Neuropsychological function and dysfunction in schizophrenia and psychotic affective disorders

Background: Mounting evidence suggests that compromised neurocognitive function is a central feature of schizophrenia. There are, however, schizophrenia patients with a normal neuropsychological (NP) performance, but estimates of the proportion of NP normal patients vary considerably between studies. Neurocognitive dysfunction is also a characteristic of other psychotic disorders, yet there are inconsistencies in the literature regarding the similarity to impairments in schizophrenia. NP normality in psychotic affective disorders has not been systematically studied.Methods: Data came from the Suffolk County Mental Health Project, an epidemiological study of first-admission patients with psychotic disorders. Respondents with a diagnosis of schizophrenia (N = 94) or schizoaffective disorder (N = 15), bipolar disorder (N = 78), and major depressive disorder (N = 48) were administered a battery of NP tests assessing 8 cognitive domains 2 years after index admission. Patients’ performance profile was compared, and their NP status was classified based on 3 previously published criteria that vary in their stringency.Results: The 4 diagnostic groups had comparable NP performance profile patterns. All groups demonstrated impairments in memory, executive functions, and attention and processing speed. However, schizophrenia patients were more impaired than the other groups on all cognitive domains. Results were not attenuated when IQ was controlled. Prevalence of NP normality ranged between 16% and 45% in schizophrenia, 20% and 33% in schizoaffective disorder, 42% and 64% in bipolar disorder, and 42% and 77% in depression, depending on the criterion employed.Conclusions: Evidence suggests that differences in NP performance between schizophrenia and psychotic affective disorders are largely quantitative. NP impairment is also common in psychotic affective disorders. A significant minority of schizophrenia patients are NP normal.     

Neuropsychological differences between first-admission schizophrenia and psychotic affective disorders

OBJECTIVE: The study compared the neuropsychological functioning of patients with first-admission schizophrenia with that of patients with first-admission psychotic affective disorders. METHOD: Data came from the Suffolk County Mental Health Project, an epidemiological study of first-admission psychotic disorders. Subjects with a diagnosis of schizophrenia (N=102) and psychotic affective disorders, including bipolar disorder with psychotic features (N=72) and major depressive disorder with psychotic features (N=49), were compared on a battery of neuropsychological tests administered 2 years after the index admission. RESULTS: Subjects with schizophrenia performed worse than those with the psychotic affective disorders, even after adjusting the results for differences in demographic characteristics and general intellectual functioning. The most consistent differences were on tests of attention, concentration, and mental tracking. The two psychotic affective disorder groups were indistinguishable in performance on the neuropsychological tests. CONCLUSIONS: Even early in its course, schizophrenia is distinguishable from psychotic affective disorders by global and specific neuropsychological deficits. These deficits might contribute to the disability and poor outcome associated with schizophrenia in the mid- and long-term course.     

The significance of psychotic affective disorders.

A study of 253 patients with primary and secondary affective disorders disclosed that psychotic features were more frequent among bipolar patients. Except for more frequent psychiatric hospitalization among unipolar patients with psychotic features, no demographic, family history, or parental home variable was found to distinguish between those with and without psychotic features. Chance variation probably accounted for the few symptoms whose frequencies were different depending on the presence or absence of psychotic features. The results failed to support the validity of a classification of affective disorders based on the presence or absence of psychotic features.     

Mood-incongruent psychotic affective illness. A historical and empirical review

The last 80 years has seen considerable controversy about the classification of patients with mood-incongruent psychotic affective illness (MICPAI). Four viewpoints can be articulated: (1) MICPAI is indistinguishable from typical forms of affective illness; (2) MICPAI is a distinct subtype of affective illness; (3) MICPAI is a form of schizoaffective illness; and (4) MICPAI is a form of schizophrenia. Using the concept of diagnostic validators, I reviewed the empirical evidence for the validity of these four viewpoints. The available evidence argues relatively strongly against the first and fourth viewpoints and rather less strongly against the third. Data from diagnostic validators tend to support the second viewpoint, which is that taken by the framers of DSM-III and DSM-III-R.     

Neuropsychological assessment of functional central nervous system disorders. I. Hemispheric functioning characteristics in schizophrenia and affective illness

The neuropsychological characteristics of a group of schizophrenic and affective patients were assessed by mean of a comprehensive neuropsychological tool, the Luria-Nebraska Neuropsychological Batter (LNNB), to determine the lateralized hemispheric neurofunctional characteristics in major functional central nervous system disorders. The results showed that schizophrenics had more right-hemisphere impairment than affectives. They do not substantiate the hypothesis of right hemisphere-lateralized malfunctioning in functional mood disorders. Psychopharmacological treatment influences neuropsychological test performance, neuroleptics having the greatest effects. Pharmacological effects other than anticholinergic ones are responsible for the negative influence on neuropsychological test performance.     

