Street slang and schizophrenia

We report the case of a 26 year old streetwise young postman who presented with a six month history of reduced occupational and social function, low mood, and lack of motivation. He complained of feeling less sociable and less interested in his friends and of being clumsy and finding it harder to think. He was otherwise fit and healthy, with no physical abnormalities, neurological signs, or objective cognitive impairments. There was no history of a recent stressor that might have precipitated his symptoms. He was referred to a specialist service for patients in the prodromal phase of psychotic illness for further assessment after he had seen his general practitioner and the local community mental health team. The differential diagnosis at this stage was depression, the prodrome of schizophrenia, or no formal clinical disorder. His premorbid occupational and social function had been good. There was no history of abnormal . social, language, and motor development and he left school with two A levels. After three years of service at the post office he had been promoted to a supervisory role. He had a good relationship with his family and had six or so good friends. There has been a number of previous heterosexual relationships, although none in the past year. Aside from smoking cannabis on two occasions when he was 19, there was no history of illicit substance use. Detailed and repeated assessment of his mental state found a normal affect, no delusions, hallucinations, or catatonia, and no cognitive dysfunction. His speech, however, was peppered with what seemed (to his middle class and older psychiatrist) to be an unusual use of words, although he said they were street slang (table).Go It was thus unclear whether he was displaying subtle signs of formal thought disorder (manifest as disorganised speech, including the use of unusual words or phrases, and neologisms) or using a "street" argot. This was a crucial diagnostic distinction as thought disorder is a feature of psychotic illnesses and can indicate a diagnosis of schizophrenia. We sought to verify his explanations using an online dictionary of slang (urbandictionary.com). To our surprise, many of the words he used were listed and the definitions accorded with those he gave (see table). We further investigated whether his speech showed evidence of thought disorder by examining recordings of his speech as he described a series of ambiguous pictures from the thematic apperception test, a procedure that elicits thought disordered speech. His speech was transcribed and rated with the thought and language index, a standardised scale for assessing thought disorder. Slang used in a linguistically appropriate way is not scored as abnormal on this scale. His score was 5.25, primarily reflecting a mild loosening of associations. For example, he described a picture of a boat on a lake thus: "There’s a boat and a tree. There seems to be a reflection. There are no beds, and I wonder why there are no beds. There’s a breeze going through the branches of the tree." His score was outside the normal range (mean for normal controls 0.88, SD 1.15) and indicates subtle thought disorder, equivalent to that evident in remitted patients with schizophrenia (mean in remitted patients 3.89, SD 2.56) but lower than that in patients with formal thought disorder (mean 27.4, SD 8.3). Over the following year his social and occupational functioning deteriorated further, and he developed frank formal thought disorder as well as grandiose and persecutory delusions to the extent that he met DSM-IV criteria for schizophrenia. His speech was assessed as before, and the thought and language index score had increased to 11.75. This mainly reflected abnormalities on items comprising "positive" thought disorder, particularly the use of neologisms such as "chronocolising" and non-sequiturs. To our knowledge this is the first case report to describe difficulties in distinguishing "street" argots from formal thought disorder. It is perhaps not surprising that slang can complicate the assessment of disorganised speech as psychotic illnesses usually develop in young adults, whereas the assessing clinician is often from an older generation (and different sociocultural background) less familiar with contemporary urban slang. Online resources offer a means of distinguishing street argot from neologisms or a peculiar use of words, and linguistic rating scales may be a useful adjunct to clinical assessment when thought disorder is subtle. Differentiating thought disorder from slang can be especially difficult in the context of "prodromal" signs of psychosis, when speech abnormalities, if present, are usually subtle. Nevertheless, accurate speech assessment is important as subtle thought disorder can, as in this case, predate the subsequent onset of schizophrenia, and early detection and treatment of psychosis might be associated with a better long term clinical outcome

