An overview on Hebephrenia, a diagnostic cornerstone in the neurodevelopmental model of Schizophrenia.

Pre-Kraepelinian observations converged in Kahlbaum's and Hecker's description of Hebephrenia. For Kraepelin, Hebephrenia was an 'idiopathic incurable dementia whose onset is in adolescence'. It became the core of 'Dementia Praecox', and then Bleulerian 'Schizophrenia'. In recent decades, the resurgence of the 'late neurodevelopment' hypothesis of schizophrenia has brought into focus Hecker's clinical reports of adolescents who, as a result of a putative loss of psychic energy, showed a rapidly progressive cognitive impairment leading to functional and behavioural disorganization. This paper summarizes the nineteenth-century conceptualization of Hebephrenia as a developmental illness.

[Hebephrenia - a viable psychopathological construct?] / Hebephrenie ­ ein brauchbares psychopathologisches Konstrukt?

Ewald Hecker was the first psychiatrist to describe the disease entity of hebephrenia in some detail, focusing mainly on disturbances of affect. Later Emil Kraepelin and Eugen Bleuler saw hebephrenia as a subtype of dementia praecox or schizophrenia. Willy Mayer-Gross and Karl Leonhard characterized hebephrenia with highly differentiated psychopathological descriptions, whereas this construct only played a minor role in the works of Klaus Conrad and Kurt Schneider. The International Classification of Diseases (ICD-10) lists hebephrenia as a subtype of schizophrenia but in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) no subtypes of schizophrenia are mentioned and the concept of hebephrenia is thus lost. Hebephrenia can be seen as an ideal type describing a psychopathological course pattern. This construct can be useful to conceptualize a group of disorders of affect which otherwise escape description, especially since these psychopathological alterations of affect are difficult to operationalize. To have a viable concept of these disorders is relevant for the prognosis and therapy planning. If the concept of hebephrenia is abolished, important psychopathological knowledge might be lost for future generations of psychiatrists.

Psychiatric Autoimmunity: N-Methyl-D-Aspartate Receptor IgG and Beyond.

BACKGROUND: Descriptions of psychiatric autoimmunity beyond N-methyl-D-aspartate (NMDA) receptor encephalitis are sparse. OBJECTIVE: To report the autoimmune psychiatric spectrum currently recognized in Mayo Clinic practice. METHODS: Medical record review, testing of stored serum and cerebrospinal fluid for IgGs reactive with synaptic receptors and ion channels, neuronal nuclear and cytoplasmic antigens (including glutamic acid decarboxylase 65-kDa isoform) and case-control comparison were conducted. Patients were categorized into group 1, all adult psychiatric inpatients tested for neural autoantibodies (2002-2011; n = 213), and group 2, all Mayo NMDA receptor IgG-positive patients (2009-2013; n = 13); healthy control subjects were also included (n = 173). RESULTS: In group 1, at least 1 serum autoantibody (but not NMDA receptor IgG) was detected in 36 of 213 psychiatric inpatients. In total, 12 patients were determined retrospectively to have high-likelihood autoimmune encephalitic diagnoses. The most commonly detected autoantibody specificities were voltage-gated potassium channel ([Kv1] VGKC) complex (6) and calcium channel (P/Q type or N type; 5). Symptoms seen were as follows: depressive (8), anxious (7), psychotic (7), disorganized (5), suicidal (3), manic (1) and catatonic (1). In group 2, among 13 NMDA receptor IgG-positive patients, 12 had encephalitis; their psychiatric symptoms were as follows: depressive (9), catatonic (9), disorganized (8), anxious (8), psychotic (7), manic (6), and suicidal (3). Catatonic symptoms were more common in the 12 NMDA receptor IgG-positive patients than in the 12 group 1 patients with high likelihood of encephalitis (p = 0.002). Antibody positivities were usually low positive in value among healthy controls (12 of 16 vs 3 of 12 group 1 encephalitis cases, p = 0.025). NMDA receptor IgG was not detected in any healthy control subject. CONCLUSIONS: A spectrum of psychiatric autoimmunity beyond NMDA-R IgG may be under-recognized. Diagnosis is facilitated by combining results of comprehensive psychiatric, laboratory, radiologic, and electrophysiologic evaluations.

Verbal working memory in individuals with schizophrenia and their first degree relatives: relationship with negative and disorganized symptoms.

