Functional cognitive disorder affects reaction time, subjective mental effort and global metacognition.

We previously hypothesized that functional cognitive disorder is characterized by heightened subjective mental effort, exhausted attentional reserve and metacognitive failure. To test this hypothesis, we administered a Stroop colour-word task in which attentional demand was varied by task difficulty (congruent versus incongruent cues) and the presence of a secondary auditory stimulus (passive or active listening to an oddball-type paradigm). We measured subjective mental effort, objective performance (reaction times and accuracy), metacognition and EEG-based biomarkers of mental workload. We tested 19 functional cognitive disorder patients and 23 healthy controls. Patients reported higher levels of depression, anxiety, fatigue, pain, sleep disruption, dissociation and obsessiveness. They rated their memory as significantly poorer than healthy controls; however, accuracy did not differ between groups in any condition. In contrast to healthy controls, patients rated their performance as poorer on the congruent Stroop task with background noise compared to silent conditions. Functional cognitive disorder was consistently associated with slower reaction times but this was not exacerbated by increased attentional demand. Patients but not healthy controls reported greater mental workload in noisy conditions but EEG biomarkers were similar between groups, regardless of task difficulty. Functional cognitive disorder has significant syndromic overlap with mood disorders and chronic fatigue and pain. It is associated with global metacognitive failure whereas local (task-specific) metacognition is only selectively impaired. Patients were slower than healthy controls, which might contribute to the 'brain fog' reported in this condition. Although subjective mental effort was increased in noisy conditions, we found no evidence of attentional exhaustion in functional cognitive disorder. Our results indicate that functional cognitive disorder is a multisystem condition affecting reaction time, subjective mental effort and global metacognition.

Caution for psychiatrists: malignant hyperthermia risks with the anesthetic agent succinylcholine (Suxamethonium) during electroconvulsive therapy.

BACKGROUND: Malignant hyperthermia is a potentially lethal condition triggered by specific anesthetic drugs, especially a depolarizing muscle relaxant of succinylcholine (Suxamethonium). Despite the frequent use of succinylcholine with electroconvulsive therapy (ECT), there has been no reported case of potentially lethal malignant hyperthermia following ECT. In addition, the time interval between the administration of succinylcholine and the onset of malignant hyperthermia has not been outlined in the context of ECT. CASE PRESENTATION: We present the case of a 79-year-old woman suffering from severe depression, who experienced severe malignant hyperthermia due to succinylcholine administration during an ECT session. She presented with a high fever of 40.2 °C, tachycardia of 140/min, hypertension with a blood pressure exceeding 200 mmHg, significant muscle rigidity, and impaired consciousness. These symptoms emerged two hours after ECT, which occurred in a psychiatric ward rather than an operating room, and reached their peak in less than 24 h. She was given 60 mg of dantrolene, which quickly reduced the muscular rigidity. Subsequently, she received two additional doses of 20 mg and 60 mg of dantrolene, which brought her fever down to 36.2 °C and completely eased her muscle rigidity within two days after ECT. CONCLUSIONS: This is the first reported case of potentially lethal malignant hyperthermia after ECT. In addition, it highlights the delayed onset of malignant hyperthermia following an ECT procedure, emphasizing the necessity for psychiatrists to recognize its onset even after the treatment. In the light of potentially lethal consequences of malignant hyperthermia, it is critically important for psychiatrists to closely monitor both intraoperative and postoperative patient's vital signs and characteristic physical presentations, promptly identify any symptomatic emergence, and treat it immediately with dantrolene.

Investigating the Link Between Subjective Depth Perception Deficits and Objective Stereoscopic Vision Deficits in Individuals With Acquired Brain Injury.

