV attention deficit hyperactivity disorder children

Offspring of individuals with schizophrenia are at increased baseline risk for a range of early mental disorders. Studies investigating the premorbid characteristics of individuals with schizophrenia indicate that they suffer from social, behavioral, attentional and neurocognitive impairments, often resembling attention deficit hyperactivity disorder (ADHD). In this study, we compared the executive functioning and general intelligence among three groups: (i) children and adolescents with DSM-IV ADHD (n=41), (ii) "high-risk" (HR) offspring of parents with DSM-IV schizophrenia, and (iii) normal comparison subjects (n=35). Our results indicated that both HR and ADHD groups had lower Verbal IQ scores. ADHD cases had significantly lower percent correct and total errors in Wisconsin Cart Sorting Test when compared with normal comparison subjects. The HR cases also had lower Performance IQ scores as well as worse abstraction--flexibility and comprehension performance. The HR group was further stratified with (HR-A) and without (HR-NA) comorbid ADHD, and HR-A subjects were significantly noted to be more impaired on most tests. The overall worse performance of HR offspring was attributable to significantly lower performance among the HR-A youth. Further, our results suggested that the most profoundly impaired HR subjects were in fact children and adolescents who also met criteria for ADHD. Future studies with broader neuropsychological test batteries are necessary to investigate the differences and similarities between ADHD and the HR-A subgroup.     

A longitudinal study of thought disorder in manic patients

To study the persistence of thought disorder in manic patients, 34 manic patients were compared with 30 schizophrenic and 30 nonpsychotic patients on four indexes of thought pathology at two phases of disorder: during the acute inpatient phase and one year after hospitalization. Patients were also compared with a control sample of 34 normal subjects. The data indicated that during the acute in hospital phase, both manic and schizophrenic patients were severely thought disordered; at follow-up, a subsample of manic patients showed severe thought disorder; despite the severe thought disorder found at follow-up in some manic and schizophrenic patients, both groups showed a significant reduction of thought pathology at follow-up; and there was a trend for a larger reduction of thought disorder in manic than in schizophrenic patients. The difference, however, was not significant when initial levels of severity were controlled.     

Cytogenetic abnormalities in attention-deficit/hyperactivity disorder

OBJECTIVE: To systematically assess the prevalence of fragile X syndrome, velocardiofacial syndrome, and other cytogenetic abnormalities in a group of children with attention-defict/hyperactivity disorder (ADHD). METHOD: Blood samples were obtained from 100 children (64 boys) with combined type ADHD and normal intelligence and analyzed for the presence of fragile X mutation expansions, the 22q11.2 microdeletion associated with velocardiofacial syndrome, and cytogenetic abnormalities that would be detected with high resolution chromosomal banding. RESULTS: One girl with ADHD had a sex chromosome aneuploidy (47,XXX). One boy had a premutation-sized allele for fragile X; no subjects showed the full mutation. Testing for 22q11.2 microdeletion was negative for all subjects with ADHD screened. None of these differences exceeded those expected by chance. CONCLUSIONS: In the absence of clinical signs or positive family history, these relatively expensive laboratory assessments are not clinically indicated for children with ADHD and normal intelligence, and are not recommended as a component of other genetic investigations of this disorder.     

Event-related potentials and thought disorder in schizophrenia

We examined the relationship between event-related potentials and thought disorder in schizophrenia. The subjects were 29 chronic schizophrenic patients. Thought disorder was assessed using the Comprehensive Index of Positive Thought Disorder developed by Harrow and colleagues (Harrow and Quinlan, 1985; Marengo et al., 1986). Auditory event-related potentials were recorded during a standard oddball task. The P300 amplitude correlated negatively with the severity of the thought disorder. The P300 amplitude in the patients with thought disorder was significantly smaller than in the patients without thought disorder. These results suggest that a reduction in P300 amplitude is associated with a fundamental impairment of information processing in schizophrenic patients.     