OBJECTIVE: To determine whether there are differences in verbal working memory amongst subjects with schizophrenia, their first degree relatives and controls, and to evaluate the influence of symptoms on these differences, as an initial step to assess whether this cognitive function is an endophenotype. METHODS: We examined 197 cases with schizophrenia, 197 first degree relatives and 200 controls through psychiatric interviews and the Letters and Numbers Sequencing test (LNS). Performance was compared among the three groups adjusting for age, sex and education level. Adjustment for "negative symptoms" and "disorganization" was performed afterwards. RESULTS: Subjects with schizophrenia showed lower performance in the LNS than their first degree relatives and the healthy controls; the effect sizes were 0.75 and 1.18 respectively. There was a small difference between relatives and controls (effect size =0.38). These differences were significant after adjustment for negative and disorganized symptoms, but the effect sizes became smaller: 0.26 for relatives vs. subjects with schizophrenia, 0.56 for controls vs. subjects with schizophrenia and 0.33 for relatives vs. controls. Among individuals with schizophrenia, performance in the LNS was not associated with disorder duration, disease onset age, antipsychotics, history of depressive episodes or substance use disorders. CONCLUSION: Results suggest verbal working memory may be considered as an endophenotype in schizophrenia.

Are there valid subtypes of schizophrenia? A grade of membership analysis.

BACKGROUND/AIMS: Cluster analysis has had limited success in establishing whether there are subtypes of schizophrenia. Grade of membership (GoM) analysis is a multivariate statistical technique which has advantages when, as in schizophrenia, individuals conforming to pure types are uncommon and mixed forms are frequent. METHODS: GoM analysis was applied to 118 chronic schizophrenic patients. The patients were of all clinical subtypes, including 13 with simple schizophrenia. Both current and 'lifetime' symptoms were assessed, and two different rating systems were used. RESULTS: Specifying 3 pure types resulted in robust findings across analyses. One pure type corresponded to paranoid schizophrenia, one to simple schizophrenia and the third combined elements of hebephrenic and catatonic schizophrenia. Specifying 4 pure types split the original 3 pure types in ways which were not clinically intuitive. CONCLUSION: GoM analysis divides schizophrenia into subtypes along conventional lines, with the proviso that hebephrenic and catatonic schizophrenic patients are not separable, at least in the chronic stage of the illness.

Does the ability to sustain attention underlie symptom severity in schizophrenia?

An association between deficits in executive control, particularly inhibitory control, and more severe negative and disorganised symptoms of schizophrenia has been widely reported. The importance of more basic aspects of attention, often referred to as 'vigilant' or 'sustained' attention, to this relationship remains unclear. This study examined the contribution of sustained attention to symptom severity using the Sustained Attention to Response Task (SART) in 69 patients with schizophrenia. We found that negative and disorganised symptom severity scores were correlated with sustained attention, working memory, and psychomotor speed. The ability to sustain attention significantly predicted variance in negative symptom severity but not disorganised symptoms, which were instead predicted by working memory performance. These data suggest that this component of attention at least partly explains variance in negative symptoms.

The architecture of cognitive control in schizophrenia.

Executive dysfunctions have long been considered a common feature of schizophrenia. However, due to their extreme heterogeneity, it is not clear whether these impairments take place at a particular level of executive functioning or non-specifically affect various aspects of behavioural control. To answer this question, we used an experimental paradigm based upon a multistage model of prefrontal executive function. This model postulates that cognitive control is organized in three hierarchically ordered control processes, operating with respect to the perceptual context (sensory and contextual controls) or the temporal episode in which the person is acting (episodic control). Twenty-four patients with schizophrenia and 24 non-psychiatric controls participated in two distinct experiments designed to separately assess each of these three levels of control. The results indicate that both sensory and episodic dimensions of cognitive control were spared in schizophrenic patients, but that they showed great difficulty in contextual conditions, as the selection of the appropriate response among competitive ones required taking into account information related to perceptual context. Contextual control can be considered as a set of executive processes mediating the hierarchical organization of behaviour. Patients' deficit in cognitive control therefore reflects a specific problem in the hierarchical control of action, leading to the selection of inappropriate behavioural representations for ongoing action plans. We also showed that this impairment was a good predictor of disorganization syndrome scores, suggesting that these clinical manifestations might result from a deficit in the combination or selection of hierarchically organized action representations.

Theory of mind in schizophrenia: the role of clinical symptomatology and neurocognition in understanding other people's thoughts and intentions.