Individuals with acquired brain injury have reported subjective complaints of depth perception deficits, but few have undergone objective assessments to confirm these deficits. As a result, the literature currently lacks reports detailing the correlation between subjective depth perception deficits and objective stereoscopic vision deficits in individuals with acquired brain injury, particularly those cases that are characterized by a clearly defined lesion. To investigate this relationship, we recruited three individuals with acquired brain injury who experienced depth perception deficits and related difficulties in their daily lives. We had them take neurologic, ophthalmological, and neuropsychological examinations. We also had them take two types of stereoscopic vision tests: a Howard-Dolman-type stereoscopic vision test and the Topcon New Objective Stereo Test. Then, we compared the results with those of two control groups: a group with damage to the right hemisphere of the brain and a group of healthy controls. Performance on the two stereoscopic vision tests was severely impaired in the three patients. One of the patients also presented with cerebral diplopia. We identified the potential neural basis of these deficits in the cuneus and the posterior section of the superior parietal lobule, which play a role in vergence fusion and are located in the caudal region of the dorso-dorsal visual pathway, which is known to be crucial not only for visual spatial perception, but also for reaching, grasping, and making hand postures in the further course of that pathway.

Changes in the heartbeat-evoked potential are associated with functional seizures.

BACKGROUND: Patients with functional seizures (FS) can experience dissociation (depersonalisation) before their seizures. Depersonalisation reflects disembodiment, which may be related to changes in interoceptive processing. The heartbeat-evoked potential (HEP) is an electroencephalogram (EEG) marker of interoceptive processing. AIM: To assess whether alterations in interoceptive processing indexed by HEP occur prior to FS and compare this with epileptic seizures (ES). METHODS: HEP amplitudes were calculated from EEG during video-EEG monitoring in 25 patients with FS and 19 patients with ES, and were compared between interictal and preictal states. HEP amplitude difference was calculated as preictal HEP amplitude minus interictal HEP amplitude. A receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of HEP amplitude difference in discriminating FS from ES. RESULTS: The FS group demonstrated a significant reduction in HEP amplitude between interictal and preictal states at F8 (effect size rB=0.612, false discovery rate (FDR)-corrected q=0.030) and C4 (rB=0.600, FDR-corrected q=0.035). No differences in HEP amplitude were found between states in the ES group. Between diagnostic groups, HEP amplitude difference differed between the FS and ES groups at F8 (rB=0.423, FDR-corrected q=0.085) and C4 (rB=0.457, FDR-corrected q=0.085). Using HEP amplitude difference at frontal and central electrodes plus sex, we found that the ROC curve demonstrated an area under the curve of 0.893, with sensitivity=0.840 and specificity=0.842. CONCLUSION: Our data support the notion that aberrant interoception occurs prior to FS. Changes in HEP amplitude may reflect a neurophysiological biomarker of FS and may have diagnostic utility in differentiating FS and ES.

Impaired cardiac modulation in patients with functional seizures: Results from a face intensity judgment task.

OBJECTIVE: Although interoceptive abnormality in patients with functional seizure (FSs) has been demonstrated using explicit tasks, implicit measurements of interoception such as the effect of interoception on perceptual brain processes have not been investigated. It has been shown that perception is normally modulated by interoceptive signals related to the different phases (systole vs diastole) of the cardiac cycle (cardiac modulation effect). Given our previous findings using explicit measures of interoception, we hypothesized that cardiac modulation would be impaired in FSs. METHODS: Thirty-two patients with FSs and 30 age- and sex-matched non-clinical individuals conducted a face intensity judgment task, in which their intensity rating when fearful or neutral faces was presented was compared between systolic and diastolic phases. They also conducted the heartbeat discrimination task as a measure of their capacity to integrate both interoceptive and exteroceptive information. RESULTS: Patients with FSs had impaired cardiac modulation of the perception of neutral faces (corrected p = .044). Individual differences in the heartbeat discrimination task predicted the degree to which cardiac modulation occurred across the whole group (p = .028). This cardiac modulation effect was significantly associated with seizure severity (p = .021). Regardless of cardiac phase, patients rated fearful facial expressions as less intense compared to control participants (p = .006). SIGNIFICANCE: These findings highlight impaired implicit cardiac modulation effects in patients with FSs. This reflects interoceptive dysfunction in patients with FSs, and an inability of the brain to integrate interoceptive signaling with perceptual processing. This may have implications for our understanding of the pathophysiology in FSs and inform novel diagnostic approaches.