Psychiatric comorbidity in adult attention deficit hyperactivity disorder: findings from multiplex families

OBJECTIVE: Patterns of psychiatric comorbidity were assessed in adults with and without attention deficit hyperactivity disorder (ADHD) identified through a genetic study of families containing multiple children with ADHD. METHOD: Lifetime ADHD and comorbid psychopathology were assessed in 435 parents of children with ADHD. Rates and mean ages at onset of comorbid psychopathology were compared in parents with lifetime ADHD, parents with persistent ADHD, and those without ADHD. Age-adjusted rates of comorbidity were compared with Kaplan-Meier survival curves. Logistic regression was used to assess additional risk factors for conditions more frequent in ADHD subjects. RESULTS: The parents with ADHD were significantly more likely to be unskilled workers and less likely to have a college degree. ADHD subjects had more lifetime psychopathology; 87% had at least one and 56% had at least two other psychiatric disorders, compared with 64% and 27%, respectively, in non-ADHD subjects. ADHD was associated with greater disruptive behavior, substance use, and mood and anxiety disorders and with earlier onset of major depression, dysthymia, oppositional defiant disorder, and conduct disorder. Group differences based on Kaplan-Meier age-corrected risks were consistent with those for raw frequency distributions. Male sex added risk for disruptive behavior disorders. Female sex and oppositional defiant disorder contributed to risk for depression and anxiety. ADHD was not a significant risk factor for substance use disorders when male sex, disruptive behavior disorders, and socioeconomic status were controlled. CONCLUSIONS: Adult ADHD is associated with significant lifetime psychiatric comorbidity that is not explained by clinical referral bias.     

DNA fragmentation decreased in schizophrenia but not bipolar disorder

BACKGROUND: Apoptosis is thought to play a role in neuronal pathology in schizophrenia and bipolar disorder. METHODS: To test this hypothesis, the Klenow method for in situ end-labeling of single-stranded DNA breaks was applied to anterior cingulate cortex from 18 healthy controls, 18 schizophrenic subjects, and 10 bipolar subjects. RESULTS: An unexpected reduction (71%) in Klenow-positive nuclei was found in schizophrenic but not in bipolar cortexes. CONCLUSIONS: To our knowledge to date, this is the first demonstration that there is much less DNA fragmentation in individuals with schizophrenia than in healthy controls and bipolar subjects, which raises a key question as to whether this alteration represents an adaptive or nonadaptive change in the regulation of intracellular signaling and mitochondrial oxidative pathways associated with apoptosis.     

Cognitive features of borderline personality disorder

Of 50 patients with borderline personality disorder, 100% reported disturbed but nonpsychotic thought, 40% (N = 20) reported quasi-psychotic thought, and none reported true psychotic thought during the past 2 years; only 14% (N = 7) reported ever experiencing true psychotic thought. Disturbed and quasi-psychotic thought was significantly more common among these patients than among patients with other axis II disorders or schizophrenia and normal control subjects; however, true psychotic thought was significantly more common among schizophrenic patients. While disturbed thought was also common among axis II disorder and schizophrenic patients, quasi-psychotic thought was reported by only one of these subjects, suggesting that quasi-psychotic thought may be a marker for borderline personality disorder.     

Differentiating bipolar disorder in Turkish prepubertal children with attention-deficit hyperactivity disorder

Background: Attention‐deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) in children are frequently comorbid conditions. Because the coexistence of ADHD and mania seriously complicates the course of the condition and the treatment of children, diagnosing or missing this comorbidity has important clinical implications. There are very few systematic studies on the subject in the literature and BPD in children is not recognized or studied in most countries other than the USA. We aimed to differentiate Turkish prepubertal children with ADHD from those with comorbid ADHD and BPD and compare their clinical characteristics. Methods: A total of 147 treatment‐ and drug‐naïve children, aged 7 to 13 years, who had been consecutively referred to the ADHD clinic, were evaluated using the Schedule for Affective Disorders and Schizophrenia for School‐age Children–Present and Lifetime version (K–SADS–PL). Parents completed the Child Behavior Checklist (CBCL) 4–18 and the Parent–Young Mania Rating Scale (P–YMRS) prior to the clinical interview. Results: Twelve children (8.2%) had comorbid bipolar disorder (ADHD + BPD). The ADHD + BPD group had significantly higher rates of depressive disorders, oppositional defiant disorder, panic disorder and a family history of bipolar disorder compared with the ADHD group. The ADHD + BPD group had significantly more problems on the CBCL scale (anxiety/depression, social problems, thought problems, aggression, externalization, and total score) and on the P–YMRS (all items except for insight) compared with the ADHD group. Conclusions: We conclude that ADHD + BPD in Turkish children represents a clinical picture different to that of ADHD alone, in which the clinical characteristics resemble those of children reported in the literature. Further long‐term follow‐up studies are needed in larger clinical and community samples.     

