Dysfunctional Learning and Verbal Memory in Patients with Elevated Tau Protein Levels and Serum Recoverin Autoantibodies—Case Series and Review

Recoverin-antibody-related disease is currently restricted to late-onset ataxia and autoimmune retinopathy, which can be paraneoplastic or not. However, cognitive dysfunction associated with recoverin antibodies has not been reported so far in a homogeneous patient group. Our case series is dedicated to describing the novel phenotype of cognitive impairment associated with recoverin antibodies. We included five patients with cognitive impairment who presented serum recoverin autoantibodies detected by immunoblots in our case series investigation. We also analyzed their psychopathology, clinical data, cerebrospinal fluid (CSF), and neuroimaging data. Five patients with cognitive impairment associated with serum recoverin antibodies exhibited profound dysfunctional learning and verbal memory. In the CSF of 40% of them, we also diagnosed axonal neurodegeneration entailing elevated tau and phosphorylated tau protein levels. Psychopathologies such as affective symptoms (restlessness, depressive mood, anxiety, complaintiveness) and formal thought disorder, such as rumination, were detected in 25–75% of the patients. We hypothesized a role of recoverin autoimmunity in the pineal gland involving consecutive modulation of hippocampus-based memory caused by an altered release of melatonin. We describe a novel phenotype of possible recoverin autoimmunity in patients with cognitive impairment. However, no clear diagnostic clues can be extracted because of the low diagnostic validity of the testing strategies applied. The possibility of recoverin antibody autoimmunity in the pineal gland correlating with a modulation of hippocampus-based memory should be further investigated.

Progressive changes in descriptive discourse in First Episode of Schizophrenia: A longitudinal computational semantics study

Computational semantics, a branch of computational linguistics, involves automated meaning analysis that relies on how words occur together in natural language. This offers a promising tool to study schizophrenia. At present, we do not know if these word level choices in speech are sensitive to illness stage (i.e. acute untreated vs. stable established state), track cognitive deficits in major domains (e.g. cognitive control, processing speed) and relate to established dimensions of formal thought disorder. Here we study samples of descriptive discourse in patients with untreated first episode of schizophrenia (x̅ 2.8 days of lifetime daily dose exposure) and healthy subjects (246 samples of 1-minute speech; n=82, FES=46, HC=36) using a co-occurrence based vector embedding of words. We obtained six-month follow-up data in a subsample (99 speech samples, n=33, FES=20, HC=13). At baseline, the evidence for higher semantic similarity during descriptive discourse in FES was substantial, compared to null difference ( Bayes Factor =6 for full description; 32 for 10-words window). Moreover, the was a linear increase in semantic similarity with time in FES compared to HC (Bayes Factor= 6). Higher semantic similarity related to lower Stroop performance (accuracy and interference, response time), and was present irrespective of the severity of clinically ascertained thought disorder. Automated analysis of non-intrusive 1-minute speech samples provides a window on cognitive control deficits, role functioning and tracks latent progression in schizophrenia.

Implications for Early Diagnosis and Treatment in Schizophrenia Due to Correlation between Auditory Perceptual Deficits and Cognitive Impairment

It is indicated that auditory perception deficits are present in schizophrenia and related to formal thought disorder. The purpose of the present study was to investigate the association of auditory deficits with cognitive impairment in schizophrenia. An experimental group of 50 schizophrenia patients completed a battery of auditory processing evaluation and a neuropsychological battery of tests. Correlations between neuropsychological battery scores and auditory processing scores were examined. Cognitive impairment was correlated with auditory processing deficits in schizophrenia patients. All neuropsychological test scores were significantly correlated with at least one auditory processing test score. Our findings support the coexistence of auditory processing disorder, severe cognitive impairment, and formal thought disorder in a subgroup of schizophrenia patients. This may have important implications in schizophrenia research, as well as in early diagnosis and nonpharmacological treatment of the disorder.

The clinical relevance of formal thought disorder in the early stages of psychosis: results from the PRONIA study

Background Formal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This study aimed to identify stable and generalizable FTD-subgroups of patients with recent-onset psychosis (ROP) by applying a comprehensive data-driven clustering approach and to test the validity of these subgroups by assessing associations between this FTD-related stratification, social and occupational functioning, and neurocognition. Methods 279 patients with ROP were recruited as part of the multi-site European PRONIA study (Personalised Prognostic Tools for Early Psychosis Management; www.pronia.eu). Five FTD-related symptoms (conceptual disorganization, poverty of content of speech, difficulty in abstract thinking, increased latency of response and poverty of speech) were assessed with Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). Results The results with two patient subgroups showing different levels of FTD were the most stable and generalizable clustering solution (predicted clustering strength value = 0.86). FTD-High subgroup had lower scores in social (pfdr < 0.001) and role (pfdr < 0.001) functioning, as well as worse neurocognitive performance in semantic (pfdr < 0.001) and phonological verbal fluency (pfdr < 0.001), short-term verbal memory (pfdr = 0.002) and abstract thinking (pfdr = 0.010), in comparison to FTD-Low group. Conclusions Clustering techniques allowed us to identify patients with more pronounced FTD showing more severe deficits in functioning and neurocognition, thus suggesting that FTD may be a relevant marker of illness severity in the early psychosis pathway.

