Abstract: "Objective To use resting-state functional magnetic resonance imaging to characterize disease-related, risk-related, and symptom-related changes of corticostriatal functional circuitry in patients with first-episode psychosis and their unaffected first-degree relatives. Design, Setting, and Participants This case-control cross-sectional study was conducted at a specialist early psychosis clinic, GlaxoSmithKline Clinical Unit, and magnetic resonance imaging facility. Nineteen patients with first-episode psychosis, 25 of their unaffected first-degree relatives, and 26 healthy control subjects were included in this study. Main Outcomes and Measures Voxelwise statistical parametric maps testing differences in the strength of functional connectivity between 6 striatal seed regions of interest (3 caudate and 3 putamen) per hemisphere and all other brain regions. Results Disease-related changes, reflecting differences between patients and control subjects, involved widespread dysregulation of corticostriatal systems characterized most prominently by a dorsal-to-ventral gradient of hypoconnectivity to hyperconnectivity between striatal and prefrontal regions. A similar gradient was evident in comparisons between relatives and control subjects, identifying it as a genetically inherited risk phenotype. In patients, functional connectivity in risk-affected and disease-affected dorsal frontostriatal circuitry correlated with the severity of both positive and negative symptoms."

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Abstract: "There is a worse prognosis for psychosis and schizophrenia when onset is in childhood or adolescence. However, outcomes are improved with early detection and treatment. Psychotic symptoms can be associated with a variety of disorders including schizophrenia, schizoaffective disorder, drug-induced psychosis, personality disorder, epilepsy and autistic spectrum disorder. Positive symptoms include hallucinations and delusions. Negative symptoms include apathy, lack of drive, poverty of speech, social withdrawal and self-neglect. The DSM IV criteria for schizophrenia include two or more of the following: hallucinations, delusions, disorganised speech, grossly disorganised or catatonic behaviour and negative symptoms. Adults may raise concerns about social withdrawal, bizarre ideas, a change in behaviour or a decline in achievement. Most children and young people with psychotic symptoms will not go on to develop psychosis or schizophrenia. Direct enquiry may be needed to elicit suspected unusual beliefs or hallucinations. To distinguish unusual ideas from delusions the ideas should be tested for fixity. For example by asking: 'Are you sure? Could there be another explanation?' Mood and anxiety symptoms should be explored. The assessment should include a developmental history with particular attention to premorbid functioning. Failure to make expected progress whether personal, social or academic is significant. Better outcomes in terms of symptoms and social function are associated with a shorter duration of untreated psychosis. The detection of psychotic symptoms in primary care therefore warrants an urgent referral to secondary care mental health services for assessment and treatment."

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Abstract: "Background Voltage-gated potassium channel (VGKC)-complex antibodies can be associated with a range of immunotherapy-responsive clinical presentations including limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. However, there are patients with positive levels in whom the significance is uncertain. Objective To evaluate the clinical significance associated with positive (>100 pM) VGKC-complex antibodies. Methods Over a 4-year period, 1053 samples were sent for testing of which 55 were positive. The clinical presentations, final diagnoses and responses to immunotherapies, when given, were assessed retrospectively and the likelihood of autoimmunity was categorised as definite, possible, unlikely or undetermined (modified from Zuliani et al 2012). Results Only 4 of the 32 patients with low-positive (100–400 pM) levels were considered definitely autoimmune, 3 with peripheral nerve hyperexcitability and 1 with a thymoma; 3 were given immunotherapies. Of the remaining 28 with low-positive levels, 13 (3 of whom had tumours) were considered possibly autoimmune, and 15 were unlikely or undetermined; 1 was given immunotherapy unsuccessfully. Of the 23 patients with high-positive (>400 pM) levels, 12 were given immunotherapies, 11 of whom showed a good response. 11 were considered definitely autoimmune, 10 with limbic encephalitis (antibody specificity: 5 LGI1, 1 contactin2, 2 negative, 2 untested) and 1 with a tumour. In the remaining 12, autoimmunity was considered possible (n=9; most had not received immunotherapies), or unlikely (n=3). Conclusions As antibody testing becomes more widely available, and many samples are referred from patients with less clear-cut diagnoses, it is important to assess the utility of the results. VGKC-complex antibodies in the range of 100–400 pM (0.1–0.4 nM) were considered clinically relevant in rare conditions with peripheral nerve hyperexcitability and appeared to associate with tumours (12.5%). By contrast high-positive (>400 pM; >0.4 nM) levels were considered definitely (38%) or possibly (49%) clinically relevant, but not all patients had a ‘classical’ limbic encephalitis and some did not receive immunotherapies."

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