Pneumonia Risk Increased by Dementia-Related Daily Living Difficulties: Poor Oral Hygiene and Dysphagia as Contributing Factors.

OBJECTIVE: Although pneumonia is the leading cause of death among patients with dementia, the specific underlying causes remain unclear. In particular, the potential connection between pneumonia risk and dementia-related daily living difficulties, such as oral hygiene practice and mobility impairment, and the use of physical restraint as a management practice, has not been extensively studied. METHODS: In our retrospective study, we included 454 admissions corresponding to 336 individual patients with dementia who were admitted to a neuropsychiatric unit due to behavioral and psychological symptoms. The admissions were divided into two groups: those who developed pneumonia while hospitalized (n=62) and those who did not (n=392). We investigated differences between the two groups in terms of dementia etiology, dementia severity, physical conditions, medical complications, medication, dementia-related difficulties in daily living, and physical restraint. To control potential confounding variables, we used mixed effects logistic regression analysis to identify risk factors for pneumonia in this cohort. RESULTS: Our study found that the development of pneumonia in patients with dementia was associated with poor oral hygiene, dysphagia, and loss of consciousness. Physical restraint and mobility impairment showed a weaker, nonsignificant association with the development of pneumonia. CONCLUSIONS: Our findings suggest that pneumonia in this population may be caused by two primary factors: increased pathogenic microorganisms in the oral cavity due to poor hygiene, and an inability to clear aspirated contents due to dysphagia and loss of consciousness. Further investigation is needed to clarify the relationship between physical restraint, mobility impairment, and pneumonia in this population.

Hypermobility in patients with functional seizures: Toward a pathobiological understanding of complex conditions.

BACKGROUND: Functional seizures (FS), otherwise known as psychogenic nonepileptic seizures (PNES), are a common symptom presenting to neurology and epilepsy clinics. There is a pressing need for further research to understand the neurobiology of FS to develop mechanistically targeted treatments. Joint hypermobility is an expression of variation in connective tissue structure along a spectrum, and it has received increasing attention in functional neurological disorders, but there is lack of evidence of its relevance in FS. METHODS: In the present study, forty-two patients with FS and a non-clinical comparison group of 34 age/sex-matched controls were recruited. Joint hypermobility of all participants was quantified using the Beighton scale. RESULTS: In our sample, 24 (57%) patients with FS, and 7 (21%) of the comparison group met criteria for joint hypermobility (p = 0.002). Our statistical model revealed that patients with FS showed a significant degree of hypermobility compared to the comparison group (odds ratio = 11.1; Confidence interval: 2.1-78.0, p = 0.008), even after controlling age, sex, anxiety, and depression. CONCLUSION: We found a significant association between FS and joint hypermobility, which was independent of anxiety and depression.

Risk of Nonalcoholic Fatty Liver Disease in Patients With Schizophrenia Treated With Antipsychotic Drugs: A Cross-sectional Study.

BACKGROUND: Although the prevalence of metabolic syndrome in patients with schizophrenia is higher than the prevalence in the general population, little is known regarding nonalcoholic fatty liver disease (NAFLD) in patients with schizophrenia. PROCEDURES: We analyzed the medical records of patients with schizophrenia/schizoaffective disorder (N = 253) who received an abdominal echography. RESULTS: In total, 108 patients (42.7%) showed NAFLD on abdominal echography. Of these, 13 patients (12.0%) showed signs of fibrosis on abdominal echography. In terms of age distribution, NAFLD was more prevalent in younger patients, particularly in female patients. We also found that body mass index, the total dose of antipsychotic drugs that carry a risk of metabolic syndrome, and the total dose of antipsychotic drugs that carry a risk of hyperprolactinemia were significantly associated with NAFLD (P < 0.001, 0.049, and 0.041, respectively). In our exploratory analysis, we found that signs of fibrosis in NAFLD were more highly associated with female patients (P = 0.023). Importantly, the risk in younger female patients may be specific to patients with schizophrenia compared with the general population. CONCLUSIONS: Considering that antipsychotic drugs were associated with the development of NAFLD, early detection and management of NAFLD should be conducted in patients with schizophrenia.