Oculomotor abnormalities in attention deficit hyperactivity disorder: a preliminary study

BACKGROUND: Prevailing hypotheses suggest that attention deficit hyperactivity disorder (ADHD) is secondary to dysfunction of motor intentional systems mediated by prefrontal circuitry. Oculomotor paradigms provide a mechanism for examining and localizing dysfunction at the interface between movement and cognition. OBJECTIVE: Three different saccade tasks (reflexive or prosaccades, antisaccades, and memory-guided saccades) were used to examine functions necessary for the planning and the execution of eye movements, including motor response preparation, response inhibition, and working memory. METHODS: The study included 19 children with ADHD, divided into two groups: a group of 8 children on methylphenidate at the time of testing and a group of 11 children not taking any psychoactive medication. Results from the two groups were compared with those from 25 age- and gender-matched normal control children. RESULTS: Both groups of children with ADHD made significantly more directional errors than did controls on the antisaccade task and significantly more anticipatory errors than did controls on the memory-guided saccade task, findings that are consistent with deficits in response inhibition. There were no significant differences in prosaccade latency, although unmedicated children with ADHD showed significantly greater variability in latency on the prosaccade task than did controls. On the memory-guided saccade task there were no significant differences in saccade accuracy; however, unmedicated children with ADHD showed longer saccade latency than did either controls or medicated children with ADHD. CONCLUSIONS: Oculomotor findings suggest that deficits in prefrontal functions, in particular response inhibition, contribute to behavioral abnormalities observed in ADHD. Findings also suggest that the administration of methylphenidate is associated with improvements in the consistency of motor response. Although there were no observed improvements in response inhibition with methylphenidate, conclusions await a design in which subjects complete testing both on and off medication.     

Communication deficits and formal thought disorder in schizophrenic children.

This study examined 31 schizophrenic children to determine if they used discourse devices that make speech coherence differently from sex and mental age matched normal children. It also investigated whether the discourse deficits of the schizophrenic children were related to clinical measures of formal thought disorder. Using Halliday and Hassan's analysis of cohesion, the authors found that schizophrenic children underutilize some discourse devices and overutilize others. Several of their discourse deficits were similar to those described in schizophrenic adults. The schizophrenic children, however, also had additional discourse deficits, which probably reflect developmental delays. The authors also demonstrated that the schizophrenic children with loose associations had different discourse deficits and discourse/IQ correlates than schizophrenic children without loose associations. The schizophrenic children receiving neuroleptic medication had lower loose associations scores than the unmedicated subjects. The authors discuss the possible confounding effect of medication and loose associations, as well as the developmental, cognitive, and clinical implications of the study's findings.     

Neuropsychological dysfunction in schizophrenia. Relation to associative thought disorder

Recent evidence suggests that cerebral atrophy with cognitive deficits is associated with negative schizophrenic symptoms, including poverty of speech and speech content. This report investigates the relationship between specific measures of neuropsychological dysfunction and four major indices of associative thought disorder in schizophrenia, to ascertain whether neuropsychologically impaired schizophrenics show more associative disturbance than neuropsychologically intact schizophrenics. Twenty neuropsychologically intact and 12 impaired schizophrenics, rigorously diagnosed by the Research Diagnostic Criteria, were administered the Luria-Nebraska Neuropsychological Battery. These two groups of schizophrenics were compared on a continuous word-association test, which included two nonverbal and two verbal measures of associative disturbance. The neuropsychologically impaired schizophrenics had slower reaction times (p less than .05), but did not differ from the neuropsychologically intact schizophrenics on the verbal measures. Results indicated a stronger relationship between neuropsychological functions and the nonverbal dimensions (p less than .02), than with the verbal measures. This challenges the assumption that a left hemisphere abnormality in schizophrenia is particularly associated with cognitive disturbance, and suggests that neuropsychologically impaired schizophrenics may show greater potential for negative schizophrenic symptoms.     