Differences in single positive formal thought disorder symptoms between closely matched acute patients with schizophrenia and mania

Formal thought disorders (FTD) are a hallmark diagnostic feature of schizophrenia (SZ) and (bipolar) mania (MA). FTD can be separated into positive (pFTD) and negative dimensions. It is unclear whether there are differences in pFTD on a single symptom level between acutely ill patients with SZ and MA, which cannot be attributed to cognitive impairment. We compared single pFTD symptoms in two groups of acutely ill patients with ICD-10 bipolar mania and schizophrenia, closely matched for age, sex, pFTD TALD score, verbal IQ and neuropsychological test performance (executive function, verbal fluency, attention, and working memory). SZ patients had higher severity of the TALD symptoms “perseverations” and “poverty of content of speech” than those with MA (Mann–Whitney U, significant, Bonferroni corrected). Speech in acute SZ patients differs from MA in that it conveys little information and adheres to previously mentioned ideas and topics. Matching for confounding variables, such as IQ and cognition, is important when comparing patients with different diagnoses.

Psychopathological Syndromes Across Affective and Psychotic Disorders Correlate With Gray Matter Volumes

Introduction More than a century of research on the neurobiological underpinnings of major psychiatric disorders (major depressive disorder [MDD], bipolar disorder [BD], schizophrenia [SZ], and schizoaffective disorder [SZA]) has been unable to identify diagnostic markers. An alternative approach is to study dimensional psychopathological syndromes that cut across categorical diagnoses. The aim of the current study was to identify gray matter volume (GMV) correlates of transdiagnostic symptom dimensions. Methods We tested the association of 5 psychopathological factors with GMV using multiple regression models in a sample of N = 1069 patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for MDD (n = 818), BD (n = 132), and SZ/SZA (n = 119). T1-weighted brain images were acquired with 3-Tesla magnetic resonance imaging and preprocessed with CAT12. Interactions analyses (diagnosis × psychopathological factor) were performed to test whether local GMV associations were driven by DSM-IV diagnosis. We further tested syndrome specific regions of interest (ROIs). Results Whole brain analysis showed a significant negative association of the positive formal thought disorder factor with GMV in the right middle frontal gyrus, the paranoid-hallucinatory syndrome in the right fusiform, and the left middle frontal gyri. ROI analyses further showed additional negative associations, including the negative syndrome with bilateral frontal opercula, positive formal thought disorder with the left amygdala-hippocampus complex, and the paranoid-hallucinatory syndrome with the left angular gyrus. None of the GMV associations interacted with DSM-IV diagnosis. Conclusions We found associations between psychopathological syndromes and regional GMV independent of diagnosis. Our findings open a new avenue for neurobiological research across disorders, using syndrome-based approaches rather than categorical diagnoses.

Formal Thought Disorder and Self-Disorder: An Empirical Study

Background: Formal thought disorder was constitutively linked to the original concept of schizophrenia and has since been one of central features supporting its diagnosis. Bleuler considered formal thought disorder as a fundamental symptom of schizophrenia among other fundamental symptoms, including ego disorders. The contemporary concept of self-disorder represents a more developed, nuanced, and systematic approach to disturbances of self-experience than the Bleulerian concept of ego disorders. As fundamental symptoms, on Bleuler's account, are persistently present in every case, an association between these symptoms could be expected. The purpose of this study was to examine the association between self-disorder and formal thought disorder.Methods: A sample of 94 diagnostically heterogeneous patients was examined for formal thought disorder using clinical rating and a proverb test. The proverb test was analyzed for two different aspects of formal thought disorder: literal responses and bizarre responses. The sample was comprehensively assessed for psychopathology, including self-disorder as measured with the Examination of Anomalous Self-Experience scale.Results: The patients, who provided bizarre responses, had a higher level of self-disorder, more negative symptoms, lower level of social functioning, and lower level of intelligence. Bizarre answers aggregated in patients diagnosed within the schizophrenia spectrum compared with patients outside the schizophrenia spectrum. We found moderate correlations between the two measures of formal thought disorder (clinically rated and bizarre responses) and self-disorder (0.454 [p &lt; 0.01] and 0.328 [p &lt; 0.01]). Literal responses did not differ between diagnostic groups and also did not correlate with bizarre responses. Specificity of bizarre responses for a diagnosis within schizophrenia spectrum was 86.89%, whereas sensitivity was 40.85%.Conclusion: The close relation between formal thought disorder and self-disorder further adds to the notion of self-disorder as a unifying psychopathological core beneath the apparently heterogeneous symptoms of schizophrenia.