Cost-effectiveness analyses of augmented cognitive behavioral therapy for pharmacotherapy-resistant depression at secondary mental health care settings.

AIM: Pharmacotherapy is the primary treatment strategy in major depression. However, two-thirds of patients remain depressed after the initial antidepressant treatment. Augmented cognitive behavioral therapy (CBT) for pharmacotherapy-resistant depression in primary mental health care settings proved effective and cost-effective. Although we reported the clinical effectiveness of augmented CBT in secondary mental health care, its cost-effectiveness has not been evaluated. Therefore, we aimed to compare the cost-effectiveness of augmented CBT adjunctive to treatment as usual (TAU) and TAU alone for pharmacotherapy-resistant depression at secondary mental health care settings. METHODS: We performed a cost-effectiveness analysis at 64 weeks, alongside a randomized controlled trial involving 80 patients who sought depression treatment at a university hospital and psychiatric hospital (one each). The cost-effectiveness was assessed by the incremental cost-effectiveness ratio (ICER) that compared the difference in costs and quality-adjusted life years, and other clinical scales, between the groups. RESULTS: The ICERs were JPY -15 278 322 and 2 026 865 for pharmacotherapy-resistant depression for all samples and those with moderate/severe symptoms at baseline, respectively. The acceptability curve demonstrates a 0.221 and 0.701 probability of the augmented CBT being cost-effective for all samples and moderate/severe depression, respectively, at the threshold of JPY 4.57 million (GBP 30 000). The sensitivity analysis supported the robustness of our results restricting for moderate/severe depression. CONCLUSION: Augmented CBT for pharmacotherapy-resistant depression is not cost-effective for all samples including mild depression. In contrast, it appeared to be cost-effective for the patients currently manifesting moderate/severe symptoms under secondary mental health care.

Trait and state interoceptive abnormalities are associated with dissociation and seizure frequency in patients with functional seizures.

OBJECTIVE: Dissociative traits represent a disturbance in selfhood that may predispose to, and trigger, functional seizures (FSs). The predictive representation and control of the internal physiological state of the body (interoception) are proposed to underpin the integrity of the sense of self ("minimal selfhood"). Therefore, discrepancies between objective and subjective aspects of interoception may relate to symptom expression in patients with FSs. Here, we tested whether individual differences in trait measures of interoception relate to dissociative symptoms, and whether state interoceptive deficits predict FS occurrence. METHODS: Forty-one participants with FSs and 30 controls completed questionnaire ratings of dissociation, and measures of (1) interoceptive accuracy (IA)-objective performance on heartbeat detection tasks; (2) trait interoceptive sensibility-subjective sensitivity to internal sensations (using the Porges Body Perception Questionnaire); and (3) state interoceptive sensibility-subjective trial-by-trial measures of confidence in heartbeat detection. Interoceptive trait prediction error (ITPE) was calculated from the discrepancy between IA and trait sensibility, and interoceptive state prediction error (ISPE) from the discrepancy between IA and state sensibility. RESULTS: Patients with FSs had significantly lower IA and greater trait interoceptive sensibility than healthy controls. ITPE was the strongest predictor of dissociation after controlling for trait anxiety and depression in a regression model. ISPE correlated significantly with FS frequency after controlling for state anxiety. SIGNIFICANCE: Patients with FSs have disturbances in interoceptive processing that predict both dissociative traits reflecting the disrupted integrity of self-representation, and the expression of FSs. These findings provide insight into the pathophysiology of functional neurological disorder, and could lead to novel diagnostic and therapeutic approaches.

