Ruth Condray

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.

Working memory capacity predicts language comprehension in schizophrenic patients

The association between language comprehension and working memory capacity was evaluated in 25 male DSM-III-R schizophrenic patients (14 inpatients; 11 outpatients), and in 11 male normal controls (no lifetime DSM-III-R disorder). Patients and controls did not differ significantly on age and education. Language comprehension was examined as a function of two types of processing demand: grammatical complexity (complex versus simple sentences) and presentation rate (accelerated versus conversational). Schizophrenic patients showed significantly reduced language comprehension and decreased working memory capacity for language, compared with controls. Patients showed general difficulty in comprehending accurately, rather than exhibiting problems with specific grammatical structures. Subject groups were highly accurate and did not differ in their ability to perceive the individual words in sentences presented at the accelerated rate (intelligibility). Presentation rate and grammatical complexity affected comprehension accuracy in all groups, however, with increases in rate and complexity producing decreases in understanding. Of most importance, theoretically, is the finding that working memory capacity predicted language comprehension accuracy in both schizophrenic patients and normal controls. Results suggest that language comprehension deficits in schizophrenic patients may involve a general dysfunction that is associated with working memory capacity for language.

Modulation of language processing in schizophrenia : Effects of context and haloperidol on the event-related potential

BACKGROUND Disturbances in language associations were among the first clinical symptoms reported for individuals described as schizophrenic (Bleuler 1911/1950). Currently, associative language disturbance is a diagnostic feature of schizophrenia (American Psychiatric Association 1994); however, the mechanisms that produce this symptom remain unknown. In the present study, two candidate psychological functions were examined: sensitivity to semantic context and expectancy (attention). METHODS Visual event-related potentials were recorded during a lexical decision task in which semantic relationship and expectancy (relatedness proportions) were varied. Semantic priming processes were compared between 34 male normal control subjects tested once and 37 male schizophrenic inpatients evaluated during their participation in a double-blind haloperidol maintenance therapy and placebo replacement protocol. RESULTS Schizophrenic patients failed to discriminate between associated and unassociated words, as measured by the amplitude of the N400 component (i.e., absence of the N400 priming effect); however, the overall mean amplitude of N400 did not differ between patients and control subjects. In addition, patients and control subjects did not differ significantly in the amplitude of N400 elicited to associated words or to unassociated words. Finally, the effect of expectancy-based processing on the magnitude of the N400 priming effect did not differ between patients and control subjects. CONCLUSIONS On the basis of these findings, a tentative hypothesis is suggested that schizophrenic patients are characterized by a pattern of indiscriminate or random spread of activation in their semantic network during the processing of single-word semantic contexts.

Automatic activation of the semantic network in schizophrenia: evidence from event-related brain potentials

BACKGROUND Language disorder associated with schizophrenia might be due to disturbances in both automatic activation and mechanisms of controlled attention. The contribution of each process to semantic memory dysfunction has not been determined for schizophrenia, and the semantic priming paradigm is well-suited for addressing this question. In the present report, event-related potentials (ERPs) elicited under conditions assumed to reveal automatic activation (short prime-target interval and low proportion of related words) are compared directly with ERPs elicited under conditions associated with controlled processing (long prime-target interval and high proportion of related words). METHODS Visual ERPs were recorded during a lexical decision task, in which semantic relationship (associated and unassociated words), expectancy (relatedness proportions), and prime-target interval (250- and 850-msec inter-stimulus intervals [ISIs]) were varied. Diagnosis and expectancy were between-subjects factors; semantic relationship and ISI were repeated measures. The N400 priming effect (enhanced negativity to unassociated words) was compared between 34 male normal control subjects tested once and 37 male schizophrenia inpatients evaluated during their participation in a double-blind haloperidol maintenance therapy and placebo replacement protocol. RESULTS The N400 priming effect for patients was significantly reduced during both pharmacologic phases, compared with controls. During haloperidol treatment, however, patients showed a significant N400 priming effect over the anterior scalp region and additionally under the automatic activation condition. The N400 priming effect was enhanced under the controlled processing condition for control subjects; this effect was not observed for patients. N400 amplitude elicited under the rapid presentation rate (250-msec ISI) differed between medicated patients and controls; groups did not differ for the 850-msec ISI. CONCLUSIONS Findings suggest that automatic activation and mechanisms of controlled attention are both disrupted during semantic memory access for schizophrenia patients. Pharmacologic agents, such as haloperidol, might enhance automatic activation of the semantic network in this patient population, as indexed by the N400 component of the ERP.

