Petra Franke

Wisconsin Card Sorting Test: an indicator of vulnerability to schizophrenia?

The Wisconsin Card Sorting Test (WCST) is a neuropsychological test, hypothesized to be an indicator of dorsolateral prefrontal cortex (DLPFC) functioning. The performance of schizophrenic patients in our sample (off medication) was worse than the performance of healthy controls in all variables of the WCST, including perseverative responses (PR) as well as non-perseverative responses (NPR). The rate of perseverative and non-perseverative responses was neither a function of the severity of the illness (measured by SANS/SAPS scales) nor the duration of the disease. Healthy siblings of schizophrenic probands revealed more perseverative responses than healthy controls, but did not show any difference with respect to the non-perseverative responses. This finding suggests that the difficulty to shift a cognitive set, reflected by the frequency of perseverative responses, is in favor of the WCST as a vulnerability marker for schizophrenia, whereas non-perseverative responses presumably indicate a state, but not a trait marker of the disease. However, the usefulness of this indicator may be limited by its association with age, which is worthy of being studied in closer detail.

Attentional abilities and measures of schizotypy: Their variation and covariation in schizophrenic patients, their siblings, and normal control subjects

Thirty-five schizophrenic patients in the early stages of illness, 26 of their healthy siblings, and 35 normal control subjects performed the Continuous Performance Test, Identical Pairs version (CPT-IP). Both schizophrenic patients and their siblings were significantly impaired in their attentional performance compared with normal subjects. These results support impaired attention as a vulnerability marker of schizophrenia and indicate that at-risk siblings of schizophrenic patients display attentional deficits comparable to those found for the offspring of schizophrenic parents. By contrast, a decline in performance with the onset of a distraction condition (auditory and visual stimuli) was seen only in schizophrenic patients; siblings and normal control subjects did not differ from one another in response to experimental distraction. Therefore, it was concluded that differential distractibility is likely to be a state marker of schizophrenia. In clinical assessments, healthy siblings rated themselves as experiencing significantly more physical anhedonia than did normal control subjects, but the siblings did not differ from normal control subjects in self-rated perceptual aberrations. Contrary to expectation, performance on the CPT-IP did not correlate significantly with either anhedonia or perceptual aberration in high-risk siblings. These results suggest that psychometrically measured psychosis proneness and neuropsychologically detected deficits may tap two nonoverlapping sources of vulnerability to schizophrenia.

A controlled family study in panic disorder

There are only a few family studies in panic disorder. Although there is some evidence that panic disorder is familial, the exact figures of the familial risk for this disorder are at variance across different studies; the impact of comorbidity and of the gender of relatives is also unclear. Family studies in panic disorder controlling for the comorbidity in probands are therefore indicated. This study presents the morbid risks in families of 40 pure panic disorder probands (DSM-III-R) without a history of psychotic disorders, major depression or alcoholism compared with families of 80 controls recruited in the general population. The relative frequency of panic disorder (DSM-III-R) in the first-degree relatives of panic disorder probands was 5.7% (the age corrected morbid risk is 7.9%) compared to 1.8% in relatives of healthy controls (age corrected morbid risk 2.3%). Agoraphobia segregated predominantly among female relatives of agoraphobic probands. An increased familial risk of major depression and of alcoholism was also observed. Comorbidity with alcoholism and major affective disorders was excluded in panic disorder probands by definition; therefore, these findings indicate that the etiological factors underlying panic disorder may overlap with those of alcoholism and those of unipolar major depression.

Assessment of Frontal Lobe Functioning in Schizophrenia and Unipolar Major Depression

This study has used neuropsychological tasks--Wisconsin Card Sort (WCST), Trail Making (TMT) A and B, Verbal Fluency, Digit Span--to compare acute and currently off-medication schizophrenics, patients with unipolar nonpsychotic major depression and healthy controls. Both patient groups differed significantly from healthy controls in their neuropsychological performance. Furthermore there was only little (quantitative) difference between schizophrenics and depressed patients in the frontal lobe associated tasks: WCST, TMT and Verbal Fluency. Depressed patients tended to perform worse than schizophrenics on Digit Span, a task hypothesized to involve other than frontal areas of the brain. Although the group of depressed patients was older than the schizophrenic sample, the effect of age may not totally explain the findings. The results indicate that there do exist disturbances in frontal lobe cognitive functioning in schizophrenia and depression. Symptomatology (SANS/SAPS) and cognitive functioning in the schizophrenic group revealed only a trend for negative symptoms to be associated with worse performance in the WCST, but were significantly correlated with negative as well as positive symptoms on the TMT.

The reliability of the SADS-LA in a family study setting.

