Kraepelinian Schizophrenia Research Articles

Revisiting Rorschach test and Minnesota Multiphasic Personality Inventory-II patterns in Kraepelinian vs. DSM-wise Schizophrenia: How They Differ and What It Means for Diagnosis.

This retrospective chart review study aimed to investigate the differences in the Rorschach test and Minnesota Multiphasic Personality Inventory (MMPI)-II profiles among patients with Kraepelinian schizophrenia, those with DSM-wise schizophrenia, and controls. Kraepelinian schizophrenia is characterised by a chronic, deteriorative disease course and a predominance of negative symptoms. Patients with Kraepelinian schizophrenia were selected based on medical record reviews. We then compared their Rorschach test and MMPI-II results with those of the DSM-wise schizophrenia group and the control group. The Rorschach test revealed a significant increase in DV2 score and a decrease in D score in patients with Kraepelinian schizophrenia compared to those with DSM-wise schizophrenia. In the MMPI-II profiles, patients with Kraepelinian schizophrenia exhibited an elevated L relative to those with DSM-wise schizophrenia. Our results suggested the value of revisiting psychological tests in clinically delineated subgroups, such as Kraepelinian schizophrenia. Although patients fall under the same diagnostic category of schizophrenia, considering different phenotypes is important when interpreting psychological test outcomes. Additionally, our study indicated that both schizophrenia groups did not show as many abnormalities as expected compared to controls. This highlights the potential value of revisiting established profiles of certain psychological tests and calls for further research on other psychological tests.

F125. POOR OUTCOME SCHIZOPHRENIA (KRAEPELINIAN SUB-TYPE): SOCIAL COGNITIVE AND NEURODEVELOPMENTAL MARKERS

BackgroundPoor outcome schizophrenia represents a public health challenge and it asks questions about neurodevelopmental mechanisms by its own. The kraepelinian schizophrenia sub-type, defined by Keefe’s criteria (1987), refers to a very poor prognosis sub-group (severe dysfunction in self-care) on the basis of the longitudinal course of the illness. Studies on kraepelinian sub-group show differences with good outcome patients regarding pre-morbid functioning, negative and disorganized symptoms, impaired performance on specific social cognitive and motor deficits (visual-motor processing, abstraction/flexibility, fine motor dexterity) (Albus and al., 1996; Bralet and al., 2006). Neurological soft signs (NSS) refer to subtle neurological abnormalities comprising deficits in sensory integration, motor coordination and sequencing of complex motor acts. Previous studies showed that NSS scores are correlated to schizophrenia, specifically among patients with poor premorbid functioning and with severe negative and disorganization symptoms. NSS could be a neurodevelopmental marker interesting to detect patients with a risk of poor prognosis. Deficits in theory of mind is correlated with disorganization and poor prognosis. The aim of our study was to explore the association between NSS, Theory of Mind and kraepelinian sub-type in order to understand better the etiopathogenic mechanisms underlying the kraepelinian sub-type.MethodsIn 2016, we recruited 2 samples of 25 schizophrenic patients, kraepelinians and no-kraepelinians, matched on sex, ages (+/- 5 years) and duration of illness (+/- 5 years) from the psychiatric departments in Picardie area (France), according to DSM-IV-TR criteria and using Keefe’s criteria. Several socio-demographical, pharmacological, clinical, cognitive and NNS (with the 3 subscores, sensory integration, motor integration and motor coordination) (Krebs and al., 2000) were collected for each patient. To compare the 2 sub-groups we used bi-variate analysis and multivariate regression analysis (p< 0,05)ResultsResults showed a worse significant NSS score among kraepelinian patients: total score, sensory integration, motor integration, motor coordination, p< 0,0001; there was no link with treatment (equ mg/day chlorpromazine). As well kraepelinians show worse significantly performance at the eye gaze test p<0,001. Multivariate analysis showed that kraepelinian sub-type is more explained significantly by eyes-test, motor integration and disorganization dimensionDiscussionPoor prognosis schizophrenia refers to specific and complex neurodevelopmental mechanisms which could be markers of a poor outcome. We must confirm these results in a larger prospective cohort from UHR and first episode assessing some specific neurodevelopmental markers using NSS and cognitive assessment. As well some specific biological markers and genes implicating in neurodevelopment and glutamatergic system could be studied in these patients. Focusing on these specific markers could contribute to define innovating combinating therapeutic strategies (pharmacological, cognitive remediation and social skills) to avoid poor prognosis.