3-Hydroxykynurenine and clinical symptoms in first-episode neuroleptic-naive patients with schizophrenia

One branch of the tryptophan catabolic cascade is the kynurenine pathway, which produces neurotoxic [3-hydroxykynurenine (3-OHKY), quinolinic acid] and neuroinhibitory (kynurenic acid) compounds. Kynurenic acid acts as a competitive antagonist at the glycine site of N-methyl-d-asparate receptors at high concentrations and as a non-competitive antagonist on the α7-nicotinic acetylcholine receptor at low concentrations. Kynurenine compounds also influence cognitive functions known to be disrupted in schizophrenia. Alterations in tryptophan metabolism are therefore of potential significance for the pathophysiology of this disorder. In this paper, tryptophan metabolites were measured from plasma using high-pressure liquid chromatography coupled with electrochemical coulometric array detection, and relationships were tested between these metabolic signatures and clinical symptoms for 25 first-episode neuroleptic-naive schizophrenia patients. Blood samples were collected and clinical and neurological symptoms were rated at baseline and again at 4 wk following initiation of treatment. Level of 3-OHKY and total clinical symptom scores were correlated when patients were unmedicated and neuroleptic-naive, and this relationship differed significantly from the correlation observed for patients 4 wk after beginning treatment. Baseline psychosis symptoms were predicted only by neurological symptoms. Moreover, baseline 3-OHKY predicted clinical change at 4 wk, with the lowest concentrations of 3-OHKY being associated with the greatest improvement in symptoms. Taken together, our findings suggest a neurotoxic product of tryptophan metabolism, 3-OHKY, predicts severity of clinical symptoms during the early phase of illness and before exposure to antipsychotic drugs. Baseline level of 3-OHKY may also predict the degree of clinical improvement following brief treatment with antipsychotics.

language comprehension in schizophrenics and their brothers

Disturbances in language functioning may be associated with familial vulnerability to schizophrenia. Language comprehension, measured by the Luria-Nebraska Relational Concepts Factor Scale, was evaluated in 36 schizophrenic probands and their nonschizophrenic adult brothers (n = 41), and in 18 normal controls. Language comprehension performance was a function of psychiatric diagnosis in the brothers. Brothers who met criteria for schizophrenia-spectrum disorders showed significantly reduced language performance compared with unaffected brothers and normal controls. Moreover, abnormal language performance was exhibited by significantly more probands and spectrum-disordered brothers than by the normal controls and the brothers without schizophrenia-spectrum disorders. Finally, language performance was not significantly different for 31 pairs of schizophrenic probands and their brothers. Impaired language comprehension appeared comparatively specific in this sample of relatives, as groups were not significantly different on measures of nonlinguistic concept formation (Wisconsin Card Sorting Test) and general intellectual functioning (WAIS-R Information and Block design). Results suggest that impaired language comprehension is associated with familial vulnerability to schizophrenia, and that this disturbance may be most severe in relatives diagnosed with schizophrenia-spectrum disorders.