SummaryThe joint-rater and test-retest reliability study of two translated versions of the SADS-LA (Schedule for Affective Disorders and Schizophrenia-Lifetime version — modified for the study of anxiety disorders), one in French and the other in German, have been tested in family study settings, in a sample of patients and firstdegree relatives. The test-retest reliability study demonstrated that identification of major affective disorders and schizophrenia was performed with sufficient reliability; however, diagnoses of subtypes of major disorders (e.g. bipolar II disorder) and identification of minor disorders was cless reliable. The implications of these findings in phenotype identification during family studies in psychiatry are discussed.

Intra- and Interhemispheric Electroencephalogram Coherence in Siblings Discordant for Schizophrenia and Healthy Volunteers

Former studies had pointed to an increased electroencephalogram (EEG) coherence in schizophrenics, but it remained unsolved whether this deviation represents the premorbid state or is only a consequence of the current or previous schizophrenic episodes. To clarify this question, we tested the hypothesis that subjects at elevated risk also reveal higher coherences compared to healthy controls. For that, intra- and interhemispheric EEG coherences were investigated in untreated schizophrenics, their healthy siblings, and healthy controls. Differences were only found regarding the intrahemispheric coherences. Both in schizophrenics and, even though to a lesser degree, in their siblings significantly higher coherence estimates were found compared to the control group. The results are in accordance with the assumption that schizophrenia is predominantly a neurodevelopmental disease. Increased coherence might be assumed to be a vulnerability marker for schizophrenia reflecting maldevelopment of the brain before onset of the disorder.

Neuropsychological indicators of the vulnerability to schizophrenia

Schizophrenia is associated with enduring deficits in neuropsychological functioning. It is widely undecided if the various aspects of neuropsychological impairment are a consequence of the disorder or if they are also present premorbidly and in populations at increased risk for schizophrenia (vulnerability markers). Neuropsychological deficits in healthy relatives of schizophrenic patients who are at an elevated risk for schizophrenia and who did not yet pass the period of risk would indicate that these deficits are vulnerability markers. This hypothesis was tested for three neuropsychological paradigms which have been proven to distinguish schizophrenic patients from controls. 33 siblings of drug-free schizophrenic probands revealed deficits has compared to 33 matched healthy controls in a blurred single target version of the Continuous Performance Test and in a multiple item version of the Span of Apprehension Test but not so in less difficult versions of both tests or in the time needed to react to stimuli with shifting modality.

Personality variations in healthy relatives of schizophrenics

A familial relationship between schizophrenia and schizotypal personality disorder is widely acknowledged; the familial relationship between schizophrenia and the broad continuum of schizoid personality variation is less clear. In a comprehensive family study healthy relatives of schizophrenics were compared by self rated personality features with relatives of unipolar depressed patients and with relatives of controls. The dimension of schizoidia was not able to distinguish the groups of relatives. However, relatives of schizophrenics (in particular male relatives) scored higher on normalized personality dimensions such as rigidity and neuroticism. Healthy relatives of probands with unipolar depression revealed a similar deviant pattern.

Positive/negative symptomatology and experimental measures of attention in schizophrenic patients

In a search for an external validation of the negative syndrome construct and the attentional impairment item on Andreasens scale, 49 unmedicated schizophrenic patients were administered the Span of Apprehension Test and a Continuous Performance Test with two levels of difficulty. This schizophrenic sample performed significantly more poorly on the attentional tests than a comparable group of 27 healthy control subjects. Depending on the difficulty of the test we found a number of significant correlations between the SANS composite score and the pertaining attentional impairment item on the one hand and experimental indices of attentional functioning on the other hand, which might corroborate the psychopathological assumptions. The implications of these results for further attempts to validate clinical concepts of the positive/negative dichotomy by experimental means will be discussed.

Subclinical thought disorder in first-degree relatives of schizophrenic patients. Results from a matched-pairs study with the Thought Disorder Index

To assess the frequency and quality of formal thought disorder in schizophrenic patients and their first‐degree relatives, a consecutive series of 36 unmedicated patients, 20 siblings of these patients and 37 normal control subjects were examined with Holzmans Thought Disorder Index (TDI). As a proof of the internal validity of this tool, the patients demonstrated significantly more thought disorder than the controls as measured by the TDI total score and various subscores, which proved the internal validity of this tool in a German‐speaking sample. In addition, in a pairwise comparison with controls who were individually matched by age and sex the patients’ siblings had a significantly higher total TDI score and nonsignificant elevations on several subscores (combinatory and flippant). As to the level of severity of the thought disorder, the siblings mostly took an intermediate position between patients and controls. In conjunction with previous reports from other authors, our findings lend further support to the notion of subclinical thought disorder as an indicator of familial vulnerability to schizophrenia.