Schizophrenia with prominent catatonic features ('catatonic schizophrenia') III. Latent class analysis of the catatonic syndrome

No reports have yet been published on catatonia using latent class analysis (LCA). This study applied LCA to a large, diagnostically homogenous sample of patients with chronic schizophrenia who also presented with catatonic symptoms. A random sample of 225 Chinese inpatients with DSM-IV schizophrenia was selected from the long-stay wards of a psychiatric hospital. Their psychopathology, extrapyramidal motor status and level of functioning were evaluated with standardized rating scales. Catatonia was rated using a modified version of the Bush-Francis Catatonia Rating Scale. LCA was then applied to the 178 patients who presented with at least one catatonic sign. In LCA a four-class solution was found to fit best the statistical model. Classes 1, 2, 3 and 4 constituted 18%, 39.4%, 20.1% and 22.5% of the whole catatonic sample, respectively. Class 1 included patients with symptoms of 'automatic' phenomena (automatic obedience, Mitgehen, waxy flexibility). Class 2 comprised patients with 'repetitive/echo' phenomena (perseveration, stereotypy, verbigeration, mannerisms and grimacing). Class 3 contained patients with symptoms of 'withdrawal' (immobility, mutism, posturing, staring and withdrawal). Class 4 consisted of 'agitated/resistive' patients, who displayed symptoms of excitement, impulsivity, negativism and combativeness. The symptom composition of these 4 classes was nearly identical with that of the four factors identified by factor analysis in the same cohort of subjects in an earlier study. In multivariate regression analysis, the 'withdrawn' class was associated with higher scores on the Scale of Assessment of Negative Symptoms and lower and higher scores for negative and positive items respectively on the Nurses' Observation Scale for Inpatient Evaluation's (NOSIE). The 'automatic' class was associated with lower values on the Simpson-Angus Extrapyramidal Side Effects Scale, and the 'repetitive/echo' class with higher scores on the NOSIE positive items. These results provide preliminary support for the notion that chronic schizophrenia patients with catatonic features can be classified into 4 distinct syndromal groups on the basis of their motor symptoms. Identifying distinct catatonic syndromes would help to find their biological substrates and to develop specific therapeutic measures.     

Schizophrenia with prominent catatonic features ('catatonic schizophrenia'): I. Demographic and clinical correlates in the chronic phase

This study set out to determine the frequency of catatonic syndrome in chronic schizophrenia and its association with sociodemographic, clinical, and treatment variables. A cross-sectional assessment of a randomly selected cohort of patients (n=225; mean age=42+/-7 years; mean length of illness=20.4+/-7.5 years) with DSM-IV schizophrenia was employed using standard rating instruments for catatonia, drug-induced extrapyramidal symptoms (EPS), and psychotic, depressive, and obsessive-compulsive symptoms. Using a rather narrow definition of catatonia [the presence of four or more signs/symptoms with at least one having a score '2' or above on the Bush-Francis Catatonia Rating Scale (BFCRS)], 72 subjects (32%) met the criteria for the catatonia group (mean number of catatonic signs/symptoms=5.9+/-2.0; mean sum score of 8.7+/-3.4 on the BFCRS). The frequency distribution of catatonic signs/symptoms in the catatonic group and in the whole sample was very similar, with mannerisms, grimacing, stereotypes, posturing, and mutism being the most frequent. In the logistic regression analysis, catatonic subjects had a significantly earlier age of onset, more negative symptoms, and were more likely to receive benzodiazepines than their noncatatonic counterparts. In multiple regression analysis, the severity of catatonia as indicated by the sum score of BFCRS was predicted only by earlier age of onset and negative symptoms. Using relatively narrow criteria, this study confirmed that, if methodically assessed, catatonic signs and symptoms are prevalent in patients with chronic schizophrenia. Catatonia can be differentiated from EPS. Catatonic features indicate a generally poor prognosis in the chronic phase of schizophrenia.     

