Impaired sustained attention and executive dysfunction: Bipolar disorder versus depression-specific markers of affective disorders

Objective

To identify neurocognitive measures that could be used as objective markers of bipolar disorder.

Methods

We examined executive function, sustained attention and short-term memory as neurocognitive domains in 18 participants with bipolar disorder in euthymic state (Beuth), 14 in depressed state (Bdep), 20 with unipolar depression (Udep) and 28 healthy control participants (HC). We conducted four-group comparisons followed by relevant post hoc analyses.

Results

Udep and Bdep, but not Beuth showed impaired executive function (p = 0.045 and p = 0.046, respectively). Both Bdep and Beuth, but not Udep, showed impaired sustained attention (p = 0.001 and p = 0.045, respectively). The four groups did not differ significantly on short-term memory. Impaired sustained attention and executive dysfunction were not associated with depression severity, duration of illness and age of illness onset. Only a small number of abnormal neurocognitive measures were associated with medication in Bdep and Beuth.

Conclusion

Impaired sustained attention appears specific to bipolar disorder and present in both Beuth and Bdep; it may represent an objective marker of bipolar disorder. Executive dysfunction by contrast, appears to be present in Udep and Bdep and likely represents a marker of depression.     

Deficits in sustained attention in schizophrenia but not in bipolar disorder

The aim of the present study was to investigate sustained attention in remitted patients with bipolar disorder and in patients with schizophrenia, as compared to each other and to healthy controls; a secondary aim was to investigate the correlations of different symptom dimensions with performance on sustained attention in the two patient groups. Participants were 29 (18 men) outpatients with schizophrenia (SZ), 19 (8 men) patients with bipolar disorder I (BP) in remission, and 30 (15 men) healthy controls (HC); all three groups were matched on age, sex ratio, and level of education. Symptom severity (positive symptoms, negative symptoms, and general psychopathology) of patients with SZ were assessed with the Greek version of the Positive and Negative Syndrome Scale (PANSS); residual affective symptoms of patients with BP were assessed with the Young Mania Rating Scale (YMRS) and the Montgomery-Asberg Depression Rating Scale (MADRS). Sustained attention was measured by means of the Penn Continuous Performance Test (PCPT). The three groups differed significantly on the PCPT scores. Patients with SZ performed more poorly than both the BP and HC groups, whereas patients with BP did not differ significantly from HC. Performance on the PCPT did not correlate significantly with scores on the YMRS and MADRS in patients with BP. Also, scores on the PCPT did not correlate significantly with scores on any of the three subscales of the PANSS. Outpatients with schizophrenia presented deficits in sustained attention, whereas patients with bipolar disorder I in remission did not manifest such impairment. These results imply that impaired sustained attention might be a more enduring deficit in schizophrenia than it appears to be in bipolar disorder.     

Neurological signs and sustained attention impairment in schizophrenia

Both neurological signs and attention impairments are often found in schizophrenia. This study addresses the extent to which neurological signs are related to sustained attention impairment. We assessed subgroups of neurological signs using the standardised Cambridge Neurological Inventory (CNI). Sustained attention was measured using a monotone counting paradigm. After taking into consideration potential confounds such as age, education level and duration of illness, we explored the correlation between sustained attention and groups of neurological signs, as well as with individual signs. We found that “motor coordination” and “disinhibition” signs were significantly related to sustained attention. The correlation with “sensory integration” just failed to reach significance after correction for multiple comparison. “Dyskinesia”, “catatonia”, “pyramidal” and “extrapyramidal” subgroups were unrelated to sustained attention. The results support the notion of heterogeneity and diversity in neurological signs (even among soft neurological signs) and argue against the use of a single global measure to embrace all soft neurological signs in schizophrenia. Received: 10 April 2000 / Accepted: 25 July 2000     

Anti-histone antibodies in schizophrenia and affective disorders

Sera from 81 psychiatric patients (51 with schizophrenia and 30 with affective disorders) were analyzed using several assays in parallel for the presence of non-organ-specific autoantibodies, namely anti-nuclear antibodies, anti-deoxyribonucleic acid antibodies (native and denatured DNA), anti-histone antibodies, anti-centromere antibodies, and anti-nuclear antigen antibodies. Nine out of the 81 sera studied were positive for the presence of anti-nuclear antibodies. Moreover, in 15 patients, significant titers of anti-histone antibodies were detected. No correlation can be drawn concerning the presence of anti-histone antibodies and the clinical situation. Although no clear association was noted with a specific class of drugs, it cannot be excluded at present that the therapeutic regimen received by the patients may explain the results observed.     

