Catatonia among adolescents with Down syndrome: a review and 2 case reports

Catatonia is a relatively common condition with an estimated prevalence of 0.6% to 17% among youth with psychiatric disorders. Certain patient groups, such as those with autism, may be at a particularly high risk for catatonia. Most of the youth with catatonia are males with a diagnosis of a bipolar disorder. We describe here 2 adolescent females, both with Down syndrome, who presented with catatonia not accompanied by significant affective or psychotic symptoms or with a general medical condition. Both patients had functioned well until the onset of catatonic symptoms. In the current classification system used in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, catatonia is described in association with schizophrenia, as a specifier of affective disorders or secondary to general medical conditions. The cases described here highlight the problem with this classification system when patients fail to meet any of the 3 diagnostic categories under which catatonia is currently described.     

The factor structure for the Positive and Negative Syndrome Scale (PANSS) in recent-onset psychosis

The Positive and Negative Syndrome Scale (PANSS) is a widely used instrument for measuring severe psychopathology in adult patients with schizophrenia. Data, primarily on chronic patients, have been used to define factors for the PANSS. The present study examines the PANSS factor structure in a large sample of subjects with recent-onset schizophrenia, schizophreniform disorder and schizoaffective disorder who had been exposed to very limited antipsychotic medication. Equamax factor analysis was conducted on PANSS baseline assessments from a multicenter, 11 country drug trial that enrolled 535 patients. The forced five-factor solution essentially corresponds to the factors most frequently described previously, namely negative, positive, disorganized (or cognitive), excited and anxiety/depression. In the exploratory analysis, a seven-factor solution was obtained, with depression and anxiety symptoms separating and a motor component emerging. The results of this study partially support the use of a five-factor model for the PANSS, but suggest that scales for catatonia, depressive and anxiety syndromes should be included in future studies.     

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.     

Catatonia: Our current understanding of its diagnosis,treatment and pathophysiology

Catatonia is a psychomotor syndrome that has been reported to occur in more than 10% of patients with acute psychiatric illnesses. Two subtypes of the syndrome have been identified. Catatonia of the retarded type is characterized by immobility, mutism, staring, rigidity, and a host of other clinical signs. Excited catatonia is a less common presentation in which patients develop prolonged periods of psychomotor agitation. Once thought to be a subtype of schizophrenia, catatonia is now recognized to occur with a broad spectrum of medical and psychiatric illnesses, particularly affective disorders. In many cases, the catatonia must be treated before any underlying conditions can be accurately diagnosed. Most patients with the syndrome respond rapidly to low-dose benzodiazepines, but electroconvulsive therapy is occasionally required. Patients with longstanding catatonia or a diagnosis of schizophrenia may be less likely to respond. The pathobiology of catatonia is poorly understood, although abnormalities in gamma-aminobutyric acid and glutamate signaling have been suggested as causative factors. Because catatonia is common, highly treatable, and associated with significant morbidity and mortality if left untreated, physicians should maintain a high level of suspicion for this complex clinical syndrome. Since 1989, we have systematically assessed patients presenting to our psychiatry service with signs of retarded catatonia. In this paper, we present a review of the current literature on catatonia along with findings from the 220 cases we have assessed and treated.     