Factor analysis of the catatonia rating scale and catatonic symptom distribution across four diagnostic groups

Catatonia is a frequent psychomotor syndrome, which has received increasing recognition over the last decade. The assessment of the catatonic syndrome requires systematic rating scales that cover the complex spectrum of catatonic motor signs and behaviors. The Catatonia Rating Scale (CRS) is such an instrument, which has been validated and which has undergone extensive reliability testing. In the present study, to further validate the CRS, the items composing this scale were submitted to principal components factor extraction followed by a varimax rotation. An analysis of variance (ANOVA) was performed to assess group differences on the extracted factors in patients with schizophrenia, pure mania, mixed mania, and major depression (N=165). Four factors were extracted, which accounted for 71.5% of the variance. The factors corresponded to the clinical syndromes of (1) catatonic excitement, (2) abnormal involuntary movements/mannerisms, (3) disturbance of volition/catalepsy, and (4) catatonic inhibition. The ANOVA revealed that each of the groups showed a distinctive catatonic symptom pattern and that the overlap between diagnostic groups was minimal. We conclude that this four-factor symptom structure of catatonia challenges the current conceptualization, which proposes only two symptom subtypes.     

Clinical relevance of chronic catatonic schizophrenia in children and adolescents: evidence from a prospective naturalistic study

The paper examines the phenomenology, diagnosis, and course of catatonia in children and adolescents. From 1993 to 2003, 21 boys and 9 girls, aged 12 to 18 years, were admitted for a catatonic syndrome (0.6% of the total inpatient population). Phenomenology and associated diagnoses were similar to those reported in the adult literature but relative frequency differed, with schizophrenia being the most frequent diagnosis. Comparison of patients with schizophrenia (n=17) to those with other diagnoses (n=13) showed that the two groups differed in terms of sex ratio, type of onset and phenomenology of catatonic symptoms, duration of hospitalization, and severity at discharge. Using discriminant function analysis, the combination of three clinical variables--male gender, duration of catatonic episode, and severity at discharge--correctly classified 100% of cases in the schizophrenia group. Catatonia is an infrequent but severe condition in young people, and is usually associated with schizophrenia. There is a need for research in the field of catatonic schizophrenia in adolescents as it appears to be a clinically relevant but understudied subgroup.     

Rating catatonia in patients with chronic schizophrenia: Rasch analysis of the Bush-Francis Catatonia Rating Scale

BACKGROUND: Catatonic signs and symptoms are frequently observed in patients with chronic schizophrenia. Clinical surveys have suggested that the composition of catatonic syndrome occurring in chronic schizophrenia may be different from what is found in acute psychiatric disorders or medical conditions. Consequently, this patient population may need tailor-made rating instruments for catatonia. The aim of the present study was to examine the suitability and accuracy of using the Bush-Francis Catatonia Rating Scale (BFCRS) in chronic schizophrenia inpatients. METHOD: The unidimensionality (optimal number of items; item fit), and the scoring scheme (the optimal number of scoring categories) of the BFCRS were determined in a random sample of 225 patients with chronic schizophrenia applying Rasch analysis. In addition, differential item functioning (DIF) analysis was also performed. RESULTS: The BFCRS proved to be unidimensional apart from three misfit and one marginally misfit items. The three misfit items were removed from the scale thereby constructing a revised version called BFCRS-R. Since the original BFCRS (BFCRS-O) showed no increase across items across steep gradients (poor endorsability of step calibrations), in BFCRS-R a binary scale ('absent' versus 'present' choices only) was constructed instead of the scoring scheme of 0-3.The 20-item BFCRS-R showed improved psychometric properties in that it had a higher item separation index than BFCRS-O. BFCRS-R mean logit was closer to zero indicating that the items on the scale and the subjects were better matched than in BFCRS-O. DIF analysis showed that certain items of both versions of BFCRS were influenced by the presence of negative symptoms. CONCLUSION: BFCRS-R is shorter and simpler than the original version and having better psychometric properties seems to be better suited for identifying and quantifying catatonia in chronic psychotic patients.     

Catatonia as a psychomotor syndrome: a rating scale and extrapyramidal motor symptoms.