精神分裂症认知功能损害与病程的关系

目的：探讨精神分裂症认知功能损害的程度与病程关系。方法;分别用韦氏记忆测验,数字划销测验和威斯康星卡片分类测验评估27例急性精神分裂症病人和31例慢性精神分裂症病人的记忆、注意和执行功能。结果：注意损害随病程的延长而加重,记忆和执行功能损害与病程无关。     

Beta-adrenergic receptor function in affective illness.

In a study of beta-adrenergic receptor sensitivity, the authors determined the response of cyclic AMP synthesis to in vitro addition of norepinephrine (NE) and isoproterenol (IP) in leukocytes of patients with affective illness and schizophrenia and of normal controls. IP-stimulated increase in 3H-cyclic AMP synthesis in depressed patients was significantly lower than in normal subjects and schizophrenic patients. These results suggest that beta-adrenergic receptor sensitivity is reduced in depressive illness.     

Familial association of schizotypal traits with psychotic and affective disorders

The criteria for schizotypal personality disorder were developed on the basis of traits observed in biologic relatives of schizophrenic and borderline schizophrenic probands from the Danish adoption studies. In this review, the relationship between schizotypal personality disorder and the schizophrenic spectrum, affective disorders, and psychotic disorders is explored. A dimension of psychosis may overlap with the schizophrenia spectrum to yield chronic schizophrenia, with the affective disorders spectrum to yield psychotic affective disorder, or by itself lead to other psychotic disorders. Schizotypal personality disorder in this model is posited to represent schizophrenia spectrum disorder that does not overlap with psychosis, whereas nonpsychotic affective disorders represent the affective disorders that do not overlap with psychosis. Delusional disorder represents another psychotic disorder that is not specifically related to either schizophrenia or the affective disorders. Evidence suggests that the schizotypal personality disorder criteria, particularly those emphasizing the negative symptoms or deficit-like symptoms of this disorder, specifically identify a unique relationship to the schizophrenia spectrum.     

Growth hormone and prolactin response to apomorphine in schizophrenia and the major affective disorders. Relation to duration of illness and depressive symptoms

The responses of serum prolactin (PRL) and growth hormone (GH) to the dopamine agonist apomorphine hydrochloride (0.75 mg subcutaneously) were studied in a large group of unmedicated hospitalized patients with functional psychoses. There were no differences in the GH response in various diagnostic groups. The PRL response was greater in patients with affective disorders. The GH response was inversely related to total duration of illness in the entire sample of patients, but this correlation was independent of age effect only in the group of patients with major depression. In schizophrenics, the effect of the two factors, age and duration of the illness, could not be separated. The apomorphine-induced GH response was significantly correlated with psychosis ratings and negative symptom scale scores. The apomorphine-induced PRL suppression correlated significantly with various measures of depression across diagnostic groups.     

Neuropsychological deficits in psychotic versus nonpsychotic major depression and no mental illness

OBJECTIVE: At least three studies have indicated that patients with psychotic major depression studied under non-drug-free conditions differ from patients with nonpsychotic major depression and healthy comparison subjects on several measures of neuropsychological performance. The current study explored specific impairments in cognitive function in subjects with psychotic major depression, subjects with nonpsychotic major depression, and healthy comparison subjects studied under drug-free conditions. METHOD: A battery of neuropsychological tests was administered to 11 patients with psychotic major depression, 32 patients with nonpsychotic major depression, and 23 normal comparison subjects under drug-free conditions. The three groups did not differ statistically in age, sex, or level of education. To ensure that participants had minimal levels of severity and endogenicity, all patients were required to have a score of at least 20 on the 21-item Hamilton Depression Rating Scale and a score of at least 7 on the Core Endogenomorphic Scale, which uses eight items from the Hamilton depression scale. RESULTS: Patients with psychotic major depression demonstrated significantly greater impairment than patients with nonpsychotic major depression and/or comparison subjects in attention and response inhibition (as measured by the Stroop color-word subscale score) as well as in verbal declarative memory (as measured by the Paragraph Recall Test). CONCLUSIONS: These data indicate that patients with psychotic major depression demonstrate impairment in functions thought to be mediated by the frontal cortex and mediotemporal lobes.     

Plasma norepinephrine level in affective disorders. Relationship to melancholia

The plasma norepinephrine (NE) level was measured in 45 depressed patients and in 41 normal control subjects. Patients who met DSM-III criteria for a major depressive episode with melancholia (MDE-MEL; N = 16), and those with MDE but with melancholia in a previous episode (MDE-PMEL; N = 8), had significantly higher levels of plasma NE than normal control subjects while lying and standing and a greater change in the levels; whereas, patients with MDE alone (N = 10) and patients with dysthymic disorder (N = 11) had levels of NE comparable with control levels. Bipolar patients (N = 7), all with current melancholia or a history of it, had significantly lower levels of NE while lying down or standing than depressed unipolar patients with similar histories of melancholia. Among unipolar patients with melancholia, nonsuppressors on the dexamethasone suppression test had significantly higher lying-down NE values than did suppressors, suggesting that dysregulation of both the hypothalamic-pituitary-adrenal axis and the peripheral sympathetic nervous system occur together in this subgroup of depressed patients.     