Variation and validation: the example of schizophrenia.

Variation and validation: the example of schizophrenia.

FDG-PET scans in patients with Kraepelinian and non-Kraepelinian schizophrenia.

We recruited 14 unmedicated patients with Kraepelinian schizophrenia (12 men and 2 women; mean age=47years old), 27 non-Kraepelinian patients (21 men and 6 women; mean age=36.4years old) and a group of 56 age- and sex-matched healthy volunteers. FDG positron emission tomography and MRI scans were coregistered for both voxel-by-voxel statistical mapping and stereotaxic regions of interest analysis. While both Kraepelinian and non-Kraepelinian patients showed equally lower uptake than healthy volunteers in the frontal lobe, the temporal lobes (Brodmann areas 20 and 21) showed significantly greater decreases in Kraepelinian than in non-Kraepelinian patients. Kraepelinian patients had lower FDG uptake in parietal regions 39 and 40, especially in the right hemisphere, while non-Kraepelinian patients had similar reductions in the left. Only non-Kraepelinian patients had lower caudate FDG uptake than healthy volunteers. While both patient groups had lower uptake than healthy volunteers in the medial dorsal nucleus of the thalamus, Kraepelinian patients alone had higher uptake in the ventral nuclei of the thalamus. Kraepelinian patients also showed higher metabolic rates in white matter. Our results are consistent with other studies indicating that Kraepelinian schizophrenia is a subgroup of schizophrenia, characterized by temporal and right parietal deficits and normal rather than reduced caudate uptake. It suggests that Kraepelinian schizophrenia may be more primarily characterized by FDG uptake decreased in both the frontal and temporal lobes, while non-Kraepelinian schizophrenia may have deficits more limited to the frontal lobe. This is consistent with some neuropsychological and prognosis reports of disordered sensory information processing in Kraepelinian schizophrenia in addition to deficits in frontal lobe executive functions shared with the non-Kraepelinian subtype.

Increased advanced glycation end-products (AGEs) assessed by skin autofluorescence in schizophrenia

BackgroundOxidative stress has been intensively studied as a key biochemical system in the pathophysiology of schizophrenia. However, little is known about the implication of oxidative stress in the development of physical illnesses in schizophrenia patients, who are characterized by high cardiovascular risk and decreased life expectancy. Advanced glycation end-products (AGEs) are considered to be markers of oxidative stress and are linked to the development of atherosclerosis. MethodsWe investigated AGE levels determined by a noninvasive skin autofluorescence (skin AF) method (AGE-Reader™) in schizophrenia patients. Skin AF was assessed in 55 schizophrenia patients without diabetes or renal disease and 55 healthy controls matched for age, gender and smoking status. Nineteen of the 55 schizophrenia patients had a severe form of the disease (Kraepelinian schizophrenia). ResultsSkin AF was significantly higher in schizophrenia patients compared to controls (2.46 ± 0.52 and 1.90 ± 0.21, respectively, p < 0.0001). Kraepelinian schizophrenia patients had significantly higher skin AF than non-Kraepelinian schizophrenia patients (p = 0.05). ConclusionsThis is the first study to demonstrate high AGE levels assessed by a noninvasive method in schizophrenia patients.

Anhedonia in Kraepelinian Schizophrenia: A Preliminary Study

Kraepelinian schizophrenia, defined as a severe form of the disease, is characterized by a high number of negative symptoms and less depression, respectively. The relationship between anhedonia and Kraepelinian schizophrenia was explored. Depressive and trait anticipatory and consummatory anhedonia were compared in Kraepelinian (n=10, M age 49.2 yr., SD=10.8) and non-Kraepelinian (n=23, M age=42.7 yr., SD=10.8) patients with schizophrenia. The Kraepelinian group had more anticipatory and consummatory anhedonia than the non-Kraepe-linian group. The two groups did not differ on depressive anhedonia or depression.

Clinical, Neurocognitive, Structural Imaging and Dermatogliphics in Schizophrenia According to Kraepelin Criteria.