Catatonic Stupor in Schizophrenic Disorders and Subsequent Medical Complications and Mortality.

OBJECTIVE: Although catatonia can occur secondary to a general medical condition, catatonia itself has been known to lead to various medical compolications. Although case reports on the association of catatonia with subsequent medical complications have been documented, no comprehensive large-scale study has been performed. To investigate specific medical complications after catatonia, we conducted a retrospective cohort study of specific medical complications of schizophrenia patients with catatonia. METHODS: The 1719 schizophrenia inpatients in our study were categorized into two groups: the catatonia group, i.e., those who exhibited catatonic stupor while they were hospitalized, and the noncatatonia group, i.e., those who never exhibited catatonic stupor. Differences between the two groups in the occurrence of subsequent medical complications were examined using linear and logistic regression analyses, and models were adjusted for potentially confounding factors. RESULTS: The catatonia group had an increased risk for mortality (odds ratio = 4.8, 95% confidence interval = 2.0-10.6, p < .01) and certain specific medical complications, i.e., pneumonia, urinary tract infection, sepsis, disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep venous thrombosis, pulmonary embolism, urinary retention, decubitus, arrhythmia, renal failure, neuroleptic malignant syndrome, hypernatremia, and liver dysfunction (all p values < .01, except for deep venous thrombosis, p = .04 in the multiple linear regression analysis). CONCLUSIONS: Catatonic stupor in schizophrenia substantially raises the risk for specific medical complications and mortality. Hyperactivity of the sympathetic nervous system, dehydration, and immobility, which are frequently involved in catatonia, might contribute to these specific medical complications. In catatonia, meticulous care for both mental and medical conditions should be taken to reduce the risk of adverse medical consequences.

Altered perception might be a symptom of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.

Most patients with N-methyl-D-aspartate receptor (NMDAR) encephalitis initially present with psychiatric symptoms. Although a delayed diagnosis may lead to a poor outcome, psychiatric symptoms that could differentiate anti-NMDAR encephalitis from other psychoses have not been fully investigated. We evaluated two patients with anti-NMDAR encephalitis who were observed by psychiatrists from onset throughout the course of disease. Both patients exhibited disorientation, memory deficits, perceptual disturbances, hallucinations, and mood liability. Among those, altered perceptions were most prominent - in particular, altered time perceptions without disorganization syndrome. The information obtained for these patients may help clinicians differentiate anti-NMDAR encephalitis from other psychoses, e.g., schizophrenia.

Predictors of readmission after successful electroconvulsive therapy for depression: a chart review study.

OBJECTIVE: The study aimed to identify the predictors for readmission after a successful electroconvulsive therapy (ECT) course. METHODS: Medical charts of patients who received ECT for major depressive episodes were reviewed. Patients' demographic characteristics and treatment parameters, such as ECT charge, seizure duration, the number of ECT sessions and pharmacotherapy, were extracted. We compared differences between those who were readmitted after successful ECT within 6 and 12 months, versus those not readmitted. We also conducted a multivariate logistic regression analysis to identify the predictors for readmission. RESULTS: Out of 51 patients who were discharged after ECT, 27 patients met the inclusion criteria and were included in the analysis. Eight patients were readmitted within 6 months after discharge, and four more patients were readmitted during the next 6-month follow up. Comparing patients who were and were not readmitted, we found no significant differences between groups, including ECT parameters such as the number of ECT sessions, average charge and final charge. No predictors for readmission were found through multivariate analysis. CONCLUSIONS: Although patients who require higher ECT charge and more sessions seem to be prone to readmission, our dataset suggested that none of these types of ECT parameters were risk factors for readmission.

Divergent thinking as a predictor of life skills in patients with schizophrenia: Evidence from the modified Tinkertoy Test.

