Network Analysis-Based Disentanglement of the Symptom Heterogeneity in Asian Patients with Schizophrenia: Findings from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics

The symptom heterogeneity of schizophrenia is consistent with Wittgenstein’s analogy of a language game. From the perspective of precision medicine, this study aimed to estimate the symptom presentation and identify the psychonectome in Asian patients, using data obtained from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics. We constructed a network structure of the Brief Psychiatric Rating Scale (BPRS) items in 1438 Asian patients with schizophrenia. Furthermore, all the BPRS items were considered to be an ordered categorical variable ranging in value from 1–7. Motor retardation was situated most centrally within the BPRS network structure, followed by depressive mood and unusual thought content. Contrastingly, hallucinatory behavior was situated least centrally within the network structure. Using a community detection algorithm, the BPRS items were organized into positive, negative, and general symptom clusters. Overall, DSM symptoms were not more central than non-DSM symptoms within the symptom network of Asian patients with schizophrenia. Thus, motor retardation, which results from the unmet needs associated with current antipsychotic medications for schizophrenia, may be a tailored treatment target for Asian patients with schizophrenia. Based on these findings, targeting non-dopamine systems (glutamate, γ-aminobutyric acid) may represent an effective strategy with respect to precision medicine for psychosis.

Poor Separation of Clinical Symptom Profiles by DSM-5 Disorder Criteria

Assessment of mental illness typically relies on a disorder classification system that is considered to be at odds with the vast disorder comorbidity and symptom heterogeneity that exists within and across patients. Patients with the same disorder diagnosis exhibit diverse symptom profiles and comorbidities creating numerous clinical and research challenges. Here we provide a quantitative analysis of the symptom heterogeneity and disorder comorbidity across a sample of 107,349 adult individuals (aged 18–85 years) from 8 English-speaking countries. Data were acquired using the Mental Health Quotient, an anonymous, online, self-report tool that comprehensively evaluates symptom profiles across 10 common mental health disorders. Dissimilarity of symptom profiles within and between disorders was then computed. We found a continuum of symptom prevalence rather than a clear separation of normal and disordered. While 58.7% of those with 5 or more clinically significant symptoms did not map to the diagnostic criteria of any of the 10 DSM-5 disorders studied, those with symptom profiles that mapped to at least one disorder had, on average, 20 clinically significant symptoms. Within this group, the heterogeneity of symptom profiles was almost as high within a disorder label as between 2 disorder labels and not separable from randomly selected groups of individuals with at least one of any of the 10 disorders. Overall, these results quantify the scale of misalignment between clinical symptom profiles and DSM-5 disorder labels and demonstrate that DSM-5 disorder criteria do not separate individuals from random when the complete mental health symptom profile of an individual is considered. Greater emphasis on empirical, disorder agnostic approaches to symptom profiling would help overcome existing challenges with heterogeneity and comorbidity, aiding clinical and research outcomes.

The uncommon is common: Structural similarities of symptom heterogeneity across mental disorders

The heterogeneity of symptoms among individuals diagnosed with the same mental disorder complicates the identification of biomarkers and the development of targeted treatments. Yet, the characteristics of this heterogeneity remain largely unknown. We investigated the frequency of disorder-specific symptom combinations, a marker of symptom heterogeneity, in five samples, each assessed for symptoms of a specific disorder (posttraumatic stress disorder, depression, anxiety, schizophrenia and burnout). The frequency of symptom combinations was heavily skewed in all samples, with most symptom combinations being reported only by few individuals. Moreover, the distribution of the symptom combination frequency could be approximated by a power-law and a log-normal distribution. This demonstrates similarities in the structure of symptom heterogeneity among mental disorders. Furthermore, we show that studies with sample sizes typical for research in mental health preclude many rare symptom combinations, limiting the validity of the obtained evidence by such studies for individuals with rare symptom combinations.

Symptom heterogeneity and patient subgroup classification among US patients with post-treatment Lyme disease: an observational study