BACKGROUND: Catatonia was first described by Kahlbaum as a psychomotor disease with motor, behavioral, and affective symptoms. In keeping with this concept, we developed a rating scale for catatonia (Northoff Catatonia Scale [NCS]) with three different categories of symptoms (i.e., motor, behavioral, affective). Furthermore, the question of the relationship among catatonic symptoms, extrapyramidal motor symptoms, and neuroleptics was addressed in the present study. METHOD: 34 acute catatonic patients and 68 age-, sex-, diagnosis-, and medication-matched psychiatric control subjects were investigated on days 0, 1, 3, 7, and 21 with the NCS, with other already validated catatonia rating scales by Rosebush, Bush (BFCRS), and Rogers (MRS), as well as with scales for hypokinetic (SEPS) and dyskinetic (AIMS) extrapyramidal motor features. Validity and reliability of the new scale, factor analysis, correlational analysis, and differences between catatonic patients and psychiatric control subjects were statistically calculated. RESULTS: NCS showed high validity (i.e., significant positive correlations [p <0.0001] with the other scales, significant differences between catatonic and control subjects), high intra-and interrater reliabilities (r = 0.80-0.96), and high affective subscores. Factor analysis revealed four factors best characterized as affective, hypoactive, hyperactive, and behavioral. Catatonic scores in NCS correlated significantly with AIMS on day 0 and SEPS on days 7 and 21. There were no significant differences in catatonic (i.e., NCS, MRS, BFCRS) and extrapyramidal (i.e., AIMS, SEPS) scores between neuroleptically treated and untreated catatonic subjects. CONCLUSIONS: The following conclusions were drawn: (1) the NCS has to be considered as a valid and reliable rating instrument for catatonia; (2) catatonia can be characterized by psychomotor symptoms encompassing motor, affective, and behavioral alterations; and (3) extrapyramidal hyperkinesias like dyskinesias are apparently closely related to catatonic symptoms which, in general, seem to be relatively independent of previous neuroleptic medication.     

精神科急性入院患者中紧张症的识别和治疗

目的回顾性分析精神科急性入院患者中紧张症的识别和治疗情况。方法对2017年10月1日至2018年10月1日我院重症精神病房急性入院患者1020例的病历资料进行回顾性分析,根据《美国精神障碍诊断与统计手册第5版》(Diagnostic and Statistical Manual of Mental Disorders,5th Edition,DSM-5)紧张症的诊断标准进行诊断,参照Bush-Francis紧张症评定量表(Bush-Francis catatonia rating scale,BFCRS)的症状定义归类确诊病例的临床表现,并比较不同治疗方案的疗效。结果确诊紧张症91例,占调查患者的8.92%。81例(89.01%)紧张症患者的基础疾病为精神分裂症。患者最常见的紧张症症状为缄默(81.32%)、兴奋(72.53%)、冲动性(71.43%)、静止/呆滞(65.93%)和作态(51.65%),另外先占观念(92.30%)和怪异念头(58.24%)也较常见。仅有7例(7.69%)患者的病历资料中曾提及“(亚)木僵”、“紧张症/综合征”等词。30例患者仅用抗精神病药治疗,治愈率为83.33%(25例),仅用抗精神病药治疗者与抗精神病药联合苯二氮 类和/或改良电休克治疗者的治愈率差异无统计学意义(X^2=1.75,P=0.63)。1例患者在肌注氟哌啶醇后出现恶性综合征。结论精神科急性入院患者中紧张症并不少见,但识别率低。抗精神病药能有效治疗紧张症,但存在出现恶性综合征的风险。     

Review of adjunctive glutamate antagonist therapy in the treatment of catatonic syndromes

Catatonia is a common neuropsychiatric syndrome which may arise from GABA-A hypoactivity, dopamine (D2) hypoactivity,and possibly glutamate NMDA hyperactivity. Amantadine and memantine have been reported as effective treatments for catatonia in selected cases, and probably mediate the presence of catatonic signs and symptoms through complex pathways involving glutamate antagonism. The authors identified 25 cases of catatonia treated with either agent. This article provides indirect evidence that glutamate antagonists may improve catatonic signs in some patients who fail to respond to established treatment, including lorazepam or electroconvulsive therapy. Further study of glutamate antagonists in the treatment of catatonia is needed.     

Clinical and cerebral blood flow changes in catatonic patients treated with ECT

Objective: To determine changes in clinical manifestations and cerebral blood flow (CBF) before and after administration of ECT to patients with catatonia due to schizophrenia or mood disorders. Methods: A sample of nine patients who met DSM-IV criteria for catatonia was studied. Patients received between 5 and 15 sessions (thrice per week) of ECT. Severity of catatonia was measured with the Modified Rogers Scale (MRS). Changes in CBF were measured with a brain single positron emission computer tomography (SPECT) that was performed 1 week before the first ECT and 1 week after the last ECT. Results: Catatonia was due to schizophrenia in five patients and mood disorders in four patients. There were no significant clinical and brain SPECT differences between these two groups before treatment. Pre- vs. post-ECT comparisons showed significant reduction of catatonic symptoms in both groups. However, patients with mood disorders needed less ECT sessions and showed greater clinical improvement. Brain SPECT showed significant increase in CBF in parietal, temporal, and occipital regions in patients with mood disorder and no significant changes in patients with schizophrenia. Conclusions: These results support the efficacy of ECT for treatment of catatonic patients, especially secondary to mood disorders, which seem to be correlated with improvements in CBF.     