Catatonic syndrome: From detection to therapy

IntroductionCatatonia is a psychomotor syndrome which can include motor, mental, behavioral and vegetative symptoms. Exclusively associated with schizophrenia until the 1970s, catatonia still remains an under-diagnosed syndrome with significant morbidity and mortality.Literature findingsAs a result of its different forms and developments, catatonic syndrome can be associated with many organic and psychiatric etiologies and confused with a variety of diagnoses. In addition to its organic complications, malignant catatonia can also be extremely severe. Several diagnostic scales are described, those of Bush and Peralta being the most widely used. Despite the recent development of the DSM-5, we can regret the lack of progress in the international classifications concerning both the recognition of the etiological diversity of this syndrome and in the clinical and therapeutic approaches to it. The diagnosis is based solely on clinical data, and needs to be completed by information from paraclinical settings, particularly with respect to detecting organic etiology. The first-line treatment is still based on the use of certain benzodiazepines or benzodiazepine-like agents such as lorazepam, diazepam and zolpidem. If the first or second line fails, or in case of malignant catatonia, electroconvulsive therapy is recommended. For the periodic form, no large-sample study has been performed on long-term treatment. A few case reports suggest the use of lithium in periodic catatonia, specifically to prevent recurrent episodes or at least to extend the inter-episode intervals. Other studies are in favor of the use of benzodiazepines, with disagreement between gradual discontinuation and long-term treatment. Concerning the management of catatonia in patients with schizophrenia, for whom first-line benzodiazepines are often insufficient, certain atypical antipsychotics such as clozapine or quetiapine appear efficient. These data are also applicable to children and adolescents.ConclusionOften neglected by practitioners, catatonic syndrome remains a common entity of which it is important to be aware, especially in case of rapid installation of the symptoms. Diagnostic scales should be used and a lorazepam test should be performed to avoid delaying the diagnosis. Second-line therapy requires further study. This concerns in particular diazepam, anti-NMDA (N-methyl-D-aspartate) and rTMS (repetitive transcranial magnetic stimulation). Some specificities of catatonia, such as the periodic form and cases in patients with schizophrenia, also require further evaluations.     

Catatonia in childhood and adolescence

Child and adolescent catatonia has been poorly investigated. A literature review was undertaken to clarify phenomenology, diagnosis, etiology, and treatment as well as ethical problems of catatonia in childhood and adolescence. Although there are no accepted standardized criteria for catatonia in childhood and adolescence, catatonic features described by child psychiatrists are similar to Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria for catatonia. With respect to etiology, the motor and behavioral symptoms that are part of catatonia bear some similarities with those seen in autism. Several case reports suggest an association between catatonia and general medical conditions. Certain drugs abused by youngsters as well as prescribed medicine can induce catatonia. Regarding catatonic cases originally diagnosed as schizophrenia, it is unclear whether all of these cases should be identified as schizophrenia or whether some of them are pervasive developmental disorders that develop psychic features in adolescence. Environmental changes preceding the onset of catatonia in patients with mood disorder play a possibly important role. Examples that suggest stress-induced catatonia, although rare, also exist. A few patients exhibit features of malignant catatonia, some without taking neuroleptics and others having taken them. Benzodiazepines and electroconvulsive therapy are considered to be effective treatments for catatonic youngsters.     

Catatonia in autistic disorder: A sign of comorbidity or variable expression?

Catatonia, once solely attributed to schizophrenia, is now thought to be associated with many disorders. Autistic disorder shares some symptoms with catatonia, namely, mutism, echopraxia/echolalia, and sterotypes. Catatonia in autism may therefore be a variant of the autistic condition. However, organic deficits and psychiatric disorders, such as bipolar disorder, have also been deficits and psychiatric disorders, such as bipolar disorder, have also been linked with the manifestation of catatonia. Individuals with autism presenting with these comorbid conditions may therefore be at increased risk for catatonia. Little is written of the association of autism and catatonia to clarify the possibility of catatonia as a variant or a sign of a comorbid condition. The authors discuss three autistic patients and suggest specific etiologies for the symptoms of catatonia which presented in these cases. The therapeutic and diagnostic importance of comorbid disorders in autism is stressed.     

The psychopathology of schizophrenia and the presence of neurological soft signs: a review