Increased Incidence of Anxiety and Depressive Disorders in Persons With Organic Solvent Exposure

Objective The purpose of this study was to determine whether the prevalence of current and past DSM-IV axis I psychiatric disorders is higher among persons with a history of exposure to organic solvents than among a demographically similar group of nonexposed control subjects. Methods Thirty-eight solvent-exposed subjects and 39 nonexposed healthy control subjects were evaluated for axis I disorder with the Structured Clinical Interview for DSM-IV. Results A significantly higher number of solvent-exposed subjects (71%) met criteria for current DSM-IV axis I disorder in comparison with control subjects (10%). The most prevalent diagnosis in exposed subjects was within the anxiety and mood clusters, with a high percentage (36%) of exposed subjects meeting criteria for a dual diagnosis of mood and anxiety disorder. There were no differences between the groups in past psychiatric disorders or current or past substance abuse or dependence. Conclusions The rates of past psychiatric disorders among solvent-exposed subjects are similar to those among normal control subjects, but the prevalence of current DSM-IV axis I psychiatric disorders is significantly higher among exposed subjects than among control subjects.

Language disorder in schizophrenia as a developmental learning disorder

Receptive language disorder in schizophrenia is hypothesized to represent a learning disorder that involves a neurodevelopmental etiology. It is argued that a preexisting developmental language disorder may characterize a subset of schizophrenia patients. A primary deficit in the temporal dynamics of brain function is assumed to cause receptive language disorder in schizophrenia. This hypothesized core deficit includes both disturbance in the processing of rapid, sequential information and disruptions to patterns of brain activation and synchronization. These timing deficits may alter the way associative connections are formed and/or accessed in semantic memory. It is suggested that abnormalities in second-messenger pathways of subcortical-cortical circuitry offer an etiological nexus for language dysfunction in schizophrenia and developmental dyslexia.

Mood and behavioral symptoms in individuals with chronic solvent exposure

Psychiatric symptoms have been reported for individuals who experience chronic exposure to low levels of organic solvents. However, it is not known what proportion of such individuals experience psychiatric disorder; which specific disorders may be characteristic of this population; or whether bioaccumulation of lead contributes to the relationship between solvent exposure and psychiatric symptoms. Twenty-nine male journeymen painters and 32 male non-painter control subjects were administered semi-structured diagnostic interviews for DSM-III-R Axis I and Axis II disorders. Career solvent exposure and blood lead levels were also measured. Painters and control subjects did not differ significantly with respect to age, intelligence, or demographic characteristics. Results showed that the probability of being diagnosed with a mood disorder differed significantly in painters (41%) and control subjects (16%). Painters (66%) and control subjects (50%) did not differ for substance use diagnoses. Groups also did not differ for personality disorders involving an onset before 25 years of age. In contrast, painters exhibited a sub-clinical pattern of personality dysfunction involving symptomatology that was measured allowing for late onset (after age 25). Finally, a significant dose-response relationship was observed between career solvent exposure, blood lead level, and personality symptoms. In summary, these data showed an increased rate of psychological disturbance in a significant and substantial number of painters. However, not all painters were so characterized. This overall pattern raises a question regarding a potential role for differential vulnerability, which requires empirical validation.

Neuropsychological assessment, depression, and past exposure to organic solvents.

This study assessed neuropsychological performance in persons with a history of exposure to organic solvents and nonexposed healthy controls. Structured clinical interviews were also done to determine current Axis I diagnosis of mood disorder to assess the contribution of mood disorder to neuropsychological performance. Solvent-exposed participants were found to have significantly reduced scores on 3 of 5 neuropsychological clusters (learning and memory, visuospatial, psychomotor speed) compared to controls. No differences were found between the groups on measures of general intelligence. Within the exposed group, 50% met current Axis I criteria for mood disorder. Hierarchical multiple regression, controlling for age and education, revealed that mood disorder was significantly related to performance on only the visuospatial domain. There was no association between mood disorder and measures of learning and memory, attention, motor speed, and general intelligence. Higher ratings of past exposure were associated with poorer scores on learning and memory tests and slower times on speeded tests. These findings are consistent with other research documenting deficits in neuropsychological and psychiatric functioning in exposed workers.