A century ago, Kraepelin stated that the distinctive feature of schizophrenia was progressive deterioration. Kraepelin criteria for schizophrenia are: (1) continuous hospitalization or complete dependence on others for obtaining basic necessities of life, (2) unemployment and (3) no remission for the past five years. We aimed to determine the clinical appearance and structural biological features of Kraepelinian schizophrenia. The sample consisted of 17 Kraepelinian patients, 30 non-Kraepelinian schizophrenic patients and 43 healthy controls. The Clinical Global Impressions (CGI) and the Positive and Negative Syndrome Scales (PANSS) were used for clinical assessment. The Frontal Assessment Battery (FAB) and the Verbal Fluency and Color Trail Test (CTT) were included in the cognitive battery. Brain magnetic resonance imaging and dermatoglyphic measurements were performed for structural features. Duration of illness, hospitalization, suicide attempts, admission type, presence of a stressor and treatment choice were similar between the two patient groups. Treatment resistance and family history of schizophrenia were more common in Kraepelinian patients. PANSS and CGI subscales scores were also higher in this group. Only the category fluency and CTT-I were different in Kraepelinian patients in comparison to the other patient group. Structural findings were not different between the three groups. Category fluency, which was lower in Kraepelinian patients, is an important marker of a degenerative process. The collection of severe clinical symptoms, family history of psychiatric illness and nonresponse to treatment in this particular group of patients points to the need to conduct further studies including cluster analysis in methodology.

Kraepelin Was Right: A Latent Class Analysis of Symptom Dimensions in Patients and Controls

Phenotypic heterogeneity within patients and controls may explain why the genetic variants contributing to schizophrenia risk explain only a fraction of the heritability. The aim of this study is to investigate quantitative and qualitative differences in psychosis symptoms in a sample including psychosis patients, their relatives, and community controls. We combined factor analysis and latent class analysis to analyze variation in Comprehensive Assessment of Symptoms and History lifetime-rated symptoms in 4286 subjects. The Wechsler Adult Intelligence Scale-Intelligence Quotient (N = 2663) and the Camberwell Assessment of Need rating scale (N = 625) were assessed in a subsample. Variation in 5 continuous dimensions (disorganization, positive, negative, mania, and depression) was accounted for by the presence of 7 homogeneous classes (Kraepelinian schizophrenia, affective psychosis, manic-depression, deficit nonpsychosis, depression, healthy, and no symptoms). Eighty-five percent of the schizophrenia patients was assigned to the Kraepelinian schizophrenia class (characterized by high scores on the 5 dimensions, low IQ, and poor outcome) while 15% was assigned to the affective psychosis class (relatively low disorganization and negative scores, normal IQ, and good outcome). In bipolar patients (91% bipolar I), 41% was assigned to the Kraepelinian schizophrenia class, 44% to the affective psychosis class, and 10% to the manic-depression class. Latent class membership was associated with intelligence in psychosis patients and in their relatives but not in community controls. In conclusion, symptom heterogeneity is more pronounced in bipolar disorder compared with schizophrenia. Reducing phenotypic heterogeneity within psychosis patients and controls may facilitate etiological research.

Depression in Kraepelinian Schizophrenia

&lt;p&gt;&lt;strong&gt;Objective.&lt;/strong&gt; Depressive symptoms are prevalent, under- recognised and clinically important in patients suffering from schizophrenia. Depressive symptoms in schizophrenia patients are associated with distinct morbidity and mortality. The objective of this study was to investigate the prevalence of depressive symptoms in a subgroup of chronic schizophrenia, Kraepelinian schizophrenia, and the association with severity of illness. Kraepelinian schizophrenia is characterised by a chronic, unremitting, severe course of illness and severe deterioration of functioning in social, work and self-care domains. &lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method.&lt;/strong&gt; The Calgary Depression Scale for Schizophrenia (CDSS) and the Clinical Global Impression Severity (CGI-S) scale were administered to 113 patients who fulfilled the criteria of Kraepelinian schizophrenia.&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results.&lt;/strong&gt; Sixty-eight males and 45 females participated in the study. Of this group, 17.7% scored 5 or more on the CDSS. The CGI-S scores indicated that almost half of the patients were moderately ill (i.e. a score of 4 on the CGI-S scale). Of the patients, 94 were receiving first-generation antipsychotic medication and 19 second- generation antipsychotic medication. Thirteen patients were also receiving antidepressant medication.&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion.&lt;/strong&gt; The findings of this study are consistent with current reports in the literature that depressive symptoms are not common in Kraepelinian schizophrenia, even though patients are moderately to severely ill in both symptom and functional domains.&lt;/p&gt;