Negative parkinsonian, depressive and catatonic symptoms in schizophrenia: a conflict of paradigms revisited

Background: To study the interrelationship pattern of negative, depressive, parkinsonian and catatonic symptoms over an exacerbation phase of schizophrenia. Method: Forty-five inpatients with a DSM-IV diagnosis of schizophrenia or schizophreniform disorder were assessed at admission and discharge for negative, depressive, parkinsonian and catatonic symptoms. A subsample of patients unmedicated at admission (n=23) was specifically analyzed. Results: Negative, parkinsonian and catatonic symptoms correlated significantly at both assessment points, as did their mean changes over the episode. At admission, depressive symptoms did not correlate with negative, parkinsonian or catatonic symptoms, but they did at discharge. Changes of depressive symptoms over the episode did not correlate with changes of the other groups of symptoms. In the patients who were unmedicated at admission, ratings of non-akinetic parkinsonism, unlike ratings of akinetic parkinsonism, worsened significantly after neuroleptic treatment. Conclusions: While negative, parkinsonian and catatonic symptoms are highly related features, depressive symptoms seem to be a relatively independent dimension of psychopathology in schizophrenia. Non-akinetic parkinsonian symptoms may be more useful than the akinetic symptoms in distinguishing primary from drug-induced negative symptoms.     

Representation of the internal world in catatonic schizophrenia

Catatonia, which until 1874 was called atonic melancholia, has remained a relative mystery despite many advances in the understanding of schizophrenia. Its typical symptoms are certainly distinctive: a motionless stupor, bizarre posturing, waxen flexibility, religious delusions, stereotyped movements, negativism, loss of will, confusion, and recurrent frenzy (Kahlbaum 1874). The processes which motivate this particular derailment of self and body have been sought in various organic etiologies, with little success. Arieti (1974) proposes several reasons for the paucity of case studies of the treatment of catatonic schizophrenia. First, catatonic schizophrenia has been declining in occurrence. Second, the symptoms themselves, such as mutism and excitement, make verbal therapy extremely difficult. Finally, catatonics often have no memory of their psychotic experiences. Psychotherapists have therefore had to rely on highly personal intuitions of their patients' crisis-in-being. Despite therapists' attention to nonverbal behavior, mutism and stupor are particularly effective hindrances to communication in psychotherapy. Psychotherapy is often not begun until the patient's symptoms ameliorate through chemotherapy and milieu support. The centrality of the verbal medium of communication in psychotherapy suggests that other approaches, using nonverbal media, may be indicated in the study of catatonia. This paper describes a treatment of a catatonic schizophrenic man which utilized movement and drama therapy. These methods were successful in evoking representations of the patient's inner life.     

Catatonia in a Psychiatric Intensive Care Facility: Incidence and Response to Benzodiazepines

This study was performed to establish the incidence of catatonia in a psychiatric intensive care unit, to test the Bush-Francis Catatonia Screening Instrument (BFCSI) and to assess the response of catatonic signs to benzodiazepines. During a 12-month period all patients admitted to a psychiatric intensive care unit were screened for catatonic signs using the BFCSI. Patients with catatonia were further assessed with the Bush-Francis Catatonia Rating Scale (BFCRS), the Modified Rogers Scale (MRS), and scales for associated psychotic and parkinsonian symptoms. They were treated with oral lorazepam or parenteral clonazepam and their responses evaluated daily. Neuroleptics were stopped for at least 3 days. Twenty four patients met the DSM IV criteria for catatonia, giving an incidence of 15% with a significantly higher proportion of non-Europeans. The most common associated diagnosis was schizophrenia (54%). Twenty two patients completed the benzodiazepine trial. All showed significant responses after 3 days of treatment. Sixteen (16/22, 73%) had full remission within 6 days, most within 2 to 4 days. Partial responders (n = 6) all had schizophrenia and were more likely to have longer pre-trial catatonic episodes. We find the BFCSI a simple and reliable tool to screen for catatonia, and our data attest to the efficacy of benzodiazepines in the treatment of catatonia.     