PURPOSE OF REVIEW: The symptoms of schizophrenia cluster in at least three subtypes: positive, negative, and disorganized. The study of these subtypes and their phenotypic markers may help our understanding of the pathophysiology of schizophrenia. Among the markers of schizophrenia are minor neurological signs, which are abnormalities in sensory and motor performance elicited by clinical examination. Evidence on whether neurological abnormalities are associated with a specific symptom subtype is considered. As recent studies have often evaluated individuals at their first psychotic episode who are antipsychotic na?ve, a review would help to clarify whether neurological soft signs are part of a neurodysfunction that underlies schizophrenia rather than the consequence of degenerative processes or of long-term pharmacological treatment. RECENT FINDINGS: A consistent association seems to emerge between an excess of neurological soft signs and severe negative symptoms. Signs associated with negative symptoms remain stable over time, and may characterize a subgroup of patients with poor illness course and outcome. Some signs, such as motor dysfunction, may be associated with a worse profile of positive symptoms, and may improve as symptoms improve. Too few studies have evaluated the association between neurological soft signs and disorganization symptoms to suggest or disconfirm any relationship. SUMMARY: Finding an association between neurological soft signs and one (or more) dimension(s) of schizophrenia in never treated patients may explain which neurological dysfunction is an intrinsic characteristic of the illness. The comparability of future studies can be improved by using the same structured rating scale for neurological soft signs and psychopathology, and by a better characterization of patient samples.     

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.     

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.     

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     

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.     

Does catatonia influence the phenomenology of childhood onset schizophrenia beyond motor symptoms?

Childhood onset schizophrenia (COS) and catatonia (C) are rare and severe psychiatric disorders. The aim of this study was to compare the phenomenology of COS with and without catatonia. We examined 33 cases consecutively referred to two major public university hospitals in Paris. There were 18 cases of COS (age=15.9+/-0.8 years) and 15 of COS+C (age=15.4+/-1.4 years). Patients were referred over the course of 3 and 9 years, respectively. Psychiatric assessment included socio-demographic, clinical and psychometric variables: the Brief Psychiatric Rating Scale (BPRS), the Scales for the Assessment of Positive (SAPS) and Negative Symptoms (SANS), and a catatonia rating scale. Patients with COS+C appeared to be more severely ill at admission and discharge compared with COS in nearly all clinical scores. They also exhibited significantly longer episode duration (50.8 weeks+/-4.8 vs 20.6+/-19.5). On the basis of multivariate logistic regression, the only clinical measure which significantly predicted group membership was the SANS Affective Flattening score (odds ratio=1.24; 95% CI=1.06-1.43). Our findings strongly suggest that catatonic COS differs from COS in ways that extend beyond motor symptoms. The SANS and SAPS scales, commonly used in schizophrenia, are not detailed enough to accurately describe catatonia in COS. The use of a catatonia rating scale is recommended to enhance recognition of and research into COS with catatonia.     

Biomathematical models of schizophrenia

This paper summarizes the work of developing and analyzing a mathematical model of schizophrenia. First the psychological and physiological studies of patients with periodic catatonia made by R. R. Gjessing are briefly described. Then a mathematical model, which is based on Gjessing's work and consists of a set of nonlinear ordinary differential equations, is derived. Gjessing showed that there was a periodic change in the basal metabolic rate associated with a periodic change in the symptoms of catatonia. This suggests a study of the thyroid control system, and since the thyroid control system is a negative feedback system, previous engineering studies are followed and a system of ordinary differential equations is used as a model. The first such model was due to Danziger and Elmergreen, and their model and improvements of their model are described. Then the models are analyzed qualitatively and the mathematical results are interpreted medically. Solutions of the system of differential equations corresponding to a stable set of symptoms in the schizophrenic patients, solutions corresponding to periodic patterns of symptoms (periodic catatonia), and solutions corresponding to random or unpredictable patterns of symptoms are obtained. The model suggests that since certain parameters are varied, various types of solutions and hence various patterns of symptoms are obtained. There are a number of unresolved questions in this study, and these problems are discussed in detail as they arise.     

Assessment of enduring deficit and negative symptom subtypes in schizophrenia.

The clinical importance of subtypes based on enduring deficit or negative symptoms was examined in a group of schizophrenic patients who were assessed twice over a 1-year period. Subgroups of patients with high levels of enduring negative or deficit symptoms, based on the Scale for the Assessment of Negative Symptoms and the Quality of Life Scale, had a poorer prognosis and were consistently worse in social adjustment, quality of life, and thought disorder over the year than were patients with less severe negative symptoms. Subtypes based on Andreasen's negative schizophrenia classification and on enduring thought disorder were only weakly related to other symptoms and social adjustment. Social-skill deficits were weakly related to the enduring negative symptom subtype and Andreasen's negative schizophrenia. The results suggest that enduring negative and deficit symptoms may be associated with a poor outcome in schizophrenia, including more severe positive symptoms, lower levels of social adjustment, and a poorer quality of life.     