Altered performance on an ocular fixation task in attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder without validated objective markers. Eye movement studies may be useful in providing objective criteria for characterizing the disorder. METHODS: We compared 53 children (29 girls) with ADHD to 44 healthy control children (18 girls) on a 21-sec fixation task. Large saccades (> 4 degrees ) away from the fixation point were analyzed. RESULTS: Children with ADHD made more large saccades that interrupted fixation than did control children (p =.001). Mean scores of the ADHD group did not change significantly with subsequent retesting on placebo (p =.11); however, there was poor intrasubject correlation (r =.16). CONCLUSIONS: Both boys and girls with ADHD made significantly more intrusive saccades during fixation than did control subjects, possibly reflecting intrinsic neurologic dysfunction; however, a probable "floor effect" obviates conclusions about the reliability of this measure.     

Differences in brain chemistry in children and adolescents with attention deficit hyperactivity disorder with and without comorbid bipolar disorder: a proton magnetic resonance spectroscopy study

OBJECTIVE: The authors' goal was to investigate phosphatidylinositol and glutamatergic metabolism in the anterior cingulate cortex of children and adolescents with attention deficit hyperactivity disorder (ADHD) alone, children with ADHD plus bipolar disorder, and children with no axis I diagnosis. METHOD: Proton spectra were acquired from a 4.8-ml voxel placed in the anterior cingulate cortex of 30 subjects who were 6 to 13 years old. Fifteen subjects had ADHD and no comorbid disorder, eight had ADHD plus bipolar disorder, and seven were healthy comparison subjects. RESULTS: Children with ADHD had a significantly higher ratio of glutamate plus glutamine to myo-inositol-containing compounds than children with ADHD plus bipolar disorder and healthy children. CONCLUSIONS: myo-Inositol-containing compounds may provide information on the action of antimanic treatments such as lithium, valproate, and carbamazepine. Glutamate and glutamine are measures of glutamatergic neurotransmission and thus may also reflect changes in serotonin and dopamine pathways.     

Schizotypal personality disorder in individuals with and without schizophrenic relatives: similarities and contrasts in neurocognitive and clinical functioning.

Schizophrenia-spectrum disorders may reflect the genotype for schizophrenia. One such disorder, Schizotypal Personality Disorder (SPD), was examined as a function of family history of schizophrenia. Clinical profiles and neurocognitive functioning were evaluated in 25 schizotypal subjects (10 SPD with schizophrenic relatives and 15 SPD without schizophrenic relatives), and in 24 normal controls. The primary finding is that vigilance performance was similarly impaired in both SPD groups. An additional neurocognitive impairment, comprehension of grammatical constructions, was observed only in the SPD group with schizophrenic relatives. Of interest, the clinical profiles of the two SPD groups did not differ significantly. These results suggest that schizotypal personality disorder is associated with a continuum of neurocognitive vulnerability that increases as a function of family history of schizophrenia.     

A controlled study of formal thought disorder in children with autism and multiple complex developmental disorders

Along with well-defined categories in classification systems (e.g., autistic disorders and attention-deficit/hyperactivity disorder (ADHD)), practitioners are confronted with many children showing mixed forms of developmental psychopathology. These clusters of symptoms are on the borderlines of more defined categories. The late Donald Cohen proposed heuristic criteria to study a group defined by impaired social sensitivity, impaired regulation of affect, and thinking disorders under the name multiple complex developmental disorders (MCDD). Although these children meet criteria for pervasive developmental disorder--not otherwise specified (PDD-NOS), they have additional important clinical features, such as thought disorder. After highlighting similarities and differences between MCDD and comparable groups (e.g., multidimensionally impaired children), this paper presents the findings of a study comparing formal thought disorder scores in children with MCDD to children with autism spectrum diagnoses, such as autistic disorder (AD), and to children with nonspectrum diagnoses, such as ADHD and anxiety disorders. METHODS: Videotaped speech samples of four groups of high-functioning, latency-aged children with MCDD, AD, ADHD, and anxiety disorders were compared to a control group of normal children using the Kiddie Formal Thought Disorder Rating Scale (K-FTDS). RESULTS: High formal thought disorder scores were found both in the AD and MCDD groups, low rates in the ADHD groups, and no thought disorder in the anxiety disorder and normal control groups. The severity of formal thought disorder was related to verbal IQ scores within the AD and MCDD groups. CONCLUSION: High formal thought scores in children with complex developmental disorders, such as AD and MCDD, appear to reflect impaired communication skills rather than early signs of psychosis.