Perceptual span in schizophrenia and affective disorders

Perceptual span was assessed in schizophrenic, bipolar affective disorder-manic, bipolar affective disorder-depressed, and nonpsychotic inpatients. Both schizophrenics and manics processed less information than depressives, and did not differ from each other. This suggests that reduced span may be a concomitant of psychoses characterized by distractibility and thought disorder, rather than a trait specific to schizophrenia.     

Genetics of schizophrenia and affective disorders

The molecular-genetic basis of non-mendelian, genetically influenced disorders (complex disorders) is beginning to be uncovered. Recently, major progress in localization and detection of disposition genes of schizophrenia and bipolar disorder was achieved. We provide a comprehensive overview of recent results of linkage and association studies in schizophrenia and bipolar disorder. Several disposition genes for schizophrenia (DTNBP1, NRG1, G72) were identified, whereas evidence for specific disposition genes in bipolar disorder is more limited. Multiple limitations of current research strategies in the search of disposition genes of complex disorders have to be considered; alternative phenotype definitions, genome-wide association studies and parallel investigation of epigenetic misregulations might overcome these limitations.     

Neurodevelopmental liabilities in schizophrenia and affective disorders

There is now considerable evidence that both schizophrenia and affective disorders have their origin at least in part in events that occur during early pre- and post-natal development. In the case of schizophrenia, many observations, for example, increased risk for schizophrenia in the offspring of mothers who had influenza A during their second trimester of pregnancy and evidence for abnormal neuronal migration in the cerebral cortex of post mortem tissue from schizophrenic patients, suggest that a second trimester insult may have occurred and that this insult may have increased the risk for the development of schizophrenia in late adolescence or early adulthood. Animal studies have found that rats that undergo exocitotoxic damage to the ventral hippocampus on postnatal day 7 develop exaggerated sensitivity to dopamine-stimulating drugs or to stressful stimuli that becomes apparent after sexual maturity but not before, providing a neurodevelopmental model of schizophrenia. Similarly, post-weaning social isolation leads to enhanced responses to dopaminergic drugs and to stress that emerges after sexual maturity. These animal models are proving to be valuable tools to study the neurobiological mechanisms mediating the influence of early insults to the nervous system on later behavioural functions. In the case of affective disorders, although the evidence is not as strong, a number of the same observations have been made suggesting that an insult during early ontogeny may lead to the development of affective disorders later in life. For example, retrospective studies of people with affective disorders showed that they were more likely to have attained motor milestones at a later age and to have had poorer academic performance as children. There is a wealth of evidence suggesting hyperfunctioning of the hypothalamic-pituitary-adrenal (HPA) axis in affective disorders. Animal studies have shown that early maternal deprivation can lead to lasting changes in the reactivity of the HPA axis to stressful stimuli, providing another link from early experience to adult psychopathology. Continued studies of the effects of pre- and early post-natal events on the development of the nervous system and the relationships of these events to schizophrenia or affective disorder will provide new insights into the mechanisms underlying these common neuropsychiatric illnesses.     