A wealth of studies has demonstrated that patients with schizophrenia are impaired in "theory of mind" (ToM). Here, we used a novel five-factor model of the Positive and Negative Syndrome Scale (PANSS) to test the hypothesis that selectivity of ToM deficits in schizophrenia depends on the predominating symptoms. We predicted that ToM impairments would be non-selective in patients with pronounced negative (NF) or disorganized symptoms (DF), whereas selective ToM impairment would occur in patients with predominant positive symptoms (PF). We recruited 50 patients diagnosed with schizophrenia or schizoaffective disorder and examined premorbid intelligence, executive functioning, ToM and psychopathology in comparison to a group of 29 healthy controls. Compared with healthy controls, patients performed more poorly on tasks involving executive functioning and ToM abilities. Using a novel PANSS five-factor model, we found a significant association of ToM deficits with the "disorganization" factor. Moreover, several individual PANSS items that were included within the disorganization factor correlated with impaired ToM, albeit the majority of correlations disappeared when controlled for executive functioning, and, to a lesser degree, when controlled for IQ. In addition, in the patient group we found interactions of poor ToM with symptoms belonging to the "emotional distress" factor of the PANSS. Contrary to expectations, associations of impaired ToM with positive symptoms were absent, and poor with regards to negative symptoms. This study lends further support to the assumption of differential associations of ToM deficits with individual symptoms and symptom clusters in schizophrenia.

Distinct conflict resolution deficits related to different facets of Schizophrenia.

An important issue in understanding the nature of conflict processing is whether it is a unitary or multidimensional construct. One way to examine this is to study whether people with impaired conflict processing exhibit a general pattern of deficits or whether they exhibit impairments in distinct aspects of conflict processing. One group who might exhibit conflict deficits are people with schizophrenia. Schizophrenia is a heterogeneous disorder, with one way to break down the heterogeneity of schizophrenia is to examine specific symptoms. Previous research has found that specific symptoms of schizophrenia are associated with specific deficits in conflict processing. In particular, disorganization is associated with increased response conflict, alogia is associated with increased retrieval conflict, and anhedonia is associated with increased emotional conflict. Moreover, there is evidence that different types of conflict processing are unassociated with each other. This evidence suggests that conflict processing is a multidimensional construct and that different aspects of schizophrenia are associated with impairments in processing different types of conflict.

[Psychopathologic and cognitive investigations in schizophrenia]. / Pszichopatológiai és kognitív vizsgálatok szkizofréniában.

UNLABELLED: The topics of the thesis are: analysing the long-term course of delusions and hallucinations in patients with psychotic disorders, in particular in the highlight of schizophrenia patients, according to the "Budapest 2000" project; and studying the feedback-guided associative learning and acquired equivalence in two groups of schizophrenia patients and matched controls. AIMS: I. 1. To study the severity, the changeability, and likelihood of appearance of delusions and hallucinations in each identified clinical group over time; 2. to differentiate the courses of illnesses along the two psychopathological symptoms. II. To investigate the cognitive dimension in schizophrenia patients regarding feedback-guided associative learning and acquired equivalence: distinguishing the deficit/non-deficit schizophrenia subtypes from each other and controls. METHODS: 221 female patients were evaluated in the first study. Originally, the subjects were classified according to Leonhardian nosological system into affective, cycloid and schizophrenia groups (at the endpoint of the study they were re-diagnosed according to DSM-IV) and were assessed at three different times (index, and 5, and 21-33-year follow-up). The Rockland-Pollin Rating Scale and "List of Specific Symptoms" were obtained at each time point in the study. In the second study 49 male and female schizophrenia patients and 20 matched controls were evaluated. They were assessed by Rutgers Acquired Equivalence Test, some frontal neuropsychological tests, and Positive and Negative Symptom Scale. RESULTS: 1. The main positive symptoms with some fluctuations persist through the illness courses. Each symptom of positive dimension shows reduction, but the severity of hallucinations shows a significant worsening after 5 years, while the severity of delusions shows mild, but not significant reduction. Affective, cycloid and schizophrenia groups were distinguished in view of the observed symptoms and social functioning, and certain schizophrenia subgroups were distinguishable based on the correlation of the two symptoms. 2. The acquired equivalence learning was similarly impaired in deficit and non-deficit patients, whereas feedback-guided associative learning was impaired only in deficit patients. Associative learning and acquired equivalence were not related to frontal lobe tests. CONCLUSIONS: 1. The two subgroups (deficit/non-deficit) of schizophrenia may be distinguished based on the observed phenomenon of cognitive dimension. 2. The classical schizophrenic subtypes (catatonic, hebephrenic, paranoid) may be differentiated based on the changes of positive dimension through the long-term follow-up investigation.

Communication disturbances, working memory, and emotion in people with elevated disorganized schizotypy.

