The distribution of Cat-301 immunoreactivity in the cerebral cortex

The distribution of the monoclonal antibody Cat -301 was examined in the cerebral cortex of macaque monkeys. Throughout the cerebral cortex, Cat -301 labelled the soma and proximal dendrites of a restricted population of neurones. The distribution was uniform within cytoarchitecturally defined areas (or subareas) but varied between them, with respect to the density of labelled neurones, the intensity of their immunoreactivity, their morphology, and their laminar distribution.Large numbers of intensely immunopositive neurones were evident in motor related areas in the frontal lobe, somatosensory areas in the parietal lobe, and areas specialised for the analysis of visual motion in the parietal and occipital lobes. The heavily labelled areas are known to be interconnected, and the Cat -301 positive cells within them were concentrated in the laminae from which their cortico- cortical connections arise. Given the critical role of somatosensory and visuospatial information in the execution of somatic and ocular movements, the heavily labelled areas may be regarded as sharing a broadly motor function.The timing of the expression of the antigen recognised by Cat -301 during development, its peri- synaptic localisation and its biochemical characteristics suggest that it may play a role in the stabilisation of 8 synaptic connections. Cat -301 may label networks of areas with a similar functional specialisation because the antigen plays such a role in relation to the specific interconnections that exist between them

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

Association of Age, Antipsychotic Medication, and Symptom Severity in Schizophrenia with Proton Magnetic Resonance Spectroscopy Brain Glutamate Level:A Mega-analysis of Individual Participant-Level Data

Importance: Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear.Objective: To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites.Data Sources: The MEDLINE database was searched to identify journal articles published between January 1, 1980, and June 3, 2020, using the following search terms: MRS or magnetic resonance spectroscopy and (1) schizophrenia or (2) psychosis or (3) UHR or (4) ARMS or (5) ultra-high risk or (6) clinical high risk or (7) genetic high risk or (8) prodrome∗ or (9) schizoaffective. Authors of 114 1H-MRS studies measuring glutamate (Glu) levels in patients with schizophrenia were contacted between January 2014 and June 2020 and asked to provide individual participant data.Study Selection: In total, 45 1H-MRS studies contributed data.Data Extraction and Synthesis: Associations of Glu, Glu plus glutamine (Glx), or total creatine plus phosphocreatine levels with age, antipsychotic medication dose, symptom severity, and functioning were assessed using linear mixed models, with study as a random factor.Main Outcomes and Measures: Glu, Glx, and Cr values in the medial frontal cortex (MFC) and medial temporal lobe (MTL).Results: In total, 42 studies were included, with data for 1251 patients with schizophrenia (mean [SD] age, 30.3 [10.4] years) and 1197 healthy volunteers (mean [SD] age, 27.5 [8.8] years). The MFC Glu (F1,1211.9= 4.311, P =.04) and Glx (F1,1079.2= 5.287, P =.02) levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant (F1,1395.9= 3.622, P =.06). In both patients and volunteers, the MFC Glu level was negatively associated with age (Glu to Cr ratio, F1,1522.4= 47.533, P &lt;.001; cerebrospinal fluid-corrected Glu, F1,1216.7= 5.610, P =.02), showing a 0.2-unit reduction per decade. In patients, antipsychotic dose (in chlorpromazine equivalents) was negatively associated with MFC Glu (estimate, 0.10 reduction per 100 mg; SE, 0.03) and MFC Glx (estimate, -0.11; SE, 0.04) levels. The MFC Glu to Cr ratio was positively associated with total symptom severity (estimate, 0.01 per 10 points; SE, 0.005) and positive symptom severity (estimate, 0.04; SE, 0.02) and was negatively associated with level of global functioning (estimate, 0.04; SE, 0.01). In the MTL, the Glx to Cr ratio was positively associated with total symptom severity (estimate, 0.06; SE, 0.03), negative symptoms (estimate, 0.2; SE, 0.07), and worse Clinical Global Impression score (estimate, 0.2 per point; SE, 0.06). The MFC creatine level increased with age (estimate, 0.2; SE, 0.05) but was not associated with either symptom severity or antipsychotic medication dose.Conclusions and Relevance: Findings from this mega-analysis suggest that lower brain Glu levels in patients with schizophrenia may be associated with antipsychotic medication exposure rather than with greater age-related decline. Higher brain Glu levels may act as a biomarker of illness severity in schizophrenia..</p

Discovery of the Interstellar Chiral Molecule Propylene Oxide (CH3_3CHCH2_2O)

Life on Earth relies on chiral molecules, that is, species not superimposable on their mirror images. This manifests itself in the selection of a single molecular handedness, or homochirality, across the biosphere. We present the astronomical detection of a chiral molecule, propylene oxide (CH$_3$CHCH$_2$O), in absorption toward the Galactic Center. Propylene oxide is detected in the gas phase in a cold, extended molecular shell around the embedded, massive protostellar clusters in the Sagittarius B2 star-forming region. This material is representative of the earliest stage of solar system evolution in which a chiral molecule has been found