Developmental precursors and biological markers for schizophrenia and affective disorders: Specificity and public health implications

Schizophrenia's developmental dimension includes causes being active early in life. Precursors are manifest before psychosis begins, and there is an emerging public health agenda including prediction and prevention. We discuss the specificity of some developmental precursors to schizophrenia as an outcome, with particular reference to longitudinal birth cohort studies. Underlying structural brain abnormalities are considered. Differences from controls are found in schizophrenia and, to a lesser extent, before affective disorder on many measures. This apparent lack of specificity may not be the case in neurobiological terms, as underlying mechanisms may be different; parsimony suggests not. This same lack of specificity may be an advantage in public health terms, raising the possibility of strategies to predict and prevent a range of psychiatric disorders, not just schizophrenia. Received: 27 March 2000 / Accepted: 14 April 2000     

Biological markers in obsessive-compulsive and affective disorders

To explore the relationship between obsessive-compulsive disorder (OCD) and affective disorder, patients with OCD were studied using a series of biological markers which have been previously reported to be abnormal in patients with affective illness. These “markers” included the dexamethasone suppression test, sleep electroencephalography, the plasma growth hormone response to clonidine, and platelet ³H-imipramine binding. Results from each of these studies suggested similarities between patients with obsessional disorder and those with affective illness. Many of these biological abnormalities were evident in obsessional patients who did not manifest depressive symptoms. As a tricyclic antidepressant, clomipramine, has been found to reduce obsessional symptoms, the relationship between these “affective-like” laboratory findings and the clinical response to clomipramine was studied in a subgroup of OCD patients. Preliminary results suggest that none of the markers studied predict clomipramine response.     

Immediate versus sustained processing in schizophrenia.

A Stroop negative priming (NP) task was used to assess immediate selective attention and priming in schizophrenia and schizoaffective disorder. Subject groups were comprised of 12 state hospital inpatients (41.8 +/- 7.5 years of age), 11 outpatients (39.8 +/- 7.5 years of age), and 16 controls (36.4 +/- 11.7 years of age). Compared with the control group and the outpatients, inpatients failed to exhibit NP [F(2,36) = 6.09, p < .01], despite exhibiting equivalent Stroop RT interference (p > .05). Error rates did not differ significantly between the 3 groups. Although medication types and dosages were similar between the 2 patient groups, length of illness was significantly longer in the inpatients (19.8 years) than in the outpatients (12.4 years; p < .05). Positive symptom ratings were also significantly higher in the inpatients. The finding of reduced NP in the state hospital patients appears to be related to severity of symptomatology and chronicity of illness.     

Time experience in patients with schizophrenia and affective disorders

BackgroundThe experience of time, or the temporal order of external and internal events, is essential for humans. In psychiatric disorders such as depression and schizophrenia, impairment of time processing has been discussed for a long time.AimsIn this explorative pilot study, therefore, the subjective time feeling as well as objective time perception were determined in patients with depression and schizophrenia, along with possible neurobiological correlates.MethodsDepressed (n = 34; 32.4 ± 9.8 years; 21 men) and schizophrenic patients (n = 31; 35.1 ± 10.7 years; 22 men) and healthy subjects (n = 33; 32.8 ± 14.3 years; 16 men) were tested using time feeling questionnaires, time perception tasks and critical flicker-fusion frequency (CFF) and loudness dependence of auditory evoked potentials (LDAEP) to determine serotonergic neurotransmission.ResultsThere were significant differences between the three groups regarding time feeling and also in time perception tasks (estimation of given time duration) and CFF (the “DOWN” condition). Regarding the LDAEP, patients with schizophrenia showed a significant negative correlation to time experience in terms of a pathologically increased serotonergic neurotransmission with disturbed time feeling.ConclusionsImpairment of time experience seems to play an important role in depression and schizophrenia, both subjectively and objectively, and novel neurobiological correlates have been uncovered. It is suggested, therefore, that alteration of experience of time should be increasingly included in the current psychopathological findings.     

Salivary secretion in the affective disorders and schizophrenia.

Salivary secretion was measured in 54 psychiatric patients comprising four diagnostic groups: schizophrenia, mania, depression and anxiety state. Detailed psychometric assessment was carried out at the time of measurement. Although salivary flow failed to show an association with either diagnostic category or mental state at the time of examination, it was positively correlated with a subjective rating of appetite. The implications of these findings are discussed.     