The role of genes, stress, and dopamine in the development of schizophrenia

The dopamine hypothesis is the longest standing pathoetiologic theory of schizophrenia. Because it was initially based on indirect evidence and findings in patients with established schizophrenia, it was unclear what role dopamine played in the onset of the disorder. However, recent studies in people at risk of schizophrenia have found elevated striatal dopamine synthesis capacity and increased dopamine release to stress. Furthermore, striatal dopamine changes have been linked to altered cortical function during cognitive tasks, in line with preclinical evidence that a circuit involving cortical projections to the striatum and midbrain may underlie the striatal dopamine changes. Other studies have shown that a number of environmental risk factors for schizophrenia, such as social isolation and childhood trauma, also affect presynaptic dopaminergic function. Advances in preclinical work and genetics have begun to unravel the molecular architecture linking dopamine, psychosis, and psychosocial stress. Included among the many genes associated with risk of schizophrenia are the gene encoding the dopamine D2 receptor and those involved in the upstream regulation of dopaminergic synthesis, through glutamatergic and gamma-aminobutyric acidergic pathways. A number of these pathways are also linked to the stress response. We review these new lines of evidence and present a model of how genes and environmental factors may sensitize the dopamine system so that it is vulnerable to acute stress, leading to progressive dysregulation and the onset of psychosis. Finally, we consider the implications for rational drug development, in particular regionally selective dopaminergic modulation, and the potential of genetic factors to stratify patients

Reduced mu opioid receptor availability in schizophrenia revealed with [11C]-carfentanil positron emission tomographic Imaging.

Negative symptoms, such as amotivation and anhedonia, are a major cause of functional impairment in schizophrenia. There are currently no licensed treatments for negative symptoms, highlighting the need to understand the molecular mechanisms underlying them. Mu-opioid receptors (MOR) in the striatum play a key role in hedonic processing and reward function and are reduced post-mortem in schizophrenia. However, it is unknown if mu-opioid receptor availability is altered in-vivo or related to negative symptoms in schizophrenia. Using [11 C]-carfentanil positron emission tomography (PET) scans in 19 schizophrenia patients and 20 age-matched healthy controls, here we show a significantly lower MOR availability in patients with schizophrenia in the striatum (Cohen's d = 0.7), and the hedonic network. In addition, we report a marked global increase in inter-regional covariance of MOR availability in schizophrenia, largely due to increased cortical-subcortical covariance

Glutamate, N-acetyl aspartate and psychotic symptoms in chronic ketamine users

Rationale: Ketamine, a non-competitive NMDA receptor antagonist, induces acute effects resembling the positive, negative and cognitive symptoms of schizophrenia. Chronic use has been suggested to lead to persistent schizophrenia-like neurobiological changes. Objectives: This study aims to test the hypothesis that chronic ketamine users have changes in brain neurochemistry and increased subthreshold psychotic symptoms compared to matched poly-drug users. Methods: Fifteen ketamine users and 13 poly-drug users were included in the study. Psychopathology was assessed using the Comprehensive Assessment of At-Risk Mental State. Creatine-scaled glutamate (Glu/Cr), glutamate + glutamine (Glu + Gln/Cr) and N-acetyl aspartate (NAA/Cr) were measured in three brain regions—anterior cingulate, left thalamus and left medial temporal cortex using proton magnetic resonance spectroscopy. Results: Chronic ketamine users had higher levels of subthreshold psychotic symptoms (p < 0.005, Cohen’s d = 1.48) and lower thalamic NAA/Cr (p < 0.01, d = 1.17) compared to non-users. There were no differences in medial temporal cortex or anterior cingulate NAA/Cr or in Glu/Cr or Glu + Gln/Cr in any brain region between the two groups. In chronic ketamine users, CAARMS severity of abnormal perceptions was directly correlated with anterior cingulate Glu/Cr (p < 0.05, r = 0.61—uncorrected), but NAA/Cr was not related to any measures of psychopathology. Conclusions: The finding of lower thalamic NAA/Cr in chronic ketamine users may be secondary to the effects of ketamine use compared to other drugs of abuse and resembles previous reports in individuals at genetic or clinical risk of schizophrenia

Brain volume in chronic ketamine users - Relationship to sub-threshold psychotic symptoms and relevance to schizophrenia

RATIONALE: Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. OBJECTIVES: We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group. METHODS: Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users. RESULTS: Ketamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p \u3c 0.05; Cohen\u27s d = 0.36-0.75). Within the cortex, ketamine users had significantly lower grey matter volumes within the frontal, temporal and parietal cortices (Cohen\u27s d 0.7-1.31; FDR p \u3c 0.05). They also had significantly higher sub-threshold psychotic symptoms (p \u3c 0.05). Frequency of ketamine use showed an inverse correlation with cerebellar volume (p \u3c 0.001), but there was no relationship between regional brain volumes and sub-threshold psychotic symptoms. CONCLUSIONS: Chronic ketamine use may cause lower grey matter volumes as well as inducing sub-threshold psychotic symptoms, although these likely arise through distinct mechanisms