Mortality in Kraepelinian schizophrenic patients: a prospective study with a median follow-up of 8.4 years

Kraepelinian schizophrenia is a subtype of schizophrenia defined by its very poor outcome. Several studies have demonstrated the validity of this distinction, but the expected excess mortality has not been investigated. The aim of the present study was to test the hypothesis that Kraepelinian schizophrenic subjects have a higher mortality rate, notably due to natural causes, than non-Kraepelinian schizophrenic subjects. The results of a prospective study with a median follow-up of 8.4 years are reported. Three hundred ten schizophrenic subjects meeting the International Classification of Diseases, 10th Revision, criteria for schizophrenia were classified on admission as Kraepelinian schizophrenia (n = 31) and non-Kraepelinian schizophrenia (n = 279); 31 deaths (16 from unnatural causes, 13 from natural causes, and 2 from undetermined causes) were observed during follow-up. Univariate and multivariate Cox regression analyses were performed using schizophrenia subtype (Kraepelinian vs non-Kraepelinian), age, and duration of illness as predictors. Schizophrenia subtype was a significant predictor of mortality in univariate analysis only for death from natural causes, and a trend was observed after adjusting for age and duration of illness. A log-rank test was used to compare mortality rates between Kraepelinian and non-Kraepelinian schizophrenic subjects and showed a significantly higher mortality rate from natural causes in Kraepelinian schizophrenia (16.7%) than in non-Kraepelinian schizophrenia (4.1%).

P.1.f.002 Link between social cognition and kraepelinian schizophrenia: impact on the functional outcome

P.1.f.002 Link between social cognition and kraepelinian schizophrenia: impact on the functional outcome

Schizophrenic patients with polydipsia and water intoxication more often have a form of schizophrenia first described by Kraepelin

Polydipsia and water intoxication (PWI) seem to be associated with a particular form of schizophrenia, first described by Kraepelin, involving negative symptoms, disorganization and poor outcome. In this study, a group of 20 schizophrenic patients with PWI was selected and matched for age, duration of illness and gender with a group of 20 schizophrenic controls with no PWI. For these patients the following measure were obtained: clinical and demographic data, Keefe's criteria for Kraepelinian schizophrenia, the Positive and Negative Syndrome Scale score and the score on Fagerström's Nicotine Dependence Scale. The group of schizophrenic patients with PWI presents significantly higher levels of negative symptoms, disorganized symptoms and general symptoms of psychopathology, and it is composed of a significantly higher percentage of Kraepelinian patients. These results show an association of polydipsia and water intoxication with Kraepelinian schizophrenia suggesting physiological hypotheses for a specific pathogenic pathway.

MRI Assessment of Gray and White Matter Distribution in Brodmann’s Areas of the Cortex in Patients With Schizophrenia With Good and Poor Outcomes

High-resolution magnetic resonance imaging (MRI) was used to compare cortical gray and white matter and CSF volumes in schizophrenia patients with poor outcomes, schizophrenia patients with good outcomes, and healthy comparison subjects. T(1)-weighted, 1.2-mm-thick MR images were acquired for 37 patients with schizophrenia and 37 healthy, age- and sex-matched comparison subjects. The patients were assigned to subgroups with poor outcomes (N=13) and good outcomes (N=24) on the basis of clinical characteristics. Poor-outcome patients were those who were continuously hospitalized or completely dependent on others for basic needs, were unemployed, and had severe negative symptoms and severe formal thought disorder. The MR images were reoriented to standard position parallel to the anterior commissure-posterior commissure line and segmented into CSF, gray matter, and white matter tissue types. The tissue types were assigned to Brodmann's areas by using the Perry postmortem histological atlas, and tissue-type volumes in the three subject groups were compared. Compared to the healthy subjects, the overall patient group had a significantly smaller mean cortical gray matter volume and significantly larger mean CSF volume, especially in the frontal lobe and left temporal lobe. The smaller frontal lobe volume in schizophrenia was confirmed for unadjusted volumes and for volumes with adjustment for whole brain volumes. Compared to patients with good outcomes, patients with poor outcomes (Kraepelinian schizophrenia) had significantly smaller gray matter volumes in the temporal and occipital lobes, but no difference between groups was found for total frontal lobe volume. Only 21% of the healthy subjects had volumes 0.5 standard deviations below the mean for healthy subjects in any area of the frontal or temporal lobes, compared with 62% of poor-outcome patients. Poor outcome in patients with schizophrenia may be associated with a more posterior distribution (posteriorization) of gray matter deficits across widely distributed cortical regions.