Problems in diagnosing schizophrenia and affective disorders among blacks

In this country schizophrenia has been consistently overdiagnosed and affective disorders underdiagnosed, particularly among blacks and lower socioeconomic groups. The general causes of such misdiagnoses include overreliance on the classic thought disorder symptoms as pathognomonic of schizophrenia and, for affective disorders, lack of clearly defined boundaries between normal and abnormal mood and failure to realize that patients with affective illness can manifest cognitive symptoms. In addition to the above factors, misdiagnosis among blacks results from such factors as cultural differences in language and mannerisms, difficulties in relating between black patients and white therapists, and the myth that blacks rarely suffer from affective disorders. Clinicians and researchers must pay more attention to the effects of cultural differences on diagnosis, and baseline behaviors and symptomatology for blacks must be established.     

Rating verbal communication impairment in schizophrenia and affective disorders

Audio recordings of interviews with 42 psychiatric patients (10 schizophrenic, 11 manic, 11 schizoaffective, and 10 depressive patients) and 10 hospitalized orthopedic patients were rated for the presence of verbal communication impairment using the system developed by Andreasen. The definitions of some categories required additional qualifying statements before agreement could be reached on their meaning and applicability in specific circumstances. Nevertheless, the results indicate that the scales can be used reliably by carefully trained, nonprofessional raters. Significant differences were found between diagnostic groups with regard to the frequency and severity of some categories of communication impairment, but the general pattern of results supports previous suggestions that these problems are not pathognomonic of schizophrenia. Based on our experience, we suggest a few changes that might be helpful to other investigators, both in the procedures used for obtaining samples of speech and the definitions of subcategories of verbal communication impairment.     

Reaction time impairment in schizophrenia and affective illness: the role of attention

A young but chronic group of schizophrenic and affective disorders patients was tested for simple reaction time (RT) and RT while engaged in a concurrent task. The affective disorders patients were subdivided by the presence of psychotic features. The results show that extreme slowing of RT is due to psychoticism and is not characteristic of nonpsychotic affective illness. Extreme intrasubject variability, however, was specific to schizophrenia, and may be a trait marker of the disorder.     

Reaction time and sustained attention in schizophrenia and its genetic predisposition

Sustained attention is affected by schizophrenia. The simplest form of Continuous Performance Test (CPT-X) is a purer test of vigilance than more demanding variants but widely thought too insensitive to detect abnormalities in those with genetic predisposition to schizophrenia. We used a 7-minute CPT to compare 61 patients diagnosed with schizophrenia, 45 of their never-psychotic relatives, and 47 control subjects. We found a significant impairment in stimulus discrimination in both patients (p=0.001) and their relatives (p=0.006). There was no difference in stimulus discrimination between relatives of patients with impaired and unimpaired stimulus discrimination. Relatives of patients with unimpaired stimulus discrimination were still inferior to controls (p=0.02). Reactions slowed in all groups equally as the test progressed. Patients showed increased mean reaction time (p<0.0001) and interquartile range (p=0.003). Relatives showed slower reaction times (p=0.01) but normal interquartile range. Groups did not differ in respect of individuals' fastest reaction times. We conclude that genetic predisposition to schizophrenia reduces performance even during a task placing minimal cognitive load on working memory and perceptual processing, suggesting impaired vigilance. Increased reaction time in the disease and its predisposition appear to be due to changes in response distribution rather than by a limitation of maximum speed. Our results raise the possibility of separating the cognitive components of vigilance, working memory and perceptual processing tapped by more demanding variants of the CPT, and draw attention to the need for consideration of dynamic neurocognitive processes in schizophrenia.     

Facial discrimination and emotional recognition in schizophrenia and affective disorders

Current research demonstrates that patients with schizophrenia display deficits in a broad range of interpersonal skills. To investigate the ability of patients with schizophrenia and major depression and normal controls to process facial stimuli, four tasks were constructed from 21 photographs of faces representing standardized poses of fundamental emotions. Two tasks were designed to investigate facial identity matching independent of emotion expressed, and two tasks were designed to test emotion recognition and emotion labeling, respectively. Results indicate that while depressed patients differed from controls only on the emotion-labeling task, those with schizophrenia showed deficits on all four tasks when compared with controls and did worse than patients with depression on the emotion tasks. The findings suggest that patients with schizophrenia are impaired on a broader range of facial perception skills than those with depression, when compared with controls.