The Catatonia Conundrum: Evidence of Psychomotor Phenomena as a Symptom Dimension in Psychotic Disorders

To provide a rational basis for reconceptualizing catatonia in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition), we briefly review historical sources, the psychopathology of catatonia, and the relevance of catatonic schizophrenia in contemporary practice and research. In contrast to Kahlbaum, Kraepelin and others (Jaspers, Kleist, and Schneider) recognized the prevalence of motor symptoms in diverse psychiatric disorders but concluded that the unique pattern and persistence of certain psychomotor phenomena defined a “catatonic” subtype of schizophrenia, based on intensive long-term studies. The enduring controversy and confusion that ensued underscores the fact that the main problem with catatonia is not just its place in Diagnostic and Statistical Manual of Mental Disorders but rather its lack of conceptual clarity. There still are no accepted principles on what makes a symptom catatonic and no consensus on which signs and symptoms constitute a catatonic syndrome. The resulting heterogeneity is reflected in treatment studies that show that stuporous catatonia in any acute disorder responds to benzodiazepines or electroconvulsive therapy, whereas catatonia in the context of chronic schizophrenia is phenomenologically different and less responsive to either modality. Although psychomotor phenomena are an intrinsic feature of acute and especially chronic schizophrenia, they are insufficiently recognized in practice and research but may have significant implications for treatment outcome and neurobiological studies. While devising a separate category of catatonia as a nonspecific syndrome has heuristic value, it may be equally if not more important to re-examine the psychopathological basis for defining psychomotor symptoms as catatonic and to re-establish psychomotor phenomena as a fundamental symptom dimension or criterion for both psychotic and mood disorders.     

Severe hypernatremia within the scope of catatonic schizophrenia

We report the case of a 57-year-old chronic schizophrenic patient who developed an acute catatonic stupor after postoperative withdrawal of neuroleptics with excessive and firstly therapy-resistant hypernatremia. Only after re-treatment with neuroleptics the hypernatremia could be compensated. A relationship between the catatonic schizophrenia and the electrolyte-disturbances can be supposed; probably in both diencephalic structures are involved. Therefore the syndrome of "acute life threatening catatonia" should be included into the differential diagnosis of uncertain metabolic disorders.     

Catatonia. II. Treatment with lorazepam and electroconvulsive therapy

Case material and retrospective studies support the use of both lorazepam and ECT in treating catatonia, but few prospective investigations exist and none employ quantitative monitoring of response. In this study we test their efficacy in an open, prospective protocol, and define a‘lorazepam test’ with predictive value for treatment. Twenty-eight patients with catatonia were treated systematically with parenteral and/or oral lorazepam for up to 5 days, and with ECT if lorazepam failed. Outcome was monitored quantitatively during the treatment phase with the Bush-Francis Catatonia Rating Scale (BFCRS). In 16 of 21 patients (76%) who received a complete trial of lorazepam (11 with initial intravenous challenge), catatonic signs resolved. A positive response to an initial parenteral challenge predicted final lorazepam response, as did length of catatonic symptoms prior to treatment. Neither demographic variables nor severity of catatonia predicted response to lorazepam. Four patients failing lorazepam responded promptly to ECT. It is concluded that lorazepam and ECT are effective treatments for catatonia. The rating scale has predictive value and displays sensitivity to change in clinical status.     

Neurocognitive,clinical and functional correlates of subjective quality of life in Asian outpatients with schizophrenia