A pilot neuropsychological study of Kraepelinian and non-Kraepelinian schizophrenia

A pilot neuropsychological study of Kraepelinian and non-Kraepelinian schizophrenia

A pilot neuropsychological study of Kraepelinian and non-Kraepelinian schizophrenia

Objective: This is the first study to report a direct comparison of neuropsychological performance in Kraepelinian vs. non-Kraepelinian schizophrenia (SZ). Methods: 17 Kraepelinian and 19 non-Kraepelinian subjects were assessed on a neuropsychological battery including the Purdue Pegboard, Schwartz' Reaction Time task, the Modified Card Sorting Test, the Wechsler's Associate Learning Test and the Digit Span. Results: Kraepelinian schizophrenia was characterized by more impaired performance on the Purdue Pegboard and the Card Sorting test. These differences remained significant when introducing, as covariates, the type of neuroleptic used, the use of anticholinergic medication, age and gender. Differences on the Reaction Time, the Associate Learning and the Digit Span tasks did not reach statistical significance. Conclusions: These results suggest that Kraepelinian schizophrenia is characterized by impaired performance on fine motor dexterity and executive functioning. These results further add to the evidence for the validity of the distinction between Kraepelinian and non-Kraepelinian schizophrenia as a strategy to better understand the factors influencing severity and/or outcome in schizophrenia.

Depression in Kraepelinian schizophrenia.

In order to improve our understanding of depression in chronic schizophrenia, depressive symptoms were assessed in institutionalized, so called Kraepelinian, patients with schizophrenia (N = 43). The patients had been ill and dependent on others for at least 5 years. Depressive symptoms as measured by the Hamilton Depression (HAM-D) scale were less prevalent in this population compared to published data on non-Kraepelinian patients. Only 5% of our Kraepelinian patients had a HAM-D score >/= 16. There was also a low prevalence of core depressive symptoms (depressed mood, suicidal ideation, and guilt). The relationship of depression to other dimensions of schizophrenia was explored. Depression had a modest positive correlation (r = 0.44) with general psychopathology as measured by the Brief Psychiatric Rating Scale (BPRS), but not with positive symptoms as measured by BPRS positive subscale or negative symptoms as measured by the Scale for the Assessment of Negative Symptoms (SANS). Depression also showed a modest positive correlation (r =.48) using the Simpson-Angus Rating Scale (SAS) for extrapyramidal symptoms (EPS). These results indicate that in Kraepelinian schizophrenia, depression is not prevalent, even though patients are severely ill both in symptom and functioning domains. The results of our analysis support that Kraepelinian schizophrenia is a distinct subtype, and raise questions regarding the boundary between schizoaffective disorder and non-Kraepelinian schizophrenia. Finally, the low rate of depression observed revives the notion that preservation of core functional abilities is important for a depressive reaction to evolve in schizophrenia.

Clinical characteristics and risk factors for Kraepelinian subtype of schizophrenia: replication of previous findings and relation to summer birth

The aims of the study were: (1) to replicate findings that patients with Kraepelinian schizophrenia constitute a distinct subgroup and (2) to examine the relationship between season of birth and the Kraepelinian subtype. Thirty-one Kraepelinian patients, defined on the basis of a longitudinal criterion—at least 5 years of continuous and complete dependence on others to maintain the basic necessities of life, including food, clothing and shelter—were compared with 279 non-Kraepelinian schizophrenic patients. All patients met ICD-10 criteria for schizophrenia and were evaluated with the Positive and Negative Syndrome Scale. Kraepelinian schizophrenic patients had more negative symptoms and were more disorganized than non-Kraepelinian patients. Positive and anxious–depressive symptoms did not differ between the two groups. Among Kraepelinian patients, there was an excess number of births in the month of July. These findings are consistent with previous reports that Kraepelinian patients could have a disease with an etiopathophysiology separate from that of other schizophrenic patients.