Aim: Patients with schizophrenia often exhibit poor life skills, posing significant clinical challenges. Life skills comprise cognitive functions crucial for planning daily activities, including divergent thinking. However, the cognitive deficits contributing to these diminished skills among patients with schizophrenia are underexplored. This study introduces a modified Tinkertoy Test (m-TTT) to investigate the correlation between life skills, divergent thinking, and psychological assessment tools in patients with schizophrenia. Methods: Fifty-two patients with schizophrenia, alongside a control group, matched for sex, age, and education, were evaluated using psychological assessment tools. For the patient group, the Life Skills Profile (LSP) and Positive and Negative Syndrome Scale were administered to measure functional abilities and psychiatric symptoms, respectively. Additionally, duration of disease and antipsychotic daily dosage levels were assessed exclusively in the patient group. Both groups were evaluated with the m-TTT, Idea Fluency Test (IFT), Design Fluency Test (DFT), and Brief Assessment of Cognition in Schizophrenia (BACS) to comprehensively assess cognitive functions. A stepwise multiple regression model was conducted to identify significant correlates of LSP total score among the patient group. Results: The schizophrenia group scored notably lower than the neurotypical controls on the m-TTT, IFT, DFT, and BACS. Our stepwise multiple regression analysis highlighted that the LSP total score was significantly correlated with the total m-TTT score and presence of negative symptoms. Conclusion: Divergent thinking could be a crucial factor in the life skills of individuals with schizophrenia. Rehabilitation programs based on this cognitive function might enhance their daily living capabilities.

Post-stroke urinary incontinence is associated with behavior control deficits and overactive bladder.

BACKGROUND: Although urinary incontinence in stroke survivors can substantially impact the patient's quality of life, the underlying neuropsychological mechanisms and its neural basis have not been adequately investigated. Therefore, we investigated this topic via neuropsychological assessment and neuroimaging in a cross-sectional study. METHODS: We recruited 71 individuals with cerebrovascular disease. The relationship between urinary incontinence and neuropsychological indices was investigated using simple linear regression analysis or Mann-Whitney U test, along with other explanatory variables, e.g., severity of overactive bladder. Variables with a p-value of <0.1 in the simple regression analysis were entered in the final multiple linear regression model to control for potential confounding factors. To carry out an in-depth examination of the neuroanatomical substrate for urinary incontinence, voxel-based lesion-behavior mapping was performed using MRIcron software. RESULTS: Behavioral control deficits and severity of overactive bladder were closely related to severity of urinary incontinence. The voxel-based lesion-behavior mapping suggests a potential role for ventromedial prefrontal cortex lesioning in the severity of urinary incontinence, although this association is not statistically significant. CONCLUSIONS: Post-stroke urinary incontinence is closely related to two factors: neurogenic overactive bladder, a physiological disinhibition of micturition reflex, and cognitive dysfunction, characterized by behavior control deficits.

Deep vein thrombosis and its risk factors in neurodegenerative diseases: A markedly higher incidence in Parkinson's disease.

BACKGROUND: Information on the incidence and risk factors of deep vein thrombosis (DVT) in neurodegenerative diseases is limited. We aimed to determine the incidence of DVT among neurodegenerative disorders (amyotrophic lateral sclerosis [ALS], Parkinson's disease [PD], multiple system atrophy [MSA], and progressive supranuclear palsy [PSP]-corticobasal syndrome [CBS]) and the risk factors for the development of DVT. METHODS: Overall, 229 hospitalized patients with neurodegenerative diseases (65 patients with ALS, 61 with PD, 53 with MSA, and 50 with PSP-CBS) were included in this study. D-dimer value and ultrasonography of the leg vein were assessed to determine the presence or absence of leg DVT. We compared the DVT incidence among each disease group. To identify the risk factors for DVT, a multivariate analysis was performed. RESULTS: Of 229 patients, 34 had leg DVT; the incidence was significantly higher in patients with PD (38%) than in those with ALS (2%), MSA (5%), or PSP-CBS (4%). Patients with DVT were older, had a smaller waist circumference, had a longer disease duration, and had a high blood pressure (BP) variability. Multivariate analysis revealed that a PD diagnosis and female sex, with a high BP variability were predictive of leg DVT. CONCLUSIONS: Among the neurodegenerative diseases, the DVT incidence was markedly higher in PD than in ALS, MSA, and PSP-CBS. Several risk factors have been identified in patients with leg DVT. Recognition of these risk factors will improve patient care and guide the appropriate use of anticoagulants.