ObjectivesTo identify underlying subgroups with distinct symptom profiles, and to characterise and compare these subgroups across a range of demographic, clinical and psychosocial factors, within a heterogeneous group of patients with well-defined post-treatment Lyme disease (PTLD).DesignA clinical case series of patents.SettingParticipants were recruited from a single-site, Lyme disease referral clinic patient population and were evaluated by physical exam, clinical laboratory testing and standardised questionnaires.ParticipantsTwo hundred and twelve participants met study criteria for PTLD, with medical record-confirmed prior Lyme disease as well as current symptoms and functional impact.ResultsExploratory factor analysis classified 30 self-reported symptoms into 6 factors: ‘Fatigue Cognitive’, ‘Ocular Disequilibrium’, ‘Infection-Type’, ‘Mood-Related’, ‘Musculoskeletal Pain’ and ‘Neurologic’. A final latent profile analysis was conducted using ‘Fatigue Cognitive’, ‘Musculoskeletal Pain’ and ‘Mood-Related’ factor-based scores, which produced three emergent symptom profiles, and participants were classified into corresponding subgroups with 59.0%, 18.9% and 22.2% of the sample, respectively. Compared with the other two groups, subgroup 1 had similarly low levels across all factors relative to the sample as a whole, and reported lower rates of disability (1.6% vs 10.0%, 12.8%; q=0.126, 0.035) and higher self-efficacy (median: 7.5 vs 6.0, 5.3; q=0.068,<0.001). Subgroup 2 had the highest ‘Musculoskeletal Pain’ factor-based scores (q≤0.001). Subgroup 3 was characterised overall by higher symptom factor-based scores, and reported higher depression (q≤0.001).ConclusionsThis analysis identified six symptom factors and three potentially clinically relevant subgroups among patients with well-characterised PTLD. We found that these subgroups were differentiated not only by symptom phenotype, but also by a range of other factors. This may serve as an initial step towards engaging with the symptom heterogeneity that has long been observed among patients with this condition.

The grotesque knot of the symptom: Heterogeneity and mutability

The present paper aims to shed light on some post-oedipal moments of the Freudian-Lacanian psychoanalysis. Going beyond the stereotypical opposition between the oedipal psychoanalysis and the anti-oedipal schizoanalysis, it endeavors to reinvestigate the semiotic nature of the knotenpunkt and the sinthome by applying some Deleuzian and Bakhtinian concepts. Thus, the knotenpunkt is described as a grotesque knot bringing together some heterogeneous elements. The involved disparate components establish a rhizomatic multiplicity irreducible to a common determiner. As far as the sinthome is concerned, it is also illustrated as a grotesque knot quilting the disseminated heterogeneous orders. In contrast to the dominant conception of the symptom with a complex mode of signifying (that is mainly bound to the oedipal topography), the knotenpunkt and the sinthome hold a kind of hyper-formative mode of signifying. As a result, the latter may be regarded as pure formators irreducible to a meaning or a certain interpretation. Finally, the paper sets out to analyze and evaluate the relationship between the sinthome and the foreclosure from a semiotic perspective. Accordingly, the sinthome is explained as a reply to foreclosure which is specifically a perceptive-imperative (retroactive) contemplation (in the light of law according to the Peircean phaneroscopy) on the rhizomatic multiplicity of psychosis (the case of schizophrenia).

Longitudinal diffusion imaging across the C9orf72 clinical spectrum

IntroductionDiscrepancies between diffusion tensor imaging (DTI) findings and functional rating scales in amyotrophic lateral sclerosis (ALS) may be due to symptom heterogeneity, particularly coexisting cognitive-behavioural dysfunction affecting non-motor regions of the brain. Carriers of expansion mutations in the C9orf72 gene, whose motor and cognitive-behavioural symptoms span a range from ALS to frontotemporal dementia, present an opportunity to evaluate the relationship between symptom heterogeneity and DTI changes.MethodsTwenty-eight C9orf72 mutation carriers with varied cognitive and motor symptoms underwent clinical evaluation and DTI imaging. Twenty returned for two or more follow-up evaluations. Each evaluation included motor, executive and behavioural scales and disease staging using the King’s college staging system.ResultsWidespread reduction of white matter integrity occurred in C9orf72 mutation carriers compared with 28 controls. The ALS Functional Rating Scale (ALSFRS-R) and King’s stage correlated with DTI measures of the corticospinal tract and mid-callosum. Cognitive and behavioural scores correlated with diffusion measures of frontal white matter. King’s stage, but not ALSFRS-R, correlated with anterior callosum DTI measures. Over a 6-month follow-up, DTI changes spread from anterior to posterior, and from deep to superficial subcortical white matter. In C9orf72 carriers with ALS or ALS-FTD, changes in corticospinal tractography measures correlated with changes in ALSFRS-R.ConclusionDiscrepancies between DTI findings and clinical measures of disease severity in ALS may partly be accounted for by cognitive-behavioural deficits affecting extramotor white matter tracts. Both ALSFRS-R and King’s stage correlated with corticospinal DTI measures. Group-level DTI changes could be detected over 6 months.