Quality of life (QOL) impairment is evident in patients with schizophrenia and is increasingly recognised as an important evaluation criterion of treatment outcome. Hence, this study aimed to identify the neurocognitive, clinical and functional parameters associated with subjective QOL in patients with schizophrenia within an Asian context, and specifically in an outpatient setting. This study was conducted on 83 outpatients with DSM-IV diagnosis of schizophrenia, and 47 age- and gender-matched healthy controls. All participants were administered with the World Health Organisation Quality of Life Assessment-Brief Form (WHOQOL-BREF) and Brief Assessment of Cognition in Schizophrenia (BACS), to measure quality of life and cognitive function respectively. Patients were also assessed for severity of psychopathology, as well as level of psychosocial functioning, using the Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) rating scales respectively. Specific psychopathology (greater severity of PANSS negative symptoms, general psychopathology subscale scores), cognitive deficits (working and verbal memories), and lower GAF scores were correlated with poorer QOL in patients. Multivariate analyses revealed that younger age, being single and lower level of psychosocial functioning were associated with poorer QOL but level of psychosocial functioning did not appear to mediate the effects of symptoms and neurocognitive deficits on QOL. Overall, this study highlighted the need for clinicians to pay more attention to these clinical, neurocognitive and functional parameters and their integrative relationships with QOL in order to optimise the treatment outcomes of patients with schizophrenia.     

Catatonia: disappeared or under-diagnosed?

BACKGROUND: Over the last century, especially during the latter half, the prevalence of the diagnosis of catatonic schizophrenia decreased considerably. Several explanations for this phenomenon have been put forward. SAMPLING AND METHODS: The present study investigated the frequency of the diagnosis of catatonic schizophrenia in a large sample of admitted psychiatric patients (n = 19,309). In addition, the presence of catatonic symptoms was studied in a sample of patients with schizophrenia (n = 701) and in a group of consecutively admitted psychotic patients (n = 139). In these two groups the effect of the diagnostic procedures on the recognition of catatonia was examined. RESULTS: The diagnosis of catatonic schizophrenia dropped from 7.8% in 1980-1989 to 1.3% in 1990-2001 (p < 0.001). In addition, a possible under-diagnosis of catatonic schizophrenia was found in an independent sample of patients with schizophrenia. Application of a systematic catatonia rating scale in patients admitted with acute psychosis identified a bimodally distributed catatonic dimension. At least 18% of these patients fulfilled the criteria for catatonia. Interestingly, the catatonic subgroup used atypical antipsychotic compounds more frequently (p < 0.05). CONCLUSIONS: The results suggest that changes in diagnostic criteria and the diagnostic procedure itself are responsible for the under-recognition of catatonia.     

Disturbed neural circuits in a subtype of chronic catatonic schizophrenia demonstrated by F-18-FDG-PET and F-18-DOPA-PET

Summary. Permanent verbal, visual scenic and coenaestetic hallucinations are the most prominent psychopathological symptoms aside from psychomotor disorders in speech-sluggish catatonia, a subtype of chronic catatonic schizophrenia according to Karl Leonhard. These continuous hallucinations serve as an excellent paradigm for the investigation of the assumed functional disturbances of cortical circuits in schizophrenia. Data from positron emission tomography (F-18-FDG-PET and F-18-DOPA-PET) from three patients with this rare phenotype were available (two cases of simple speech-sluggish catatonia, one case of a combined speech-prompt/speech-sluggish subtype) and were compared with a control collective. During their permanent hallucinations, all catatonic patients showed a clear bitemporal hypometabolism in the F-18-FDG-PET. Both patients with the simple speech-sluggish catatonia showed an additional bilateral thalamic hypermetabolism and an additional bilateral hypometabolism of the frontal cortex, especially on the left side. In contrast, the patient with the combined speech-prompt/speech-sluggish catatonia showed a bilateral thalamic hypometabolism combined with a bifrontal cortical hypermetabolism. However, the left/right ratio of the frontal cortex also showed a lateralisation effect with a clear relative hypometabolism of the left frontal cortex. The F-18-DOPA-PET of both schizophrenic patients with simple speech-sluggish catatonia showed a normal F-18-DOPA storage in the striatum, whereas in the right putamen of the patient with the combined form a higher right/left ratio in F-DOPA storage was discernible, indicating an additional lateralized influence of the dopaminergic system in this subtype of chronic catatonic schizophrenia. Most likely, the prominent bitemporal F-18-FDG- hypometabolism in these chronic schizophrenic patients with speech-sluggish catatonia suffering from permanent continuous hallucinations, reflects a deficit in sensoric gating following prenatal cortical neurodevelopmental disturbances. However, the functional disturbances underlying hallucinations in "the schizophrenias" seem to be more complex; in different subtypes of the schizophrenic spectrum disorder hallucinations seem to be based on alterations in additional cortical and subcortical brain regions. Received February 2, 2001; accepted March 30, 2001