Dopaminergic effects of carbamazepine. Relationship to clinical response in affective illness

Carbamazepine, a drug used widely to treat epilepsy and trigeminal neuralgia, has been shown to be effective in the acute and prophylactic treatment of manic-depressive illness. While the time course of its antimanic effects parallels that of classic neuroleptics, indirect clinical evidence, such as lack of parkinsonian side effects and tardive dyskinesia, suggests that carbamazepine does not act by blocking dopamine receptors. To assess the effects of carbamazepine on dopamine mechanisms, we measured the dopamine metabolite homovanillic acid (HVA) in the cerebrospinal fluid of affectively ill patients before and after treatment. Carbamazepine did not alter basal concentrations of HVA, but decreased probenecid-induced accumulations of HVA, paralleling results in animal studies. In 25 patients, lower baseline cerebrospinal fluid HVA levels were related to subsequent better acute antidepressive responses to carbamazepine. While the precise mechanism of carbamazepine's effects on dopaminergic systems remains to be determined, this study provides further evidence that carbamazepine does not have a biochemical profile typical of neuroleptics.     

Relationship of object loss during development to hypothalamic-pituitary-adrenal axis function during major affective illness later in life.

Although many studies have attempted to determine whether early object loss influences the risk of developing major affective illness in adulthood, there are few empirical data relating early loss to subsequent hypothalamic-pituitary-adrenal (HPA) axis dysfunction in adulthood. Forty-five psychiatric inpatients admitted for an active major affective illness, all of whom had a previous history of a significant permanent object loss (by death only), were studied retrospectively in this preliminary investigation to examine whether the type and timing of object loss experienced earlier in life would discriminate affectively ill patients who exhibit HPA dysfunction. Several loss variables were found to be statistically significant predictors of cortisol responses following glucocorticoid challenge. A median split of the distribution was used to classify patients into early loss (< or = 19 years) and late loss (> or = 20 years) groups. Analyses for all subjects, early and late loss combined, showed that late loss was associated with higher 11 p.m. cortisol levels. Within the early loss group, however, age of first loss was the most significant predictor of 4 p.m. cortisol levels after dexamethasone challenge. Consistent with the hypothesis that childhood object loss may be associated with long-term alterations in HPA axis function, younger age of loss correlated significantly with higher 4 p.m. cortisol responses. These preliminary data suggest that future prospective investigation of the neurobiological as well as psychosocial consequences of various types of early loss warrant further study.     

Chest pain with negative cardiac diagnostic studies. Relationship to psychiatric illness

A total of 98 patients with chest pain and no prior history of organic heart disease underwent a structured psychiatric interview at the time of cardiac diagnostic testing, either coronary arteriography or exercise treadmill. Patients with negative cardiac test results were significantly younger and more likely to be female, endorsed a greater number of autonomic symptoms with their chest pain, and were more likely to report atypical chest pain. These patients had significantly higher scores on measures of anxiety and negative life events and significantly greater prevalences of DSM-III panic disorder (47% vs. 6%), major depression (39% vs. 8%), and two or more simple phobias (43% vs. 12%) than did patients with cardiac test results demonstrating coronary artery disease. Using logistic regression, a model was developed to estimate the probability of negative cardiac test results from patient characteristics and psychiatric diagnoses.     

右大脑半球梗死患者情感性语韵障碍的研究

目的研究右大脑半球对汉语情感性语韵作用的特点并探讨其机制。方法运用Ｒｏｓｓ创建的床边检查法并参照Ｈｕｇｈｅｓ等的方式加以修订，包括情感性语韵和汉语声调产生的测试检查３９例首发单灶右半球梗死病人和４０例年龄、性别、文化匹配的正常对照。结果３９例右半球梗死病人２７例异常（６９％），其中皮质病变异常率９０％，皮质下病变５０％。本组发现６种类型的失语韵症，其皮质病变部位基本对应于左半球产生相应失语症的语言组织。汉语声调产生的结果示两组无差别。结论右半球对汉语情感性语韵的加工起重要作用，损伤时产生失语韵症。右半球情感性语言组织镜像于左半球陈述性语言组织。汉语声调主要由左半球加工，不影响情感性语韵的侧性化     

Correlates of the affective impact of auditory hallucinations in psychotic disorders

While many who hear auditory hallucinations (AHs) experience them as unpleasant, some do not. Little is known about the correlates of AHs that are not unpleasant, or of the characteristics of those who hear them. To better understand this symptom, we used a comprehensive structured interview schedule to study 199 subjects who had experienced AHs. Subjects' responses to AHs were combined into two indexes: one assessing total affective impact and the other assessing the affective direction (positive or negative). Subjects who had grandiose delusions experienced their AHs more positively. AHs that were more frequent, lasted longer, and were louder were experienced more negatively. AHs heard in the second person and those related to people with whom the subjects had personal relationships were more positive than those heard in the third person. Many other aspects of AHs were unrelated to total affective impact or direction. It is argued that the positive evaluation of voices by subjects requires greater attention than it has received previously. Implications for assessment, clinical practice, and research are discussed.