This study examined whether people with elevated disorganized schizotypy would differ from control participants on characteristics associated with disorganization symptoms in schizophrenia and also whether disorganized schizotypy was associated with problems processing emotion. People with disorganized schizotypy (n=32) exhibited greater communication disturbances (CD) than control participants (n=34) for emotionally negative topics but not for positive topics. In addition, the disorganized group exhibited poorer performance on a working memory task but not on a psychometrically matched verbal intelligence task. In addition, poor working memory was associated with increased CD for negative topics and, after controlling for group differences in working memory, group differences in CD were not significant. Moreover, the disorganized group exhibited greater emotional ambivalence and ambivalence was associated with increased CD in the disorganized group. These results suggest that people with disorganized schizotypy exhibit some similar characteristics to people with schizophrenia who have disorganization symptoms and that disorganized schizotypy is also associated with poor emotion processing.

Delay of gratification and executive performance in individuals with schizophrenia: putative role for eating behavior and body weight regulation.

OBJECTIVE: Impairment in executive functions and disturbed weight regulation are common features in individuals with schizophrenia on antipsychotics. Still, the clinical management of weight gain, including educational programs, is insufficient. Therefore, we hypothesized that distinct executive impairment is associated with the inability to self-control food intake. METHOD: In the present study we investigated the performance in a paradigm analyzing the executive subfunction "delay of gratification" in individuals with schizophrenia (n=29) compared with controls (n=23) and the interrelationship between delay of gratification, overall executive functioning, reported eating behavior and the BMI. We applied a board-game paradigm to operationalize delay of gratification: on designated fields individuals need to decide about a small amount of immediate reinforcement versus double the amount in the end. Appetite and eating behavior were assessed by self-report scales, executive functioning by BADS. RESULTS: We found that the patients performed significantly worse in our paradigm and that this is associated with lower executive functioning. However, the interrelationship between all parameters is complex: there is a significant positive correlation between the reported perceived appetite and executive functioning whereas the reported restrained eating behavior, significantly more frequent in patients, is correlated with low executive functioning and high disinhibition in eating situations. CONCLUSIONS: We conclude that executive functions are necessary to successfully manage eating behavior. Thus, better understanding of the cognitive mechanisms might help to support the patients more efficiently in their tough job to keep control.

Three cases of schizophrenia for which olanzapine was effective after early acute phase.

AIMS: It clarifies a difference between early acute phase and late acute phase in medication. METHODS: The present report describes three patients with schizophrenia who presented with restlessness and excitement requiring hospitalization. RESULTS: Treatment with risperidone solution orally or parenteral haloperidol until the day after admission, followed by olanzapine, successfully improved the clinical condition of the patients. In the early stage of hospitalization, selection of fast-acting drugs that can be administered to uncooperative patients is considered preferable, focusing on rapid control of symptoms and behavioral disorders, whereas after this early stage, olanzapine is preferable for improving patient compliance in addition to stabilizing symptoms. CONCLUSIONS: Because the target symptoms differ between the early and late acute phases, the term 'acute phase' used in the broad sense should be divided into two units, each requiring a different therapeutic strategy, and independent clinical approaches should be considered in order to provide more suitable treatment.

Disorganised schizotypy is selectively associated with poorer semantic processing in non-clinical individuals.

The nature and severity of semantic memory (SM) impairments in schizophrenia has been related to symptoms, mainly formal thought disorder (FTD), and other clinical factors like length of illness. Symptom-related studies in schizophrenia are often confounded by clinical factors, for example medication and hospitalisations. We completed a schizotypy analogue study to examine the relationship between SM processing and FTD using an analogue schizotypy score referred to as cognitive disorganisation. Sixty individuals without a history of mental illness (M=22.92, SD=2.70) completed a schizotypy questionnaire and three semantic tasks - naming pictures, category fluency and semantic priming. Only decreasing fluency was associated with increasing cognitive disorganisation scores (p=0.029). In line with the prevailing dyssemantic theories, the results highlight that cognitive disorganisation is associated with some difficulties in SM processes, though not all. The observed differential relationships of SM processes to disorganised schizotypy are discussed in relation to previous work, and in terms of potential developmental trajectories for SM impairment in schizophrenia.

Benefits of combining aripiprazole to clozapine: three case reports.

OBJECTIVE: A substantial number of patients treated with clozapine shows insufficient response. The author presents the results of adding aripiprazole in patients resistant to clozapine. METHOD: Three cases of individuals with psychotic symptoms despite clozapine use and with significant side effects that were treated via this combination are presented. Response was evaluated by clinical assessment. RESULTS: Good clinical results were obtained in all three patients, with improvement of psychotic symptoms and of some of the side effects of clozapine. CONCLUSION: The findings from this case series suggest that adjunctive therapy with aripiprazole can be of benefit for treating clozapine resistant schizophrenic patients.