Kraepelinian schizophrenia: A replication in an independent sample

Chronic, unremitting schizophrenic patients, who for the past 5 years had been either continuously hospitalized or completely dependent on others for their survival are designated Kraepelinians according to Emil Kraepelin’s description of dementia praecox. Previous studies from our center have demonstrated that Kraepelinian patients more consistently received a diagnosis of schizophrenia across a variety of cross-sectional and longitudinal diagnostic criteria and had more severe negative symptoms and formal thought disorder compared to a group of age-matched non-Kraepelinian chronic schizophrenic patients. In addition, Kraepelinian schizophrenics had a greater morbid risk for schizophrenia spectrum disorders in their first-degree relatives, had a greater left-to-right asymmetry of their lateral cerebral ventricles, and had less of a prospective response to a standard dose of haloperidol. On the other hand, the severity of positive symptoms did not distinguish Kraepelinian schizophrenics from other chronic schizophrenic patients. This study presents data on a completely independent sample of 22 Kraepelinian and 86 non-Kraepelinian schizophrenic patients. Initial data analyses suggest a replication of the findings reported on the original cohort. Kraepelinian patients had more severe negative symptoms (p < 0.002) and formal thought disorder (p c 0.001) than non-Kraepelinian chronic schizophrenic patients. The first degree relatives of Kraepelinian patients had a greater morbid risk for schizophrenia spectrum disorders than the relatives of other chronic schizophrenic patients (z = 3.3 1, p < 0.001). CT ventricular measures indicated a left frontal horn enlargement in Kraepelinian patients relative to nonKraepelinians (p < 0.05). These analyses provide independent confirmation that Kraepelinian schizophrenic patients, who require institutionalization or institution-like care, differ from other schizophrenic patients on measures of clinical presentation and family history, suggesting that these patients are a relatively homogenous subgroup of schizophrenics with very severe symptoms and uniformly poor outcomes.

Characteristics of kraepelinian schizophrenia: Independent replication study : Ede Frecska, M.D., Miklos Losonczy, M.D., Richard S.E. Keefe, Ph.D., Robert T. McQueeney, M.D., Daniel Lobel, Ph.D., Seth Apter, M.A., Kenneth L. Davis, M.D. Mount Sinai School of Medicine, New York, NY 10029

Characteristics of kraepelinian schizophrenia: Independent replication study : Ede Frecska, M.D., Miklos Losonczy, M.D., Richard S.E. Keefe, Ph.D., Robert T. McQueeney, M.D., Daniel Lobel, Ph.D., Seth Apter, M.A., Kenneth L. Davis, M.D. Mount Sinai School of Medicine, New York, NY 10029

Diagnostic issues in chronic schizophrenia: kraepelinian schizophrenia, undifferentiated schizophrenia, and state-independent negative symptoms

Data are presented concerning three recent clinical distinctions in schizophrenia: kraepelinian versus non-kraepelinian patients; mixed versus simple undifferentiated subtypes; and state-dependent versus state-independent negative symptoms. Schizophrenic patients who have been ill and dependent on others for the past 5 years (‘kraepelinians’) were compared to other chronic schizophrenics. The kraepelinian patients met the criteria for schizophrenia by more diagnostic systems than other patients, were less responsive to haloperidol, had more severe negative symptoms and formal thought disorder, and had similarly severe positive symptoms. They also had cerebral ventricles that demonstrated more left-to-right asymmetry and a greater family history of schizophrenia spectrum disorders. Mixed undifferentiated schizophrenic patients, who met criteria for more than one schizophrenic subtype, were compared to simple undifferentiated schizophrenic patients, who met criteria for no subtype. The mixed group was characterized by more severe positive and negative symptoms and formal thought disorder, worse social functioning, and a worse response to haloperidol. In a subgroup of patients who were studied once while in a state of exacerbation and once while in a state of relative remission, the negative symptoms of inattention and affective flattening were state-dependent, while anhedonia-asociality was state-independent.