Correction: A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

This article was published online on June 27, 2022. An error was subsequently identified in the article, and the following correction should be noted: In the original publication, section 4.6, page 667, the reference cited in the first full sentence in column 2 and in Table 5 on the same page that read: “This information can be used to optimize clozapine dosage (Table 5) [103].” “Table 5 Therapeutic drug monitoring (TDM)-informed decision-making algorithm for clozapine-treated patientsa [103]” “Adapted by permission from reference [103]” Should read: “This information can be used to optimize clozapine dosage (Table 5) [104].” “Table 5 Therapeutic drug monitoring (TDM)-informed decision-making algorithm for clozapine-treated patientsa [104]” “Adapted by permission from reference [104]” The original article has been corrected. © The Author(s) 2022

A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

Treatment-resistant schizophrenia (TRS) will affect about one in three patients with schizophrenia. Clozapine is the only treatment approved for TRS, and patients should be treated as soon as possible to improve their chances of achieving remission. Despite its effectiveness, concern over side effects, monitoring requirements, and inexperience with prescribing often result in long delays that can expose patients to unnecessary risks and compromise their chances of achieving favorable long-term outcomes. We critically reviewed the literature on clozapine use in TRS, focusing on guidelines, systematic reviews, and algorithms to identify strategies for improving clozapine safety and tolerability. Based on this, we have provided an overview of strategies to support early initiation of clozapine in patients with TRS based on the latest evidence and our clinical experience, and have summarized the key elements in a practical, evidence-based checklist for identifying and managing patients with TRS, with the aim of increasing confidence in prescribing and monitoring clozapine therapy

Cognitive dysfunction in schizophrenia: An expert group paper on the current state of the art.

Cognitive impairment in schizophrenia represents one of the main obstacles to clinical and functional recovery. This expert group paper brings together experts in schizophrenia treatment to discuss scientific progress in the domain of cognitive impairment to address cognitive impairments and their consequences in the most effective way. We report on the onset and course of cognitive deficits, linking them to the alterations in brain function and structure in schizophrenia and discussing their role in predicting the transition to psychosis in people at risk. We then address the assessment tools with reference to functioning and social cognition, examining the role of subjective measures and addressing new methods for measuring functional outcomes including technology based approaches. Finally, we briefly review treatment options for cognitive deficits, focusing on cognitive remediation programs, highlighting their effects on brain activity and conclude with the potential benefit of individualized integrated interventions combing cognitive remediation with other approaches

A cross-sectional MR study of body fat volumes and distribution in chronic schizophrenia

Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265AbstractPeople with schizophrenia show higher risk for abdominal obesity than the general population, which could contribute to excess mortality. However, it is unclear whether this is driven by alterations in abdominal fat partitioning. Here, we test the hypothesis that individuals with schizophrenia show a higher proportion of visceral to total body fat measured using magnetic resonance imaging (MRI). We recruited 38 participants with schizophrenia and 38 healthy controls matched on age, sex, ethnicity, and body mass index. We found no significant differences in body fat distribution between groups, suggesting that increased abdominal obesity in schizophrenia is not associated with altered fat distribution.</jats:p

The relationship between glutamate, dopamine, and cortical gray matter: A simultaneous PET-MR study

Prefrontal cortex has been shown to regulate striatal dopaminergic function via glutamatergic mechanisms in preclinical studies. Concurrent disruption of these systems is also often seen in neuropsychiatric disease. The simultaneous measurement of striatal dopamine signaling, cortical gray matter, and glutamate levels is therefore of major interest, but has not been previously reported. In the current study, twenty-eight healthy subjects underwent 2 simultaneous [11C]-( + )-PHNO PET-MRI scans, once after placebo and once after amphetamine in a double-blind randomized cross-over design, to measure striatal dopamine release, striatal dopamine receptor (D2/3R) availability, anterior cingulate glutamate+glutamine (Glx) levels, and cortical gray matter volumes at the same time. Voxel-based morphometry was used to investigate associations between neurochemical measures and gray matter volumes. Whole striatum D2/3R availability was positively associated with prefrontal cortex gray matter volume (pFWE corrected = 0.048). This relationship was mainly driven by associative receptor availability (pFWE corrected = 0.023). In addition, an interaction effect was observed between sensorimotor striatum D2/3R availability and anterior cingulate Glx, such that in individuals with greater anterior cingulate Glx concentrations, D2/3R availability was negatively associated with right frontal cortex gray matter volumes, while a positive D2/3R-gray matter association was observed in individuals with lower anterior cingulate Glx levels (pFWE corrected = 0.047). These results are consistent with the hypothesis that the prefrontal cortex is involved in regulation of striatal dopamine function. Furthermore, the observed associations raise the possibility that this regulation may be modulated by anterior cingulate glutamate concentrations