Prevalence of aggression in hospitalized patients with schizophrenia in China: A meta-analysis.

INTRODUCTION: Aggression is a major concern in psychiatric inpatient care. Variations in study designs, settings, populations and data collection methods render comparisons of the prevalence of aggressive behavior in high-risk settings difficult. We proposed to estimate the pooled prevalence of aggression among inpatients with schizophrenia in China. METHODS: Reports on aggressive behaviour involving physical contact or risks of interpersonal violence, in schizophrenia in Chinese general psychiatric wards were retrieved by using computer-assisted searches and manual searches of the reference lists of the relevant literature. Statistical analyses were conducted using the Comprehensive Meta-Analysis V2 software. Potential sources of heterogeneity were analyzed with Cochrane's Q analysis. RESULTS: The search yielded 19 eligible studies involving a total of 3,941 schizophrenia patients. The prevalence of aggressive behavior in psychiatric wards ranged between 15.3% and 53.2%. The pooled prevalence of aggression was 35.4% (95% CI: 29.7%, 41.4%). The most commonly reported significant risk factors for aggression were positive psychotic symptoms: hostility or suspiciousness, 78.9% (15 studies); delusions, 63.2% (12 studies); disorganized behavior, 26.3% (5 studies); and auditory hallucinations, 10.5% (2 studies); together with: past history of aggression, 42.1% (8 studies); and involuntary admission, 10.5% (2 studies). CONCLUSIONS: Aggressive behaviour is common in Chinese inpatients with schizophrenia. The prevalence figures indicate the need to identify reliable clinical and illness predictors for aggression in inpatient psychiatric wards and to test investigations aimed at reducing aggressive episodes and their adverse outcomes.

Schizophrenia and processing of facial emotions: sex matters.

The aim of this study was to examine sex differences in emotion processing in patients with schizophrenia and control subjects. To this end, 53 patients with schizophrenia (28 men and 25 women), and 42 controls (21 men and 21 women) were assessed with the use of a facial affect recognition morphing task. Accuracy and sensitivity scores were measured. Women performed better than men in labelling negative emotions. On the same task, patients performed worse than control subjects, irrespective of sex, although the largest degree of impairment was seen in male patients. In conclusion, emotion perception was disproportionally affected in men with schizophrenia relative to women. This may explain, in part, why women with schizophrenia are less impaired in social life than men suffering from this illness.

Hippocampal pyramidal cell orientation in schizophrenia. A controlled neurohistologic study of the Yakovlev collection.

The finding of marked disorganization of the hippocampal pyramidal cell layer in the brains of schizophrenic patients has recently been reported. The present study was undertaken to determine whether similar abnormalities could be found in the brains of a population of schizophrenic patients, most of whom were never exposed to neuroleptics. Though statistical analysis of 2808 pyramidal cells failed to reveal significantly greater disorganization in a group of seven alleged schizophrenic brains than in brains of age-matched, nonpsychotic controls, the data suggest a relationship between the degree of pyramidal cell disarray and the severity of behavioral impairment due to psychosis. The implications and pitfalls in interpreting these findings are discussed.

Natural history of schizophrenia subtypes. I. Longitudinal study of paranoid, hebephrenic, and undifferentiated schizophrenia.

To explore the validity of different approaches for subtyping schizophrenia, the conditions of 187 schizophrenic patients from the Chestnut Lodge follow-up study were rediagnosed with the use of classic subtype criteria. Independently collected data allowed construction of a longitudinal profile of the natural history of illness for patients who met operational criteria for paranoid (n = 78), hebephrenic (n = 26), and undifferentiated (n = 83) schizophrenia. Paranoid schizophrenia had an older age at onset, often developed rapidly in individuals with good premorbid functioning, tended to be intermittent during the first 5 years of illness, and was most associated with good outcome or recovery. Hebephrenia had an earlier age at onset, often developed insidiously, and was associated with a greater family history of psychopathology, poor premorbid functioning, and, frequently, a continuous illness with a poor long-term prognosis. While also early and insidious in onset, unlike hebephrenia, undifferentiated schizophrenia was poorly distinguished from the patients' premorbid state, associated with an early history of behavioral difficulties, and often resulted in a continuous but stable disability. We discuss implications for nosology. Although distinctive patterns were discernible, the considerable heterogeneity within subtypes calls for continued efforts to develop and explore alternate classification schemes.