Aberrant heartbeat-evoked potential in schizophrenia.

Self-disturbance is considered a core feature underlying the psychopathology of schizophrenia. Interoception has an important role in the development of a sense of self, leading to increased interest in the potential contribution of abnormal interoception to self-disturbances in schizophrenia. Several neuropsychological studies have demonstrated aberrant interoception in schizophrenia. However, cortical interoceptive processing has not yet been thoroughly investigated. Thus, we sought to examine resting-state heartbeat-evoked potential (HEP) in this population. We hypothesized that patients with schizophrenia would exhibit significant alterations in HEP compared to healthy controls (HCs). In this cross-sectional electroencephalogram (EEG) study, we compared the HEPs between age- and sex-matched groups of patients with schizophrenia and HCs. A 10-min resting-state EEG with eyes closed and an electrocardiogram (ECG) were recorded and analyzed for the time window of 450 ms to 500 ms after an ECG R peak. A positive HEP shift was observed in the frontal-central regions (F [1, 82] = 7.402, p = 0.008, partial η2 = 0.009) in patients with schizophrenia (n = 61) when compared with HCs (n = 31) after adjusting for confounders such as age, sex, and heart rate. A cluster-based correction analysis revealed that the HEP around the right frontal area (Fp2, F4, and F8) showed the most significant group differences (F [1, 82] = 10.079, p = 0.002, partial η2 = 0.021), with a peak at the F4 electrode site (F [1, 82] = 12.646, p < 0.001, partial η2 = 0.069). We observed no correlation between HEP and symptoms in patients with schizophrenia. A positive shift of HEP during the late component could reflect a trait abnormality in schizophrenia. Further research is required to determine the association between the altered cortical interoceptive processing indexed with HEP and self-disturbances in schizophrenia.

Disease Progression Patterns of Brain Morphology in Schizophrenia: More Progressed Stages in Treatment Resistance.

BACKGROUND AND HYPOTHESIS: Given the heterogeneity and possible disease progression in schizophrenia, identifying the neurobiological subtypes and progression patterns in each patient may lead to novel biomarkers. Here, we adopted data-driven machine-learning techniques to identify the progression patterns of brain morphological changes in schizophrenia and investigate the association with treatment resistance. STUDY DESIGN: In this cross-sectional multicenter study, we included 177 patients with schizophrenia, characterized by treatment response or resistance, with 3D T1-weighted magnetic resonance imaging. Cortical thickness and subcortical volumes calculated by FreeSurfer were converted into z scores using 73 healthy controls data. The Subtype and Stage Inference (SuStaIn) algorithm was used for unsupervised machine-learning analysis. STUDY RESULTS: SuStaIn identified 3 different subtypes: (1) subcortical volume reduction (SC) type (73 patients), in which volume reduction of subcortical structures occurs first and moderate cortical thinning follows, (2) globus pallidus hypertrophy and cortical thinning (GP-CX) type (42 patients), in which globus pallidus hypertrophy initially occurs followed by progressive cortical thinning, and (3) cortical thinning (pure CX) type (39 patients), in which thinning of the insular and lateral temporal lobe cortices primarily happens. The remaining 23 patients were assigned to baseline stage of progression (no change). SuStaIn also found 84 stages of progression, and treatment-resistant schizophrenia showed significantly more progressed stages than treatment-responsive cases (P = .001). The GP-CX type presented earlier stages than the pure CX type (P = .009). CONCLUSIONS: The brain morphological progressions in schizophrenia can be classified into 3 subtypes, and treatment resistance was associated with more progressed stages, which may suggest a novel biomarker.