Biomathematical Models of Schizophrenia

This paper summarizes the work of developing and analyzing a mathematical model of schizophrenia. First the psychological and physiological studies of patients with periodic catatonia made by R. R. Gjessing are briefly described. Then a mathematical model, which is based on Gjessing’s work and consists of a set of nonlinear ordinary differential equations, is derived. Gjessing showed that there was a periodic change in the basal metabolic rate associated with a periodic change in the symptoms of catatonia. This suggests a study of the thyroid control system, and since the thyroid control system is a negative feedback system, previous engineering studies are followed and a system of ordinary differential equations is used as a model. The first such model was due to Danziger and Elmergreen, and their model and improvements of their model are described. Then the models are analyzed qualitatively and the mathematical results are interpreted medically. Solutions of the system of differential equations corresponding to a stable set of symptoms in the schizophrenic patients, solutions corresponding to periodic patterns of symptoms (periodic catatonia), and solutions corresponding to random or unpredictable patterns of symptoms are obtained. The model suggests that since certain parameters are varied, various types of solutions and hence various patterns of symptoms are obtained. There are a number of unresolved questions in this study, and these problems are discussed in detail as they arise.     

Successful treatment of co-occurring catatonia and obsessive-compulsive disorder with concurrent electroconvulsive therapy and benzodiazepine administration

ABSTRACT: Catatonia, associated with a variety of medical and psychiatric conditions such as mood disorders and schizophrenia, is frequently treated with either benzodiazepines or with electroconvulsive therapy (ECT) in treatment-resistant cases. Simultaneous treatment with both is usually avoided. Here, we report a case of the use of the benzodiazepine antagonist flumazenil before ECT to facilitate the simultaneous use of lorazepam and ECT for the treatment of co-occurring catatonia and obsessive-compulsive disorder. Both catatonia and obsessive-compulsive disorder symptoms improved in the patient. Physicians should be aware of flumazenil as a clinical tool for use in treatment-resistant cases.     

Schizophrenia with preserved insight is associated with increased perfusion of the precuneus

Background: Preserved insight into illness has been suggested to be predictive of outcome in patients with schizophrenia. We aimed to investigate the functional substrate underlying preserved insight in these patients. Methods: We recruited patients with paranoid schizophrenia and healthy controls matched for age and sex. Patients were grouped according to preserved or impaired insight into illness using the Scale to assess Unawareness of Mental Disorder (SUMD). Whole-brain technetium-99m ethyl cysteinate dimer single photon emission computed tomography regional cerebral blood flow was compared at the voxel level between the 2 groups using a statistical parametric map (voxel-level significance of p < 0.001, uncorrected; cluster level significance of p < 0.05, uncorrected). Results: We enrolled 31 right-handed patients with schizophrenia and 18 controls in our study. Twenty-one (67.7%) patients had preserved insight. The 2 groups did not differ significantly in demographic and clinical characteristics or in treatment. Compared with controls, the whole group of patients showed bilateral frontotemporal hypoperfusions, with no statistical difference between patients with preserved or impaired insight for these areas. Patients with preserved insight showed significantly increased perfusion of the bilateral precuneus relative to those with impaired insight. Limitations: Patients with subtypes other than paranoid schizophrenia have to be investigated to assess whether involvement of the precuneus in patients with preserved insight can be identified across the full spectrum of subtypes and symptoms of schizophrenia. Moreover, our study concerned only the central dimension (awareness of mental disorder) of 1 scale (SUMD); other dimensions of insight could be studied. Conclusion: Our results show that schizophrenia with preserved insight is associated with greater perfusion of the precuneus, a brain area known to be involved in self- consciousness, suggesting a compensatory mechanism of fronto - temporal impairment.